BASIC AND TRANSLATIONAL MEDICINE
BASIC RESEARCH OF CARDIOVASCULAR DISEASE
[GW30-e0006]
Qing Wang, Huiming Zhang, Congping Su, Hui Luo, Wenchao Jiao, Shuzhen Guo
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
OBJECTIVES The aim of this study was to evaluate the protective effect of sweroside on excessive isoproterenol induced heart failure in mice and to explore its target and mechanism.
METHODS Heart failure mice model was established by subcutaneous injection of excessive isoprenaline. Mice were randomly divided into four groups including control group, model group, sweroside group and captopril group. Cardiac function was evaluated by echocardiography, myocardial pathological changes were detected by Hematoxylin and eosin staining (HE staining). Drug targets were predicted by BAT-MAN-TCM database, and protein expression was detected by Western blot.
RESULTS Compared with the control group, the left ventricle ejection fraction (LVEF) and left ventricle fractional shortening (LVFS) of the model group decreased by 37.84 and 48.04% respectively. Left ventricular internal systolic diameter (LVIDs) increased to about 3.06±0.51 mm (1.86±0.59 mm in the control group), with an increase of more than 50%. Compared with the model group, EF of sweroside group increased to 71.83±4.82%, which was close to the control group, FS increased by 71.79%, LVIDs decreased by 30.82%. The above data had statistical significance (P<0.01). In Histopathological examination, thinned left ventricular wall, thinned myocardial fiber, scattered necrosis of myocardial cells, as well as aggregation of inflammatory cells were found in model mice. The morphology of myocardial tissue were obtained approximate normal by sweroside. The BAT-MAN-TCM database suggests that sweroside may play a therapeutic role in heart failure through ATPase Na+/K+Transporting Subunit Alpha1(ATP1A1). Western blot results showed that ATP1A1 protein expression was down-regulated in the model group, and the content of ATP1A1 protein was increased in the sweroside group.
CONCLUSIONS Sweroside can significantly improve the heart failure induced by excessive isoproterenol in mice, and the mechanism may be related to the increase of ATP1A1 protein expression and the improvement of myocardial energy metabolism.
[GW30-e0011]
Yarmolenko Olga, Bumeister Valentyna, Prykhodko Olga, Demikhova Nadiia, Bumeister Lina, Khotyeev Yegor
Sumy State University
OBJECTIVES Diabetes mellitus is one of the most common non-communicable diseases. Today, more than 382 million people with diabetes live on the planet. The dynamics of development is increasing every year. Diabetes mellitus is one of the main causes of cardiovascular pathologies. The purpose of our work was to establish the age-old peculiarities of the effect of alloxan diabetes on the heart of rats. The features of changes in internal organs are studied on experimental animal models in order to improve the methods of correction of adverse effects of diabetes mellitus on the body and, in particular, on the heart. One of the inductors of diabetes is alloxan.
METHODS The study was performed on 12 mature and 12 young white male rats, divided into two groups: control and experimental (6 in each). Animal retention and experiments were carried out in accordance with the requirements of the “General Ethical Principles of Animal Experiments”, adopted by the First National Congress on Bioethics (Kyiv, 2001). Animals of the experimental group administered once daily alloxan intraperitoneally at a dose of 40 mg/kg. From the 7th to the 10th day after the administration of alloxan, the level of glucose in the blood that was steadily elevated was measured. One month after the induction, the animals were withdrawn from the experiment with an anesthetized lung of decapitation. Hearts were digested according to the method of Avtandilov, separately weighed parts of the heart behind Muller. For histological examination, the ventricles were fixed in a 10% neutral formalin solution over the course of the day, dehydrated in alcohols of increasing concentration, and poured into paraffin. The sections of the myocardium were stained with hematoxylin-eosin and studied using a light microscope Olympus BH-2.
RESULTS Under conditions of alloxan diabetes in mature rats there is an increase in the heart mass by 41.09% (P<0.0001), left ventricle is 56% (P><0.0001), right ventricle is 31.46% (P><0.0001), the left ventricle area was 31.77% (P><0.0001), right ventricle 45.89% (P=0.0008). Atrial weight decreases by 64% (P><0.0001), the ventricular index is 14.94% (P=0.0014), the planimetric index is unreliable. Histologically, the polymorphism of nuclei of cardio-myocytes, local disorientation of muscle fibers and their cytolysis were revealed. Spacing gaps are expanded (stromal edema). Vessels of uneven filling: in some fields, the vessels are empty, in others – the aggregation of erythrocytes in vessels, capillary hyperemia, edema around the vessels. In young rats, an increase in left ventricular mass is observed at 33.48% (P=0.0327), left ventricular area is 18.22% (P=0.0061), right ventricle is 20% (P=0.0287). Atrial weight decreases by 38.78% (P=0.0035), ventricular index is 15.19% (P=0.0036). Other indicators are unreliable. Histologically – the polymorphism of the nuclei of cardiomyocytes, the disorientation of muscle fibers. Unidirectional contents of the vessel: in some fields the vessels are empty, in others the aggregation of red blood cells.
CONCLUSIONS In alloxan diabetes, an increase in the mass of the heart with an overwhelming left ventricular hypertrophy, cardiomyocytes and vascular disorders in the myocardium of experimental animals was detected. The violations of the structural components of the wall of the heart are detected. This indicates a low functional activity of the heart, which leads to cardiovascular pathologies.
[GW30-e0029]
Xin Su, Daoquan Peng
The Second Xiangya Hospital of Central South University
OBJECTIVES Obesity is associated with metabolic syndromes. The hallmark of obesity is excessive lipid storage in adipose tissue. As is known, the adipose tissue has such abundant adipose-derived mesenchymal stem cells (AMSCs), which can differentiate into mature adipocytes by imbalance between energy intake and expenditure.
Apolipoprotein A5 (ApoA5) is a novel apolipoprotein. Recently, evidence indicates that lower plasma level of ApoA5 was found in obese subjects and was inversely correlated with BMI. However, the underlying mechanisms are ambiguous. On the other hand, it is noteworthy that ApoA5 could also modulate TG storage in hepatocytes, indicating a crucial intracellular role of ApoA5 in TG metabolism. Since adipocytes provide the largest storage depot for TG, we hypothesized apoA5 might also target to adipocytes and regulate TG storage. The aims of this research were to explore the effect of ApoA5 in AMSCs adipogenesis and the underlying mechanisms.
METHODS We isolated AMSCs from the epigastric adipocyte tissue of the patients underwent abdominal surgery. The pre-adipocytes were treated with adipogenesis medium and human recombinant ApoA5 protein. Then we harvested cells at 7th, 14th, 21st days after adipogenesis. The following tests were performed: (1) effects of ApoA5 on morphological changes of intracellular lipid droplets were observed under microscope; (2) effects of ApoA5 on intracellular TG content were observed by spectrophotometry; (3) effects of ApoA1 on modulating the gene expression levels of the adipogenesis-related markers, such as C/EBPα, C/EBPβ, PPARγ, aP2 and FAS, were detected by PCR; (4) effects of ApoA1 on modulating the gene expression levels of CIDEC were detected by PCR; (5) distribution of ApoA5 and CIDEC were observed by confocal microscope; (6) ApoA5 antibody and CIDEC antibody were used for CO-IP observe whether ApoA5 interacts with CIDEC; (7) we silenced and over-expressed the CIDEC gene in AMSCs. The function of CIDEC in AMSCs adipogenesis was investigated and the effects of ApoA5 on CIDEC expression were detected; (8) the effect of ApoA5 on adipogenesis was further detected in AMSCs with CIDEC-silenced or over-expressed.
RESULTS The main results were listed as follows: (1) ApoA5 could reduce the amount of lipid droplets and decrease the TG content in adipocytes during the adipogenesis; (2) ApoA5 could down-regulate the gene expression level of C/EBPα, C/EBPβ, PPARγ, aP2 and FAS during the adipogenesis; (3) ApoA5 could down-regulate the gene and protein expression level of CIDEC during the adipogenesis; (4) ApoA5 co-localized and had interaction with CIDEC in the surface of lipid droplets; (5) the effect of ApoA5 on inhibiting adipogenesis was attenuated in AMSCs with SORT1 gene over-expression.
CONCLUSIONS In conclusions, our results confirm that CIDEC plays an important role in the adipogenesis of human AMSCs. Furthermore, the results indicate that apoA5 acts as a negative regulator of adipogenesis differentiation in human AMSCs through the inhibition of adipogenesis differentiation-related factors and the promotion the intracellular gene and expression level of CIDEC. The present data provide insight into the mechanisms of the inhibitory effects of ApoA5 and suggest that the inhibitory activity of ApoA5 indicates a potential pharmacological intervention specifically directed toward obesity.
[GW30-e0030]
Xin Su, Shuai Wang, Daoquan Peng
The Second Xiangya Hospital of Central South University
OBJECTIVES Obesity is associated with a series of metabolic syndromes. The hallmark of obesity is excessive lipid storage in adipose tissue. As is known, the adipose tissue has such abundant adipose-derived mesenchymal stem cells (AMSCs), which can differentiate into mature adipocytes by imbalance between energy intake and expenditure.
Apolipoprotein A1 (ApoA1) is the major protein component of HDL. In addition to anti-atherogenic function of ApoA1, recent works focused on ApoA1 in affecting the process of obesity and the lipid metabolism in mature adipocytes, demonstrating that APOA1 gene SNPs were related to obesity and reduced plasma ApoA1 level was associated with increased prevalence of obesity. However, the underlying mechanisms are ambiguous. The aim of this study was to examine the anti-obesity effect of ApoA1 and the potential mechanisms by which ApoA1 influencing human AMSCs adipogenesis.
METHODS We isolated AMSCs from the epigastric adipocyte tissue of the patients underwent abdominal surgery. The pre-adipocytes were treated with adipogenesis medium and ApoA1 protein. Then we harvested cells at 7th, 14th days after adipogenesis. The following tests were performed separately: (1) effects of ApoA1 on the morphological changes of intracellular lipid droplets were observed by Oil red O staining under microscope; (2) effects of ApoA1 on the intracellular TG content were observed by spectrophotometry; (3) effects of ApoA1 on modulating the expression levels of the adipogenesis-related markers, such as C/EBPα, C/EBPβ, FABP4 and FAS, were detected by PCR and Western Blot; (4) by lentiviral transfection technology, we silenced and over-expressed the SORT1 gene in AMSCs. The function of sortilin in AMSCs adipogenesis was investigated and the effects of ApoA1 on sortilin expression were detected by PCR and Western blot; (5) the effect of apoA1 on adipogenesis was further detected in AMSCs with SORT1-silenced or over-expressed.
RESULTS The main results were listed as follows: (1) ApoA1 could reduce the amount of lipid droplets and decrease the TG content synergistically in adipocytes during the adipogenesis; (2) ApoA1 could down-regulate the gene and protein expression level of C/EBPα, C/EBPβ, FABP4 and FAS during the adipogenesis; (3) Sortilin plays an important role in AMSCs adipogenesis. Silencing SORT1 gene could promote excessive adipogenesis of AMSCs, while over-expression of SORT1 gene inhibits the AMSCs adipogenesis; (4) ApoA1 could up-regulate the gene and protein level of sortilin during the adipogenesis; (5) the effect of ApoA1 on inhibiting adipogenesis was attenuated in AMSCs with silencing SORT1 gene; however, there was no significant changes of the effect of ApoA1 on inhibiting adipogenesis in AMSCs with overexpressed SORT1 gene.
CONCLUSIONS In conclusions, our results confirm that sortilin plays an important role in the adipogenesis of human AMSCs. Furthermore, the results indicate that ApoA1 acts as a negative regulator of adipogenesis differentiation in human AMSCs through the inhibition of adipogenesis differentiation-related factors and the promotion the intracellular gene and expression level of sortilin. The present data provide insight into the mechanisms of the inhibitory effects of ApoA1 and suggest that the inhibitory activity of ApoA1 indicates a potential pharmacological intervention specifically directed toward obesity.
[GW30-e0038]
Yajuan Ni, Deng Jie, Liu Xin, Li Qing, Ni Yajuan
Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University
OBJECTIVES Apoptosis of myocardial cells has been shown to be a critical step provoking heart failure. Studies indicated that mitochondrial oxidative stress and excessive production of mitochondrial ROS in heart failure was tightly linked to activation of apoptosis. ECH was used as a traditional Chinese herbal medicine, it has been shown to possess powerful ability of anti-oxidant and anti-apoptosis properties in kinds of cells, but whether it affects myocardial apoptosis in the heart failure remain unknown. The present study investigated the effects of ECH on heart failure and myocardial apoptosis of rats induced by ISO in vivo and on mitochondrial oxidative stress of AC-16 cells induced by ISO and explored the underlying mechanisms in vitro.
METHODS Heart failure rats were induced by ISO, ECH was treated by intraperitoneal injection, echocardiography was performed to evaluate heart function, TUNEL was used to detect myocardial apoptosis in vivo. In vitro AC-16 cells were cultured, mitochondrial oxidative stress was induced by ISO, ECH was pre-treated. Apoptotic cells were detected by flow cytometry, the level of mitochondrial ROS were measured by luminol chemiluminescence, 8-OHdG was used to evaluate the oxidative damage of mitochondrial DNA, mitochondrial membrane potential was detected by JC-1, carbonylation of mitochondrial proteins were measured using Elisa, mitochondrial lipid peroxidation were measured using TBARS assay, intracellular ROS were measured with flow cytometry.
RESULTS The results demonstrated that ECH significantly improved the heart function and reduced myocardial apoptosis of heart failure rats induced by ISO in vivo, and inhibited oxidative damage of mitochondrial DNA, protected mitochondrial membrane potential, reduced intracellular ROS, prevented carbonylation of mitochondrial proteins and mitochondrial lipid peroxidation, suppressed production of mitochondrial ROS, and -subsequently inhibited intracellular ROS of AC-16 cells induced by ISO in vitro.
CONCLUSIONS We concluded that ECH significantly inhibited myocardial apoptosis and improved heart function of heart failure rats induced by ISO via suppressing mitochondrial oxidative stress. It was suggested that ECH was a potential drug treatment for heart failure.
[GW30-e0051]
Wu Junyan 1 , Wang Lei 2 , Zhou Jiansheng 3 , Zhang Yanling 1
1Institute of Cardiovascular Diseases, Taian Maternal and Children’s Hospital, Taian, China
2Department of Pediatric Surgery, Soochow University Affiliated Children’s Hospital, Suzhou, China
3John Curtin School of Medical Research, Australian National University, Australia
OBJECTIVES Hydronephrosis is commonly caused by an obstruction of the urine flow from the kidney. The condition involves a dilation and distention of the renal pelvis. Hydronephrosis may be either acute or chronic in nature. It was reported a postnatal infant had hypoplastic left heart with hydronephrosis, indicating that there may be a relationship between hydronephrosis and heart disease. However, whether hydronephrosis causes cardiac damage and affects the RAS in the heart remains unknown. Thus, we assessed BP, heart weight and the expression of components of the RAS in the heart in hydronephrotic mice treated with AT1 receptor blockade and ACE inhibitor.
METHODS Hydronephrosis was induced by left ureteral ligation in Balb/C mice except sham-operated animals. Blood pressure was measured by the tail-cuff method using photoelectric volume oscillometry. At postmortem, heart weight was balanced. The levels of cardiac ACE, ACE2 and Mas receptor were measured by RT-PCR and Western blot after treatment of losartan or enalapril. Plasma renin activity (PRA), Ang I and Ang II were measured by radioimmunoassay using commercial kits.
RESULTS In the normal kidney the tubules were intact while they disappeared in the hydronephrotic kidney. Blood pressure did not significantly change after the left ureteral ligation. Hydronephrosis led to an increase of ACE level and a decreased of ACE2 and Mas receptor in the heart. Losartan decreased cardiac ACE level, but ACE2 and Mas receptor levels significantly increased in hydronephrotic mice (P<0.01). Enalapril increased ACE2 levels (P<0.01), but did not affect Mas receptor in the heart. PRA decreased in hydronephrotic mice, but significantly increased by losartan or enalapril. Plasma Ang II level decreased in hydronephrotic mice (P<0.05). Administration of losartan was accompanied by a rise in plasma Ang I and Ang II concentrations in hydronephrotic animals (P<0.05). Enalapril also increased levels of Ang I (P<0.01) and Ang II (P<0.05) in the circulation.
CONCLUSIONS In this study, we found that Hydronephrosis increased cardiac ACE, suppressed ACE2 and Mas receptor levels. Furthermore, AT1 blockade caused sustained activation of cardiac ACE2 and Mas receptor, but ACE inhibitor had the limitation of such activation of Mas receptor in hydronephrotic animals. These findings may lead to an exciting new area in the clinical administration of AT1 receptor blockade. These results also suggest that activation of cardiac ACE2 by both enalapril and losartan may protect against the adverse effects of activated RAS and renal impairment. Thus, we propose that the change of cardiac ACE2 and Mas receptor expression induced by hydronephrosis can be an important target of strategies for preventing cardiovascular damage. The observations of the different molecular mechanisms of losartan and enalapril could be helpful for better options in the treatment of cardiovascular diseases.
This study was supported by Science and Technology Department of Shandong Province (No. 2016GSF201207) and the Natural Science Foundation of China (No. 81270336). *equal contribution; #Correspondence.
[GW30-e0052]
Jia Su, Xiaomin Chen
Department of Cardiology, Ningbo No. 1 Hospital, Ningbo, Zhejiang, P.R. China
OBJECTIVES MicroRNA (miRNA) can be used as predictive biomarkers for cardiovascular diseases, especially for acute myocardial infarction (AMI). However, few reports have focused on the value of exosomal miRNAs in the mechanism of the pathophysiological process from stable coronary artery disease (SCAD) to AMI.
METHODS Exosomes were isolated via ExoQuick precipitation after serum samples were collected. The exosomes were then identified by transmission electron microscopy (TEM), Western blotting, and nanoparticle-tracking analysis (NTA). The differential expression of miRNAs in exosomes from 6 AMI and 6 matching SCAD patients was screened using Agilent Human miRNA Microarrays. Target genes of the candidate miRNAs were predicted via an online miRNA database, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Further validation was conducted through quantitative real-time PCR (qRT-PCR) with 60 exosome (30 AMI and 30 SCAD) samples.
RESULTS The expression of 13 miRNAs (miRNA-4507, miRNA-3656, miRNA-6803-5p, miRNA-7108-5p, miRNA-6850-5p, miRNA-4486, miRNA-6741-5p, miRNA-1227-5p, miRNA-3195, miRNA-4634, miRNA-7975, miRNA-6798-3p, and miRNA-1915-3p) was significantly down-regulated in the AMI samples compared with the SCAD samples. In addition, we identified various target genes that are mainly involved in the pathways of cardiac rehabilitation and remodelling, such as the signalling pathways activated downstream by Nerve Growth Factor (NGF) and Fibroblast growth Factor Receptors (FGFRs). Validation of the expression of candidate miRNAs indicated that exosomal miRNA-1915-3p, miRNA-4507, and miRNA-3656 were significantly less expressed in AMI samples than in SCAD samples, and ROC curve (AUC) analysis showed that the expression of these miRNAs resulted in good predictive accuracy [miRNA-1915-3p (AUC 0.772); miRNA-4507 (AUC: 0.684); and miRNA-3656 (AUC: 0.771)], suggesting that serum exosomal miRNA-1915-3p, miRNA-4507, and miRNA-3656 might be predictive for AMI at an early stage. Correlation analysis revealed that the expression of miRNA-1915-3p was negatively correlated with the PLT (r=–0.479, P=0.038), the expression of miRNA-4507 was negatively correlated with LDL-c (r=–0.5, P=0.029), and the expression of miRNA-3656 was related to the LVEF (r=0.471, P=0.042).
CONCLUSIONS Exosomal miRNA-1915-3p, miRNA-4507, and miRNA-3656 might play an important role in the pathophysiology of acute myocardial infarction and could serve as clinical diagnostic biomarkers.
[GW30-e0053]
Jia Su, Xiaomin Chen
Department of Cardiology, Ningbo No. 1 Hospital, Ningbo, Zhejiang, P.R. China
OBJECTIVES The failure of therapeutic response to clopidogrel in platelet inhibition, which is called clopidogrel resistance (CR), is more likely to cause cardiovascular events. We aimed to study the contribution of promoter DNA methylation of paraoxonase 1 (PON1) to the risk of clopidogrel poor response.
METHODS Through VerifyNow P2Y12 assay, patient’ platelet functions were measured. Among 57 non-CR and 49 CR patients, the levels of DNA -methylation in four CpG dinucleotides on the PON1 promoter were tested using bisulfite pyrosequencing technology. Besides, the relative expression of PON1 mRNA was analysed by quantitative real-time PCR. Logistic regression was applied to investigate the interatcion of PON1 methylation and clinical -factors in CR.
RESULTS In the subgroup with dyslipidaemia, we discovered that higher CpG4 levels of the PON1 promoter indicated a poorer clopidogrel response (cases versus controls (%): 51.500±14.742 versus 43.308±10.891, =0.036), and the PON1 mRNA expression was reduced in CR patients. Additionally, the logistic regression indicated that higher level of albumin and the index of ALT were related with a lower risk of CR, and the index of AST as well as the quantity of stent may be positively associated with CR.
CONCLUSIONS The DNA methylation of CpG4 in the PON1 promoter would lead to a low expression of PON1 mRNA, which might induce clopidogrel resistance in the patients with dyslipidaemia, and the number of stents might be a risk for CR.
[GW30-e0056]
Kun Lian, Ling Tao
Department of Cardiology, Xijing Hospital, Fourth Military Medical University
OBJECTIVES Diabetic patients are more sensitive tomyocardial ischemia-reperfusion (MI/R) injury. Branched-chain amino acids (BCAA) catabolism is defective and mitochondrial phosphatase 2C (PP2Cm) expression is reduced in the diabetic state. However, the role of PP2Cm and BCAA in diabetes with MI/R injury remains unclear. This study aims to determine the mechanism of reduced PP2Cm expression and investigate whether PP2Cm and BCAA have a cardioprotective effect in diabetes with MI/R injury.
METHODS C57BL/6 mice were fed a high-fat diet (HFD) and injected intraperitoneally with a dose of streptozotocin (25 mg/kg) twice to generate T2DM model mice. C57BL/6 mice (WT), type 2 diabetes (T2DM), PP2Cm–/– mice, were used in this study. For T2DM mice, PP2Cm-specific adenovirus was delivered to generate diabetic mice with PP2Cm overexpression. The T2DM mice were also treated with with BDK inhibitor BT2, while the PP2Cm–/– mice were treated with MnTBAP (manganese (III) tetrakis (4-benzoic acid)porphyrin chloride). Myocardial infarction/reperfusion (MI/R) was produced simultaneously in all types of mice. Additionally, WT and PP2Cm–/– mice treated with BT2 and expressing adenovirus were analyzed. H9C2 cells were treated with BCAA and BCKA. After H9C2 cells were treated with BCKA and underwent simulated ischemia-reperfusion (SI/R), BT2 and MnTBAP were added. Cardiac function, apoptosis, BCAA metabolism and oxidative damage were assayed.
RESULTS PP2Cm protein levels were significantly decreased in the diabetic heart. Under PP2Cm-overexpressing T2DM mice injury, cardiac function was improved due to a decrease of myocardial infarct size and the increase of LVEF. The Apoptosis rate was decreased as evidenced by Caspase-3 activity and the number of TUNEL positive cardiomyocytes. Cardiac BCAA and BCKA levels, as well as the ratio of p-BCKDE1α/BCKDE1α significantly increased (P<0.01) and BCKD activity significantly decreased (P<0.01) in T2DM mice. After BT2 treatment in T2DM mice with MI/R injury, the BCAA cataboliam defect was alleviated. At the same time, an improvement of Cardiac function and reduction of apoptosis was observed. In PP2Cm–/– mice, aBCAA catabolism defect and MI/R injury was observed. After PP2Cm overexpression and BT2 treatment, BCAA catabolism defect and MI/R injury was obviously alleviated. In PP2Cm–/– mice, oxidative damage was observed evident as an the increases in superoxide concentration, a decrease of MnSOD, complex I and III activities, and ATP levels as well as mitochondrial damage. Supplementation with MnTBAP obviously ameliorated this oxidative damage and MI/R injury in PP2Cm–/– mice. Treatment with BCKA (1.5-3 mM) resulted in significant decreases cell viability, and significant increases in the percentage of LDH release, apoptosis in H9C2 cells with SI/R injury. After BT2 and MnTBAP treatment, these effects were obviously alleviated.
CONCLUSIONS T2DM induced a downregulation of PP2Cm and reduced the defect of BCAA metabolism. PP2Cm directly mediated the defect of BCAA catabolism and oxidative damage. Overexpression PP2Cm alleviated MI/R injury by reducing the catabolism of BCAA and oxidative damage.
[GW30-e0060]
Chao Li 1,2 , Shijun Zhang 3 , Zhibo Gai 1,2 , Yunlun Li 1
1Shandong University of Traditional Chinese Medicine
2Department of Clinical Pharmacology and Toxicology, University Hospital of Zurich
3Shandong University of Traditional Chinese Medicine, Jinan, China
OBJECTIVES Obesity is a major contributor to myocardial cell apoptosis, fibrosis and ventricle hypertrophy, and associated with the increased risk of hypertrophic cardiomyopathy. Obeticholic acid (OCA), a farnesoid X receptor agonist, is a key regulator of lipid metabolism, inflammatory, fibrosis and metabolic pathways. This study was performed to investigate the effect and mechanism of OCA on obesity-induced myocardial injury.
METHODS C57Bl/6 mice were fed with a 45% high fat diet (HFD) or a standard diet. Biochemical parameters and myocardial pathological changes were examined. Energy metabolism in isolated working heart using radioactive was also tested to reveal the mechanism of myocardial injury. In vitro, 3D cell culture, mitochondria damage and ATP production of C2C12 cells cultured with palmitic acid (PA) in the absence or presence of OCA were tested.
RESULTS The body weight of HFD C57Bl/6 mice has increased by 22.7% compared with mice fed with normal diet. In addition, HFD-induced obese mice developed cardiac hypertrophy, fibrosis, inflammation, apoptosis, oxidative injury, which was rescued by OCA treatment. There was also a remarkably mitochondria damage in the obese mice and OCA prevented against the mitochondria damage. In vitro, 3D cell culture showed that PA reduced the myocardial contraction and viability. PA also increased the apoptosis rate of C2C12 cells and induced mitochondrial damage identified by the Tom20 level and ATP production assay. OCA showed a protective effect against PA-induced mitochondrial damage and myocardial damage. The results of energy metabolism in isolated working heart further indicated that the contribution of glucose oxidation to ATP production is lower than palmitate oxidation in HFD-induced obese mice heart, and OCA promoted glucose oxidation to protect against PA-induced mitochondrial damage.
CONCLUSIONS The present data suggested that OCA reduced the myocardial cell apoptosis, fibrosis and inflammation in the HFD-induced obese C57Bl/6 mice. OCA also protected cardiomyocytes against PA-induced mitochondria damage through promoting glucose oxidation. Our findings provide evidence for the protective role of OCA in myocardial cells.
[GW30-e0072]
Kun Lian, Chengxiang Li
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710032, China
OBJECTIVES We hypothesized that pretreatment of dADSCs with mitoTEMPO, a mitochondrial ROS scavenger, may improve their function. We found that pretreatment of dADSCs with mitoTEMPO for three passages enhanced their proangiogenic function and improved their protective effects against critical limb ischemia in streptozotocin (STZ)-induced diabetic mice. This finding suggested that a short-term pretreatment of dADSCs with a mitochondrial ROS scavenger restored their proangiogenic capacity both in vitro and in vivo.
METHODS Animals/Isolation, culture, and characterization of ADSCs/Cell viability assay/Multidifferentiation potential of ADSCs/Scratch and cell migration assays/Proangiogenic analysis of ADSCs/Establishment of a critical limb ischemia model in diabetic mice/Bioluminescence imaging of ADSCs in vivo/Confocal imaging/Western blotting/Statistical analysis.
RESULTS (1) Pretreatment of dADSCs with mitoTEMPO scavenged mitochondrial ROS and improved multidifferentiation potential. (2) Pretreatment of dADSCs with mitoTEMPO improved migration capacity. (3) Pretreatment of dADSCs with mitoTEMPO enhanced proangiogenic capacity. (4) Enhancement of mitochondrial antioxidant capacity contributed to the proangiogenic effects of mitoTEMPO pretreatment on dADSCs. (5) Pretreatment of dADSCs with mitoTEMPO improved their survival in diabetic mice with critical limb ischemia. (6) Pretreatment of dADSCs with mitoTEMPO improved their proangiogenic effects in diabetic mice with critical limb ischemia.
CONCLUSIONS These findings suggested that short-term pretreatment of dADSCs with a mitochondrial ROS scavenger restored their normal functions, which may be an effective strategy for improving the therapeutic effects of ADSC-based therapies in patients with diabetes.
[GW30-e0073]
Yanling Zhang 1 , Junyan Wu 1 , Jingjun Zhang 2 , Yanling Zhang 1
1Institute of Cardiovascular Diseases, Taian Maternal and Children’s Hospital, Taian
2Shandong First Medical University and Shandong Academy of Medical Sciences, China
OBJECTIVES Binding of renin and prorenin to the (pro)renin receptor ((P)RR) increases their enzymatic activity and upregulates the expression of pro-fibrotic genes in vitro. Expression of (P)RR is increased in the heart and kidney of hypertensive and diabetic animals. However, its mechanism in organ damage in the heart remains unclear. To determine whether increased expression of (P)RR is sufficient to induce cardiac injury, we investigated roles of (P)RR and phospholipase C-β3 (PLC-β3) on myocardial injury and myocardial fibrosis, providing a theoretical basis for in-depth understanding of the hypertension pathogenesis.
METHODS Fifty SD rats were randomly divided into five groups (n=10/group). Control: sham operation was done without the aortic ligation; Aortic ligation (AL): abdominal aortic ligation was carried out; U73122 treated (U): AL and PLC-β3 inhibitor, U73122 (40 |µ/kg/d) were given; HRP treated (H): AL and (P)RR inhibitor, HRP (4 μg/kg/d) given; Combined group (U+H), AL, U73122 and HRP given as the same doses above. Blood pressure was measured by the tail-cuff method using photoelectric volume oscillometry. Levels of ACE2, Mas, angiotensinogen (AOG), renin, collagen I, collagen III were measured in the heart.
RESULTS Blood pressure significantly rose after aortic ligation surgery. Levels of ACE2 and Mas receptor in the heart was significantly decreased in AL rats than in control (P<0.01). However, ACE2 and Mas in HRP, U and U+H groups increased significantly (P<0.01) following U73122 and HRP administration. AOG and renin levels in AL rats increased significantly (P<0.01). U73122, HRP and the combination treatment lowered AOG and renin expression (P<0.01). In addition, cardiac collagen I and III levels were decreased with U73122 or HRP treatment compared to AL hypertensive rats (P<0.01).
CONCLUSIONS The results showed that aortic ligation led to hypertension. Both U73122 and HRP reduced the activity of renin and AOG and increased expression of protective factors, i.e., cardiac ACE2 and Mas receptor that play an important role in the reduction of risks of hypertension and cardiac injuries. Furthermore, the inhibition of (P)RR and PLC-β3 by HRP and U73122 resulted in a decrease of cardiac collagen I, III levels, and blood pressure as well, demonstrating that activation of (P)RR and PLC-β3 could cause cardiac fibrosis and hypertension in this animal model.
This study was supported by Science and Technology Department of Shandong Province (Grant No. 2016GSF201207) and the National Natural Science Foundation of China (Grant No. 81270336). *Correspondence
[GW30-e0081]
Yao Dai, Yao Dai
The First Affiliated Hospital of Anhui Medical University
OBJECTIVES Atherogenesis initiated by internalization of oxidized low density lipoprotein (ox-LDL) in macrophages via their membrane scavenger receptors that facilitate them transforming into lipid-like foam cells. Recently, glucagon-like peptide-1receptor (GLP-1R) has been shown to mediate this process without fully elucidated mechanism. By bioinformatic prediction, we found GLP-1R is a potential target gene of miR-192-5p, which give the birth to this study that tests their crosstalk in ox-LDL induced atherogenesis.
METHODS Primary human macrophages treated with ox-LDL were transfected with hsa-miR-192-5p mimic or inhibitor to determine the role of miR-192-5p in GLP-1R expression and downstream events. Exendin 9-39, a competitive antagonist of GLP-1R, was used to confirm the effect of GLP-1R in miR-192-5p regulated pathway. Luciferase assay was used to verify direct target gene of miR-192-5p. Gain and loss experiments were used to prove the effect of miR-192-5p in atherosclerotic mouse model.
RESULTS miR-192-5p mimic decreased GLP-1R and increasedLectin-like ox-LDL receptor-1 (LOX-1) and CD36 expression, as well as ROS production and foam cell formation, while its inhibitor showed the opposite effects. Exendin 9-39 almost completely reversed the effect of miR-192-5p inhibitor. Luciferase assay verified that 3ʹ UTR region of GLP-1R mRNA is a direct target of miR-192-5p. Ablation of miR-192-5p in ApoE–/– mice fed high fat diet increased GLP-1R expression and decreased CD36 and LOX-1 expressions and lipid accumulation in aorta.
CONCLUSIONS Ox-LDL induces foam cell formation by upregulating miR-192-5p that inhibits GLP-1R expression. These findings help to understand the mechanism of atherogenesis.
[GW30-e0087]
Yang Yang 1,2 , Tian Ye 1
1Department of Cardiology, The First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin 150001, P. R. China
2Department of Cardiology, The Affiliated Xiamen Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen 361004, China
OBJECTIVES Emerging evidence indicates that macrophage functional polarization is critically involved in the development of atherosclerosis (AS). Herein we sought to examine the role of 5-Aminolaevulinic acid (ALA)-mediated non-lethal sonodynamic therapy (NL-SDT) in macrophage subset polarization and atherosclerotic lesion stability, and explore the potential underlying mechanism.
METHODS Mouse primary bone marrow (BM) derived cells were differentiated into macrophages using granulocyte macrophage colony stimulating factor in vitro. Macrophages were then polarized into proinflammatory M1 cells by interferon-γ and lipopolysaccharide. Western blot assay, transmission electron microscopy and GFP-LC3 transfection were used to detect the induction of autophagy by NL-SDT. Levels of intracellular reactive oxygen species (ROS) following NL-SDT were evaluated by staining with the fluorescent probe CellROX® Green Reagent. We performed semi-quantitative detection of 18 phosphorylated mouse proteins to investigate the molecular mechanism underlying NL-SDT induction of autophagy. Western blot, flow cytometry, arginase assay and ELISA were done to examine the effects of NL-SDT on -macrophage polarization. Oil red O staining, cholesterol/cholesteryl ester quantitation assay, RT-PCR and cholesterol efflux fluorometric assay were carried out to determine the effects of cholesterol efflux induced by NL-SDT. We utilized NL-SDT on Western diet-fed apoE–/– mice in vivo. Hematoxylin and eosin staining and TUNEL assays were performed to evaluate the atherosclerotic plaque size and apoptosis within the atheroma. Histopathology was used to determine percentages of lipid, collagen, macrophages and smooth muscle cells. The macrophage-subset cell numbers within the atheroma were detected by immunofluorescent staining and flow cytometry. To explore the mechanisms of NL-SDT stabilizing atherosclerotic plaques, mice were pretreated with specific pharmacological inhibitors.
RESULTS Using Western diet-fed apoE–/– mouse and chimeric EGFP BM apoE–/– mouse models, we demonstrated that NL-SDT promoted phenotypic switching of both BM-derived and resident macrophages from M1 to M2 and significantly inhibited the progression of AS. Further mechanistic studies indicated that NL-SDT enhanced macrophage differentiation toward the M2 phenotype by activating the ROS–5′ AMP-activated protein kinase (AMPK)α–mammalian target of rapamycin complex 1 (mTORC1)–autophagy signaling pathway in murine BM-derived M1 macrophages (BMDM1s). Moreover, NL-SDT treatment drastically reduced the lipid droplets, mainly due to the promotion of HDL-mediated cholesterol efflux in vitro. Specifically, application of pharmacological inhibitors in animal model had reciprocal effect on macrophage polarization induced by NL-SDT.
CONCLUSIONS These findings highlight that NL-SDT treatment engages a virtuous cycle that enhances M1-to-M2 polarization, cholesterol efflux and anti-inflammatory reactions in advanced plaque in vivo and in BMDM1s in vitro via activating AMPK–mTORC1–autophagy pathway, a fundamental discovery that might help elucidate the mechanism underlying NL-SDT as a potential treatment to prevent atherothrombotic events.
[GW30-e0089]
Cairong Li 1 , Xinyuan Zhao 1 , Cairong Li 1,2
1Department of Medicine, Hubei University of Science and Technology, 88 Xianning Road, Xianning 437100, China
2Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning 437100, China
OBJECTIVES Doxorubicin (DOX) is an effective anticancer drug, however its clinical application is limited due to its cardiotoxicity. Therefore, identification of effective agents against DOX-induced cardiotoxicity is of critical importance. Tetrahydroxystilbene glucoside (TSG) is extracted from a famous Chinese herbal medicine which is widely used as an antiaging agent in history. This study aimed to determine the beneficial role of TSG in DOX-induced cardiotoxicity in vitro and explored the underlying mechanisms.
METHODS H9c2 cardiomyocytes were pretreated with different concentrations (50, 100 and 200 μM) of TSG prior to DOX exposure. Levels of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione (GSH), matrix metalloproteinase (MMP), lactic dehydrogenase (LDH) and caspase-3 were measured by ELISA method, the protein expression of NF-κB, silent mating type information regulation 2 homolog 1 (SIRT1) and adenosine monophosphate-activated protein kinase(AMPK)were detected by Western blot. The mRNA expressions of NADPH oxidase isoforms p67phox, p22phox, and p91phox were detected by qPCR.
RESULTS TSG pretreatment increased cell viability, SOD, catalase, and GPx activities, GSH levels, MMP and the GSH/GSSG ratio; decreased LDH and caspase-3 activities, MDA and ROS levels, mPTP opening and the percentage of apoptotic cells. TSG pretreatment also blunted the mRNA expression of NADPH oxidase isoforms p67phox, p22phox, and p91phox, and abated oxidative stress. TSG pretreatment dramatically restored the decrease of SIRT1, AMPKα and pAMPKα protein expression in doxorubicin-induced cardiotoxicity.
CONCLUSIONS The results showed that TSG pretreatment significantly increased cell viability, inhibited LDH release, and suppressed cell apoptosis induced by DOX. Additionally, TSG pretreatment attenuated the loss of mitochondrial membrane potential and cytochrome c release. These findings also indicate that the protective mechanisms of TSG against doxorubicin-induced cardiotoxicity are involved in the alleviation of energy metabolism.
ACKNOWLEDGEMENTS This work was supported by the Foundation from Department of Education of Hubei Province (17Y110), Hubei Natural Science Foundation (2017CFB410), and the Foundation from Hubei University of Science and Technology (LCZX201515, 2018-19XZY06).
[GW30-e0096]
Xiuzhu Weng 1,2 , Xing Luo 1,2 , Xiaoxuan Bai 1,2 , Dongyang Liu 1,2 , Ying Lv 1,2 , Shan Zhang 1,2 , Chen Zhao 1,2 , Ming Zeng 1,2 , Haibo Jia 1,2 , Bo Yu 1,2
1Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University
2The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin
OBJECTIVES Atherosclerosis (AS) is considered to be a major underlying cause of cardiovascular disease and a leading cause of cardiac death in developing countries. In addition to a metabolic disease, AS is a complex, long lasting and continuously evolving inflammatory disease characterized by remodeling of the arteries. Cell death and inflammation are inextricably linked with their effectors modulating the process of AS. Pyroptosis is a novel programmed death which is characterized by the formation of inflammasome. And NLRP3 inflammasomes are the most classical and widely studied among numerous forms of inflammasomes. It has been proved that pyroptosis can accelerate progression of AS through promoting the release of inflammatory cytokines such as IL-1β and IL-18. Macrophages are the major inflammatory cells in all stages of AS. The different functional attributes of macrophages influence the initiation of lesions, their progression to advanced atheromata, their complication, and their responses to therapies. What’s more, the NLRP3 inflammasomes are highly expressed in macrophages in atherosclerotic plaque. Thus inhibition of pyroptosis in macrophages can be a potential therapy for AS. Apigenin (API) is a natural flavonoid compound and exist in various vegetables, fruits and medicinal plants extensively. Its antioxidant, anticancer and anti-inflammatory effects have been widely studied, and studies have shown that API has anti-atherosclerosis function via up-regulating cholesterol efflux. However, its effects and mechanisms on the pyroptosis in macrophages are still unclear. The purpose of this study was to explore the effects of API on the pyroptosis in macrophages, and discuss the possible mechanisms of it.
METHODS THP-1 was induced into macrophage by treating with 0.5 nM PMA. The cells were divided into the following five groups: control group, LPS+ATP group, 10 nM, 20 nM, and 50 nM API pretreatment group. The solvent or 10 nM, 20 nM, 50 nM API were used as pretreatments before inducing macrophages pyroptosis. One solvent group was used as control group, and the other groups were conducted with lipopolysaccharide (LPS) and ATP to induce pyroptosis. The Apoptosis and Necrosis Assay Kit and fluorescence microscope were used to detect the rate of cell pyroptosis. RT-PCR was conducted to measure the expression levels of NLRP3, Caspase-1, and IL-1β. Western blot was used to evaluate the protein expression of NLRP3, Caspase-1, IL-1β, and AMPK.
RESULTS Compared with LPS+ATP group, API at the concentrations of 10 nM, 20 nM and 50 nM significantly decreased the cell pyroptosis rate (P<0.05). The mRNA expression levels of NLRP3, Caspase-1, and IL-1β in API pretreatment groups are lower than control and LPS+ATP group in a concentration-dependent manner (P<0.001). The expression levels of key regulatory proteins in cell pyroptosis, including NLRP3 and caspase-1, were obviously lower in API pretreatment groups than LPS+ATP group, especially in 20 nM, and 50 nM API pretreatment groups (P<0.05). As a substrate of caspase-1 and a most used imflammatory marker for pyroptosis, API pretreatment reduced the protein expression of IL-1β (P<0.05). And the protein expression of AMPK shown the same trend with Caspase-1 (P<0.05).
CONCLUSIONS API can inhibit the pyroptosis in macrophages and this effect can be achieved by regulating AMPK signaling pathways. Furthermore, using API to inhibit pyroptosis in macrophages may be a potential therapy for slowing the initiation and progression of AS.
[GW30-e0106]
Yaoyao Zhou, Shenwen Fu
Department of Cardiology, Jinhua Municipal Hospital, Jinhua 321004, China
OBJECTIVES Curcumin is a natural polyphenol with a variety of properties. The aim of our study was to investigate whether curcumin could mitigate the atherosclerosis pathogenesis and explore its immunomodulatory effect on macrophage phenotype together with the underlying molecular mechanisms.
METHODS The apolipoprotein E deficient (ApoE–/– ) mice were employed to establish atherosclerosis model, alone or combined with curcumin treatment. The aortas were isolated for histological evaluation and gene expression analysis. The RAW 264.7 cells were polarized to M1 cells by lipopolysaccharide (LPS) and treated with different curcumin concentrations. Quantitative real-time polymerase chain reaction (PCR) and Western blot analysis were carried out to examine the effect of curcumin on inflammatory response and the Toll-like receptor 4 (TLR4)-mitogen-activated protein kinases (MAPKs)/nuclear factor (NF)-κB pathway in macrophage.
RESULTS Curcumin significantly alleviated atherosclerotic burden and enhanced plaque stability in experimental AS model. Also, curcumin was capable to suppress M1 phenotype and promote M2 macrophage in vivo. Furthermore, the in vitro experiment showed that curcumin inhibited the gene expression of pro-inflammatory cytokines TNF-α and IL-6, as well as the phosphorylation of p38, ERK1/2, JNK1/2, IKK, IKBα and p65. With the assistance of specific inhibitors, TLR4-MAPK/NF-κB was verified to be involved in M1 polarization and inflammatory response.
CONCLUSIONS Our findings suggested the anti-atherogenic effect of curcumin could, at least in part, derive from polarizing pro-atherogenic M1 macrophages to repressive M2 phenotypes. These actions may be attributed to the inhibition of TLR4-MAPK/NF-κB signaling pathway. These results may shed some light on the atheroprotective mechanism of curcumin and exhibit the potential of curcumin as a therapeutic approach for the prevention and treatment of AS.
[GW30-e0115]
Teng Ying 1,2 , Wenying Wang 3 , Danqing Hu 1 , Zhixiong Wei 1 , Lingzhen Wu 1 , Jun Fang 1
1Fujian Medical University union hospital
2The First Affiliated Hospital of Jiangxi Medical College
3First People’s hospital of Fuzhou
OBJECTIVES Endothelial-mesenchymal transition (EndMT) was significant for atherosclerosis (AS). Adropin exerts direct effects on the endothelium. This study aims to explore whether adropin can alleviate AS and its molecular mechanism.
METHODS Apolipoprotein E knockout (ApoE–/– ) mice were fed with high fat for 13 weeks to establish AS mode. ApoE–/– mice were divided in three groups: (i) Normal dieting group; ii) High fat dieting group; iii) High fat dieting+Adropin group: adropin (105 μg/kg×d was injected intraperitoneally in mice for 13 weeks. We also established EndMT by inducing human umbilical vein endothelial cells (HUVECs) with hydrogen peroxide (H 2 O 2 ) in vitro cell culture models. Cells were divided into four groups: i) Control group; ii) H 2 O 2 group; iii) H 2 O 2 +Adropin group; iv) H 2 O 2 +Adropin+TGF-β plasmid group. Oil red O staining was used to detect the lipid area in AS plaque and HE staining to determine the plaque area in mice. The number of spindle cells transformed from stroma was counted on day 0, 2, 4 and 6 of cell culture. The relative expressions of TGF-β1, TGF-β2, TGF-βR, CD31, VE-cadherin, α-SMA, SM22α, phosphor-Smad2/3 and FSP-1 mRNA were measured by Western-Blot and (or) RT-PCR. The expression of α-SMA and CD31 were also measured by immunofluorescence. Serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglyceride (TG) were detected by automatic biochemical analysis.
RESULTS In vivo animal model, adropin reduced the incidence of AS, inhibited lipid accumulation in atheroselerotic plaque (P<0.05), increased the expression of CD31 and VE-cadherin (P<0.05), and decreased the expression of α-SMA and FSP-1 (P<0.05). The external supplementation of adropin decreased the expression of Adropin (P<0.05). However, adropin did not decrease serum TC, LDL-C, HDL-C, TG levels and body weight. In the experiment of HUVECs in vitro, adropin inhibited the morphological changes of endothelial cells and the expression of α-SMA (most obvious on day 6). The expression of CD31, VE-cadherin, α-SMA and SM22α were consistent with those in vivo animal experiment. Adropin decreased the expression of TGF-β1 and TGF-β2 (P<0.05), and inhibited the phosphorylation of Smad2/3 which is the downstream signal protein of TGF-β (P<0.05). Transfection of TGF-β plasmid inhibited the effect of adropin on reducing EndMT and inhibiting the TGF-β/Smad2/3 signaling pathway.
CONCLUSIONS Adropin can alleviate AS in ApoE–/– mice that is likely mediated via inhibiting EndMT through TGF-β/Smad2/3 signaling pathway. Adropin represents a novel target to limit AS not directly by regulating lipid levels.
[GW30-e0126]
Cho Kyung-Hyun
LipoLab, Smart-Aging Convergence Research Center, College of Medicine, Yeungnam University
OBJECTIVES Metabolic syndrome is closely associated with higher risk of hypertension, cardiovascular disease, diabetes and stroke. It has been reported that Cuban policosanol improves lipid parameters and HDL functionality in human participants. The aim of the present study was to investigate the long-term effects of policosanol supplementation on blood pressure (BP) and the lipid profile in healthy Korean participants with pre-hypertension.
METHODS This randomized, double-blinded, and placebo-controlled trial included 84 healthy participants who were randomly assigned to three groups receiving 10 mg of policosanol, 20 mg of policosanol, or placebo upto 24 weeks.
RESULTS The BP, lipid profile, and anthropometric factors were measured pre- and post-intervention and then compared. Based on an average of three measurements of brachial BP, the policosanol 20 mg group showed the most significant reduction in average systolic BP (SBP) from 138±12 mmHg at week 0–126±13 mmHg at week 24 (P<0.0001). The policosanol 10 mg group showed a 4% reduction in SBP from 135 mmHg at week 0–128 mmHg at week 24 (P=0.016), whereas the placebo group showed no change in BP between weeks 0 and 24. The policosanol consumption for 12 weeks, the policosanol 20 mg group exhibited the most significant reduction of BP, up to 7.7% reduction of average systolic BP (SBP) from 136.3±6.1 mmHg (week 0) to 125.8±8.7 mmHg (P><0.001). Between group comparisons using repeated measures ANOVA analysis showed that the policosanol 20 mg group had a significant reduction of SBP (P=0.020) and a reduction of DBP (P=0.035). The policosanol 10 mg and 20 mg groups showed significant reductions in aortic SBP of 7.4 and 8.3%, respectively. The policosanol groups showed significant reductions of total cholesterol (TC) of 9.6 and 8.6% for 10 mg and 20 mg of policosanol, respectively. Lipoprotein functionality improved by policosanol to be more anti-atherogenic; LDL showed more anti-oxidant while HDL showed more anti-glycation properties.
CONCLUSIONS Consumption of policosanol resulted in significant reductions of peripheral SBP and DBP, aortic SBP and DBP, and mean arterial pressure (MAP) and serum TC and LDL-C with elevation of %HDL-C.
[GW30-e0135]
Cong Fu 1,10 , Qiancheng Xu 2 , Shengxing Tang 1 , Yuhan Cao 3 , Can Liu 4 , Juan Li 5 , Yihua Wang 6 , Yan Qian 7 , Fei Shi 8 , Jingmin Gui 9 , Qun Fan 1 , Yang Ling 1 , Cong Fu 1,10
1Department of Cardiology, Yi Ji Shan Hospital Affiliated to Wan Nan Medical College, Wuhu, AnHui, China
2Department of Critical Care Medicine, Yi Ji Shan Hospital Affiliated to Wan Nan Medical College, Wuhu, AnHui, China
3Department of Nephrology, Yi Ji Shan Hospital Affiliated to Wan Nan Medical College, Wuhu, AnHui, China
4Department of Anesthesiology, Yi Ji Shan Hospital Affiliated to Wan Nan Medical College, Wuhu, AnHui, China
5Department of Nephrology, the Second People’s Hospital of Wuhu, Wuhu, AnHui, China
6Department of Emergency Intensive Care Unit, Yi Ji Shan Hospital Affiliated to Wan Nan Medical College, Wuhu, AnHui, China
7Department of Critical Care Medicine, the Second People’s Hospital of Wuhu, Wuhu, AnHui, China
8Department of Critical Care Medicine, Wuhu Hospital for Traditional Chinese Medicine, Wuhu, AnHui, China
9Department of Critical Care Medicine, the First People’s Hospital of Wuhu, Wuhu, AnHui, China
10Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wann Nan Medical College)
OBJECTIVES Myeloid-derived suppressor cells (MDSCs) play key roles in sepsis, but whether bone marrow is considered the only source remains unclear. The current knowledge about the mechanism of MDSCs leading to myocardial injury in sepsis is poor. The aim of this study is to determine the role of splenic MDSCs in sepsis induced myocardial injury.
METHODS In sepsis patients with cardiac dysfunction, the circulating percentage of CD14−CD11b+ and serum concentrations of IL-6 and IL-1β were measured. A mouse sepsis model was established through caecum ligation and puncture (CLP). Animals were divided into four groups: control, sham, CLP and CLP+splenectomy (CLPS). Plasma concentrations of IL-6, IL-1β, TnI and NT-proBNP were measured. CD11b+Gr-1+ cells were detected by immunofluorescence staining and RT-PCR. Myocardial injury was detected by HE, Masson and TUNEL staining. The expression of mTOR, P53 and caspase-3 was measured by Western blot.
RESULTS In sepsis patients, circulating MDSCs were increased, and the plasma concentrations of IL-6 and IL-1β were elevated. The plasma concentrations of IL-6 and IL-1β were correlated with the ratio of circulating MDSCs. In the mouse sepsis model, the spleen was the major source of CD11b+Gr-1+ cells that migrated into circulation and the heart in sepsis. Echocardiography and serum biomarkers showed that cardiomyocyte damage and cardiac hypofunction in sepsis induced myocardial injury. The expression of CD11b, Gr-1 and pro-inflammatory cytokines in the heart was significantly higher in sepsis patients than that in controls. Pathological staining and TUNEL staining showed obvious myocardial damage and cell apoptosis. The Western blot analysis indicated that in the heart, the activation of mTOR was inhibited and that the expression of P53 and caspase-3 was elevated in sepsis-induced myocardial injury.
CONCLUSIONS In sepsis-induced myocardial injury, splenic reservoir CD11b+Gr-1+ cells rapidly migrated into circulation and the heart, further impairing heart function via the high expression of P53 through the inhibition of mTOR.
[GW30-e0142]
Jianqing She 1,2 , Yuewu 1,2 , Yangyang Deng 1,2 , Zuyi Yuan 1,2
1Cardiovascular Department, First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710048
2Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an 710048
OBJECTIVES Heart failure (HF) is associated with profound changes in cardiac metabolism. Coronary ischemia is one of the leading cause for heart failure. Yet few studies have discussed metabolic alterations in different stages of heart failure based on global metabolomics profile. In this study, by measuring serum metabolic profile in discovery and validation cohorts, we aim to characterize the metabolic profile and identifies potential biomarkers in heart failure patients at different stages.
METHODS Consecutive patients admitted to hospital for ischemic HF were enrolled in the discovery phase and validation phase. Demographic and biochemical measurements were performed afterwards. Serum samples were obtained after overnight fasting, and coronary angiography was performed afterwards to confirm the diagnosis. Nontargeted metabolomics was applied to demonstrate global metabolic profile in control and different levels of heart failure patients.
RESULTS We have found significant alteration of amino acids and free fatty acids levels, which exhibited prognostic value for severe ischemic HF. Besides, serum amino acids began to change during early stage HF, identified as potential biomarkers for early stage HF. Pathway analyses further shed light on factors underlying amino acids metabolism. Serum amino acid profile exhibited differential correlation pattern to clinical factors in HF patients as compared to control. The dysregulated amino acids profile and enriched pathways were further validated in the secondary cohort.
CONCLUSIONS Using non-targeted metabolic profiling in cohorts based on HF levels, we have successfully identified a group of circulating metabolites that were significantly altered in early stage and late stage HF. The amino acid metabolic signatures shed light on potential new biomarkers and therapeutics for preventing and treating HF.
[GW30-e0149]
Xiangbin Zhong 1,2,3 , Xiaodong Zhuang 1,3 , Huaqiang Zhou 2,4 , Xinxue Liao 1,3
1The First Affiliated Hospital of Sun Yat-sen University
2Sun Yat-sen University School of Medicine
3NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
4Sun Yat-Sen University Cancer Center
OBJECTIVES Try to find out the mechanism leading to the prevalence of YA-CHD through comparing differentially expressed genes (DEGs) among YA-CHD patients and healthy young aged adults, and further investigate the differences through gene oncology analysis (GO analysis), KEGG pathway analysis, protein-protein interaction network analysis (PPI network analysis) and the interaction between important modules.
METHODS Dataset GSE 12288 from Gene Expression Omnibus was imported and performed comprehensive bioinformatics analysis, including gene ontology analysis (GO analysis), pathway analysis, protein-protein interaction network analysis and core network analysis.
RESULTS RAP1A, which regulates platelet integrin activation and has a critical role in platelet production, was significantly up regulated, while TNKS2, which keeps the integrity of the leukocyte telomere structure and shows a significant association with longevity, was significantly downregulated. Biological process analysis showed “phagosome” pathway was mostly significant related to YA-CHD. Innate immune response module and type I interferon signaling module, interacts with IRF1, may major in the regulation of YA-CHD progression and maybe the potential therapeutic target of YA-CHD.
CONCLUSIONS RAP1A and TNKS2 may serve as novel biomarkers in predicting the onset of YA-CHD. Further studies about weather IRF1 influence YA-CHD through regulating innate immune type I interferon signaling pathway was needed.
[GW30-e0154]
Yousef Rasmi 1 , Fereshteh Ghaffari 1 , Shahram Seyedi 2 , MirHossein SeyedMohammadzad 3 , Alireza Rostamzadeh 3 , Elmira Roshani 1
1Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
2Department of Immunology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
3Department of Cardiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
OBJECTIVES Endothelial microparticles (EMPs), membrane-shed vesicles that are generated from the endothelial cells surface in response to cellular dysfunction and/or damage, has been showed that can be involved in inflammatory process, blood coagulation and endothelial dysfunction. In addition, studies suggest that microvascular coronary dysfunction plays a crucial role in cardiac syndrome X (CSX). The objective of this study was to evaluate the EMP levels in patients with CSX and normal subjects.
METHODS CSX patients (n=40) A were selected from individuals who referred to Department of Cardiology, UMSU, Urmia. Control group (n=19) were selected from healthy subjects without any disease related to endothelial dysfunction. They were matched according gender and BMI. We measured the level of VE-Cadherin by flowcytometery using CD144 monoclonal antibody in the peripheral blood of patients and control subjects.
RESULTS CD144 endothelial microparticles count were 30.79±19.01 counts/μL in CSX patients versus 26.92±11.98 counts/μL in healthy control subjects, P=0.51. CD144 endothelial microparticles percent were 2.13±1.64% in CSX patients versus 1.32±0.93% in healthy control subjects, P=0.10.
CONCLUSIONS Findings indicate that VE-Cadherin CD144 EMP levels increase in CSX patients but VE-Cadherin levels in CSX patients were not significantly higher than healthy control subjects. Endothelial and microparticles may increase risk of thrombosis in CSX.
[GW30-e0157]
Fan Yang 2 , Rongrong Wu 1 , Zhi Jiang 2 , Jinghai Chen 1 , Jinliang Nan 1 , Sheng an Su 1 , Na Zhang 1 , Chen Wang 1 , Jing Zhao 1 , Cheng Ni 1 , Yingchao Wang 1 , Wangxing Hu 1 , Zhiru Zeng 1 , Keyang Zhu 1 , Xianbao Liu 1 , Xinyang Hu 1 , Wei Zhu 1 , Jian an Wang 1
1Department of Cardiology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China
2Department of Cardiology, Guizhou Provincial People’s Hospital, Guizhou, China
OBJECTIVES Accumulating evidence revealed that mesenchymal stem cells (MSCs) confer cardioprotection against myocardial infarction (MI). However, the poor survival and engraftment rate of the transplanted cells limited their therapeutic efficacy in the heart. The enhanced leptin production associated with hypoxia preconditioning contributed to the improved MSCs survival. Mitochondrial integrity determines the cellular fate. Thus, we aimed to investigate whether leptin can enhance mitochondrial integrity of human MSCs (hMSCs) to protect against various stress.
METHODS In vivo, we constructed MI-mouse model and transplantated the leptin-overexpressing hMSCs into the infarcted heart to analyze hMSCs survival and cardiac function. In vitro, we exposed leptin pretreated hMSCs into glucose and serum deprivation under hypoxia (GSDH) stress for an additional 24 h. We detected the mitochondrial microstructure, function and the proteins related to mitochondrial homeostasis.
RESULTS In vivo, transplantation of leptin-overexpressing hMSCs into the infarcted heart resulted in improved cell viability, leading to enhanced angiogenesis and cardiac function. In vitro, pretreatment of hMSCs with recombinant leptin (hMSCs-Leppre) displayed improved cell survival against severe ischemic condition (glucose and serum deprivation under hypoxia), which was associated with increased mitochondrial fusion. Subsequently, Optic atrophy 1 (OPA1), a mitochondrial inner membrane protein that regulates fusion and cristae structure, was significantly elevated in the hMSCs-Leppre group, and the protection of leptin was abrogated by targeting OPA1 with a selective siRNA. Furthermore, OMA1, a mitochondrial protease that cleaves OPA1, decreased in a leptin-dependent manner. Pretreatment of cells with an inhibitor of the proteasome (MG132) prevented leptin-induced OMA1 degradation, implicating the ubiquitination/proteasome system as a part of the protective leptin pathway. In addition, GSK3 inhibitor (SB216763) was also involved in the degradation of OMA1.
CONCLUSIONS In conclusion, in the hostile microenvironment caused by MI, (a) leptin can maintain the mitochondrial integrity and prolong the survival of hMSCs; (b) leptin-mediated mitochondrial integrity requires phosphorylation of GSK3 as a prerequisite for ubiquitination-depended degradation of OMA1 and attenuation of longOPA1 cleavage. Thus, leptin targeting the GSK3/OMA1/OPA1 signaling pathway can optimize hMSCs therapy for cardiovascular diseases such as MI.
[GW30-e0158]
Tengfei Liu, Ying Zhou, Liu Tengfei
Shijitan Hospital
OBJECTIVES Although anti-platelet drugs are widely used in clinic, there still exist a small proportion of coronary artery disease (CAD) patients with drug-eluting stent implantation who during regular drug therapy experienced cardiocvascular events, some of them experience in-stent restenosis (ISR). In our study, we try to elucidate the correlation between CMTM5 gene and the risk of ISR, detected the effects and mechanisms of CMTM5-stimulated genes on human vascular endothelial proliferation and migration.
METHODS A total of 131 CAD patients with drug-eluting stent implantation were enrolled in this study, with a mean 36 months’ follow up, 39 patients occurred in-stent restenosis event. CMTM5 gene expression was detected by RT-PCR. DNA methylation levels on CMTM5 promoter were tested by the bisulfate pyrosequencing technology. Serum CMTM5 level was assessedby Elisa kit. HUVEC were infected by CMTM5 overexpression adenovirus and RNA interference lentivirus. Scrape injury analysis and Transwell migration model were used to investigate effects of CMTM5 on ECs migration, while cell counting, MTT, Brdu and flow cytometry were performed to detect the ECs proliferation in different groups. Expression of signaling pathway proteins PI3K, p-Akt and CycD1 were detected through immunoblotting in all groups.
RESULTS Low CMTM5 gene expression and serum CMTM5 level associated with increased restenosis risk in a cohort of 306 patients undergoing coronary angioplasty and stent placement (P<0.05). What’s more, high methylation ratio in CMTM5 promoter was inversely correlated with low expression of CMTM5. Overexpression of CMTM5 attenuated ECs migration and proliferation. a. The scrape injury assay and Transwell migration model suggested that CMTM5 overexpression attenuated but its suppression promoted migration of ECs compared to the normal and EO-MOCK groups. b. The cell count, MTT, and Flow cytometry assay results showed that proliferation of ECs was attenuated in CMTM5 overexpression group and enhanced in the CMTM5 suppression group. Western blot results suggested that protein expressions of PI3K/p-Akt signal pathway decreased in the CMTM5 overexpression group and increased in CMTM5 suppression group. Transwell migration model showed that CMTM5 suppression promoted ECs migration through the PI3K/Akt signal transduction pathway. Flow cytometry indicated that PI3K/Akt signal pathways were involved in the regulation of proliferation of ECs.
CONCLUSIONS The evidence from our study indicates that CMTM5 might be a new biomarker in assessing aspirin clinical efficacy and low CMTM5 promoter methylation may bring new hints to elaborate the pathogenesis of in-stent restenosis. CMTM5 suppression facilitates migration and proliferation of ECs through PI3K/Akt signal pathway and contributes to the maintenance of vascular homeostasis. This may provide a promising approach for the prevention and treatment of ISR and late stent thrombosis after PCI.
[GW30-e0162]
Saiyang Xie 1,2 , Wei Deng 1,2
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
2Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, China
OBJECTIVES Our study aimed to determine whether TLR7 is involved in sepsis-induced myocardial dysfunction (SIMD) and, if so, to investigate the underlying molecular mechanisms.
METHODS C57/BL mice (WT) and TLR7–/– mice were subjected to 20 mg/kg lipopolysaccharide (LPS) challenge for 6 h, 12 h, 24 h and 48 h to induce septic cardiomyopathy. Cardiac function was evaluated by echocardiography and hemodynamic. Calcium transients and calcium sparks elicited by electrical stimulation in cardiomyocytes isolated from the indicated mice were observed with confocal microscope. Furthermore, we gathered hearts to detect expression of calcium transients related proteins by Western blot and RT-qPCR. In addition, the hearts were harvested to test the SERCA2a activity and evaluated by HE, Immunohistochemistry and immunofluorescence. To explore the mechanism, WT (Wild-type littermates) mice and cardiac-specific TLR7-transgenic (TLR7-cTG) mice were subjected to PKC specific inhibitor (Go6983) administration for 2 weeks before LPS treatment. Calcium transients and related proteins were evaluated as mentioned above. In the end, we verified the role and mechanisms of TLR7 in septic cardiomyocyte injury by using Ad-GFP-TLR7 and TLR7 siRNA in Neonatal rat cardiomyocyte.
RESULTS After 10 days of intraperitoneal injection of LPS, the total mortality of TLR7 KO mice was 26.4% higher than that of WT mice. Echocardiography and hemodynamic parameters showed that the cardiac function of TLR7–/– mice was significantly deteriorated. The CD68 immunohistochemistry and TUNEL staining showed that inflammatory and apoptosis were enhanced in the TLR7 KO group and the WT group within 24 hours, but there was no difference between the two groups, which was consistent with the results of Western and RT-PCR. Calcium spark and calcium transient detection in cardiomyocytes showed that TLR7 KO mice had the reduced calcium transient amplitude, prolonged time of Ca2+ uptake and the decreased SERCA2a activity, without changing calcium sparks. At the mechanistic level, PKC immunofluorescence staining showed that the expression of PKC in the sarcoplasmic/endoplasmic reticulum was significantly downregulated in TLR7 KO group. Western and qPCR results showed that the expression of PKC, p-PLB (Ser16) was downregulated while the level of PLB was up-regulated. Meanwhile, the expression level of SERCA2a and RyR2 did not change. Therefore, we hypothesized that TLR7 can attenuate LPS-induced sepsis myocardial dysfunction by increasing the recruitment of PKC in the sarcoplasmic reticulum, up-regulating the level of p-PLB (Ser16), increasing the Ca2+-transporting activity of SERCA2a, and maintaining calcium homeostasis in SIMD. In addition, the mice in TLR7-cTg group attenuated LPS-induced sepsis cardiomyopathy, but the cardioprotective effect of TLR7 was abolished after administration of the tail vein PKC-specific inhibitor. Moreover, the utilization of Ad-GFP-TLR7 overexpressing TLR7 in neonatal rat cardiomyocytes alleviated the Calcium homeostasis imbalance and cardiomyocyte injury induced by LPS, while TLR7 siRNA treament has the opposite effect.
CONCLUSIONS TLR7 deficiency aggravates LPS-induced cardiac dysfunction. However, TLR7 overexpression can attenuate LPS-induced cardiac function by enhancing PKC and increasing the Ca2+-transporting activity of SERCA2a in the sarcoplasmic/endoplasmic reticulum. Therefore, retaining the expression of TLR7 may be a potential therapeutic strategy for sepsis-induced myocardial dysfunction (SIMD).
[GW30-e0171]
Yihong Chen, Chun Liang
Shanghai Changzheng Hospital
OBJECTIVES Nε-carboxymethyl-lysine (CML), a major isoform of advanced glycation end products (AGEs), plays a crucial role in the functional damage of diabetes mellitus. However, it is not clear whether ALT-711 (alagebrium), an inhibitor of AGEs, is capable to rescue CML-induced poor angiogenesis, as well as the underlying mechanism. Here, we tested the hypothesis that alagebrium improves the angiogenic function damage induced by CML via miR-27b/anti-angiogenic protein thrombospondin-1 (TSP-1) signaling.
METHODS Male diabetic mice and normal mice with critical hindlimb ischemia were performed to investigate the impaired angiogenesis in diabetes mellitus and whether miR-27b/TSP-1 signaling is involved in the pathology of it. Then, we used the commercial products CML-BSA and alagebrium on human umbilical cord-derived endothelial cells (HUVECs), in combination with the miR-27b mimic/inhibitor and TSP-1 over-expression plasmids, to determine the effects of alagebrium and miR-27b/TSP-1 on angiogenesis in vitro.
RESULTS Compared with control mice, lower blood flow recovery and less capillary density were appeared in the ischemic lower limb of diabetic mice with the decreased vascular endothelial growth factor (VEGF) and miR-27b expression, whereas the increased TSP-1 expression. Likewise, the tube formation ability of HUVECs in CML-BSA was impaired, which is followed by down-regulated VEGF and miR-27b expression and the up-regulated TSP-1 expression. The trend was reversed by alagebrium, not only on tube network formation, but also on expression of VEGF, miR-27b and TSP-1. MiR-27b mimic contributed to promoted tube formation and positive regulation of VEGF, while decreased TSP-1 expression. And these effects of miR-27b mimic were all abolished when TSP-1 was overexpressed. In addition, miR-27b silencing suppressed the tube formation promotion and VEGF expression improvement induced by alagebrium under CML-BSA treatment, inversely, augmented TSP-1 expression.
CONCLUSIONS These novel findings illustrated that CML exposure severely impairs functional angiogenesis of HUVECs and AGEs inhibitor rescued the damage via miR-27b/TSP-1 signaling cascades, which will provide some new therapeutic strategies to diabetic patients with critical limb ischemia.
[GW30-e0172]
Shuaibo Huang, Chun Liang
Shanghai Changzheng Hospital
OBJECTIVES TGF-bs regulate fibroblast responses, by activating Smad2 or Smad3 signaling, or via Smad-independent pathways. We have previously demonstrated that fibroblast-specific Smad3 is critically implicated in repair of the infarcted heart. However, the role of fibroblast Smad2 in myocardial infarction remains unknown. This study investigates the role of fibroblast-specific Smad2 signaling in myocardial infarction, and explores the mechanisms responsible for the distinct effects of Smad2 and Smad3.
METHODS In a mouse model of myocardial infarction, Smad2 activation in infarct myofibroblasts peaked 7 days after coronary occlusion. In vitro, TGF-b1, -b2 and b3, but not angiotensin 2 and bone morphogenetic proteins-2, -4 and -7, activated fibroblast Smad2. Myofibroblast-specific Smad2 and Smad3 knockout mice (FS2KO, FS3KO) and corresponding control littermates underwent non-reperfused infarction.
RESULTS In contrast to the increase in rupture rates and adverse remodeling in FS3KO mice, FS2KO animals had mortality comparable to Smad2 fl/fl controls, and exhibited a modest but transient improvement in dysfunction after 7 days of coronary occlusion. At the 28 day timepoint, FS2KO and Smad2 fl/fl mice had comparable adverse remodeling. Although both FS3KO and FS2KO animals had increased myofibroblast density in the infarct, only FS3KO mice exhibited impaired scar organization, associated with perturbed alignment of infarct myofibroblasts. In vitro, Smad3 but not Smad2 knockdown downmodulated fibroblast a2 and a5 integrin expression. Moreover, Smad3 knockdown reduced expression of the GTPase RhoA, whereas Smad2 knockdown markedly increased fibroblast RhoA levels. Smad3-dependent integrin expression may be important for fibroblast activation, whereas RhoA may transduce planar cell polarity pathway signals, essential for fibroblast alignment.
CONCLUSIONS Myofibroblast-specific Smad3, but not Smad2 is required for formation of aligned myofibroblast arrays in the infarct. The distinct in vivo effects of myofibroblast Smad2 and Smad3 may involve Smad3-dependent integrin synthesis, and contrasting effects of Smad2 and Smad3 on RhoA expression.
[GW30-e0223]
Jigang He 1 , Hongrong Li 1 , Jinxiu Han 1 , Beibei Li 1 , Dan Yan 1 , Hongyuan Li 1 , Ping Wang 1 , Ying Luo 2
1Department of Cardiac and Vascular Surgery, First People’s Hospital of Yunnan Province
2Kunming University of Science and Technology
OBJECTIVES This study aimed to investigate whether exosomes secreted by mouse GATA-4-expressing bone marrow mesenchymal stem cells (BMSCs) could induce BMSC differentiation into myocyte precursors, decrease cardiomyocyte apoptosis, and improve cardiac function following myocardial infarction (MI).
METHODS BMSCs were transduced with a lentivirus carrying a doxycycline (DOX)-inducible GATA-4 or control lentivirus, and secreted exosomes from these BMSCs were collected and co-cultured with BMSCs or cardiomyocytes under hypoxic and serum free conditions. Furthermore, exosomes were injected into mice 48 h after MI. Cardiac function was evaluated by echocardiography at 48, 72, and 96 h after exosome treatment.
RESULTS Quantitative PCR showed that co-culture of BMSCs with GATA-4-BMSC exosomes increased cardiomyocyte-related marker expression. Co-culture of GATA-4-BMSC exosomes with cardiomyocytes in anoxic conditions decreased apoptosis as detected by flow cytometry. Injection of GATA-4-BMSC exosomes in mice 48 h after MI increased cardiac function over the next 96 h; increased cardiac blood vessel density and number of c-kit-positive cells and decreased apoptotic cardiomyocyte cells were also observed. Differential expression of candidate differentiation- and apoptosis-related miRNAs and proteins that may mediate these effects was also identified.
CONCLUSIONS Exosomes isolated from GATA-4-expressing BMSCs induce differentiation of BMSCs into cardiomyocyte-like cells, decrease anoxia-induced cardiomyocyte apoptosis, and improve myocardial function after infarction.
[GW30-e0225]
Zhigang Zhu, Yaqian Huang, Hongfang Jin, Junbao Du
Peking University First Hospital
OBJECTIVES This study aims to explore the regulatory role of SO 2 in vascular smooth muscle cell phenotype transformation and the molecular mechanisms.
METHODS Smooth muscle cells were supplemented with SO 2 donor, and the effects of SO 2 on smooth muscle cell contractile phenotype marker proteins and synthetic phenotypic marker proteins were observed to elucidate the regulation of SO 2 on smooth muscle cell phenotype transformation. By targeting serum response factor/myocardin, the molecular mechanism for SO 2 regulation of smooth muscle cell phenotype transformation was explored.
RESULTS Compared with the control group, the expression of contractile phenotype markers (SMA, SM22α and Smoothelin) was down-regulated and the expression of synthetic phenotypic markers (OPN and PCNA) was up-regulated after the stimulation with PDGF-BB. During this process, the SO 2 /AAT pathway was down-regulated, including decreased AAT1 protein expression, decreased AAT activity and decreased SO 2 content. In PDGF-BB-stimulated vascular smooth muscle cells, pre-incubation of SO 2 donor up-regulated the expression of contractile phenotype markers, while the expression of synthetic phenotypic marker molecules was down-regulated, indicating that SO 2 maintained the contractile phenotype of vascular smooth muscle cells. We found that the binding of SRF to myocardin was reduced after vascular smooth muscle cells were stimulated with PDGF-BB, and the pre-incubation with SO 2 increased the binding of SRF to myocardin.
CONCLUSIONS Endogenous SO 2 promotes the expression of contractile phenotype markers in vascular smooth muscle cells by promoting the binding of SRF to myocardin, and maintains the contractile phenotype of vascular smooth muscle cells.
[GW30-e0233]
Zulong Sheng, Wenbin Lu, Zulong Sheng
Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China
OBJECTIVES MicroRNAs (miRNAs) have been shown to play crucial roles in the occurrence, development, and treatment of many cardiovascular diseases. Coronary heart disease (CAD)-related miRNAs are still a growing research area. miR-7b was reported to be downregulated in acute myocardial infarction (AMI) myocardium tissues. However, it remains largely unknown whether miR-7b is involved in the pathogenesis and progression of the AMI ischemia/reperfusion (I/R) injury.
METHODS Male C57BL/6 J mice and H9C2 cells were used as models in this study. Masson staining, real-time polymerase chain reaction, Western blot analysis, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling immunofluorescence staining assays were performed to detect the related indicators in the study. SPSS 17.0 software was used to calculate the experimental data.
RESULTS The results showed that miR-7b expression is downregulated after I/R in mice, and miR-7b could inhibit apoptosis in I/R-induced H9C2 cells via upregulating hypoxia-inducible factor 1a (HIF1a). The inhibitory effect of miR-7b on I/R-induced apoptosis in H9C2 cells was blocked by HIF1a silencing. In addition, our data suggested that the p-P38 pathway may be involved in the role of miR-7 in I/R-induced H9C2 cell apoptosis.
CONCLUSIONS We confirmed that the overexpression of miR-7b inhibits I/R-induced apoptosis in H9C2 cells by targeting the HIF1a/p-P38 pathway. Our findings not only demonstrate the potential role of miR-7b in attenuating I/R-induced apoptosis but also provide a new insight into the better prevention of the I/R injury by mediating HIF-1 and p-P38.
[GW30-e0243]
Xiaoqun Wang, Jiawei Chen, Zhuhui Liu, Chang Li, Xinyi Shu, Ying Shen, Ruiyan Zhang, Lin Lu, Weifeng Shen, Xiaoqun Wang
Department of Cardiology, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine
OBJECTIVES C1q/TNF-related protein (CTRP) 1 is a newly identified adipokine with identical structural domains of adiponectin but displaying distinct functions. We previously showed that CTRP1 promotes the development of atherosclerosis by increasing vascular inflammation and endothelial dysfunction. We hypothesized that CTRP1 plays a key role in modulating vasodilation through the adipo-vascular axis.
METHODS Vascular dilatory responsiveness was compared by intravital microscopy of cremaster arterioles between obese CTRP1 transgenic (Tg-CTRP1), CTRP1 knockout (CTRP1 KO) and C57 wild type (WT) control mice fed with high-fat diet. Adipose tissue (AT) transplantation was performed to examine the role of CTRP1 on vasodilation via the adipose-vascular axis. The mechanisms by which CTRP1 modulates vasodilation was investigated.
RESULTS We found a marked impairment of endothelium-dependent arteriolar dilation in obese models of Tg-CTRP1 mice, whereas vasodilation was markedly enhanced in CTRP1 KO mice as compared to WT controls. By performing visceral AT transplantation, we detected that vasodilation was impaired in C57 mice transplanted with AT of Tg-CTRP1 mice but unaffected with that of CTRP1-KO mice. Meanwhile, elevated production of reactive oxygen species (ROS) was detected in the vascular wall of mice transplanted with AT of Tg-CTRP1 animals. In cultured endothelial cells, reduced nitric oxide (NO) bioavailability was observed when incubated with conditioned media of adipocytes or recombinant CTRP1. Furthermore, we found endothelial nitric oxide synthase (eNOS) phosphorylation was inhibited while uncoupling of eNOS dimers was increased by CTPR1 in an arginase-1-dependent pathway. Inhibition of arginase activity by synthetic chemicals markedly improved CTRP1-dependent vasodilatory dysfunction.
CONCLUSIONS These data define the essential role of the AT-derived CTRP1 in mediating vasodilatory dysfunction, as well as propose a novel mechanism that increased arginase activity by CTRP1 leads to eNOS dysfunction, reduced NO biosynthesis and enhanced ROS production.
[GW30-e0244]
Xiaoqun Wang, Jiawei Chen, Chang Li, Zhuhui Liu, Ruiyan Zhang, Weifeng Shen, Lin Lu, Xiaoqun Wang
Department of Cardiology, Rui Jin Hospital, Shanghai Jiao-Tong University School of Medicine
OBJECTIVES Mutations in CCDC11, a coiled-coil domain containing protein, are associated with embryonic asymmetry including situs inversus totalis, heterotaxy syndrome, and congenital heart defects. The molecular functions of CCDC11 in adults under different pathophysiological conditions remain totally undetermined. In this study, we sought to investigate the role of CCDC11 in the pathogenesis of adverse cardiac remodeling and dysfunction.
METHODS Animal models of pressure overload-induced cardiac hypertrophy were established either by transverse aortic constriction (TAC) or infusion of angiotensin II through a mini-osmotic pump. Myocardial expression of CCDC11 was enhanced or silenced by intramyocardial injection of adeno-associated virus to delivery CCDC11 short hairpin RNA or complementary DNA, respectively. The role of CCDC11 in cardiac dysfunction and remodeling was then evaluated.
RESULTS Pressure overload resulted in substantially increased expression levels of CCDC11 in mouse myocardium. Immunohistochemistry analysis revealed that increased CCDC1 was abundantly enriched in hypertrophic cardiomyocytes. In isolated mouse adult cardiomyocytes, knockdown of CCDC11 markedly reversed cell enlargement, reorganization of cytoskeleton proteins, oxidative stress, and upregulation of ANP (atrial natriuretic peptide), Col I (collagen type I), Col III (collagen type III), MMP (matrix metalloproteinase)-2 and MMP-9 in response to angiotensin II stimulation. Overexpression of CCDC11 significantly promoted hypertrophic cardiac remodeling and dysfunction, whereas silencing of CCDC11, in turn, remarkably attenuated the development of cardiac hypertrophy, left ventricular dilatation, and dysfunction in pressure overload animal models.
CONCLUSIONS The upregulation of CCDC11 during hypertrophic heart disease facilitates maladaptive cardiac remodeling and left ventricular dysfunction. Pharmacological interventions targeting at CCDC11 may constitute a therapeutic target in the future.
[GW30-e0250]
Yanggan Wang, Yanggan Wang
Zhongnan Hospital of Wuhan University and Medical Research Institute of Wuhan University, Wuhan University, Wuhan, China
OBJECTIVES Cardiac necrosis is considered as an electrical barrier that slows the pass by electrical conduction, forming the base of reentry. However, this concept has never been demonstrated in the beating heart.
METHODS We produced a lesion in the left ventricle of rats with absolute ethanol, and the changes of ventricular excitation threshold (VET), ventricular conduction time (VCT) and effective refractory period (ERP) were measured and the arrhythmia score was determined.
RESULTS VET was dramatically reduced after lesion induction. Interestingly, the VCT was shortened along with a shortening of ERP, indicating a facilitation of excitation conduction. With the progressive shortening of pacing interval, the VET and VCT further decreased. A higher arrhythmia score was recorded by induction of ectopic stimulation at the remote peripheral than the boundary of the lesion.
CONCLUSIONS Lesion production did not suppress but rather facilitate impulse induction and propagation in vivo, especially for the ectopic excitations. These alterations facilitate ectopic beats induction and increase the susceptibility to ventricular arrhythmia after cardiac lesion, e.g. myocardial infarction.
[GW30-e0252]
Di Fan, QiZhu Tang
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
OBJECTIVES The imbalance resolution of inflammation is the main cause of Adverse remodeling after myocardial infarction (MI). P21 is a central regulator of innate and adaptive immunity, but the role of p21 in MI is unclear. Here, we show that p21 expression increased in heart tissue after MI, and mainly derived from macrophages.
METHODS Induced myocardial infarction using Ligation of the left anterior descending coronary artery. Morphological changes, echocardiographic parameters, histological analyses and markers were used to evaluate cardiac function and healing.
RESULTS P21 deficiency causes less collagen fibril formation in the infarct area which lead to cardiac rupture, characterized by larger LV volumes, worse LV dysfunction, and a worse ejection fraction. P21 deletion decreased expression of M2 macrophage markers, impaired resolution of infarct healing. The overexpression of p21 promotes the transformation of M2 macrophages and fibroblast activation. Depleted of macrophages were unable to further increase LV dysfunction and cardiac rupture in p21 knockout mice. Furthermore, an external supply of macrophages, infected by adenoviral to overexpress constitutively p21, was able to improve catastrophic prognosis in mice post-MI.
CONCLUSIONS We define p21 as an essential molecular switch leading to M2 macrophage activation in post-MI, suggesting that p21 may represent a therapeutic target for the prevention of cardiac rupture after MI.
[GW30-e0253]
Luxun Tang, Wei Wang, Chunyu Zeng
Daping Hospital, Army Medical University
OBJECTIVES The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart is difficult to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferation capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation.
METHODS In neonatal mice, we inhibited glucokinase (GCK) to inhibit glycolysis and inhibited carnitine palmityl transferase 1 (CPT1) to inhibit fatty acid oxidation, and observed changes in cardiomyocyte proliferation. Myocardial infarction (MI) models were established in adult mice, and cardiomyocyte proliferation was observed after cardiac specific cpt1a knockout, AAV9 injection or CPT1 inhibitor etomoxir treatment.
RESULTS In neonatal mice, blockade of glycolysis by inhibiting GCK reduced cardiomyocyte proliferation, while blockade of fatty acid oxidation by inhibiting CPT1 delayed the cell cycle arrest in cardiomyocytes. Cardiac-specific Cpt1a deletion promoted cardiomyocyte proliferation and improved cardiac function in post-MI mice. This may have clinical significance, because inhibition of CPT1 by AAV9 carrying shCPT1-GFP or etomoxir, an inhibitor of mitochondrial CPT1, replicated the results in mice with MI. CPT1 inhibition stimulated the expression of cell cycle genes including cyclin A2, cyclin B2, and Plk1, which is probably mediated by inhibition of p38-MAPK and activation of PI3K-Akt signaling pathways, because overexpression of p38-MAPK or inhibition of PI3K or AKT blocked the etomoxir-mediated proliferation of cardiomyocytes.
CONCLUSIONS Inhibition of fatty acid oxidation by targeting CPT1 is a potential therapeutic strategy for stimulating cardiomyocyte proliferation and protection of heart from MI injury. The CPT1 inhibition-induced cardiomyocyte proliferation is through a p38-MAPK and PI3K-Akt-dependent mechanism.
[GW30-e0257]
Huolan Zhu 1,2 , Ren Yirong 1,2 , Fang Wang 1,2
1Department of Cardiology, Beijing Hospital, National Center of Gerontology, Beijing 100730, China
2Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, PR China
OBJECTIVES To systematically evaluate the efficacy of immune-adsorption therapy on the improvement of heart function in dilated cardiomyopathy (DCM) patients.
METHODS Search studies about immune-adsorption therapy for DCM patients in the Cochrane library, Pubmed, Embase, Web of Science, Medline and CNKI database. The retrieval time was from April 22, 2019. The literature was reviewed and screened independently by two investigators according to inclusion and exclusion criteria. Disagreement was discussed by two investigators. Data were extracted and meta-analysis was performed using software Revman5.3.
RESULTS Eight studies and 361 patients were included. Meta-analysis showed that: 1. LVEF significantly improved 3 months after immuno-adsorption therapy compared with before treatment (SMD=−6.02, 95% CI: −7.12~−4.92, P<0.0001). At 6 months after treatment, LVEF improved compared with that before treatment significantly (SMD=−6.7, 95% CI: −6.91~−6.49, P<0.0001). The results also showed that 1 year after treatment, LVEF significantly improved compared than that before treatment (SMD=−7.42, 95% CI: −9.09~−5.39, P<0.0001). 2. at 3 months after treatment, LVEDd reduced compared with that before treatment, and the difference was statistically significant (SMD=3.01, 95% CI: 2.76–C3.27, P<0.0001). 3. at 3 months after treatment, the LVEF of the treatment group was higher than that of the control group, with statistical difference (SMD=8.39, 95% CI: 7.75~9.02, P<0.0001). But LVEDd reduction was not statistically significant. (SMD=−3.11, 90% CI: −13.47~7.42, P=0.062).
CONCLUSIONS Immuno-adsorption therapy can improve left ventricular remodeling and heart function in patients with dilated cardiomyopathy. Compared with control group, immune-adsorption therapy can improve LVEF in the treatment group in 3 months after treatment.
[GW30-e0265]
Shuang Qu, Liao Qiao, Chunyu Zeng
Daping Hospital, Third Military Medical University
OBJECTIVES Myocardial infarction (MI) has been a worldwide problem. How to increase to proliferation ability become the main target to treat MI. This study is helpful for us to explore new treatment of cardiomyocyte loss after diseases such as MI.
METHODS LKB1 siRNA treatment and immunofluorescence (IF) was used to evaluate the proliferation rate of cardiomyocytes. Westernblot assay was used to detect the change of protein after LKB1 siRNA treatment. Adult mouse MI model and AAV9 injected to mice heart were used to evaluate the proliferation rate of adult cardiomyocyte.
RESULTS As the proliferation ability is decreased, the expression of LKB1 is increased. LKB1 siRNA treatment and IF shows that the expression of Ki67 and pH3 in cardiomyocytes were increased when LKB1 decreased. Westernblot shows that the expression of YAP and cyclin D were increased, and the level of phospho-YAP was decreased when LKB1 decreased. AAV9-LKB1-shRNA injected to mice heart after MI and the Edu staining shows that after treatment, the proliferation of adult cardiomyocyte was increased.
CONCLUSIONS LKB1 expression is negatively associated with cardiomyocyte proliferation. LKB1 inhibition induces cardiomyocyte proliferation by upregulating YAP and Cyclin D. LKB1 might be a potential treating target for stimulating cardiac regeneration after diseases such as MI.
[GW30-e0267]
Jinyun Zhu, Yun Zhao, Hong Yu
Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University
OBJECTIVES Growth differentiation factor 11 (GDF11), a transforming growth factor β superfamily member. The roles of GDF11 in heart diseases and cardiomyocytes (CMs) remain unclear, and little is known about the physiological and pathological functions of GDF11 in cardiomyocytes and heart. Thus, it need to elucidate the cell-specific roles of GDF11 in heart under physiological and pathological conditions.
METHODS Since the GDF11 global knockout in mice resulted in perinatal lethality, we used three cardiac specific Cre line mice (Nkx2.5-Cre, cTnT-Cre, and Myh6-MerCreMer) to identify the cardiac function of GDF11 in embryonic and adult period. Mice were subjected to pressure overload caused by transverse aortic constriction (TAC) and myocardial infarction (MI). Cardiac injury was evaluated using pathological analysis, echocardiograph, haemodynamics, transmission electron microscopy, calcium transient and molecular analysis. In vitro, neonatal and adult CMs of knockout mice were used. Knockdown or overexpression of GDF11 was achieved by siRNA or lentiviral transduction of GDF11 in CMs, respectively. CMs hypertrophy was induced by culturing CMs with phenylephrine (PE) (50 μM) for 24 h. CMs under hypoxia and serum deprivation condition were to mimic the microenvironment of MI. RNA-seq was performed to identify signaling pathway and downstream targets of GDF11 in CMs.
RESULTS GDF11 was mainly derived from CMs in the heart. GDF11 expression increased in patient’s heart with dilated cardiomyopathy (DCM) and MI. It also increased in mouse’s heart after TAC and MI. Under basal conditions, the knockout mice have normal left ventricular structure and function. In order to identify whether GDF11 deletion at the early stage of CMs development could affect embryonic survival and cardiac morphology, GDF11 floxed mice were crossed with Nkx2.5-Cre and cTnT-Cre Tg. GDF11 deletion in early stage of CMs development does not affect the birth rate at the expected Mendelian ratios, and all mice appeared normal and showed no significant perturbations in the cardiac development. However, deficiency of GDF11 accelerated cardiac dysfunction with left ventricular dilatation, impaired angiogenesis and more fibrosis after TAC and MI.
Moreover, the conditioned medium derived from GDF11 overexpressed CMs had more VEGF expression. It also stimulated tube formation of HUVECs significantly as compared with the null-vector group. The stimulation would be reversed by adding VEGF neutralized antibody into the conditioned medium. In addition to the communication with endothelial cells, CMs overexpressed GDF11 could also influence fibroblast via the secretion of anti-fibrosis mediators.
Furthermore, RNA-seq shown the activation of protein synthesis signaling pathways after overexpressed GDF11 in CMs. We testified that GDF11 enhances Smad2/3 signaling and AKT-mTOR activity in cultured CMs, contributing to VEGF production and anti-fibrosis mediators. In contrast, blockage of TGFβ-Smad pathway and AKT activity by TGF-β receptor inhibitor (SB431542), Smad3 inhibitor (SIS3) and AKT inhibitors (MK-2206) blunted GDF11 overexpression–induced paracrine effect of pro-angiogenesis. GDF11 overexpression in heart with AAV9-GDF11 during TAC rescued the detrimental cardiac function of CKO mice.
CONCLUSIONS GDF11 is necessary for the maintain cardiac function after pathological injury, which actions as an autocrine/paracrine regulatory factor, possibly through the mechanism of activation of TGFβ-Smad and AKT-mTOR signaling axis.
[GW30-e0268]
Yanggan Wang, Yanggan Wang
Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China
OBJECTIVES Doxorubicin (DOX) is an effective anticancer agent. Its clinical use is, however, limited due to its detrimental side effects, especially the cardiotoxicity. 3′,4′-dihydroxyflavonol (DiOHF) is a recently developed potent synthetic flavonoid which has been reported to exert anti- oxidative activity in myocardial ischemia-reperfusion injury and maintain the normal mitochondrial function. The aim of this study was to explore the protective effects of DiOHF on the DOX-induced cardiotoxicity.
METHODS We established DOX-induced cardiotoxicity models in H9C2 cells by incubating them with 1 μM DOX and in BALB/c mice treated with DOX (20 mg/kg, i.p.).
RESULTS DiOHF effectively prevented and reversed the DOX-induced cardiotoxicity, including ROS production, mitochondrial dysfunction, and apoptosis. The cardiotoxicity was accompanied by ERK1/2 activation and abolished by the silence of ERK1, rather than ERK2. Furthermore, treatment with DOX in mice induced an increase in serum CK-MB level and myocardial fibrosis with a reduction in left ventricular (LV) function. These changes were diminished by DiOHF administration.
CONCLUSIONS DiOHF suppresses and reverses the DOX-induced cardiotoxicity by inhibiting ROS release, preserving mitochondrial function and reducing apoptosis through activation of the ERK1 signaling.
[GW30-e0269]
Fengyuan Wang 1,2 , Congxin Huang 1,2
1Department of Cardiology, Renmin Hospital of Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China
2Cardiovascular Research Institute, Wuhan University
OBJECTIVES Sinoatrial node (SAN) contains <10,000 genuine pacemaker cells and some mesenchymal cells. Pacemaker cells dysfunction could cause cardiac electrical impulse conduction disorder, which further leads to circulatory collapse and has lethality for patients. Biological pacemaker is aimed to find a replacement for SAN to better treat bradycardia. Transcription factor TBX18 has been successfully applied for constructing biological pacemaker. And vascular smooth muscle cells (VSMCs) of the ascending aorta and SAN originated from the second heart field. The study explored whether ascending aortic smooth muscle cells in vitro could be reprogrammed into pacemaker-like cells with human TBX18.
METHODS The vascular smooth muscle cells of ascending aorta were cultured by tissue block adherence. After 4–7 days, the cell morphology was observed under light microscope. After passaging, the cells were randomly divided into TBX18 group, GFP group and Null group. TBX18 group was transfected with adenovirus carrying TBX18 transcription factor and green fluorescent protein (GFP), and GFP group was transfected with equal amount of GFP adenovirus as empty virus. And blank group was not transfected with virus as control group (Null group). Three groups of transcription factors TBX3, Shox2, HCN4, NKx2.5 and cardiomyocyte specificity cardiac troponin I (cTnI) were detected by RT-qPCR and Western blot after 4 days. And the expression of HCN4 protein in TBX18 group and GFP group was detected by immunofluorescence. In addition, funny current (I f current) was detected by the whole cell patch clamp.
RESULTS The purity of vascular smooth muscle cells reached above 90% with α-SMA and MHC antibody. By overexpressing TBX18, the transfected VSMCs expressed high levels of TBX3, Shox2, HCN4 and cTnI and low level of NKx2.5 in both RT-qPCR and Western blot. The result of immunofluorescence showed that HCN4 protein (red fluorescence) in the TBX18 group was expressed and almost consistent with green fluorescent protein and cell nucleus (blue fluorescence), while the GFP group showed barely red fluorescence. I f current recorded by patch clamp appeared the time and voltage dependence in TBX18 group, which the amplitude of I f density was from –5.164±0.662 pA/pF to –0.765±0.358 pA/pF (n=14). And I f current could be blocked Cs+ (4 mM/L).
CONCLUSIONS Transcription factor TBX18 could reprogram vascular smooth muscle cells of ascending aorta into pacemaker-like cells in vitro.
[GW30-e0270]
Lin Yin 1,2 , Congxin Huang 1,2
1Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China
2Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China
OBJECTIVES Biological pacing is the production of a specific gene or cell-induced cell-like cell by genetic engineering to construct a pacing site similar to the atrial junction to replace the original damaged pacing cell, and to obtain the desired heart rate for the patient to be able to meet the normal physiological activity. Transfecting the adenovirus overexpressing prrx1 into BADSCs, our study aimed to investigate whether overexpression of prrx1 can successfully induce the differentiation of BADSCs into sinus nodel cells and construct biological pacing.
METHODS BADSCs of SD rats were isolated and cultured, and the cells were identified by flow cytometry when they were passaged to passages 3–5. The experimental groups were divided into two groups: BADSCs were transfected with empty adenovirus GFP and adenovirus prrx1 (ie, Ad-GFP group, Ad-prrx1 group). Cell morphology and fluorescence intensity were observed under fluorescence microscope. After 5¡§C7 days of virus transfection, sinus node cell-associated pacing protein (HCN4) and ion channel (Cacnalg, encoding T-type calcium channel) as well as the expression levels of transcription factors (TBX18, ISL-1, pitx2, shox2, etc.) were detected by Western blot and RT-qPCR. Then immunofluorescence assay to detect whether cell co-expressed prrx1 with HCN4, TBX18 and ISL-1. Finally, whole-cell patch clamp technique records pacing current If.
RESULTS The newly isolated cells were round, and after being attached to the wall, they were long fusiform and spirally growing. After identification by flow cytological cell surface molecules, the isolated cells showed CD90 positive and almost no CD45, indicating that BADSCs were successfully isolated from rats. Repeated experiments confirmed that the optimal MOI for adenovirus transfection of BADSCs was 100. After 5¡§C7 days of transfection of adenovirus into cells, the biochemical tests showed that the mRNA levels and protein expressions of pacing-related factors (TBX18, ISL-1, HCN4, shox2, Cacnalg) in Ad-prrx1 group were significantly higher than those in Ad-GFP group. However, the expression level of pitx2 was decreased, and there was a statistical difference between the two groups (P<0.05). Immunofluorescence showed that prrx1 co-expressed with TBX18, ISL-1 and HCN4 in Ad-prrx1 group, but no expression of pacing-related protein was found in Ad-GFP group. Whole cell patch clamps were able to record the If current in the experimental group and this current was blocked by 4 mmol/L CsCl.
CONCLUSIONS Overexpression of prrx1 can successfully induce the differentiation of BADSCs into sinus node-like cells with biochemical characteristics and electrophysiological characteristics.
[GW30-e0284]
Lan Wang, Shu Lin
Department of Cardiology, Southwest Hospital, Third Military Medical University
OBJECTIVES The stem cell therapy to treat myocardial infarction (MI) has shown disappointed results largely due to the poor survival of transplanted stem cells in the MI region. We propose a combination therapy by targeted delivery of neuropeptide Y (NPY) to MI region to improve the micro-environment, which may enhance the survival of transplanted stem cells, and further improve the cardiac function.
METHODS In this study, P-selectin conjugated immunoliposomes containing NPY were given to the MI mouse through tail vein injection immediately after surgery. Adipose-derived stem cells (ADSCs) were transplanted to the MI region one week later. Left ventricular percent fractional shortening were measured 1 week and 4 weeks post MI using echocardiography.
RESULTS Results indicate that MI rats with no treatment lost 7% contractility (˜40% of its heart function) from 1 week to 4 weeks post-MI. Either targeted NPY or ADSCs treatment alone can slow down the loss by half to 5%. The combination of targeted NPY and ADSCs treatment further decreased the contractility.
CONCLUSIONS So we can use the mature liposomal drug delivery technology to NPY efficient and specific delivery to the myocardial infarction site to improve blood supply and microenvironment, myocardial regeneration, and repair the myocardial infarction to improve the purpose of heart function. Furthermore, the application of immunoliposomal drug loading technology in myocardial tissue repair, which not only provides new possibilities for the clinical treatment of myocardial infarction; but can also use this technology, for other diseases diagnosis and treatment to provide a new idea by combining different disease conditions.
[GW30-e0290]
Xing Yujie, Zhu Ling, Ma Meijuan, Xu Jing, Wang Junkui
Shannxi Provincial People’s Hospital
OBJECTIVES To explore the role of Wnt/β-catenin signaling pathway in the differentiation of rat bone marrow mesenchymal stem cells (BMMSCs) into cardiomyocytes.
METHODS The third generation BMMSCs were divided into two groups: (1) angiotensin II (Ang II) and 5-azacytidine (5-aza) group (final concentration was 0.1 μmol/L and 10 μmol/L respectively); (2) the control group, only choosing basic medium for induction. After induction for 24 hours, the induction medium was abandoned and cultured in complete medium for 4 weeks. Morphological changes, proliferation ability, induction differentiation rate, expression of α-actin and ultrastructure were respectively detected by inverted phase contrast microscopy, MTT, flow cytometry, immunofluorescence staining and transmission electron microscopy. The expression level of Wnt and β-catenin was detected by Western Blotting.
RESULTS BMMSCs showed various morphologies in primary culture. After passage, BMMSCs grew in long shuttle shape and showed uniform growth after induction. MTT assay showed that the growth rate of Ang II combined with 5-aza group was faster than that of control group. Flow cytometry showed that the induction rate of cardiomyocytes in Ang II combined with 5-aza group was (31.2±1.7)% and that in control group was (1.1±0.2)%. Immunofluorescence staining showed BMMSCs after induction expressed α-actin positively. The myofilament and gap junction were observed by transmission electron microscopy. Western Blotting results showed that the expression levels of Wnt and β-catenin in Ang II combined with 5-aza group were significantly higher than those in control group.
CONCLUSIONS Wnt/β-catenin signaling pathway plays an important role in promoting the differentiation of BMMSCs into cardiomyocytes induced by Ang II combined with 5-aza.
[GW30-e0295]
Qingqing Wu, Qizhu Tang
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China
OBJECTIVES High-mobility group AT-hook1 (HMGA1, formerly HMG-I/Y), known as an architectural transcription factor, has been involved in a great many of biological processes. Whereas, its effect on cardiac remodeling in diabetic cardiomyopathy remains vague to a great extent. The aim of this study is to elucidate the functional role of HMGA1 on cardiac remodeling in diabetic cardiomyopathy.
METHODS Adeno-associated virus 9 (AAV9) combined with HMGA1 and shHMGA1 were employed to overexpress or knockdown HMGA1 expression in the streptozotocin induced diabetes mice. Cardiac structure and functions were measured by echocardiography and hemodynamic examinations. Primary cardiomyocytes were used to perform gain/loss-of-function assays in vitro.
RESULTS In this study task, we figured out that HMGA1 was up-regulated in diabetic mice heart and high glucose stimulated cardiomyocytes. Overexpression HGMA1 accelerated high glucose induced cardiomyocytes inflammation and apoptosis, while HMGA1 knockdown relieved inflammation and apoptosis in cardiomyocytes. Overexpression HGMA1 via retro-orbital venous plexus injection of AAV9-HMGA1 caused deteriorated inflammatory response, increased apoptosis and reduced heart function in streptozotocin caused diabetic mice heart. Knockdown of HMGA1 by AAV9-shHMGA1 injection caused ameliorating cardiac remodeling. Mechanismly, we found that HMGA1 regulated autophagy by regulating P27/CDK2/mTOR signaling but not AKT, ERK and AMPKα. Autophagy inhibitor 3-MA, and bafilomycin A1 abrogated the protective effect of HMGA1 silencing. Autophagy inducer rapamycin blocked HMGA1 overexpression induced deteriorating effects in vitro. Moreover, we found that CDK2 silence or P27 overexpression also blocked HMGA1 overexpression induced deteriorating effects in vitro. P27 overexpression in vivo increased autophagy in mice heart and counteracted HMGA1 overexpression induced increased cardiac remodeling in diabetic mice. Furthermore, the regulating effect of HMGA1 on P27 was mediated by miR-222, while was confirm by luciferase reporter. And miR-222 antagomir counteracted HMGA1 overexpression induced deteriorating effects in vitro.
CONCLUSIONS Taken together, our data indicate that HMGA1 aggregates diabetic cardiomyopathy by directly regulating miR-222 promoter activity that inhibits P27/mTOR induced autophagy.
[GW30-e0300]
Peier Chen, Jianfeng Zhong, Can Chen
The Affiliated Hospital of Guangdong Medical University
OBJECTIVES This study investigated the related miRNA-324-5p changes of EPCs in peripheral blood of patients with (AMI), and analyzed the molecular mechanism of EPCs injury.
METHODS The peripheral blood of healthy volunteers and patients with ST-segment elevation myocardial infarction (STEMI) was clinically collected. EPCs were transfected by miR-324-5p mimic and simultaneously handled it with hydrogen peroxide (H 2 O 2 ) to inducing EPCs injury. At 24 hrs after H 2 O 2 treatment, cell viability, the up-take capacity on DiI-Ac-LDL and carrying ability on FITC-UEA-l and multiplication capacity were analyzed. The mechanism process were carefully researched by valued the characteristics of the mitochondrion morphology, membrane potential, ATP levels and the expressing apoptosis pathways.
RESULTS (1) EPCs derived from peripheral blood were obtained by density gradient centrifugation and cultured in vitro and identified. (2) Small RNA sequencing indicated that the expression level of miR-324-5p in peripheral blood EPCs of patients with STEMI was significantly lower compared to healthy volunteers. The Mtfr1 has been confirmed as a targeted gene of miR-324-5p through miRTarBase software and western blot. (3) The miR-324-5p mimic units could be contributed for the improvement of viability, the up-take capacity on DiI-Ac-LDL and carrying ability on FITC-UEA-l and multiplication capacity on oxidative stress-injured EPCs. (4) miR-324-5p could suppress mitochondrial fragmentation, promote membrane potential and ATP levels, as well as protect against oxidative stress-induced EPCs apoptosis.
CONCLUSIONS Our results suggested that miR-324-5p protects against oxidative stress-induced EPCs injury by regulating Mtfr1.
[GW30-e0305]
Jiayu Diao 1 , Lin Lin 2 , Gang Fan 2 , Guang Yang 1 , Xiaowei Yao 1 , Penghua You 1 , Wenqi Han 1 , Jizhao Deng 1 , Jiayu Diao 1
1Cardiovascular Medicine Department, Shaanxi Provincial People’s Hospital
2Cardiovascular Medicine Department, The Second Affiliated Hospital of Xi’an Jiaotong University
OBJECTIVES To evaluate the effects of resveratrol (RES) on high glucose (HG)-induced decreased mitophagy level and mitochondrial injury in cardiomyocytes.
METHODS H9c2 rat cardiomyocytes were randomly divided into four groups: control group, HG group, HG+RES group, and HG+RES+cyclosporinea (mitophagy inhibitor) group. The levels of mitophagy, mitochondrial function, including reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), mitochondrial respiratory chain complex enzyme activities and adenosine triphosphate (ATP) content, and cell activities were measured in each group.
RESULTS RES improved mitophagy suppressed by HG in cardiomyocytes, as the expressions of PINK1 and Parkin increased and the aggregation of LC3 in mitochondria raised. RES inhibited the production of ROS, increased the level of MMP, restored the activities of mitochondrial respiratory chain complex enzymes, increased ATP content, and consequently improved cell activities in cardiomyocytes cultured with HG. However, the above protective effects of RES on cardiomyocytes cultured with HG were attenuated by cyclosporinea.
CONCLUSIONS Improvement of mitophagy by RES has protective effects on HG-induced mitochondrial injury in cardiomyocytes.
[GW30-e0311]
Zhongming Shao 1 , Keke Wang 1 , Shuya Zhang 2 , Caixia Wu 1 , Yuan Zou 1 , Zhihua Shen 1 , Junli Guo 2 , Wei Jie 1
1Department of Pathology, School of Basic Medicine Sciences, Guangdong Medical University, Zhanjiang 5240233, P.R. China
2Cardiovascular Institute of the First Affiliated Hospital, Hainan Medical University, Haikou 571199, P.R. China
OBJECTIVES To explore the feasibility of the editing RhoE gene in H9C2 cardiomycytes based on CRISPR/Cas9 technology and enrichment of the signaling pathways following RhoE knockout.
METHODS Three rat RhoE knockout lentviral vectors (LV-RhoE-sgRNA-Cas9) and one negative control vector (LV-NC-Cas9) were constructed based on Cas9-containing lentviral vector GV392 (U6-sgRNA-EIF1a-Cas9-FLAG-P2A-puro), and the corresponding lentvirus particles were packaged. Viruses were then infected rat H9C2 cardiomyocytes and Cruiser enzyme digestion was used to screen the effective sgRNA, following western blotting analysis of RhoE expression in puromycin-stressed H9C2 cells. After whole genome expression chips were performed, the ingenuity pathway analysis (IPA) was used to analyze the changes of gene expression profiles and enrich the signal pathways that changed significantly. Finally, quantitative RT-PCR and western blot were used to verify the expression of some differential changes genes.
RESULTS Three sgRNAs targeting RhoE and one non-specific sgRNA were designed. Four lentviral vectors named LV-RhoE-sgRNA1-Cas9, LV-RhoE-sgRNA2-Cas9, LV-RhoE-sgRNA3-Cas9 and LV-NC-Cas9 were constructed, and the associated viral particles with a titer of 3×108 TU/mL were successfully obtained. Cruiser digestion confirmed the sgRNA1 displayed the obvious targeting effects against RhoE. With the help of Cas9 protein, sgRNA1 effectively led to editing RhoE gene. Western blot analysis confirmed that the expression of RhoE in mixed H9C2 cell pools was significantly decreased. After infected H9C2 cells with LV-RhoE-sgRNA1-Cas9, 417 genes were up-regulated and 412 genes were down-regulated. IPA analysis indicated that oncostatin M (OSM) signaling, superpathway of cholesterol biosynthesis, interferon signaling, regulation of actin-based motility by Rho and cell proliferation signals were most significantly affected followed RhoE knockout, which was further confirmed by quantitative RT-PCR and western blot analysis of some associated molecules expression. Interesting, cholesterol was predicted to be strongly activated (Z-score=4.423, P=5.86×10–12) and SCAP is predicted to be strongly suppressed (Z-score=–4.617, P=2.12×10–18) after RhoE knockout. And functional analysis indicated that RhoE was involved in cell death and survival, cell movement, tumorigenesis, organism development, gene expression and cardiovascular diseases.
CONCLUSIONS (1) For the first time, we successfully edit the RhoE gene in rat cardiomyocyte H9C2 through CRISPR/Cas9 technology. (2) We obtain the global gene expression profiles of RhoE deficiency in H9C2 cardiomyocytes. (3) IPA analysis suggests that RhoE plays a crucial role in many diseases and functions through mediating multiple signaling pathways, which provides a potential target for future intervention.
[GW30-e0312]
Kyung-Hyun Cho, SukJeong Kim
LipoLab, Smart-Aging Convergence Research Center, College of Medicine, Yeungnam University
OBJECTIVES Low serum HDL-C is a risk factor of cardiovascular disease and dementia. However, there has been no study to elucidate correlation of household income and HDL-C level in adult population.
METHODS We selected 5535 subjects (20–80 year-old) from Korean national health and nutrition examination survey 2017 (KNHNES, n=2469 men, n=3066 women). They were classified into five level of household income grade from 1 (the lowest) to 5 (the highest). They also classified based on HDL-C level from quintile 1 (.
RESULTS Generally, in both gender, higher HDL-C group showed larger percentage of income grade 5 and the lowest HDL-C group showed the largest percentage of income grade 1. Both group exhibited significant increase of average income grade depends on increase of HDL-C level (men, P=0.03; women, P<0.001). In low HDL-C quintile, the lower income grade is directly associated with the lower HDL-C level, suggesting that the poverty is directly associated with low HDL-C. Women group showed 3.3-fold higher incidence of dementia than men group at age 80’s. Sharp decrease of HDL-C after 50’s is associated with dramatic increase of dementia incidence in women, while men group showed relatively mild decrease of HDL-C and less dementia incidence than women group.
CONCLUSIONS In conclusion, in both gender, lower income group showed larger percentage of low-HDL-C prevalence. The decline of HDL-C after middle age was strongly associated with explosive increase of dementia in elderly.
[GW30-e0338]
Wei Zhuang 1,2 , Jianbin Gong 2
1The First Clinical Medical College, Nanjing University of Chinese Medicine
2Jinling Clinical Medical College of Nanjing University of Chinese Medicine
3College of Veterinary Medicine, Yangzhou University
OBJECTIVES RAGE is involved in the progression of atherosclerosis and improves endothelial dysfunction and suppresses vascular inflammation. The aim of this study was to investigate the cellular apoptosis and intracellular level of oxidative stress whether mediated by the receptor of advanced glycation end products (RAGE) in human coronary artery endothelial cells (HCAECs) under constant and intermittent high glucose (IHG) conditions in vitro.
METHODS Cellular viability was evaluated by 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay. Apoptosis of HCAECs was analyzed by flow cytometry analysis, and the transcript and protein levels of Caspase-3 and RAGE were detected by RT-qPCR and Western blotting respectively. Oxidative stress markers (MDA and GSH) and intracellular ROS level were detected by relevant assay kit. The expression quantity of RAGE was knockdown used the shRNA mediated by lentivirus in HCAECs.
RESULTS The results shown that in the intermittent high glucose group, the cell viability was significantly decreased and the apoptosis rate, the expression level of ROS, MDA, GSH, Caspase-3 and RAGE were significantly increased when compared to control and constant high glucose. Furthermore, these effects can significantly inhibit by the insulin treatment in the intermittent high glucose group. Knockdown the expression level of RAGE can significantly attenuate the badly effects induced by IHG.
CONCLUSIONS These results indicated that intermittent high glucose is more deleterious to HCAECs than constant high glucose, which may be due to the aggravation of cellular apoptosis and oxidative stress, and those effects may mediate by RAGE pathway.
[GW30-e0342]
Zhihui Liu, Xingliang Zou, Tao Jing
Chongqing Institute of Interventional Cardiology, Department of Cardiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China
OBJECTIVES Endothelial, as a barrier between blood and blood vessels, plays an important role in vascular homeostasis. Endothelial injury can cause the formation of vascular restenosis after percutaneous coronary intervention. Exosomes have been a hot topic in cardiovascular diseases in recent years, but exosomes have not been reported in terms of vascular restenosis. The aim of this study was to investigate the protective effects and potential mechanisms of mesenchymal stem cell derived-exosomes (MSC-Exo) on hypoxic-injured Endothelial cells (HEC).
METHODS In this study, we established a model of HEC under hypoxic conditions. Exosomes were isolated from MSC by using an exosome purification kit. HEC were treated with exosomes to examine their effects on cell proliferation, migration, invasion and apoptosis. The expression of the MAPK/Erk1/2 pathway and its downstream related proteins was then examined.
RESULTS In the model, iNOS was highly expressed and eNOS was lowly expressed compared to the normal group. MSC-Exo were verified through transmission electron microscopy, NTA particle size analysis and western blot and transported to HEC. MSC-Exo could accelerate the proliferation and migration and reduce the apoptosis of HEC. Compared with those in the untreated group, Western blot results showed that the expression levels of PCNA, CyclinD1, MMP9, MMP2, Vimentin and P-Erk1/2 proteins in MSC-Exo group were significantly up-regulated under hypoxic conditions. Importantly, the MAPK/Erk1/2 pathway inhibitor is capable of inhibiting the expression changes of the above related proteins induced by MSC-Exo.
CONCLUSIONS MSC-Exo promote the proliferation and migration of HEC by activating the MAPK/Erk1/2 pathway. Besides, MSC-Exo mediate the expression of PCNA, CyclinD1, MMP9, MMP2, and Vimentin proteins. This study is expected to play a role in the repair of cardiovascular injury and has certain clinical reference value.
[GW30-e0352]
Guangyao Zang, Bo Li, Jinchuan Yan
Department of Cardiology, Affiliated Hospital of Jiangsu University
OBJECTIVES Activated ECs play an important role in the development of AS which is partly attributed to the formation of neointima resulting from abnormal VSMCs hyperplasia. TET2 was reported as a major regulator of VSMCs phenotypic switch and protect EC from noxious stimulus and to repress inflammation in AS. The purpose of the present study is to determine whether activation of CD137 signaling can regulate VSMCs function by altering endothelial tet2 expression and to explore the potential mechanisms.
METHODS VSMCs were isolated from C57BL/6J mice. The influence of ECs on VSMCs was analyzed using a co-culture system. Western blotting was used to detect the protein expression levels of tet2 and CD9, CD81, CD63 as well as VSMCs phenotypic markers. RT-PCR was performed to detect mRNA levels of tet2. EdU proliferation assay and transwell migration assay were employed to assess VSMCs functions. EXO-spin kits were used to extract and purified exosomes. Transmission electron microscopy, Nanoparticle Tracking Analyzer was applied to characterize exosomes. Tet2 overexpression lentivirus was used to perform gain-of-function experiments.
RESULTS (1) Activation of endothelial CD137 signaling decreased tet2 expression and exosomes tet2. (2) ECs derived exosomes were internalized by VSMCs and inhibited phenotypic switch in vitro and neointimal formation in vivo. (3) Exosomes derived from CD137 activated ECs showed weakened protective effects on VSMCs.
CONCLUSIONS Activation of endothelial CD137 signaling by CD137L attenuated the repressive effects of EC-derived exosomes on PDGF-BB induced VSMCs phenotypic switch and neointimal formation after carotid injury.
[GW30-e0362]
Yuan Gao, Yingxian Sun
Department of Cardiology, The First Hospital of China Medical University
OBJECTIVES This study aimed to explore the underlying marker genes associated with hypertension by bioinformatics analyses.
METHODS A gene expression profile (GSE54015) was downloaded. The differentially expressed genes (DEGs) between the normotensive female (NF) and hypertensive female (HF), and between the normotensive male (NM) and hypertensive male (HM) groups were analyzed. Gene Ontology (GO) and pathway enrichment analyses were performed, followed by protein-protein interaction (PPI) network construction. The transcription factors (TFs), and the common DEGs between the HF and HM groups were then analyzed.
RESULTS In total, 411 DEGs were identified between the HF and NF groups, and 418 DEGs were identified between the HM and NM groups. The upregulated DEGs in the HF and HM groups were enriched in 9 GO terms, including oxidation reduction, such as cytochrome P450, family 4, subfamily b, polypeptide 1 (Cyp4b1) and cytochrome P450, family 4, subfamily a, polypeptide 31 Cyp4a31). The downregulated DEGs were mainly enriched in GO terms related to hormone metabolic processes. In the PPI network, cytochrome P450, family 2, subfamily e, polypeptide 1 (Cyp2e1) had the highest degree in all 3 analysis methods in the HF group. Additionally, 4 TFs were identified from the 2 groups of data, including sterol regulatory element binding transcription factor 1 (Srebf1), estrogen receptor 1 (Esr1), retinoid X receptor gamma (Rxrg) and peroxisome proliferator-activated receptor gamma (Pparg). The intersection genes were mainly enriched in GO terms related to the extracellular region.
CONCLUSIONS On the whole, our data indicate that the DEGs, Cyp4b1, Cyp4a31 and Loxl2, and the TFs, Esr1, Pparg and Rxrg, are associated with the progression of hypertension, and may thus serve as potential therapeutic targets in this disease.
[GW30-e0366]
Zou Lu, Dalin Jia
The First Affiliated Hospital of China Medical University
OBJECTIVES To explore the role of the endoplasmic reticulum (ER) stress-mediated apoptosis pathway in palmitate (PA)-induced cardiomyocyte lipotoxicity.
METHODS H9c2 cells were treated with various doses (100, 200 and 400 μM) of PA to mimic cardiomyocyte lipotoxicity in vitro. Oil Red O staining was used to determine the accumulation of intracellular lipids. An MTT assay was used to determine the cell viability. Lactate dehydrogenase (LDH) activity was used to measure the injury of H9c2 cells. Flow cytometry analysis was used to detect apoptosis. Western blotting was used to evaluate the expression change of ER stress-mediated apoptosis pathway proteins, including 78 kDa glucose-regulated protein (GRP78), eukaryotic initiation factor 2 α (eIF2α), protein kinase R-like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP) and cleaved caspase-12.
RESULTS Various doses of PA promoted excessive lipid deposition in cardiomyocytes and resulted in decreased cell viability, and increased the LDH activity and apoptosis rate in a dose-dependent manner. Furthermore, the expression of GRP78, a marker of ER stress, and the phosphorylation of eIF2α and PERK were increased following treatment with PA. Notably, the levels of CHOP and cleaved caspase-12, critical regulators of ER stress-mediated apoptosis pathway, were also elevated, and this effect was reversed by a specific ER stress inhibitor (4-phenyl butyric acid).
CONCLUSIONS The results of the current study demonstrated that PA induces myocardial lipotoxic injury by triggering ER stress and the ER stress-mediated apoptosis pathway.
[GW30-e0375]
Zuowen He, Dao Wen Wang
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
OBJECTIVES Adenosine 2A receptor (A 2A R) play a crucial role in the pathophysiological process of the cardiovascular diseases. However, the role of A 2A R plays in aortic remodeling remains puzzling. This study explored the effects and mechanisms of A 2A R on aortic remodeling from the perspective of macrophage migration.
METHODS Dynamic changes in adenosine-A 2A R system and proportions of CD11b+F4/80+ aortic macrophages (AM) in process of aortic remodeling were detected in C57BL/6 mice infused with Ang-II. Next, the role of A 2A R in aortic remodeling, the numbers of macrophages mobilized into and out of the aorta and emigrating to iliac lymph node, CC chemokine receptor 7 (CCR7) (CCL19 receptor) expression level and internalization were observed in mice with macrophage knockout of A 2A R or receiving A 2A R– /– bone marrow transplantation. The roles of CCR7 in mediating A 2A R signaling were investigated in Ang II infused A 2A R-cKO mice treated with CCR7 antibody.
RESULTS Adenosine-A 2A R in macrophages promotes Ang-II-induced aortic remodeling and macrophages accumulation in the aorta, which is inhibited by A 2A R knockout in macrophages. Moreover, macrophage A 2A R knockout inhibited macrophage accumulation by inhibiting macrophages retention via promoting macrophages emigration to draining lymph node without affecting macrophages proliferation and apoptosis in the aorta. Effects of macrophage A 2A R knockout are correlated with restoring expression and surface content of CCR7. Consistently, A 2A R activation inhibited CC-chemokine ligand 19 (CCL19) induced aortic macrophages migration, but has no effect on CC-chemokine ligand 2 (CCL2) induced monocytes migration. The effects of A 2A R activation are associated with downregulation and internalization of CCR7. Bone marrow transplantation experiments showed that A 2A R– /– bone marrow relieved Ang-II-induced aortic remodeling, macrophages retention, CCR7 downregulation and internalization, which was rescued by A 2A R+/+ bone marrow transplantation. Furthermore, CCR7 antibody treatment blocked all protective effects observed in A 2A R-cKO mice including attenuation of aortic remodeling and macrophages retention.
CONCLUSIONS A 2A R activation in macrophages mediate Ang-II induced macrophages accumulation and subsequent aortic remodeling by inhibiting macrophages emigration to draining lymph node and consequently promoting retention of macrophages through regulating CCR7 expression and internalization.
[GW30-e0378]
Jing Cao 1 , Zhaoya Liu 1 , Qian Xu 2 , Ruizheng Shi 1 , Guogang Zhang 1
1Department of Cardiovascular Medicine, Xiangya Hospital, Central South University
2Department of Cardiothoracic Surgery, Xiangya Hospital, Central South University
OBJECTIVES It is widely accepted that reactive oxygen species (ROS) derived from advanced glycation end products (AGEs)-induced activation of NADPH oxidases plays an essential role in the pathological process of diabetic vascular endothelial dysfunction. Peroxidasin (PXDN) is one of family of peroxidases that generates hypochlorous acid (HOCl) from hydrogen peroxide (H 2 O 2 ) and is primarily expressed in cardiovascular tissues. The specific role of PXDN in mediating diabetic vascular endothelial dysfunction has not been reported. Thus, the aim of this present study was to elucidate the role and potential mechanism by which PXDN promotes the pathogenesis of diabetic vascular endothelial dysfunction induced by AGEs.
METHODS Twelve-week-old diabetic experimental mice (db/db) were compared to non-diabetic control mice (db/m). Vasodilatation of aortic rings isolated from db/db and db/m mice were measured by wire myograph. The expression of receptor for advanced glycation end products (RAGE), NADPH oxidase 2 (NOX2), PXDN, and 3-Chlorotyrosine (3-Cl-Tyr) as well as the phosphorylation of Akt (p-Akt) and endothelial nitric oxide synthase (p-eNOS) in aortas was assessed by western blot. The plasma Nitric Oxide (NO) was detected by Griess assay. Expression and location of PXDN, RAGE and 3-Cl-Tyr in mesenteric arteries and aortas were also analyzed by immunofluorescence staining. In vitro experiments were performed in human umbilical vein endothelial cells (HUVECs). HUVECs with PXDN knockdown by siRNA, pretreatment with HOCl or the Akt inhibitor MK2206, or reduction of H 2 O 2 production by si-NOX2 and H 2 O 2 scavengers were treated with AGEs and the expression of RAGE, NOX2, PXDN, 3-Cl-Tyr, p-Akt, and p-eNOS was measured by western blot, the NO production of cell supernatant was detected by Griess assay.
RESULTS Compared to non-diabetic mice, acetylcholine (Ach)-induced endothelium-dependent relaxation was significantly inhibited in db/db mice. Furthermore, db/db mice had increased expression of RAGE, NOX2, PXDN, 3-Cl-Tyr and lower levels of p-Akt and p-eNOS compared to db/m mice. HUVECs treated with AGEs had significantly elevated expression of RAGE, NOX2, PXDN and 3-Cl-Tyr, while p-Akt, p-eNOS and NO levels were reduced. PXDN silencing attenuated the effect of AGE treatment on 3-Cl-Tyr, p-Akt, p-eNOS and NO levels. Additionally, HOCl treatment alone as well as HOCl in addition to treatment with Akt inhibitor MK2206 blocked phosphorylation of Akt and eNOS, reducing NO production. Furthermore, NOX2 silencing and H 2 O 2 inhibitors attenuated AGEs-induced up-regulation of PXDN and generation of HOCl, restored endothelial function.
CONCLUSIONS PXDN promotes AGEs-induced diabetic vascular endothelial dysfunction by attenuating eNOS phosphorylation on Ser1177 via NOX2/PXDN/HOCl/Akt pathway.
[GW30-e0386]
Lili Tan, Bo Yu
The First Hospital of China Medical University
OBJECTIVES To propose and verify a hypothesis that miR-17-5p knockdown may mitigate atherosclerotic lesions using atherosclerotic ApoE–/– mice as serum microRNA-17-5p (miR-17-5p) is elevated in patients with atherosclerosis.
METHODS Peripheral blood leucocytes were obtained from 30 AS patients and 30 healthy controls from April, 2016 to June, 2016. C57BL/6 and ApoE–/– mice (male, 6 weeks of old, 18–22 g) were purchased and were assigned to either a non-AS group (n=6) or the AS groups (n=6 per group).
RESULTS The level of miR-17-5p was higher while the level of very low density lipoprotein receptor (VLDLR), a predicted target of miR-17-5p, was lower in the peripheral blood lymphocytes (PBLs) of atherosclerosis patients as compared with control PBLs. ApoE–/– mice fed with a high-cholesterol diet displayed marked atherosclerotic vascular lesions, which were ameliorated after treatment with antagomiR-17-5p. Moreover, the decreased VLDLR in atherosclerotic mice was partly restored when miR-17-5p was antagonized. Further, luciferase assay confirmed VLDLR as a direct target of miR-17-5p in vascular smooth muscle cells (VSMCs). In addition, the elevated expression of proprotein convertase subtilisin kexin 9 (PCSK9), a secreted protease that binds to and promotes VLDLR degradation, in the atherosclerotic mice was suppressed by antagomiR-17-5p.
CONCLUSIONS A novel interaction between miR-17-5p and VLDLR is revealed and suggests that miR-17-5p may be a potential therapeutic target for AS.
[GW30-e0388]
Fang Wu, Yuelan Zhang
The First Hospital of China Medical University
OBJECTIVES The present study aimed to elucidate the role of Notch signaling in the development of myocardial infarction (MI) concomitant with diabetes in vivo and in vitro and evaluated the therapeutic effect of the Notch signaling in vitro.
METHODS Streptozotocin-induced diabetic rats were subjected to 25 min of ischemia and 2 h of reperfusion. Cardiac troponin T (cTnT) and creatine kinase-MB (CK-MB) isoenzyme levels were detected. Infarct size was measured by 2,3,5-triphenyltetrazolium chloride staining. Myocardial apoptosis and fibrosis were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Masson Trichrome staining, respectively. The mRNA and protein levels of Notch signaling components, including Notch1, Notch4, Delta-like 1, Jagged1, Mastermind-like protein 1 and p300, were quantified by reverse transcription-quantitative polymerase chain reaction and western blotting analyses, respectively. H9c2 cells were treated with/without 33 mM high glucose (HG) and/or subjected to hypoxia in the presence/absence of Jagged1. Cell viability and apoptosis were determined by MTT assay and Annexin V-fluorescein isothiocyanate/propidium iodide assay. Levels of the Notch signaling pathway members were examined.
RESULTS The present findings revealed that diabetes elevated CK-MB and cTnT, increased infarct size, induced myocardial apoptosis and inhibited the Notch signaling pathway in vivo after ischemia/reperfusion. Ischemia/reperfusion augmented the severity of MI in diabetic rats. Furthermore, HG reduced cell viability and induced cell apoptosis in H9c2 cells after hypoxia exposure, which was inhibited by Jagged1. We also found that HG inhibited Notch signaling in H9c2 cells after hypoxia, whereas Jagged1 exerted its cardioprotective effect on hypoxic injury (in HG environments or not) by activating the Notch signaling pathway.
CONCLUSIONS In conclusion, these findings suggest that diabetes promoted the progression of MI in vivo and in vitro via the inhibition of the Notch signaling pathway. Jagged1 may protect against MI in in vitro models by activating Notch signaling.
[GW30-e0399]
Zhenguo Dai, Shuang Yang, Yu Bo, Shuang Yang
The Second Affiliated Hospital of Harbin Medical University
OBJECTIVES Corin was found decreased in coronary heart disease (CHD) recently, which may reflect pathological dysfunction. But there is no data about the plasma corin changing after the onset of Non-ST Segment Elevation Acute Coronary Syndrome (NSTACS). This study is to examine the plasma corin levels in different time points in patients with NSTACS.
METHODS Fifty NSTACS patients without severe heart failure (men 30 and women 20) and 50 healthy individuals were enrolled in this study. Elisa method was used to determine plasma corin levels at 4 time points (admission, 24 h, 48 h, 72 h) respectively in these patients.
RESULTS The decreased plasma corin concentrations were found in both male and female patients when compared with the normal controls on admission. In NSTACS patients, plasma corin levels are significantly decreased than that in the healthy controls (820.354±122.543 versus 1420.123±457.235, P<0.001) on admission and reached the peak level of 989.241±253.717 pg/mL at about 2 days after admission, then the level of plasma corin decreased to 746.161±369.264 pg/mL at the third day after admission. There were more patients with Unstable Angina (UA) than Non-ST Segment Elevation Myocardial Infraction (NSTEMI) (35 versus 15, P<0.001).
CONCLUSIONS Plasma corin levels were found decreased in NSTACS patients compared with normal healthy individuals, which may reflect the dysfunction of the heart in patients with NSTACS.
[GW30-e0403]
Liu Menglu 1 , Hu Jinzhu 1 , Hong Kui 1,2
1Cardiovascular Department, The Second Affiliated Hospital of Nanchang University
2Key Laboratory of Molecular Medicine of Jiang Xi, The Second Affiliated Hospital of Nanchang University
OBJECTIVES Short QT syndrome (SQTS) is a highly malignant hereditary arrhythmia characterized by shortened QTc, ventricular tachyarrhythmias (ventricular tachycardia and ventricular fibrillation) results in syncope and sudden death. The cardiac sodium channel alpha subunit (Nav1.5) encoded by the SCN5A gene is a key protein that maintains the normal excitability of cardiomyocytes and its mutation causes various congenital arrhythmias. Nav1.5 binds to a variety of proteins which form a multiprotein complex to regulate the sodium channel function. MOG1 protein is a novel sodium channel regulatory protein which promotes Nav1.5 intracellular trafficking to plasma membranes, but its specific regulatory mechanism remains unclear. Our team’s previous study screened the sodium channel SCN5A mutation E428G was associated with SQTS, but its role in SQTS and the specific pathogenesis are still unclear. To investigate the effect of E428G on the electrophysiological function of Nav1.5 and the role of MOG1.
METHODS The wild-type (WT) plasmid of Nav1.5 and MOG1 were constructed. At the same time, the mutant (E428G) plasmid was constructed by gene-directed mutagenesis technique using wild-type Nav1.5 as a template. The above plasmids were transfected into human embryonic kidney 293T cells (HEK293T), and the experiment was divided into four groups: WT, E428G, WT+MOG1, E428G+MOG1. Whole cell patch clamp, cell membrane protein separation and immunoblotting technique were used to analyze the electrophysiological properties of sodium ion channels and their expression on cell membranes.
RESULTS Cell electrophysiological studies showed that the E428G mutation resulted in a 70% increase in peak sodium current, and a 30% reduction in late sodium current, steady state activation (SSA) and steady-state inactivation curve (SSA) revealed a hyperpolarization shift compared to the WT group. In the WT group, the peak sodium current was significantly increased 1.5 times after the expression of MOG1, the SSA curve shifted to the negative polarization direction, and the SSI curve did not shift significantly. However, the E428G mutant group overexpressed MOG1 revealed that the peak sodium current decreased by 30% significantly, the SSA curve shifted to the negative polarization direction and the SSI curve has no significant offset. In addition, compared with the WT+MOG1 group, the peak sodium current and the late sodium current of the E428G+MOG1 group were reduced by 50 and 30%, respectively, the SSA curve shifted toward the negative polarization direction, and the SSI curve did not shift significantly. Western blots showed that E4258G increased the sodium channel membrane protein by 1.8-fold compared with the WT group. When overexpressing MOG1, MOG1 increased the sodium channel membrane protein of the WT group by 70%, while MOG1 reduced the expression of sodium channel membrane protein by about 37% in the E428G group. In addition, there was no significant change in cell membrane protein expression of E428G+MOG1 sodium channel compared to WT+MOG1.
CONCLUSIONS The E428G mutation resulted in a significant loss of sodium channel function (late sodium current decreases), which may be the electrophysiological mechanism by which this mutation causes SQTS. MOG1 showed different effects on wild-type and mutant (E428G) Nav1.5: Promoted transport of wild-type Nav1.5 to the membrane and inhibited transport of mutant (E428G) Nav1.5 to the membrane.
[GW30-e0440]
Qiaozi Wang 1 , Zheyong Huang 1 , Junbo Ge 1,2
1Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China
2Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
OBJECTIVES Human cardiomyocytes (CMs) could not sustain their proliferative activity after birth thus it would be insufficient to compensate for the lost CMs after injury such as myocardial infarction, resulting in nearly irreversible cardiac dysfunction and terminal heart failure. Regulation of the Hippo pathway to promote endogenous CM proliferation has emerged as a promising strategy for heart regeneration. Previous studies have shown that the microRNA cluster miR302–367 negatively regulates the Hippo pathway, promoting CM proliferation. This study aims to determine whether another microRNA, miR-10b has any role in the regulation of cardiomyocyte proliferation and, if so, to explore the underlying mechanisms.
METHODS Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were produced by standard protocol of small molecules and served as the model to carry out our study. Quantitative PCR (qPCR) was performed to determine the expression pattern of miR-10b during the differentiation process. Gain- and loss-of-function assays were conducted to determine the role of mir-10b in CMs proliferation including immunofluorescent staining and qPCR. Flow cytometry was also used to explore the possible role of miR-10b in protecting CMs against apoptosis. We used bioinformatics analysis to predict the potential targets of miR-10b, luciferase reporter assays and RNA pulldown were used to confirm the relationship between miR-10b and the target genes. Further experiments were performed to explore the underlying mechanisms such as Western blotting, rescue and block assays.
RESULTS We found that the expression of microRNA-10b-5p (miR-10b) decreased during the maturation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs). In hESC-CMs, overexpression of miR-10b promoted the proliferation capacity, as revealed by both EdU and Ki67 staining. Increased expression of a variety of cell proliferation–associated genes, including PCNA, RACGAP1, NUSAP1, and CCNB, was detected by qRT-PCR as well. Conversely, knockdown of miR-10b suppressed cell cycle re-entry. Disorganized sarcomeres were observed after transfecting miR-10b proving that CMs were in a more dedifferentiated state. Moreover, Flow cytometry analysis showed that miR-10b transfection significantly reduced cell apoptosis compared to NC. qRT-PCR and luciferase assays helped us narrow down the potential targets predicted by bioinformatics screening, which we hypothesized that LAST1 was a major potential target. Overexpression of miR-10b led to decreased luciferase activity of the reporter with WT LATS1-3′UTR, indicating that LATS1 could be the direct target of miR-10b. Western blot analysis further showed that overexpression of miR-10b decreased LATS1 expression at the protein level. Furthermore, we tested the subcellular localization of YAP in hESC-CMs after transfection of miR-10b mimics or si-LATS1. The immunostaining results showed that transfection of miR-10b mimics or si-LATS1 increased the ratio of nuclear- to cytoplasmic-localized YAP.
CONCLUSIONS In summary, our study demonstrated that overexpression of miR-10b can activate hESC-CMs proliferation. Moreover, LATS1 is a direct functional target of miR10b and that miR-10b promotes hESC-CM proliferation, at least in part, by downregulating LATS1. Furthermore, we showed that miR-10b functioned, at least in part, by targeting LATS1. Our study suggests that miR-10b is a promising molecule for heart regeneration.
[GW30-e0446]
Xu Zhenyan 1,2 , Liu Hualong 1 , Jiang Zhenhong 1 , Hong Kui 1,2
1Cardiovascular Department, The Second Affiliated Hospital of Nanchang University
2Key Laboratory of Molecular Medicine of JiangXi, The Second Affiliated Hospital of Nanchang University
OBJECTIVES Study the genotype-phenotype correlation between the desmosomal genes and ARVC by meta-analysis, and provide important clinical application basis for genetic testing in ARVC clinical individualized diagnosis and risk stratification.
METHODS This study systematically searched for the relationship between the mutations in desmosomal genes published in the Cochrane Library, PubMed, and Elsevier databases and the clinical phenotype of ARVC. Data was extracted and meta-analysis was performed using Revman 5.3 software. The Cochrane Q test and the I2 statistic were used to evaluate the consistency of the included studies. The statistical analysis used a random effects model to conduct meta-analysis of common clinical features of ARVC, including patient demographic information and phenotypic characteristics based on diagnostic criterias.
RESULTS Genotype-phenotype association meta-analysis of desmosomal genes and ARVC: In total, 15 studies involving 1435 patients were included. The presence of desmosomal gene mutations was associated with a younger onset age of ARVC (32.9±14.7 vs. 41.3±13.1 years; P=0.007), a higher incidence of T wave inversion in V 1 –V 3 leads (76.3 vs. 57.5%; P<0.00001) or family history of ARVC (23.4 vs. 8.17%; P=0.008). There was a statistically significant difference in the proportion of patients with a specific diagnosis of ARVC compared with those with a critical or probable diagnosis (RD=0.37; 95% CI, 0.22–0.52; P<0.00001). There was no difference in the proportion of males between desmosomal-positive and desmosomal-negative patients (69.6 vs. 66.8%; P=0.52). The presence of desmosomal gene mutations was not associated with global or regional structural and functional alterations (49.8 vs. 47.2%; P=0.29), epsilon wave (22.4 vs. 22.1%; P=0.43), sustained or non-sustained ventricular tachycardia (54.3 vs. 52.6%; P=0.19) and ventricular tachycardia of left bundle-branch morphology (60.8 vs. 59.0%; P=0.14).
Meta-analysis of genotype-phenotype association between PKP2 and ARVC: A total of 11 articles were included, including 1090 patients with ARVC. Compared with patients with ARVC caused by non-PKP2 gene mutation, the age of onset of PKP2 gene mutation was smaller (32.0±10.3 years vs. 34.7±13.2 years; P=0.03), and the incidence of T-wave inversion in V 1 –V 3 lead Higher (78.6 vs. 64.3%; P<0.00001) and a higher probability of family genetic history (19.2 vs. 6.7%, P<0.0001). In male patients, there was no significant difference in the incidence of ARVC between the two (desmosomal group vs. non-desmosomal group) (68.3 vs. 68.9%; P=0.60). In addition, syncope (23.2 vs. 32.2%; P=0.36), ventricular tachycardia (63.5 vs. 60.5%; P=0.34), Epsilon wave (18.1 vs. 20.0%); Left bundle branch block ventricular tachycardia (60.4 vs. 58.8%; P=0.08), late potential and terminal activation duration prolongation in signal averaged electrocardiogram (62.9 vs. 55.2%; P=0.24), 24 h of premature ventricular beats > 500 (42.2 vs. 51.7%; P=0.87), ICD implantation (49.4 vs. 61.6%; P=0.89) there was no statistical difference.
CONCLUSIONS Patients with desmosomal gene mutations are characterized with an earlier onset age, a higher incidence of T wave inversion in V 1 –V 3 leads and a strong family history of ARVC; Patients with ARVC who have mutations in the PKP2 gene have clinical features such as younger onset age, higher incidence of T-wave inversion in the chest lead, and more family history.
[GW30-e0447]
Li Shuai 1 , Zhu Wengen 1 , Lai Wei 1 , Yu Jianhua 1 , Wan Rong 2 , Hong Kui 1,2
1Cardiovascular Department, The Second Affiliated Hospital of Nanchang University
2Key Laboratory of Molecular Medicine of JiangXi, The Second Affiliated Hospital of Nanchang University
OBJECTIVES To investigate the mechanism of arrhythmia induced by pantoprazole in mice under hypokalemia.
METHODS Mice were randomly divided into control group, pantoprazole group, hypokalemic control group and hypokalemic pantoprazole group, n=20 per group. Pantoprazole 20 mg/(kg×d) was intraperitoneally injected for 5 weeks in pantoprazole group, the same amount of normal saline was given in control group. Hypokalemic control group and hypokalemic pantoprazole group were given intraperitoneal injection of furosemide 30 mg/(kg×d) for 1 week at the end of the fourth week of treatment with normal saline or pantoprazole. After 5 weeks, the ECG parameters (heart rate, PR interval, QRS interval, QTc interval) and spontaneous arrhythmia were monitored by Data Sciences International (DSI). The cardiac structure and functional status were recorded by echocardiography. The blood samples were withdrawn from the inferior vena cava. The changes of the mRNA and protein expression of hyperpolarization-activated and cyclic nucleotide-cation channels 2 and 4 (HCN2 and HCN4), cardiac voltage-gated sodium channel alpha subunit (SCN5A), L-type calcium channel alpha subunit (CACNA1C) and T-type calcium channel alpha subunit (CACNA1G) were analysed by real-time fluorescence quantitative PCR and Western blot technology.
RESULTS In the basal state, compared with the control group, the heart rate was decreased and the PR interval was prolonged in pantoprazole group (P<0.01; P<0.05); in the hypokalemic state, the heart rate and PR interval of hypokalemic pantoprazole group were further decreased and prolonged, respectively (P<0.01; P<0.05), and 4 mice developed sinus arrest while the hypokalemic control group did not appear (P<0.05). However, there was no significant difference in the QRS and QTc interval between pantoprazole group and control group in the basal and hypokalemic states, respectively. In the basal state, the expressions of HCN4 mRNA and protein in pantoprazole group were lower than those in control group (P<0.01), and the expressions in hypokalemic pantoprazole group were lower than those in hypokalemic control group (P<0.01). The expression of HCN2 mRNA in pantoprazole group was lower than that in control group (P<0.05), which was further decreased in hypokalemic pantoprazole group compared with hypokalemic control group (P<0.01).
CONCLUSIONS It is found that pantoprazole may lead to bradyarrhythmia in mice under hypokalemia, which may be related to abnormal expression of HCN2 and HCN4. Clinicians should be aware of adverse cardiovascular effects when using pantoprazole.
[GW30-e0453]
Ji Li
University of South Florida
OBJECTIVES Activated protein C (APC), an activated protease of protein C zymogen, functions as an anticoagulant and a cellular homeostasis modulator with anti-inflammatory activities. Endothelial protein C receptor (EPCR) is crucial for APC signaling pathway. We revealed that APC is also an AMP-activated protein kinase (AMPK) agonist that exhibits cardioprotective effects against ischemic injury. We hypothesized that APC as an endogenous AMPK agonist could rescue an age-related impaired ischemic AMPK activity and improve the resistance of aged hearts to ischemic insults.
METHODS Cardioprotective effects of wild-type APC (APC-WT) and two derivatives, APC-2Cys (no anticoagulant activity) and APC-E170A (no cytoprotective activity) were examined after 45 min of ischemia and 24 h of reperfusion (I/R). APC activity and the expression levels of EPCR were monitored with/without I/R insults.
RESULTS APC treatment showed better beneficial effects on aged versus young hearts I/R injury. Moreover, APC’s cardioprotection against I/R insults is independent of its anticoagulant activity. Both APC-WT and APC-2Cys derivative, but not the non-cytoprotective APC-E170A ameliorated cardiac systolic dysfunction and attenuated myocardial infarct size caused by I/R insults. APC-WT activated AMPK and inhibited inflammation in the ischemic heart. Intriguingly, APC-AMPK activation modulated post-ischemic cardiac metabolism by increasing glucose/fatty acid oxidation ratio. APC generation was impaired in aged versus young hearts during I/R due to excessive shedding of EPCR. Both young and aged hearts exhibited similar protein C zomygen level and APC activity under physiological conditions. However, APC activity was abolished in aged but not young mice during I/R indicating an age-related impaired APC generation. There were significantly decreased cellular EPCR accumulation in aged versus young hearts during I/R linking the causation of the impaired APC generation to exaggerated EPCR shedding.
CONCLUSIONS APC signaling is impaired in aged versus young hearts in responding to I/R stress due to substantial shedding of EPCR, thus APC administration protects aged hearts against I/R insults through activating AMPK and suppressing inflammation.
[GW30-e0460]
Hualin Yan 1 , Yifei Li 2 , Yan Luo 1
1Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, China
2Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu, China
OBJECTIVES To establish cardiac pathological remodeling models and sequence the possible important regulated microRNA (miRNA) through next-generation microRNA sequencing; To elucidate the possible regulatory mechanism of miR-199a/214 inhibition in neonatal rat ventricular cardiomyocyte hypertrophy model.
METHODS Cardiac pathological remodeling models were established by peritoneal injection of isoproterenol 30 mg/kg/d for seven consecutive days. Cardiac function was detected by using Vevo2100 ultrasound system. HE, Masson staining and biomarkers (ANP/BNP/β-MHC) were used to evaluate the pathological changes of cardiomyocytes. MiRNA expression profile of myocardium in cardiac pathological remodeling group and control group were detected by miRNA sequencing; Established cardiac hypertrophy model of neonatal rat ventricular cardiomyocytes (NRVMs), and transfected cardiomyocytes with miR-199a and miR-214 mimic or inhibitor. The morphology and size changes of cardiomyocytes were detected by confocal microscope through SAA and DAPI staining; Bioinformatics databases were used to predict the target of miR-199a and miR-214. Luciferase recombinant reporter plasmid with 3′-UTR of predicted target gene and the miR-199a/214 mimic was co-transfected into H293T cells to verify the targeting of miR-199a/214.
RESULTS Echocardiography showed that the LVEF, LVFS were significantly decreased, and LVSD was dramatically increased in the cardiac pathological remodeling. HE staining showed obvious ventricular septal hypertrophy, thickened ventricular wall and hypertrophy of cardiomyocytes in cardiac pathological remodeling. Masson staining showed that the collagen fibers in cardiac pathological remodeling were significantly increased. The ANP, BNP and β-MHC were significantly upregulated in cardiac remodeling; According to the analysis of all the 495 miRNAs in rat, we screened 137 miRNA expression with significant changes (fold change >2.0 or <0.5) in terms of TPM (Transcripts per million). Based on the comparison of the expression levels of these 137 miRNAs, we found that compared with the control group, there are 26 dramatic altered miRNAs expression in cardiac remodeling, 16 of which were not reported of cardiac function before; The α-actinin staining and the count of cell surface area of cardiomyocyte showed that the surface area of cardiomyocytes was significantly larger than that of the control group; after miR-199a and miR-214 were overexpressed, the expression of miR-199a and miR-214 were significantly upregulated compared with the control group. And the cardiomyocytes size was significantly reduced by miR-199a and miR-214 inhibition.
CONCLUSIONS MiRNAs are important regulators in cardiac pathological remodeling and the inhibition of miR-199a/214 in NRVM hypertrophy can significantly attenuate cardiomyocyte hypertrophy.
[GW30-e0461]
Xiaopei Liu, Bofang Zhang, Gen Liu, Hongyi Zhao, Qi Hu, Jing Chen
Department of Cardiology, Renmin Hospital of Wuhan University
OBJECTIVES Recently, emerging studies have verified that KDM3A involved in an important epigenetic mechanism in cardiovascular diseases. Our previous studies confirmed that KDM3A regulated the function of smooth muscle cells in high glucose environment and vascular remodeling in diabetes mellitus, the underlying mechanism was that KDM3A could regulate the inflammatory response. According to the above findings, we arrive the conclusion that KDM3A may play a central role in the inflammatory response of the cardiovascular system. Meanwhile, owing to macrophages play a key role in inflammatory repair after myocardial infarction, we attempt to explore whether KDM3A could regulate the polarization of macrophages to affect the inflammatory response after myocardial infarction and targeting KDM3A could influence the prognosis of myocardial infarction and adverse left ventricular (LV) remodeling.
METHODS In order to explore whether KDM3A could affect the function of macrophages, our experiment was randomly divided into three groups in vitro: (a) control group: The BMDMs without any treatment; (b) AdshRNA group: The BMDMs were infected by AdshRNA; (c) AdshKDM3A group: The BMDMs were infected by AdshKDM3A. Four groups were divided randomly in vivo: (a) wild-type rat sham operation group (WT-SO); (b) KDM3A knockout rat sham operation group (KO-SO); (c) WT-MI operation group; (d) KO-MI operation group. We analyzed the function of macrophages by phagocytosis and migration assay, and explored the polarization of macrophages. The expression of macrophage inflammation related genes in acute inflammatory phase and surface makers were detected by western blotting and immunofluorescence assay. Echocardiography, Masson’s trichrome staining and Hematoxylin & Eosin (H&E) staining were detected the cardiac ventricular function.
RESULTS Inhibition of the expression of KDM3A in BMDMs led to the decrease of phagocytosis and attenuated the migration ability respond to chemokines of myocardial cell necrosis. Further, KDM3A deficiency led to increase in secretion of pro-inflammatory cytokines and more differentiation of macrophages into M1 phenotype under the LPS stimulation, but the ability of macrophages differentiated into M2 phenotype were inhibited under the IL-4 stimulation in vitro. Remarkably, there was a significantly difference in the infiltration of M1 and M2 macrophages between KO-MI and WT-MI groups at 7 days post-MI, we observed that more M1 macrophages (CD86+) infiltration and higher M1/M2 (CD86+/CD206+) ratio in the myocardial infarction area of KO-MI rats. WT-MI rats, on the other hand, were more infiltrated of M2 macrophages (CD206+). Western blot analysis revealed that the secretion trend of M1 (TNF-α, iNOS, CD86) or M2 (Arg-1, Ym-1, CD206) related phenotypic markers and cytokines in the two groups were consistent in vitro. Importantly, in the post-MI both left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) at seven days and one month, fibrosis and cardiac function at 7 days in KO-MI group were worse than those in WT-MI group. Among above all, we confirmed IRF4 as downstream effector of KDM3A-dependent pathway to modulate macrophages polarization by western blot analysis.
CONCLUSIONS KDM3A plays an indispensable role in cardiac repair progress and LV remodeling by modulating macrophages phenotype in the post-MI via IRF4 signaling pathway, therefore suggesting a promising therapy to treat post-MI injuring.
[GW30-e0465]
Yang Guo 1 , Guanyi Guo 2 , Xueshan Cao 3
1Department of Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China
2Department of Internal Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
3Department of Molecular and Cellular Physiology, Institute of Medicine, Academic Assembly, Shinshu University, Nagano, Japan
OBJECTIVES Hypertension is one of major risk factors to human health and influenced by various factors, including metabolism, immune, etc. Recent studies show gut microbiota can affect many human systems, such as immune, metabolic, and circulation systems; the composition of gut microbiota is altered in many diseases and disorders. However, the association between hypertension or blood pressure and gut microbiota remains unclear. In the present study, we aim to evaluate microbiota alteration in hypertension using a method of systematic review.
METHODS PubMed, EMBASE, and Web of Science databases were searched until March 2019 to identify eligible articles. Additional articles search according to specific authors in this field were also identified. Inclusion criteria were case-control studies based on stool samples with hypertension group and control group written in English or Chinese. Microbiota measures included alpha diversity index, beta diversity comparison, differential taxa, etc. Newcastle-Ottawa quality assessment scale (NOS) was used to assess the quality of the included studies.
RESULTS Six studies, with a total sample size of 590, were enrolled in this systematic review. The average score of NOS was 6.3, which was a score of high-quality category. We found alpha diversity in hypertension decreased significantly compared with control groups. For beta diversity analysis, hypertension cases can separate significantly with controls in both studies based on 16S rRNA sequencing and metagenomic analysis. Additionally, gut microbiota of hypertension showed over-growth of Prevotella, Klebsiella, Parabacteroides, etc.; whereas Faecalibacterium, Roseburia, etc. were higher in controls. In terms of function prediction analyses, the hypertensive gut microbiota exhibited increased lipid metabolism, including lipopolysaccharide biosynthesis and steroid degradation, biosynthesis of phenylalanine and phosphatidylethanolamine, etc., and decreased metabolism of amino acid and some hydrolase family. Two gut microbial marker-based model to predict hypertension were developed with the area under the receiver operator characteristic curve (AUC) of 0.81 (95% CI: 0.53–1.00) and 0.78 (95% CI: 0.73–0.82).
CONCLUSIONS Hypertensive gut microbiota shows alterations in alpha diversity, beta diversity, taxa composition, and metabolism. These findings provide new insights for causality study and new gut-based therapies of hypertension. Further validation studies of specific bacteria and function genes in large population are needed.
[GW30-e0498]
Deming Fu, Yuwan Hu, Xiao Wang, Jing Zhao, Lili Bai, Deming Fu
The Second Hospital of Shanxi Medical University
OBJECTIVES To investigate the protective effects of bisoprolol (Biso) on cardiomyocyte apoptosis by inhibiting the activity of calmodulin kinase II (CaMKII) and express of NF-κB in ischemic-reperfusion (I/R) injury rats.
METHODS Sixty SD rats were randomly divided into Sham, I/R+Vehicle, I/R+Biso, Sham+Biso groups. The changes of cardiac function were evaluated by ultrasound cardiograph and catheterization. The area at risk (AAR) and infarct size were evaluated by TTC staining, the AAR was expressed as a percentage of the left ventricular area (AAR/LV). The plasma norepinephrine (NE) and the activity of myocardial CaMKII were measured by ELISA, and the expression of NF-κB was detected by Western blot. Cardiomyocyte apoptosis was examined by agarose gel electrophoresis and TUNEL’s method. The mRNA levels of bax and bcl-2 were determined by RT-PCR.
RESULTS Compared with I/R+Vehicle, bisoprolol significantly decreased the infarct size and improved cardiac function, decreased plasma NE, and inhibited the activity of myocardial CaMKII and the express of NF-κB. Moreover, bisoprolol decreased the apoptosis index and the mRNA express of bax/bcl-2, and had no obviously DNA ladder.
CONCLUSIONS Biso could improve cardiac function and inhibit cardiomyocyte apoptosis by decreasing NE in plasma and inhibiting the activity of CaMKII and the express of NF-κB in I/R rats.
[GW30-e0503]
Xiaodong Wang, Xiaodong Wang
Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine
OBJECTIVES Long non-coding RNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) plays an important role in the pathophysiological process of inflammation. We aimed to investigate MALAT1 and its function in modulating miRNA-181a-3p and Bcl-2 in lipopolysaccharide (LPS)-induced acute lung injury (ALI).
METHODS We analysed MALAT1 in ALI patients, as well as the rat and alveolar epithelial cell models of LPS-induced injury. The expression of MALAT1 and miRNA-181a-3p were evaluated by qRT-PCR, and Bcl-2 was measured by western blot. Inflammatory factors tumor necrosis factor (TNF)-α, Interleukin (IL)-1β and IL-6 mRNA levels were also quantified by qRT-PCR. Luciferase reporter assay was used to verify direct interaction between MALAT1 and miRNA-181a-3p, or miRNA-181a-3p and Bcl-2. Transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) assay was performed to detect alveolar epithelial cell apoptosis.
RESULTS Serum MALAT1 and Bcl-2 levels decreased in ALI patients, whereas miRNA-181a-3p, TNF-α, IL-1β and IL-6 levels increased (P<0.01, Figure 1). MALAT1 was inversely correlated to miRNA-181a-3p (R=–0.508, P=0.0031, Figure 2) in ALI patients. MALAT1 transfection downregulated miRNA-181a-3p level and upregulated Bcl-2 expression, alleviating alveolar epithelial cell apoptosis (Figure 3), whereas siMALAT1 reversed the effect both in rats and alveolar epithelial cells (Figure 4). MiRNA-181a-3p downregulated the Bcl-2 expression both in LPS-induced ALI rats and alveolar epithelial cells, as well as promoted apoptosis (Figure 5). TNF-α, IL-1β and IL-6 levels increased after LPS stimulation and decreased after MALAT1 transfection (Figure 6).
CONCLUSIONS The results demonstrate that LPS-induced ALI decreases lncRNA MALAT1, increases miRNA-181a-3p and inflammatory factor expression, downregulates the Bcl-2 level and promotes alveolar epithelial cell apoptosis. Overexpression of MALAT1 may protect alveolar epithelial cells from LPS-induced ALI via downregulating of miRNA-181a-3p.
[GW30-e0521]
Jiahe Xie 1 , Yuhua Hu 1 , Qingrui Li 1 , Hairuo Lin 2 , Zhenhuan Chen 2 , Yiming Zhong 1 , Dongming Xie 1 , Yulin Liao 2
1Department of Cardiology, First Affiliated Hospital of Gannan Medical University, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou 341000, PR China
2Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
OBJECTIVES A woman’s age at final pregnancy is correlated with post-reproductive longevity, and we previously reported a phenomenon termed myocardial hypertrophic preconditioning. Based on these data, we investigated whether myocardial hypertrophic preconditioning during pregnancy created anti-hypertrophic memory and cardiac resistance to subsequent pathological hypertrophic stress, as well slowing progression to heart failure.
METHODS In C57BL/6 mice, cardiac hypertrophy was induced by either transverse aortic constriction (TAC) or infusion of angiotensin II (Ang II). In addition, hypertrophy of cultured neonatal rat ventricular cardiomyocytes (NRVCs) was induced by exposure to Ang II. To assess the influence of preconditioning, mice at 3 weeks postpartum received Ang II infusion or TAC for the same period as the control group, or NRVCs were cultured with Ang II for 12 h and without it for 24 h, followed by re-exposure to Ang II for 48 h like control cultures.
RESULTS In C57BL/6 mice, the heart weight/body weight ratio and expression of fetal genes (ANP and β-MHC) were significantly lower after preconditioning. In addition, the lung weight/body weight ratio was significantly lower in the preconditioned group at 4 weeks after TAC. Consistent results were obtained with cultured NRVCs after Ang II treatment. Activation of FoxO3a was significantly enhanced in the hearts of postpartum mice and in preconditioned NRVCs, and this change persisted after re-exposure to the hypertrophic stimulus. Silencing of FoxO3a attenuated the anti-hypertrophic effect of pregnancy preconditioning in mice with Ang II infusion and increased cardiomyocyte growth and apoptosis, while overexpression of FoxO3a prevented such changes.
CONCLUSIONS Myocardial hypertrophic preconditioning induced by pregnancy confers resistance to subsequent hypertrophic stress and slows progression to heart failure. FoxO3a is involved in cardiac protection by pregnancy hypertrophic preconditioning.
[GW30-e0522]
Ma Sai 1 , Wang Lei 1 , Gong Jianbin 1 , Cao Feng 3 , Ren Jun 2
1The General Hospital of Eastern Theater Command
2University of Wyoming
3Chinese PLA General Hospital
OBJECTIVES Nicotinamide riboside (NR) is widely used as a NAD+ precursor vitamin. Supplementation with NR has been shown to protect against metabolic disease in mammals. However, the potential effect of NR in alcoholic cardiomyopathy (ACM) has not been well elucidated. This study was designed to examine the effect of NR supplementation on the progression of alcoholic cardiomyopathy.
METHODS Alcoholic cardiomyopathy was established using chronic alcoholic diet containing 36% kcal from ethanol. Echocardiography and IonOptixMyoCam were used to evaluate cardiac contractile function.
RESULTS Our data revealed that NR alleviated alcohol consumption-induced changes in myocardial and cardiomyocyte contractile function as well as cardiac remodeling. To examine the possible involvement of mitophagy in NR-induced beneficial effects, FUNDC1–/– mice with mitophagy deficiency were employed. Interestingly, NR-induced beneficial effect against alcoholic cardiomyopathy was partially attenuated in FUNDC1–/– mice, indicating a role for FUNDC1-mediated mitophagy in NR-offered cardioprotection. In vitro study using H9c2 myoblasts suggested that NR regulated mitochondrial homeostasis through induction of FUNDC1-dependent mitophagy, as suggested by mitophagy-related protein expressions and Mitotracker-LC3 dots overlay. NR treatment enhanced cellular NAD+ level, consequently elevated NAD+-dependent mitochondrial sirtuin SIRT3 activity. Using mass spectrum assay and Co-IP, PGAM5, which functions to phosphorylate FUNDC1 at serine 13 (Ser13), was found to interact with and deacetylated by SIRT3 following NR administration.
CONCLUSIONS Taken together, our results revealed a protective effect of NR supplementation against alcoholic cardiomyopathy possibly associated with a SIRT3-PGAM5-FUNDC1- dependent regulation of mitophagy. These findings suggested the therapeutic potential of the vitamin B3 precursor of NAD+ in the management of alcoholic cardiomyopathy.
[GW30-e0530]
Xiaoxuan Bai 1,2 , Xing Luo 1,2 , Xiuzhu Weng 1,2 , Dongyang Liu 1,2 , Ying Lv 1,2 , Shan Zhang 1,2 , Chen Zhao 1,2 , Ming Zeng 1,2 , Haibo Jia 1,2 , Bo Yu 1,2
1Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, People’s Republic of China
2The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin 150086, People’s Republic of China
OBJECTIVES The incidence of atherosclerosis has increased dramatically in recent decades and has resulted in serious harm to human health. Atherosclerosis is a leading cause of death in developed countries and is characterized by the deposition of fibrous tissues and lipids in the intima of elastic arteries, leading to thrombus formation and structural damage marked by thickening and hardening of the vessel walls. Cell death and inflammation play critical roles at various stages of atherosclerosis. Pyroptosis is a pro-inflammatory form of regulated cell death and is dependent on the formation of inflammasome including NLRP3 and Caspase-1. In recent years, many studies have found that macrophage pyroptosis may play an important role in the progression of atherosclerosis. Therefore, finding a drug that can inhibit the pyroptosis of macrophages may delay the progression of atherosclerosis. Luteolin is a natural flavone, a subtype of flavonoid, which is abundant in edible plants, including broccoli, green chilies, onion leaf, French beans, carrots, white radish, clover blossom and ragweed pollen. A number of previous studies have reported that luteolin possesses beneficial medicinal properties, including anti-oxidant, anti-inflammatory and anti-aging actions. However, the effect of luteolin on atherosclerosis remains unclear. The aim of this study was to investigate the effects of luteolin on the pyroptosis in macrophages, and discuss the possible mechanisms of it.
METHODS Human THP-1 was induced into macrophages by treating with 0.5 nM PMA and then conducted with lipopolysaccharide (LPS) and ATP to induce pyroptosis. Before induction, we select 10 nM, 20 nM, 50 nM luteolin to pretreat macrophages. The cells were divided into the following five groups: control group, LPS+ATP group, 10 nM, 20 nM, and 50 nM luteolin pretreatment group. The Apoptosis and Necrosis Assay Kit and fluorescence microscope were used to detect the rate of cell pyroptosis. RT-PCR was conducted to measure the expression levels of NLRP3, Caspase-1, IL-1β and GSDMD. Western Blot was used to evaluate the protein expression of NLRP3, Caspase-1, IL-1β, GSDMD, AMPK and SIRT1.
RESULTS After pretreatment with luteolin, the rate of pyroptosis decreased obviously in comparison with that in LPS+ATP group (P<0.05). And the mRNA expression levels of NLRP3, Caspase-1, IL-1β and GSDMD in luteolin pretreatment groups are lower than control and LPS+ATP group in a concentration-dependent manner (P<0.05), so same as the protein levels. In addition, the protein expression of AMPK and SIRT1 show the downward trend in luteolin pretreatment groups.
CONCLUSIONS The results of the present study suggest that luteolin prevents the progression of atherosclerosis by decreasing macrophage pyroptosis during atherosclerosis, which is mediated by mechanisms including AMPK/SIRT1/NLRP3/GSDMD signaling.
[GW30-e0531]
Zhongwei Liu, Shuo Pan, Ling Zhu, Junkui Wang, Zhongwei Liu
Shaanxi Provincial People’s Hospital
OBJECTIVES This study was aimed to investigate the role and mechanism of MKKs/p38 MAPK signaling in ox-LDL induced inflammation in macrophages.
METHODS ox-LDL at various concentrations were used to stimulate human THP-1 macrophages. specific p38 MAPK inhibitor SB203580 was used to inhibit the phosphorylation of p38 MAPK. Specific siRNA were used to silence MKK3 and MKK6. DCFH-DA fluorescent stain was used to detect the intracellular ROS. Concentrations of IL18 and TNFα in cell culture supernatant was measured by ELISA. Western blotting was used to assess the phosphorylations of MK3, MKK6 and p38 MAPK as well as the expressions of IL18 and TNFα in macrophages.
RESULTS Compared with control, after ox-LDL stimulation, the intracellular ROS level, culture medium supernatant IL18 and TNFα concentrations, the phosphorylations of MKK3, MKK6 and p38 MAPK, the expression of IL18 and TNFα in macrophages were significantly increased (P<0.05) in a ox-LDL concentration- dependent manner (P<0.05). The TAC was decreased dramatically by ox-LDL stimulation in a concentration- dependent manner (P<0.05). SB203580 significantly inhibited phosphorylation of p38 MAPK (P<0.05). siRNAs significantly silenced MKK3 and MKK6 respectively (P<0.05). SB203580 and siRNAs significantly decreased IL18 and TNFα in both culture medium supernatant and macrophages (P<0.05) without significant suppression on ROS level (P>0.05).
CONCLUSIONS ox-LDL stimulation increased intracellular ROS which further activated MKKs/p38 MAPK signaling to induce inflammation in macrophages.
[GW30-e0532]
Zhongwei Liu, Ling Zhu, Shuo Pan, Gongchang Guan, Zhongwei Liu
Shaanxi Provincial People’s Hospital
OBJECTIVES Phenotype shifting of vascular smooth muscle cells (VSMCs) was indicated to play a role at initial stage of atherosclerotic plaque formation by facilitating extracellular matrix deposition. This study was aimed to investigate the involved possible molecular mechanisms of advanced glycation end products (AGEs) induced fibrotic responses in VSMCs.
METHODS Cultured human coronary smooth muscle cells (HCSMCs) were exposed to AGEs. The apoptosis signal- regulating kinase 1 (ASK1) specific inhibitor AGI-1067 and siRNAs silencing mkk3, mkk6 and p38 mapk were used to treat the cells respectively. Activations of MKK3, MKK6 and p38 MAPK were assessed by immunoblotting. Fibrotic response was assessed by fluorescence immunohistochemistry staining of collagen I and VIII. Activation of Immunoprecipitation determined the association of ASK1 and its inhibitor thioredoxin. A kinase assay was used to determine the ASK1 activity.
RESULTS AGEs incubation significantly activated ASK1, MKK3 and MKK6 which lead to activation of p38 MAPK, resulting in up-regulated fibrotic response in HCSMCs. However, siRNAs knocking down mkk3, mkk6 and p38 mapk impaired this fibrotic response. AGI-1067 administration not only dramatically inhibited the activation of ASK1/MKKs/p38 MAPK, but also suppressed the expression of the down- stream proteins including transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), collagen I and collagen VIII in HCSMCs exposed to AGEs.
CONCLUSIONS ASK1/MKKs/p38 MAPK pathway was activated by AGEs, leading to fibrotic response in VSMCs.
[GW30-e0533]
Zhongwei Liu, Shuo Pan, Junkui Wang, Zhongwei Liu
Shaanxi Provincial People’s Hospital
OBJECTIVES Featured by heart dysfunction, the diabetic cardiomyopathy is causing mortality and morbidity in type 2 diabetes mellitus patients. This study was aimed to investigate the molecular mechanisms of advanced glycation end products (AGEs)-induced cardiac dysfunctions.
METHODS Rats and isolated primary myocytes were exposed to AGEs. Left ventricular hemodynamic parameters were used to assess the cardiac function. Cell apoptosis was detected with TUNEL assay. Calcium indicator was used to determine the intracellular calcium concentration (Ca2+](i)). The molecular coupling between FK506-binding protein 12.6 (FKBP12.6) and ryanodine receptor 2 (RyR2) was evaluated by immunoprecipitation. Apoptotic protein expressions were measured by western blotting. The activity of RyR2 was measured by [H-3]-ryanodine binding assay.
RESULTS AGEs exposure impaired systolic and diastolic functions and induced apoptosis in myocardium. AGEs exposure also elevated [Ca2+](i), decreased mitochondrial membrane potential (MMP) and induced cell apoptosis in myocardium and cultured myocytes. AGEs impaired association between FKBP12.6 and RyR2 and further increased RyR2 activity in vivo and in vitro. The expression levels of cytochrome c and active caspase3 were elevated by AGEs exposure.
CONCLUSIONS AGEs induced cardiac dysfunctions by modulating RyR2-mediated calcium overload- triggered myocardial apoptosis.
[GW30-e0550]
Song Lai, Haiyi Yu, Youyi Zhang, Han Xiao, Wei Gao
Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China
OBJECTIVES The aim of the study is to investigate the effect of GDF15 on energy metabolism in heart failure. To elucidate the mechanism of GDF15 on the regulation of glycolysis and mitochondrial oxidative respiration in heart failure induced by sympathetic stress.
METHODS The replication-deficient adenoviral vectors were utilized to overexpress or knockdown GDF15 in neonatal rat cardiomyocytes (NRCM). XFe96 Extracellular Flux Analyzer (Seahorse Biosciences) was used to detect the energy phenotype of cardiomyocytes, which were stimulated by ISO (10–5 M) or corresponding control. Both mitochondrial oxygen consumption rate (OCR) and rate of extracellular acidification (ECAR) were recorded by Seahorse Analyzer. The direct measurement was recorded as the baseline OCR, followed by the addition of ISO (10–5 M) to observe the oxidative respiration level after sympathetic overactivation, and oligomycin (2 μM) to measure the ATP-linked OCR, the oxidative phosphorylation uncoupler FCCP (2 μM) to indicate the maximal respiration. Finally, rotenone (1 μM) and antimycin A (1 μM) were injected to determine non-mitochondrial respiration. In ECAR test, after ECAR-baseline were recorded, ISO (10–5 M) were added to observe the effects of sympathetic overactivation on cell oxidative respiration, then glucose (10 mM) was added to measure glycolysis, and oligomycin (2 μM) to measure the glycolytic capacity. Lastly, 2-DG (50 mM) was injected to determine non-glycolytic acidification. In vivo, GDF15–/– and wild type Wistar rats were subcutaneously injected with ISO 10 mg/kg/day or corresponding saline solution for 4 weeks, then the Vevo 2100 Imaging System were utilized to observe the cardiac structure and function. To explore the key mechanisms of GDF15 in regulating glucolysis, differentially expressed genes (DEGs) were analyzed and screened from Gene Expression Omnibus (GEO) datasets (GSE 7033) using a bioinformatics approach.
RESULTS Overexpression of GDF15 increased the glycolysis, glycolytic capacity and glycolytic reserve of cardiomyocytes indicated by ECAR analysis. GDF15 also enhanced the oxidative respiration of mitochondria, including ATP production and maximum respiration in cardiomyocytes. Conversely, knockdown of GDF15 resulted in significantly reduced glycolysis, glycolytic capacity and glycolytic reserve of cardiomyocytes, and slightly reduced mitochondrial oxidative respiration level compared with the control group. We found that compared with the wild type, the incidence and mortality of heart failure in GDF15–/– rats increased significantly. RNA-seq data analyzed by KEGG showed that GDF15 knockout leading to LDHA upregulation by 5.19 times and ALDH1A3 downregulation by 14.96 times.
CONCLUSIONS GDF15 is increased in ISO-induced heart failure rats, GDF15 promotes myocardial cell glycolysis and mitochondrial oxidation to increase the production of ATP. GDF15 makes the energy metabolism of cardiomyocytes tend to a compensatory state and plays a protective role on metabolic failure of cardiac myocytes induced by sympathetic overactivation.
[GW30-e0556]
Xi Hu, Haiyi Yu, Han Xiao, Wei Gao
Peking University Third Hospital
OBJECTIVES MicroRNAs (miRNAs) have been proved to be involved in myocardial infarction (MI), and they function by targeting 3′-untranslated region (3′-UTR) of specific messenger RNA (mRNA). However, only a small number of miRNAs exert their functions in that way, and we speculated there should be novel mechanisms for miRNAs. It’s recently reported that nuclear miR-122 can directly regulate the biogenesis of miR-21 at the posttranscriptional level through forming hybridization between mature miRNAs and primary miRNA (pri-miRNA), which is based on generally accepted miRNA silencing mechanism, but no such mechanisms have been reported in MI yet. Therefore, we conducted this study to determine whether there were such miRNA-miRNA duplexes involved in the pathogenesis of MI.
METHODS We constructed microRNA correlation matrices of circulating miRNAs assessed in the datasets of GSE61741. In this context, we focused on miRNA pairs with negatively correlated expression levels, since negative correlation is a necessary feature of the novel mechanism of action of miRNAs. To determine how MI affected the miRNA correlations, we compared the difference of miRNA correlation coefficients in the two groups by Fisher’s Z score. In addition to negative correlation, appropriate complementary binding between one primary microRNA and another mature microRNA is also a prerequisite for this new mechanism, and the site binding to the mature microRNA seed region must be located within 1000 nucleotides away from the 3′ or 5′ ends of premature microRNA transcript, and the minimum free energy of the binding should be lower than −20 kcal/mol. Here, RNAhyrid was used to identify if there were proper binding sites between the miRNA pairs. Those miRNA pairs, which hold appropriate binding sites, were defined as duplexes and may be involved in the pathogenesis of MI through a new mechanism of action of microRNAs. KEGG and Go slim analysis were conducted to reveal the functions of these nominated miRNA pairs. Further, to figure out whether these duplexes could discriminate MI patients from the healthy individuals, we compared the diagnostic value of each single miRNA of the duplex and the union of them by plotting the ROC based on another completely independent dataset GSE31568.
RESULTS (1) By comparing the Z scores, we screened out 444 miRNA pairs in which negative correlation coefficients increased or decreased significantly in MI group compared with healthy group. (2) 9 miRNA pairs out of 444 have at least one binding site between one primary microRNA and another mature microRNA. (3) The nominated 9 miRNA pairs were functionally associated with signaling pathways involved in MI, such as MAPK (FDR, 1.15E-02) and hippo signaling pathways (FDR, 4.70E-06), and cellular nitrogen compound metabolic process (FDR, 5.26E-116). (4) We analyzed diagnostic value of the duplexes for MI, and found that six pairs, which werehsa-miR-516b-3p & hsa-miR-1285-3p, hsa-miR-521 & hsa-miR-1285-3p, hsa-miR-339-5p & hsa-miR-663a, hsa-miR-593-5p & hsa-miR-193a-5p, hsa-miR-362-5p & hsa-miR-767-5p, hsa-let-7a-5p & hsa-miR-142-5p, had larger area under ROC (AUC) when they were combined than separately analyzed.
CONCLUSIONS We found that six pairs of microRNAs were associated with MI by a new mechanism of forming duplexes. Combined application of each pair of microRNAs in the duplex can significantly improve the diagnostic value of MI.
[GW30-e0558]
Zhulan Cai, QiZhu Tang
Department of Cardiology, Renmin Hospital of Wuhan University
OBJECTIVES The High Mobility Group A1 (HMGA1) proteins, serving as a dynamic regulator of gene transcription and chromatin remodeling, plays an influential part in the pathogenesis of a variety of cardiovascular diseases. However, the precise role of HMGA1 in sepsis induced cardiomyopathy (SIC) remains unclear. This study was designed to illustrate the effect of HMGA1 involved in SIC.
METHODS Cardiomyocyte-specific HMGA1 overexpression was obtained using an adeno-associated virus system with intramyocardial injection in mice heart. The model of SIC in mice was constructed via intraperitoneal injection of lipopolysaccharide (LPS) for 6 h. H9c2 rat cardiomyocytes was stimulated with LPS for 12 h. Western blotting was used to detect the expression level of the protein, PCR was applied to exam the transcription level of RNA, and TUNEL staining was utilized to test the apoptosis level of the cells.
RESULTS HMGA1 expression was upregulated in murine inflammatory hearts as well as LPS stimulated H9c2 cardiomyocytes. HMGA1-overexpressing exhibited aggravated cardiac dysfunction, cardiac inflammation as well as cardiac apoptosis following LPS treatment both in vivo and in vitro experiment. Interestingly, HMGA1 knockdown in H9c2 cardiomyocytes attenuated LPS-induced cardiomyocyte inflammation, but aggravated cell apoptosis. Mechanismly, we found that overexpression of HMGA1 induced increased expression of cyclooxygenase-2 (COX-2). COX-2 inhibitor blunted the aggravation of inflammation and apoptosis in HMGA1 overexpressed H9c2 cardiomyocytes. Whereas, HMGA1 knockdown induced a reduction in signal transducer and activators of transcription 3 (STAT3) expression. STAT3 agonist reversed HMGA1 silence induced anti-inflammatory effects, while ameliorated cell apoptosis induced by LPS.
CONCLUSIONS In conclusion, our results suggest that overexpression of HMGA1 aggravated cardiomyocytes inflammation and apoptosis by up-regulating COX-2 expression, while silence of HMGA1 expression attenuated inflammation but aggregated cell apoptosis via down-regulation of STAT3.
[GW30-e0564]
Zhiteng Chen, Haifeng Zhang, Jingfeng Wang
Sun Yat-sen Memorial Hospital
OBJECTIVES Cardiac fibrosis is considered as the key pathophysiology of heart disease. Looking for a target to interfere in cardiac fibrosis exerts great influence. The heart contains a heterogeneous group of cells. Fibroblast is a hot focus for fibrosis research. Recently, several LncRNAs prove to participate. In different physiological functions of different cells by regulating glycolysis. Moreover, it is demonstrated that glycolysis contributes to fibrosis. However, it is still not clear whether lncRNAs exert influence on cardiac fibrosis via regulating glycolysis.
METHODS We use human primary cardiac fibroblast for the vitro test and papillares musculi (PM) from human cardiac valvulectomy (nonfibrotic heart tissue) and ventricular aneurysm tissue (VA) from human ventricular aneurysm resection (fibrotic heart tissue) for vivo tissue detection test. For the knocked down and rescue test, we use siRNA and adenovirus plasmid respectively. Western blog, PCR, Elisa detection and fluorescence in situ hybridization dectection (Fish) were main tools to detect the markers of activation of fibroblast while CCK8 assays, transwell and scratch test are main tests to assess the function of fibroblast.
RESULTS We searched lncRNAs which had reported on Pubmed to be in correlation with glycolysis and detected their expression in cardiac fibroblasts activation model induced by TGF β1 by RT-qPCR. As a result, 28 lncRNAs were found and detected. Among them, Linc00092 exhibited the most significant change. To further explore the function of Linc00092 in cardiac fibrosis, we dectected the expression of Linc00092 in papillares musculi (PM) from human cardiac valvulectomy (nonfibrotic heart tissue) and ventricular aneurysm tissue (VA) from human ventricular aneurysm resection (fibrotic heart tissue). As a result, the expression of Linc00092 decreased in VA compared with PM. Furthermore, we demonstrated that Linc00092 was mainly expressed in fibroblast rather than cardiomyocyte by a fluorescence co-localization test with fluorescence probe of Linc00092, cardiac troponin T (marker of cardiomyocyte) and vimentin (marker of fibroblast). Then we knocked down Linc00092 with siRNA and overexpressed it with Linc00092 adenovirus plasmid. We found that its knocked down could not only increase the expression of α-SMA and COLIA1 but also strengthen the ability of proliferation, migration and the secretion of COLIA1 of cardiac fibroblast together with intensive glycolysis. On the contrary, over-expression of Linc00092 could exert the opposite effect by decreasing the expression of CTGF and inhibiting the ability of proliferation, migration and the secretion of COLIA1 of cardiac fibroblast together with lessened glycolysis. Besides, we could reverse the increased expression of α-SMA and COLIA1 after knocking down Linc00092 with the help of 2-deoxyglucose, a glycolysis inhibitor. On the contrary, when we overexpressed PKM2, a key enzyme of glycolysis, the expression of α-SMA and CTGF increased.
CONCLUSIONS Glycolysis contributes to the activation of cardiac fibroblast. Linc00092 could alleviate the activation of cardiac fibroblast via inhibiting glycolysis.
[GW30-e0565]
Maoxiong Wu, Haifeng Zhang, Yangxin Chen, Jingfeng Wang
Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, PRC
OBJECTIVES Prolonged endoplasmic reticulum stress (ER stress) is the key mechanism in cardiac lipotoxicity-induced apoptosis. IL-33 is a potent cardiac protector but the role of IL-33 in cardiac lipotoxicity and ER stress is unknown. Autophagy is essential to maintain homeostasis but its role in cardiomyocytes ER stress also be elusive.
METHODS Effects of IL-33 on lipotoxicity, ER stress and autophagy were assess using db/db mice and palmitic acid (PA) treated cardiomyocytes. The role of ER stress and autophagy in the effects conferred by IL-33 and the mechanism that IL-33 regulates ER stress and autophagy were investigated.
RESULTS db/db mice and PA treatment were associated with enhanced ER stress and apoptosis, which could be reversed by ER stress inhibitor. PA inhibited autophagosome formation and impair autophagic flux. IL-33 and the autophagy inducer, rapamycin, improved cardiac diastolic function, released ER stress, cardiac lipid accumulation and apoptosis. The non-selective autophagy inhibitors, either 3-MA or wortmannin, abolished the effects of IL-33 in reducing ER stress and apoptosis. By gene expression profile analysis, we identified insulin like growth factor binding protein 3 (IGFBP3) as one of the genes mostly distinct between treatments with or without IL-33. siRNA against IGFBP3 mRNA significantly dismissed the effects of IL-33 on ER stress, autophagy and apoptosis.
CONCLUSIONS IL-33 released cardiac lipotoxicity via alleviating ER stress and promoting autophagy. IGFBP3 is essential for IL-33 induced ER stress resolution and autophagy enhancement during cardiac lipotoxicity.
[GW30-e0569]
Jing Chen, Huang Zheyong
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University
OBJECTIVES Poor cell homing limits efficacy of cardiac cellular therapy. The cyclo Arg-Gly-Asp (cRGD) peptide binds with high specificity to platelet which is involved in repair of tissue injury.
METHODS Here, we assessed if cRGD-modified stem cells had enhanced platelet-mediated homing ability resulting in better functional recovery and structural preservation in a rat myocardial injury model. cRGD-modified mesenchymal stem cells (cRGD-MSCs) were obtained via membrane fusion with cRGD-modified liposomes. The cRGD-MSCs targeting ability of platelet was examined both in vitro and in vivo.
RESULTS Under both static and flow conditions in vitro, cRGD peptide significantly enhanced MSCs binding and capture ability to platelet. cRGD-MSCs showed higher accumulation than unmodified MSCs in injured rat myocardium in acute phase after administration, resulting in better structural preservation and functional recovery.
CONCLUSIONS Platelet is therefore a novel target for enhancing homing of transplanted cells to injured myocardium, and the platelet-targeting delivery system maybe a generalizable platform technology for regenerative medicine.
[GW30-e0575]
Chenkai Wu, Zhaowei Zhu, Qiming Liu, Zhenfei Fang, Xinqun Hu, Shenghua Zhou
Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University
OBJECTIVES Adenosine deaminases that act on RNA (ADARs) catalyze adenosine to inosine conversion in RNA. ADAR1 plays a critical role in the differentiating cells in embryo and adult tissues to support the cell’s survival, differentiation and maturation. Previous studies have shown that ADAR1 knockout in mice results in embryonic lethality with impaired vascular development. But the precise roles of ADAR1 in the endothelium remain elusive. We used a mice model to determine the effect of endothelial cell (EC)-specific knockout of ADAR1 on vascular homeostasis.
METHODS Wild-type (WT) mice, ADAR1–/– mice, ADAR1ECKO mice, -ADAR1flox/flox mice and Human umbilical vein endothelial cells (HUVECs) were used. Knockdown of ADAR1 was mediated by siRNA carried by Lipofectamine 2000. Tissues were collected for histological observation or transmission electron microscope detection. Vascular permeability was measured by Evans Blue-labeled albumin in vivo and in vitro. Hindlimb ischemia model and aorta ring assay were used in mice and tube formation assay was used in HUVECs. Expression protein was measured by Western blotting or Immunofluorescence.
RESULTS We show that EC-specific disruption of ADAR1 in mice caused partial postnatal lethality and lung defects. Vascular permeability was enhanced in ADAR1ECKO mice, which may be associated with dilated interendothelial junctions and decreased Caveolin-1 expression. Angiogenesis was inhibited by deletion of ADAR1 in vivo and in vitro. Knockdown of ADAR1 in ECs resulted in marked inhibition of VE-Cadherin, which could be recovered by a peptide encoding the caveolin-1 scaffolding domain.
CONCLUSIONS Our findings establish a crucial role of an ADAR1/Caveolin-1 axis in endothelial homeostasis
[GW30-e0598]
Shiyang Xie, Shiyang Xie
First Affiliated Hospital, Henan University of Traditional Chinese Medicine
OBJECTIVES This study was designed to determine the effects of Shenfuyixin formula (SFYX) on the myocardial cell apoptosis and apoptosis-related factors in rats with HF induced by myocardial infarction (MI).
METHODS HF was induced by the ligation of left anterior descending coronary artery in adult male Sprague-Dawley rats. Based on the cardiac function at week 4 after MI, all rats were randomly divided into 5 groups: Sham-operated group; HF+vehicle group; routine dose of SFYX group (1.76 g/kg/d) and high dose of SFYX group (8.8 g/kg/d), and lorsartan group (10 mg/kg/d). Equivalent distilled water was given to rats in sham and model groups, and the corresponding drugs dissolved in distilled water were orally gavaged in the drug intervention groups once a day, each group was given medication or water for 4 weeks. The left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured by echocardiography at week 4 after the delivery. The apoptotic index of cardiomyocytes was evaluated by TUNEL staining. The protein expressions of apoptosis-related factors Bcl-2, Bax and caspase-3 were determined by Western blot.
RESULTS Compared to HF+vehicle group, SFYX at the dose of 8.8 g/kg/day attenuated the increases in LVEDD (10.21±0.70 vs. 8.77±1.10 mm, P<0.01) and LVESD (8.89±0.55 vs. 6.16±1.53 cm, P<0.01), and the decreases in LVEF (31.64±13.10 vs. 55.20±14.28%, P<0.01) and LVFS (15.54±6.20 vs. 30.72±9.73%, P<0.01) at week 8 after MI. The apoptotic index of cardiomyocytes was decreased in high dose of SFYX rats compared to HF+vehicle rats (8.52±2.70 vs. 16.17±1.41%, P<0.01). In addition, treatment with SFYX at the dose of 8.8 g/kg/day inhibited the expression of Caspase3 and Bax compared to HF+vehicle rats at week 8 after MI (Caspase3: 1.18±0.10 vs. 1.66±0.25% GAPDH arbitrary units, P<0.05; Bax: 0.66±0.19 vs. 1.28±0.13% GAPDH arbitrary units, P<0.01), and increased the ratio of Bcl-2/Bax (1.21±0.23% vs. 0.54±0.06%, P<0.01).
CONCLUSIONS Our studies showed that SFYX administered after HF improved cardiac function, and inhibited left ventricular dilatation and the apoptosis of myocardial cells. The results were associated with the decreased expression of Caspase3 and Bax. Our data suggest that SFYX may inhibit myocardial apoptosis and improve cardiac function, which were associated with the inhibition of the overexpression of apoptotic factors Bax and caspase-3 in rats with HF following MI.
[GW30-e0608]
Yao Chen 1,2 , Linshuang Zhang 1,2 , Yongfen Qi 1,2
1Laboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University, Beijing 100191, China
2Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing 100191, China
OBJECTIVES Vascular calcification is a very common phenomenon in the elderly. Intermedin (IMD) is a cardiovascular bioactive peptide maintaining vascular homeostasis and inhibiting vascular calcification. In this study, we aimed to investigate whether IMD 1-53 attenuates aging-associated vascular calcification.
METHODS Aging-associated vascular calcification was induced by vitamin D3 plus nicotine (VDN) in old rats. In vitro, senescence-related calcification of vascular smooth muscle cells (VSMCs) in rats, human and IMDSMC–/– mice were induced using osteogenic media. Rats or VSMCs were treated with IMD 1-53 peptide.
RESULTS Old rats treated with VDN showed more severe calcification in aortas compared with young control group, and with decreased expression of IMD. Exogenous administration of IMD 1-53 significantly reduced the calcium deposition, destruction of vascular structure and collagen contents in old VDN rats. IMD 1-53 also inhibited the transdifferentiation of VSMCs from a contractile to an osteogenic phenotype in old calcified aortas. Moreover, aging-related markers p16, p21 and β-galactosidase were all markedly decreased by -IMD 1-53 . Mechanistically, IMD 1-53 significantly increased the antiaging factor sirt1 expression and decreased the sirt1 substrate acely-p53/total-p53 level. These results were further confirmed in both rat and human senescent calcified VSMCs in vitro. Furthermore, the inhibitory effects of IMD 1-53 on calcification and senescence were blocked by sirt1 knockdown. In addition, IMD-deficient VSMCs showed severe senescence features coincided with osteogenic transition, and had significantly decreased expression of sirt1 as compared with VSMCs from wild type mice.
CONCLUSIONS IMD deficient VSMCs are more prone to senescence and calcification, and administration of IMD 1-53 can attenuate aging-associated vascular calcification by upregulating sirt1.
[GW30-e0611]
Liang Liu, Xian Jin, Cheng Xing Shen
Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
OBJECTIVES Background: Endothelial mesenchymal transition (EndMT) plays a key role in the development of cardiac fibrosis (CF) after acute myocardial infarction (AMI). Our previous study has showed that the expression of Amphiregulin (AR) was enhanced after MI and promoted CF by inducing cardiac fibroblast activation. However, the role of AR on EndMT post MI is still unknown. This study aimed to explore the impact of AR on EndMT post MI and related mechanisms.
METHODS HUVECs and MAECs were originated from the umbilical cord of healthy women and the abdominal aorta of C57BL6 mice (8–12 weeks old) respectively. The two types of cells were deposed with different concentrations of AR (0, 10, 100, 1000 pg/mL) and then the cell viability and apoptosis were measured by CCk-8 assay and Annexin V-PE/7-AAD. Western bolt, Real-time PCR, Immunofluorescence were used to detect the cell markers of EndMT at 48 h in endothelial cells after AR stimulation. In vivo, We extracted the myocardium of the border area, the infarct zone and the infarct border zone in the heart of MI mice to detect the expression level of AR at different time points (1, 3, 5, 7, 28 days). Artificially synthesized AR lentivirus (AR-shRNA) was used to knock down the expression of AR in MI mice and then the mice were randomly divided into four groups: Sham group, MI group, MI-shNC group and MI-shAR group. WB, RT-PCR, Immunofluorescence techniques were used to detect the changes of EndMT in the infarct border area, the cardiac ultrasonography was used to detect cardiac function and the Picrosirius Red staining was used to measure CF in those mice. In vitro and vivo Western bolt were used to detect the signaling pathway of AR inducing EndMT in endothelial cells and myocardium in MI mice.
RESULTS In vivo, EndMT which was verified by co-labeling of cells with the myofibroblast and endothelial cell markers was significantly declined after lentivirus-AR-shRNA delivered into the infarct border zone post MI. Moreover, silencing AR ameliorated cardiac function by decreasing the extent of CF of MI mice. In vitro, endothelial cells treatment with AR promoted cell proliferation and anti-apoptotic capacity. In addition, EndMT which was confirmed by detecting the markers of endothelial cells and fibroblast, the expression of epidermal growth factor receptor (EGFR) and the downstream genes such as PI3K/AKT and β-cateninon in endothelial cells was significantly enhanced after stimulation with AR. All these effects could be eliminated by EGFR inhibitor. Furthermore, in vivo, EGFR and the downstream genes in infarct border zone were all significantly decreased in MI mice which were injected with lentivirus-AR-shRNA.
CONCLUSIONS Our results demonstrate that AR induces CF post MI not only by directly activating cardiac fibroblast but also by enhancing EndMT in endothelial cells. All the results show that AR plays a key role in promoting CF post MI. Targeting regulation of AR may provide a new potential therapeutic option for CF after MI.
[GW30-e0612]
Jianyi Li 1,2,3 , Yue Cheng 1,2,3 , Xi Wang 1,2,3
1Department of Cardiology, Renmin Hospital of Wuhan University
2Cardiovascular Research Institute, Wuhan University
3Hubei Key Laboratory of Cardiolog
OBJECTIVES Optogenetics is a low-invasive, flexible and highly selective intervention. The purpose of our experiment is as follows: (1) explore optogenetic defibrillation and the possible mechanism of continuous illumination defibrillation. (2) explore the effects of optogenetic termination and electric termination of myocardial infarction ventricular tachyarrhythmia (VT) in vivo.
METHODS Systemic delivery via right jugular vein injection of (AAV9-CAG-hChR2(H134R)-mCherry) were performed in juvenile SD rats to achieve the light sensitive protein Channelrhodopsin-2 transfer throughout the whole heart. Ventilation, thoracotomy and recording ECG were performed after anesthesia in rats. Every heart was illuminated by 473 nm laser or electrical stimulated on the right ventricle in a train of 30 pulses at 8 Hz to test the threshold of light intensity or electrical pacing voltage. After that, myocardial infarction was induced by ligation of the left anterior descending coronary artery, and then VT was induced by electrical burst stimulation (10 v, 50 Hz, 2 s). First, we investigated the effects of optogenetic defibrillation and its underlying mechanism by different illumination modes of multiple light intensity (2, 4, 8, 10, 20 times threshold intensity) and pulse duration (20, 50, 200, 500 and 1000 ms). Then, the VT termination process during 20 s after burst stimulation was investigated in different performance: optical termination, 1 s constant -illumination repeated in 4 episodes with 1 s interval (470 nm, 20 times threshold intensity); electrical termination, anti-tachycardia pacing (ATP) in 8 pulses of 8 Hz with 2 ms duration in 4 times pacing threshold; natural recovery from VA, without optical or electrical intervention. Recovery time was defined as the time from the end of the burst stimulation to the recovery of sinus rhythm, and the termination rate was the percentage of sinus rhythm recovery after the end of burst stimulation with or without any intervention.
RESULTS (1) We demonstrated that VT could be terminated by illumination of the right ventricle at 20 times threshold intensity in 1 s with the successful defibrillation rate of 95±2.673% (mean±SEM; N=7). Herein, the successful optogenetic defibrillation rate was strongly depending on light intensity (N=5, n=50 episodes, P=0.0118) and duration of illumination (N=5, n=50 episodes, P<0.0001). In regard to mechanism of optogenetic defibrillation, we observed that higher light intensity and longer pulse duration were more conducive to induce an episode of light-triggered focal excitement by ChR2-mediated depolarization. (2) We analyzed the recovery time and the termination rate. The sequence of recovery time was optical termination (7.328±0.3623 s)<electric termination (10.31±0.4482 s)<natural recovery (12.97±0.3834 s). And we confirmed that the termination rate of optical illumination (86.14±4.145%) was higher than those of ATP (63.5±6.371%) and natural recovery (47.71±5.476%).
CONCLUSIONS Optogenetic defibrillation is a highly effective intervention and optogenetic manipulation can shorten recovery time and increased the termination rate in myocardial infarction ventricular arrhythmia. We believe that optogenetic approach is potentially to be translated into more efficient and pain-free clinical termination of ventricular arrhythmia.
[GW30-e0613]
Xiaoli Luo, Junwei Shen, Jue Li
Tongji University School of Medicine
OBJECTIVES Overwork is an important cause of cardiovascular diseases such as coronary heart disease, hypertension, arrhythmia. The research on cardiovascular damage caused by overwork stress mainly stays in epidemics and populations, and lacks deep molecular mechanism research. This study aims to construct an animal model of overwork that causes cardiovascular damage and to explore its outcomes and mechanisms.
METHODS Five C57BL/6 mice were placed in a plastic box with a water depth of 0.8 cm and a size of 29 cm×8 cm×5 cm for 8 h/day for 30 days to simulate overworked state caused by stress factors such as fatigue, lack of sleep, fear and anxiety. Then we performed echocardiography to detect functional and structural changes in the mouse heart, and initially explored its mechanism through transcriptome sequencing
RESULTS In the overworked group, the left ventricular ejection fraction (EF) and fractional shortening (FS) were significantly decreased (EF: 36.57 vs. 49.44%, FS: 17.49 vs. 24.57%), while the left ventricular internal diameter both in the systolic phase (LVIDs) and in the diastolic phase (LVIDd) were significantly increased, compared with normal mice. In addition, transcriptome sequencing indicated that a large number of gene expression was significantly up-regulated or down-regulated in the myocardial tissue of the overworked mice. The sequencing cluster analysis revealed that immune system, GPCR signaling, platelet activation and glucose metabolism-related expression were elevated in overworked group.
CONCLUSIONS We have developed an overworked mouse model that leads to dilated cardiomyopathy and heart failure, which is available for molecular mechanisms of cardiovascular diseases caused by overwork-related stress. And this study suggests that immune system, GPCR signaling, platelet activation and glucose metabolism are associated with cardiovascular damage after overwork.
[GW30-e0638]
Chen Juan, Liu Ran, Hua Liangliang, Li Cairong, Cai Fei
Hubei Key Laboratory of Diabetes and Angiopathy, Hubei University of Science and Technology
OBJECTIVES The over consumption of a high-fat diet, which increases the levels of the saturated free fatty acid palmitate in the serum, is one of the contributing factors in overweight or obese. In this study, H9C2 cardiomyocytes treated with palmitic acid (PA) were used as hyperlipidemia model. The protective effect of geniposide (Gen) against PA-induced cardiomyocyte lipotoxicity and its underlying mechanism was investigated.
METHODS The experimental groups were divided as follows: Control group, PA group (200 μM), Gen+PA group (320 μM Gen+200 μM PA) and Gen group (320 μM Gen). The cell viability was measured by CCK-8 kit. Oxidative stress was detected by DHE (ROS) staining and MDA kit. Apoptosis related proteins (Bax, Cleaved-Caspase-3, and Bcl-2), inflammatory proteins (NLRP3) and signal pathway related proteins (AKT, GSK-3β, PICK1, and PKR2) were examined by Western Blot.
RESULTS In H9C2 cardiomyocytes treated with Gen and PA, the fluorescence intensity of DHE (ROS) was significantly decreased, and the content of MDA was decreased. Furthermore, PA treatment increased the expression of Cleaved-Caspase-3 and Bax and decreased the expression of Bcl-2 in H9C2 cardiomyocytes, which were reversed by pretreatment of Gen. Additionally, administration of Gen inhibited the increased expression of NLRP3 protein and enhanced the decreased expressions of p-Akt and p-GSK-3β induced by PA. Finally, treatment with PA induced the decreased expression of PKR2 and PICK1, which were reversed by pretreatment of Gen.
CONCLUSIONS The protective effect of geniposide on palmitate-induced H9C2 lipotoxicity injury is closely related to the inhibition of oxidative stress, inflammation and apoptosis via regulating PK2 pathway. This work was supported by the Foundation from Department of Education of Hubei Province (17Y110), Nature Science Foundation of China (81870576) and the Foundation of Hubei University of Science and Technology (LCZX201515, 2018-19XZY06). Correspondence author: xncf@163.com
[GW30-e0640]
Yuanyuan Liu 1 , Yuanxun Huang 2 , Xiaofei Han 3 , Jia Zhao 4 , Shuai Wang 4
1Wuhan Institute of Physical Education
2Wuhan Institute of Bioengineering
3Hubei Vocational College of Physical Education
4Hubei University
OBJECTIVES Flavanones is a chemical entity nature of this substance has not been found, but a derivative of flavanones present in many foods and plants, these derivatives collectively Flavanones is. If you come up with black tea extract antioxidant substances fatigue, help people learn more about the composition and effectiveness of black tea, research Flavanones developed for a sports drink with Chinese characteristics, sports supplements and health products has important significance.
METHODS Forty male SD rats, first of all before the experiment rats were adaptive swimming practice time a week, once a day. 1.2 days to swim 15 minutes a day; 3rd and 4th day swim 20 minutes a day; first five days to swim 25 minutes a day. After a week feeding adaptation, the rats were randomly divided into four groups: control group, 10, 10 gavage group, the exercise group 10, fed plus exercise group 10. Exercise group and exercise group fed a 12-week swimming training. Sports 7 days a week. Swimming water temperature controlled at about 30°C. Section l, 2 cycles per R swim 15 minutes; 3 and 4 weeks daily swim 20 minutes; daily swim 25 minutes after the first five weeks. Gavage group without any movement, fed seven times a week, the concentration is 150/mg×mg–1. Control group was not fed anything sports and. Four groups of rats were using ordinary food, free access to water. After 12 weeks, once for four groups of rats after exhaustive exercise, exhaustive record time, exhaustive criteria: rats for underwater sports, submerged 10 s are not free floating, uncoordinated limb movement, choking water, remove no turn after J reflective, can be judged as exhaustive. Fish were killed after exhaustive. Remove the blood, measured gastrocnemius indicators.
RESULTS (1) SOD activity: Sports rats fed blood, gastrocnemius high SOD activity than simply fed group and the exercise group. (2) GPX activity: Sports rats fed blood, gastrocnemius GPX activity than simply fed the high group and the exercise group. (3) MDA levels: Sport rats fed blood, gastrocnemius MDA level than mere gavage group and exercise group at the end. (4) During exhaustive exercise length: longer than the mere movement of the head group and administered orally during exercise group rats after exhaustive exercise. (5) Muscle lactate content: Sports rats fed blood lactic acid content than pure gastrocnemius hunger fed group and the exercise group at the end.
CONCLUSIONS (1) Flavanones can effectively improve the body’s SOD enzyme activity, thereby clearing the body of oxygen anion radicals generated by the movement to reduce the freedom of machine damage to body cells and increase the body’s antioxidant capacity. (2) Flavanones GSH-PX can increase the body’s enzyme activity, thus reducing the body’s H2O2, reducing peroxide damage to the body, increasing the body’s antioxidant capacity. (3) Flavanones MDA can reduce the level of the body, thereby protecting the body’s cells and increase the body’s antioxidant capacity. (4) Flavanones can effectively clear the muscles of lactic acid, increases the body’s athletic ability. (5) Flavanones can effectively improve the exhaustive time in rats, increased exercise capacity.
[GW30-e0647]
Linshuang Zhang 1,2 , Yao Chen 1,2 , Yongfen Qi 1,2
1Laboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University, Beijing, China
2Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing, China
OBJECTIVES Pathological cardiac remodeling involved cardiac hypertrophy, fibrosis and dysfunction. Intermedin (IMD) had a cardiovascular protective effect in previous reports. However, as a paracrine/autocrine peptide, the protective role of endogenous IMD against cardiac remodeling and the underlying mechanism had not been elucidated.
METHODS Pathological remodeling models were induced by abdominal aorta constriction for 4 weeks or angiotensin II (Ang II) infusion for 2 weeks in IMD transgenic, IMD knockout and Klotho knockdown mice. Cultured neonatal rat cardiomyocytes were pre-treated by IMD before Ang II stimulation. Small interfering RNAs were added to knockdown the expression of Klotho in vitro. Western blot, real-time PCR, histological staining, echocardiography and hemodynamics were used to detect the role of IMD in cardiac remodeling.
RESULTS Cardiac hypertrophy, fibrosis and dysfunction were significantly alleviated in IMD transgenic mice compared with wildtype mice, as well as the expression of Klotho was up-regulated. On the contrary, cardiac remodeling was aggravated in IMD knockout mice as expected. Hypertension induced by Ang II infusion rather than abdominal aorta constriction was mitigated by IMD. However, the cardioprotective effect of IMD was blocked in Klotho knockdown mice. The similar results were found in cultured cardiomyocytes. Notably, the benefits of IMD for hypertension were not affected by Klotho. Mechanistically, IMD inhibited phosphorylation of Ca2+/calmodulin dependent protein kinases II and expression of calcineurin to protect against cardiac hypertrophy through up-regulating Klotho. Furthermore, we found that peroxisome proliferators-activated receptor γ (PPARγ) mediated the role of IMD up-regulating Klotho.
CONCLUSIONS In summary, pathological remodeling was inhibited by endogenous IMD, which maintained Ca2+ homeostasis by up-regulating Klotho via activating PPARγ pathway.
[GW30-e0652]
Xueli Zhao, Liwen Liu, Xuanying Wang, Jing Wang, Juan Zhang, Liwen Liu
Department of Ultrasound, Xijing Hypertrophic Cardiomyopathy Center, Xijing Hospital, Fourth Military Medical University
OBJECTIVES Currently unsatisfactory treatment of cardiac hypertrophy is due to the unbridled myocardial fibrosis. Melatonin have been demonstrated to promote cardiac hypertrophy and accompanied fibrosis in previous studies. But it is not clinically appealing due to its short lasting time against the hostile microenvironment.
METHODS Herein, to overcome these therapeutic hurdles. Magnetic and CHP-based dual targeting melatonin–loaded nanoparticles (CHP-mel@SPIONs) were prepared used for double emusion and carbodiimides, then the general properties were investigated. Ex vivo targeting was analyzed by fluorescence imaging in vivo and fluorescence microscopy. For the animal study, we utilized a transverse aortic constriction surgery (TAC) induced cardiac hypertrophy rat model. Animals were treated with either saline, non-targeting mel@SPIONs, targeting CHP-mel@SPIONs, or targeting CHP-mel@SPIONs+M 8 weeks after surgery. Echocardiography was performed after treatment. And then animals were sacrificed, and organs were collected for histological analysis and RT-PCR.
RESULTS The engineered magnetic polymeric nanoparticles CHP-mel@SPIONs are 221±13 nm in size with negative zeta potential of –33.34±0.88 mV and shown to be spherical in shape. The CHP-mel@SPIONs displays the most excellent drug encapsulation capacity of SPIO and melatonin separately, and magnetic properties were characterized by determination of magnetic hysteresis curves and transverse relaxation rates. CHP-mel@SPIONs with external magnetic field (M) group has longer blood circulation and more effective accumulation at heart site than CHP-mel@SPIONs and mel@SPIONs groups, enhanced transfection efficiency with minimized polymer use. As expected, in vivo therapeutic evaluations showed that CHP-mel@SPIONs+M group has augmented anti-hyperthrophy and anti-myocardial fibrosis effect comprehensively compared to other treatments, revealing high efficiency in cardiac-targeted delivery and effective cardioprotection.
CONCLUSIONS Our results demonstrate this simple biocompatible dual-targeting nanoagent can act as a potential candidate for clinical guided therapy of heart disease.
[GW30-e0665]
Jia Gao, Zhijun Meng, Wenxia Liu, Caihong Liu, Jinghong Fan, Jing Wang, Yajing Wang
Shanxi Medical University
OBJECTIVES The study aims to determine whether nicotine causes vascular adiponectin resistance in C57 mice with a high-fat diet (HFD).
METHODS Adult male C57 mice were randomly divided into 4 groups, normal diet (ND) group, HFD group, nicotine group, nicotine+HFD group, fed for 12 weeks, the level of total APN and HMW APN in the circulation was measured at different time periods.
RESULTS Compared with the ND group, the total APN of the nicotine+high-fat diet group was significantly increased at 6 weeks, and the HFD group and the nicotine group was significantly increased at 8 weeks, and then decreased rapidly. HMW APN in the nicotine+HFD group was significantly increased at 8 weeks, the HFD group and the nicotine group was significantly increased at 12 weeks, and then decreased rapidly. In the nicotine+HFD group, the HFD group, and the nicotine group, recombinant globular APN (gAPN) induced aortic ring vasodilation was significantly reduced at 12 weeks.
CONCLUSIONS The above experiments indicate that nicotine can cause adiponectin resistance in HFD C57 mice.
[GW30-e0688]
Cong Fu 1,4 , Qiancheng Xu 2 , Shengxing Tang 1 , Yuhan Cao 3 , Cong Fu 1,4
1Department of Cardiology, Yi Ji Shan Hospital affiliated to Wan Nan Medical College, Wuhu, Anhui, China
2Department of Critical Care Medicine, Yi Ji Shan hospital affiliated to Wan Nan Medical College, Wuhu, Anhui, China
3Department of Nephrology, Yi Ji Shan hospital affiliated to Wan Nan Medical College, Wuhu, Anhui, China
4Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College)
OBJECTIVES Ticagrelor provided clinical outcomes in patients with acute coronary syndromes not only due to the anti-platelet effect but also the myocardial protection. The aim of this study is to determine if the ticagrelor display the myocardial protecting effect in sepsis induced myocardial injury.
METHODS C57BL6J mice received oral ticagrelor (50 mg/kg) for 7 days and underwent caecum ligation and puncture (CLP) after the last dose of ticagrelor. Adenosine-receptor antagonist (CGS15943) was administered (10 mg/kg, intraperitoneal injection) in some of the CLP mice to block the adenosine pathway 2 h before CLP. After 24 h from CLP, cardiac echocardiography was used to measure the heart function before mice heart and blood was collected. HE staining was used to observe the pathological changes and TUNEL staining was applied to determine the cardiomyocyte apoptosis. ELISA was used to determine the blood concentration of TNF-α and IL-6. qRT-PCR was used to determine the relative expression of TNF-α and IL-6 in myocardial tissue. Western blot was used to determine the expression of signal molecular in myocardial tissue.
RESULTS In ticagrelor group, HE staining showed that less inflammatory cell infiltration and TUNEL showed the less cardiomyocyte apoptosis compared to no ticagrelor group. cardiac echocardiography showed the reserved heart function in ticagrelor group compared to no ticagrelor. The concentration of TNF-α and IL-6 in blood and relative expression of TNF-α and IL-6 in myocardial tissue was significantly lower in ticagrelor group than no ticagrelor. Adenosine-receptor antagonist significantly block the protective effect of ticagrelor. Western blot further showed that ticagrelor activate the phosphorylation of AKT and mTOR. Adenosine-receptor antagonist inhibit the activation of AKT and mTOR.
CONCLUSIONS Ticagrelor reduced the myocardial injury in sepsis mice model. The protective effect was dependent on adenosine-receptor activation with downstream upregulation of phosphorylation of AKT and mTOR.
[GW30-e0692]
Zhen Sun, Wang Zhongqun, Wang Zhongqun
Affiliated Hospital of Jiangsu University
OBJECTIVES To investigate the mechanism of macro-/micro-calcification transfomation in diabetic vascular calcification.
METHODS Thirty patients with diabetic foot amputation were enrolled from June 2016 to June 2018. Calcium content of each anterior tibial artery was measured and patients were divided into less calcification group (calcium content <5 μmol/mg) and more calcification group (≥5 μmol/mg). Calcification types in plaques was detected and immunohistochemical staining was carried out to show RAGE/gal-3 expression. And then an in vivo and an in vitro diabetic vascular calcification model were established. After silencing RAGE or gal-3, calcification morphology was measured and sortilin expression was determined. Sortilin was further blocked or over-expressed on the base of RAGE/gal-3 silencing to investigate the effect of sortilin on the progression of calcification. Finally, SEM detection and NTA were performed to detect the aggregation of matrix vesicles during the formation of macro-/micro-calcification.
RESULTS Macro- and micro-calcification were both found in human anterior tibial artery plaques. After silencing RAGE, macrocalcification formed. And the blockage of galectin-3 introduced the formation of microcalcification. Sortilin overexpression induced larger calcified nodules formation. Meanwhile, SEM and NTA showed that with the up-regulation of sortilin, the matrix vesicles aggregated earlier.
CONCLUSIONS RAGE transmitted microcalcification signals and gal-3 delivered macrocalcification signals both through sortilin.
[GW30-e0705]
Chiyu Liu, Jingfeng Wang
Sun Yat-Sen Memorial Hospital
OBJECTIVES Atherosclerosis (AS) is a common disease that seriously endangers human health. This study aims to identify unknown hub genes involved in the progression of atherosclerosis by using the bioinformatic methods so that we can provide evidence to further clarify the molecular biological mechanism of atherosclerosis and to select drug intervention targets in the future.
METHODS Dataset one (GSE43292) and Dataset two (GSE28829) were downloaded from the GEO. Two datasets shared similar grouping scheme (group of early lesion and advanced lesion). Raw probe-level microarray data were preprocessed using the oligo package in R3.5.2 language. Differentially expressed genes (DEGs) were screened by using limma package in R. Weighted gene co-expression network analysis (WGCNA) was performed to screen out disease-related modules and identify hub genes. Functional annotation for the DEGs of each module was carried out by GO, DO analysis with R package. The software cytoscape was used to visualize local regulatory networks associated with the hub genes.
RESULTS For Dataset one, differential expression analysis screened 795 DEGs including 482 upregulated genes and 313 downregulated genes in group of advanced lesion. For Dataset two, there were 903 DEGs including 604 -upregulated genes and 299 downregulated genes. WGCNA showed that module “lightgreen” was significantly positively correlated with the progression of atherosclerosis in Dataset one while in Dataset two it was module “brown”. GO enrichment analysis showed that DEGs in both modules were mainly involved in activation of immune cells, secretory granule membrane, cytokine activity and so on, which not only indicated biological function of these DEGs, but also suggested that the two modules were exactly similar. DO enrichment analysis showed that DEGs in both modules were significantly enriched in arteriosclerosis. The two modules identified 7 hub genes in common from 208 DEGs shared by two modules including LAIR1, PIK3AP1, HAVCR2, RBM47, HCK, CD53 and TYROBP. Local co-expression networks for these 7 hub genes were constructed through cytoscape and there were 66 highly co-expressed relationships between hub genes and their related candidate genes in each module. The two modules shared 20 highly co-expressed relationships.
CONCLUSIONS In this study, 7 hub genes shared by Dataset one and two were highly expressed in the group of advanced lesion compared to group of early lesion and significantly positively correlated with the progression of atherosclerosis, meaning that these genes were upstream in the regulatory network and might become biomarkers in the progression of atherosclerosis and drug intervention targets in the future. Twenty highly co-expressed relationships between hub genes and their related candidate genes were screened out to further elucidate the underlying molecular pathways and interaction mechanisms of these hub genes in the progression of atherosclerosis, which still need to be verified by a large number of subsequent fundamental and clinical studies.
[GW30-e0712]
Yina Wang, Benrong Zheng, Boxiong Jiang
The Third Affiliated Hospital of Sun Yat-sen University
OBJECTIVES Our previous study indicated that mRNA and protein of connective tissue growth factor (CTGF) was high expression in atrial tissue of the patient with rheumatic heart disease (RHD). The aim of this work was to assess the expression of serum CTGF in RHD patients and its association with myocardial fibrosis.
METHODS Forty patients with rheumatic heart diseases (RHD) and 19 healthy volunteers were enrolled as study group (SG) and control group (CG) in this study. The right atrial muscles samples of SG were obtained during heart valve replacement surgery. Serum CTGF from all participants was detected using a direct high sensitivity sandwich ELISA kit. The mRNA and protein expression of CTGF in right atrial muscles of SG were detected by semiquantitative RT-PCR and immunohistochemistry technique. Masson’s trichrome-stained sections was used to evaluate the level of myocardial fibrosis. The area of fibrosis was measured by imaging analysis system, qualified by PU value. SPSS package was used to analyze the relationship between the expression of CTGF and the area of myocardial fibrosis. A P-value<0.05 was considered statistically significant.
RESULTS Serum CTGF concentrations increased significantly in SG compared to CG (85.62±27.61 vs 40.81±19.65, P<0.01). In SG, the expression of serum CTGF was correlated positively with CTGF mRNA, CTGF protein in atrial muscles and the area of myocardial fibrosis (r=0.874; r=0.776; r=0.85, P<0.01). The expression of serum CTGF in SG didn’t show correlation with gender, age and case history (r=–0.32; r=0.121; r=0.084, P>0.05), but remarkably correlated with cardiac functional gradings (r=0.484, P<0.05).
CONCLUSIONS Serum CTGF was high expression in RHD patients; it may play an important role in the process of myocardial fibrosis in RHD.
[GW30-e0714]
Chenchangzhe 1 , Songchenxi 2 , Doukefei 1 , Songxiantao 2
1Beijing Anzhen Hospital, Capital Medical University
2Fuwai Hospital, Chinese Academy of Medical Sciences
OBJECTIVES To investigate whether Se@SiO 2 could improve adverse ventricular remodeling after MI and whether the underlying mechanism is associated with its anti-oxidative effects.
METHODS Sprague Dawley Rats were randomized into the following 5 groups and received the indicated treatment 48 hours after MI induction: (1) Sham control group; (2) Control group; (3) ACEI group; (4) Low-dose Se@SiO 2 group; (5) High-dose Se@SiO 2 group. Cardiac function of rats was assessed by echocardiography. The area of MI size and interstitial fibrosis were assessed by Masson’s trichrome staining and sirius red staining, respectively. The expression of TGF-β in myocardium was determined by western blot.
RESULTS After 28 days, both low and high does SeO 2 attenuated the increase in ventricular weight and dimension compared with vehicle group. Compared with vehicle group, low-dose SeO 2 group had higher LVEF (52.45±3.42% vs. 38.21±5.13%, P<0.05), smaller diastolic left ventricular inner diameter (8.32±0.40 mm vs. 9.60±0.42 mm, P<0.05), and smaller systolic left ventricular inner diameter (6.49±0.34 mm vs. 8.17±0.53 mm, P<0.05). Low-dose SeO 2 group also had smaller MI size (27.50±0.39% vs. 45.27±0.72%, P<0.05) and reduced interstitial fibrosis in noninfarct area (2.76±0.14% vs. 5.27±0.21%, P<0.05). Expression of TNF-β was significantly lower in low-dose SeO 2 group than in vehicle group (relative expression: 0.27 vs. 0.55, P<0.05). The above effect was greater in high-dose group. SeO 2 treatment also significantly reduced oxidative stress level and apoptosis in cardiomyocytes treated with H 2 O 2 .
CONCLUSIONS We found a protective effect of SeO 2 in adverse remodeling post myocardial infarction. The underlying mechanisms may be associated with the anti-oxidative stress effect of SeO 2 .
[GW30-e0721]
Yongzheng Guo 1 , Yuehua You 1 , Dingyi Lv 1 , Suxin Luo 1 , Yong Xia 1,2,3
1Division of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
2Institute of Life Science, Chongqing Medical University, Chongqing 400016, China
3Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, The Ohio State University College of Medicine, OH 43210, USA
OBJECTIVES Our aim was to investigate the role of inducible nitric oxide synthase (iNOS) in cardiac sterile inflammation and its relationship to mitochondrial damage and cGAS-STING pathway in pressure overload-induced heart failure.
METHODS Transverse aortic constriction (TAC) was used to induce heart failure both in iNOS–/– mutant and wild-type mice. Echocardiography, transmission electron microscopy, RT-PCR and immunohistochemistry were applied to study the role of iNOS and cGAS-STING pathway in the development of heart failure.
RESULTS In wild-type mice, TAC resulted in increased myocardial iNOS expression, cardiac hypertension and dysfunction, whereas iNOS-deficient mice displayed much less cardiac hypertrophy and dysfunction. Consistent with these findings, iNOS deficient attenuated mitochondrial dysfunction and significantly reduce the release of mtDNA in the failing heart. The cGAS¡§CSTING pathway, which results in mtDNA-induced inflammatory responses, was highly activated in WT mice 4 weeks after TAC but not in iNOS–/– mice. In vitro, hypoxia can induce the expression of iNOS and active cGAS-STING pathway in neonatal rat cardiomyocytes. Pharmacological blocking iNOS can inhibit the activation of cGAS-STING pathway.
CONCLUSIONS These data demonstrate that iNOS contribute to mtDNA release from damaged mitochondria and trigger cardiac inflammation via cGAS-STING pathway in pressure overload-induced heart failure, which suggests a potential therapeutic target for heart failure.
[GW30-e0728]
Tianxin Geng, Jinchuan Yan
Affiliated Hospital of Jiangsu University
OBJECTIVES To investigate whether CD137 signaling can promote angiogenesis via regulating macrophage M1/M2 polarization.
METHODS (1) The primary peritoneal macrophages in mice induced by 3% thiglycollate broth were divided into three groups: control group, CD137 signaling activated group and CD137 signaling inhibited group, detecting various specific markers of M1 and M2 macrophages to observe the phenotype change of macrophages, and the macrophages protein expression of CD137, CD86 and CD206 was detected by flow cytometry (FCM). The mRNA and protein expression of induced nitric oxide synthase (iNOS), arginase-1(Arg-1) was respectively determined by Western blot and RT-PCR determine. The secretion levels of IL-12 and IL-10 in culture supernatant of macrophages was detected by ELISA. (2) Macrophages were co-cultured with the endothelial cells (bEnd.3), and macrophages were implanted in the upper chamber, endothelial cells were implanted in stromal glue of the lower chamber. The experiment was divided into three groups: the control group, CD137 signaling activated group and PPAR-γ (peroxisome proliferator-activated receptor-γ) inhibited group, and test tube formation ability of endothelial cells in each group.
RESULTS (1) The purity of primary peritoneal macrophages in mice was (97.93±1.31)%; The expression of CD137 on the surface of macrophages was (97.40±2.70)%. (2) Compared with control group, the expression levels of Arg-1 mRNA and protein in CD137 signaling activated group were significantly increased (P<0.05), and the expression of iNOS mRNA and protein were significantly decreased (P<0.05); the expression of Arg-1 mRNA and protein in CD137 signaling inhibited group were significantly lower than CD137 signaling activated group (P<0.05), the expression levels of iNOS mRNA and protein were increased (P<0.05). FCM results showed that the average fluorescence intensity of CD206 in CD137 signaling activated group was higher than control group (P<0.05), while the average fluorescence intensity of CD86 was lower than control group (P<0.01); the expression of CD206 in the CD137 signaling inhibited group was significantly lower than CD137 signaling activated group (P<0.05), the expression of CD86 was higher than CD137 signaling activated group (P<0.01). ELISA showed that the secretion of IL-10 in CD137 signaling activated group was higher than control group (P<0.01), and the secretion level of IL-12 was significantly lower than control group (P<0.01); the secretion of IL-10 in CD137 signaling inhibited group was significantly lower than CD137 signaling activated group (P<0.05), and the secretion of IL-12 was significantly increased (P<0.05). (3) Values of the formation of tube length and branch number in CD137 signaling activated group were both longer than control group (P<0.05). The formation of the tube length and branch number in PPAR-γ inhibited group were less than CD137 signaling activated group (P<0.05).
CONCLUSIONS CD137 signaling can promote angiogenesis by regulating macrophage M1/M2 polarization.
[GW30-e0736]
Meixia Ren, Fan Lin, Pengli Zhu
Department of Geriatric Medicine, Fujian Provincial Center for Geriatrics, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350000, China
OBJECTIVES A recent genome-wide association study identified a novel gene locus with splicing factor 3a subunit 3 (SF3A3) to be significantly related with blood pressure (BP), we aim to functionally characterize the biological role of SF3A3 in the BP control and hypertension development.
METHODS Materials and Methods Bioinformatic tools were utilized to prioritize the investigation. A collection of primary human smooth muscle (SMC) and endothelial (EC) cells were genotyped for SF3A3 BP-related variant. Ang-II induced SMCs and hypertensive mice were constructed as well. Endogenous SF3A3 mRNA and protein levels were assessed by qRT-PCR and western blotting. Mice systolic and diastolic BP were measured with a tail-cuff.
RESULTS The SF3A3 gene risk allele was associated with higher endogenous mRNA and protein levels in human SMCs. No such characteristics were observed in ECs. Elevated levels of SF3A3 were also identified in Ang-II induced SMCs and hypertensive mice arteries.
CONCLUSIONS The findings in this study have suggested a potential role of SF3A3 in the BP control and hypertension development.
[GW30-e0743]
Yunli Shen, Hao Zheng, Shiyu Gong, Yihan Chen
Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine
OBJECTIVES Myocardial delivery of magnetic iron oxide nanoparticles (MNPs) might produce iron overload-induced myocardial injury, and the oxidative stress was regarded as the main mechanism. Therefore, we speculated antioxidant modification might be a reasonable strategy to mitigate the toxicity of MNPs.
METHODS Antioxidant N-acetylcysteine (NAC) was loaded into magnetic mesoporous silica coated Fe 3 O 4 nanoparticles. Neonatal rat Hypoxia/Reoxygenation (H/R) cardiomyocytes were incubated with nanoparticles for 24 h. The ROS levels of cardiomyocytes were detected by DHE 24 hours after the injection. The lipid peroxidation products (MDA and 8-iso-PGF2 alpha), DNA peroxidation products (8-OHDG), the antioxidant enzyme system (SOD, CAT, GSH-Px) and GSH were detected by ELASA and biochemical methods. The expression levels of endoplasmic reticulum stress protein CHOP and GRP78, autophagy related protein P62, LC3-I and LC3-II were measured by Western Blot. Apoptosis of cardiomyocytes was detected by Annexin V-FITC and PI staining.
RESULTS NAC can effectively mitigate iron-induced oxidative injury of cardiomyocytes, evidenced by reduced production of MDA, 8-iso-PGF2α and 8-OHDG and maintained concentrations of SOD, CAT, GSH-Px and GSH in ELASA and biochemical tests; down-regulated expression of CHOP, GRP78, p62 and LC3-II proteins in Western Blot, and less cardiomyocytes apoptosis in flow cytometric analysis.
CONCLUSIONS NAC modifying could suppress the toxic effects of Fe 3 O 4 nanoparticles in H/R cardiomyocytes model in vitro, indicating a promising strategy to improve the safety of iron oxide nanoparticles.
[GW30-e0744]
Chuangjia Hu 1 , Xiangzhong Wu 2 , Yingbi Zhou 2
1Department of Cardiology, First Affiliated Hospital, Shantou University Medical College, Shantou, China
2Cardiovascular Research Center, Shantou University Medical College, Shantou, China
OBJECTIVES Endothelial dysfunction, which leads to ischemic events under atherosclerotic conditions, can be attenuated by antagonizing the thromboxane-prostanoid receptor (TP) that mediates the vasoconstrictor effect of prostanoids including prostacyclin (PGI 2 ). This study aimed to determine whether antagonizing the E prostanoid receptor-3 (EP3; which can also be activated by PGI 2 ) adds to the effect of TP deficiency (TP–/– ) under atherosclerotic conditions and if so, the underlying mechanism(s). Endothelial dysfunction, which leads to ischemic events under atherosclerotic conditions, can be attenuated by antagonizing the thromboxane-prostanoid receptor (TP) that mediates the vasoconstrictor effect of prostanoids including prostacyclin (PGI 2 ). This study aimed to determine whether antagonizing the E prostanoid receptor-3 (EP3; which can also be activated by PGI 2 ) adds to the effect of TP deficiency (TP–/– ) under atherosclerotic conditions and if so, the underlying mechanism(s).
METHODS Atherosclerosis was induced in ApoE–/– mice and those with ApoE–/– and TP–/– . For functional studies, Rings of the abdominal aorta with plaques were used to study vasomotor reactions of atherosclerotic conditions. COX-1, PGI 2 synthase (PGIS), eNOS, TP, EP3 and IP were detected by Western blot and/or qPCR in abdominal aortas. The PGI 2 metabolite 6-keto-PGF 1a produced in abdominal aortas was measured with an EIA kit.
RESULTS Here we show that in the abdominal aortic rings with plaques of ApoE–/– /TP–/– mice, although a biphasic force (which was larger than that of non-atherosclerotic controls) blunting the relaxation evoked by the endothelial muscarinic agonist ACh in ApoE–/– counterparts was largely removed the relaxation was still smaller than that of non-atherosclerotic TP–/– mice. Interestingly, EP3 antagonism not only increased the above relaxation, but also reversed a contraction (which was smaller than that of similar ApoE–/– vessels) evoked by ACh under NO synthase-inhibited conditions of atherosclerotic ApoE–/– /TP–/– rings into a relaxation sensitive to I prostanoid receptor antagonism. Also, in ApoE–/– atherosclerotic vessels the expression of endothelial NO synthase was decreased, yet the production of PGI 2 (which evokes contraction via both TP and EP3) evoked by ACh was unaltered compared to non-atherosclerotic conditions.
CONCLUSIONS Therefore, even after TP-mediated effect was removed, additional EP3 blockade is needed to fully uncover the dilator action of natively produced PGI 2 that can add to the reduced endothelium-mediated dilator function observed under atherosclerotic conditions.
[GW30-e0745]
Xue Liu, Xiaoliang Jiang, Xing Liu, Xianxian Wu, Zhiwei Yang
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC)
OBJECTIVES Hypertrophic cardiomyopathy (HCM) is an inherited and ongoing chronic vascular disease which requires timely and effective treatment. Genetic therapy has been shown to ameliorate hypertrophic cardiac damage. However, due to the continuous flow of liquid in the heart chamber, powerful nucleic acid delivery vehicles are essential for effective gene therapy. The gene Drd5 was proved related to HCM in our previous study, Herein, we aimed to test whether one multifunctional delivery polycation (SS-HPT) of tobramycin-based hyperbranded polyaminoglycoside could successfully used for targeted nucleic acid therapy, and investigating the effect of SS-HPT/Drd5 plasmid on hypertensive cardiac damage and regulation mechanism.
METHODS C57 mice were performed transverse aortic constriction (TAC), two weeks later, SS-HPT/Drd5 plasmid or SS-HPT/Drd5 siRNA was given in HCM mouse model for 4 weeks. Cardiac hypertrophy, fibrosis and dysfunction were determined as well as the expression of Drd5
RESULTS It is first reported that D5R expression in left ventricle continuously decreased in the progression of HCM, and seriously degraded in heart failure patients, which play a crucial role in maintaining cardiac function. D5R plasmid can be effectively delivered by SS-HPT/Drd5 plasmid for the early and precise treatment of HCM in mouse model. Specific targeted D5R in early stage of HCM exhibits impressive performances in attenuated cardiac hypertrophy, fibrosis and dysfunction in via preventing ROS production and autophagy. In contrast, SS-HPT/Drd5 siRNA accelerate the deterioration of myocardial function seriously, which promote the progression of MCH to heart failure. Moreover, SS-HPT, constructed from topamycin, shows excellent biocompatibility and can effective suppress inflammation during HCM development.
CONCLUSIONS Our data emphasize a specific-target and anti-inflammatory role of SS-HPT/Drd5 plasmid and their importance for myocardio healthy. The proposed powerful nucleic acid delivery polycation accurately bombing damaged cardiomyopathy would provide promising precise therapy platforms of cardiovascular diseases.
[GW30-e0751]
Yu Xu, Tianxin Geng, Guangyao Zang, Chen Shao, Zhongqun Wang, Jinchuan Yan
Department of Cardiology, Affiliated Hospital of Jiangsu University
OBJECTIVES Vascular calcification is considered as an active process in which vascular smooth muscle cells (VSMCs) plays a critical role. Activation of CD137 in vivo has been reported to promote vascular calcification in mouse atherosclerosis. Matrix metalloproteinase-9 (MMP-9) mainly expressed on macrophages, also known as gelatinase B, is as well as involved in vascular calcification. On the basis of these achievements, we tested the hypothesis that CD137-CD137L signaling regulates VSMC calcification via modulating macrophage production of MMP-9.
METHODS Aortic VSMCs and peritoneal macrophages (PMs) were isolated from C57BL/6J mice, respectively. We used a PM /VSMC co-culture system to investigate the role of MMP-9 in the regulation of CD137-CD137L signaling-induced VSMCs calcification. Gelatin zymography was performed to detect MMP-9 activity. The expression of calcification-related proteins Runt-related transcription factor 2 (RUNX2) and osteopontin (OPN) was determined by western blot. The quantitative colorimetric method was applied to detect calcium ion concentration and alkaline phosphatase (ALP) activity. Von Kossa and alizarin red staining were used to observe the severity of VSMC-calcification.
RESULTS CD137-CD137L signaling induced MMP-9 production from macrophage in a time dependent manner. Treatment with recombinant CD137L protein alone did not stimulate VSMCs calcification. The expression levels of RUNX2 and OPN were significantly higher in VSMCs than that cultured with macrophage without stimulation after recombinant CD137L protein was added to the PM/VSMC co-culture system. Consistent with this finding, CD137-CD137L signaling obviously enhanced calcium deposition and ALP activity in the PM/VSMC co-cultures. Furthermore, SB-3CT, which was a specific inhibitor of gelatinases, alleviated calcification induced by CD137-CD137 axis, accompanied with reduced expression of RUNX2 and OPN.
CONCLUSIONS These data indicate that activated CD137-CD137L signaling contributes to the formation of vascular calcification by upregulating the expression of matrix metalloproteinase-9 (MMP-9) secreted from macrophage. Thus, inhibition of CD137-CD137L signaling pathway and MMP-9 might be a promising strategy to prevent vascular calcification.
[GW30-e0752]
Chunshu Hao, Genshan Ma, Lijuan Chen
Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, Nanjing, China
OBJECTIVES Exosomes play an important role in intercellular signaling and exert regulatory functions by carrying bioactive molecules. GATA4 is an early cardiac-specific transcription factor, and endogenous GATA4-positive cells play a critical role in cardioprotection after myocardial injury. This study investigated the cardioprotective capabilities of exosomes derived from GATA4-Overexpressing Cardiosphere-Derived Cells (GATA4-Exo) and the underlying mechanisms through the delivery of microRNAs (miRNAs) to regulate target proteins in myocardial infarction.
METHODS Exosomes were harvested from CDCs by ultracentrifugation. The morphology of the CDCs-derived particles was observed under a transmission electron microscope (TEM). miRNA array experiment was used to test the differential expression of the miRNAs between exosomes derived from GATA4-Overexpressing CDCs (CDCsGATA4) and control CDCs (CDCsNC). Double luciferase reporter assay was applied to confirm that miR221 directly targets the 3′UTR of the gene of phosphate and tension homology deleted on chromsome ten (PTEN) gene. Echocardiography and Masson trichrome staining were used to determine the extent of cardiac function and myocardial infarct size.
RESULTS Exosomes were isolated and purified from CDCsGATA4 and CDCsNC. When hypoxia-injured H9C2 were treated with GATA4-Exo vs. NC-Exo, an improved H9C2 survival rate (P<0.05) and reduced H9C2 apoptosis were observed with GATA4-Exo compared with NC-Exo. Microarray analysis of the exosomal miRNAs revealed significantly increased expression of miR221 in GATA4-Exo compared with NC-Exo. Direct intramyocardial transplantation of GATA4-Exo at the border of an ischemic region following ligation of the left anterior descending coronary artery significantly restored cardiac contractile function and reduced infarct size. In terms of mechanism, real-time PCR revealed that miR221 levels were higher in H9C2 treated with GATA4-Exo compared with those treated with NC-Exo (317%, P<0.001). We then transfected H9C2 with miR221 mimic and miR221 inhibitor. miR221-mimic-transfected vs. miR221-inhibitor-transfected H9C2 demonstrated a significantly increased survival rate (P<0.01) following exposure to hypoxic condition. The dual-luciferase reporter gene assay confirmed the PTEN gene as a target of miR221. Western blot analysis showed that H9C2 treated with GATA-4-Exo exhibited lower PTEN protein expression and higher p-Akt expression compared with NC-Exo-treated cells.
CONCLUSIONS Collectively, exosomes derived from GATA4-Overexpressing CDCs protect cardiomyocytes against apoptosis via the miR221-mediated PTEN-PI3K/AKT signaling pathway.
[GW30-e0754]
Jiayu Shi, Haiyan Pan
Affiliated Hospital of Nantong University
OBJECTIVES Aims Our previous research has established that ectopic trypsin was expressed in aortic artery and up-regulated in atherosclerotic plaques. Distribution of trypsin was overlapped with that of matrix metalloproteinase-9. As matrix metalloproteinase-9, which could be activated by trypsin, plays trigger roles in the process of plaque rupture. The purpose of this study was to explore the possible roles of trypsin in process of atherosclerotic plaque inflammation and the effects of trypsin inhibitor aprotinin on plaque stability in rabbit models, thus providing a new strategy for stabilizing atherosclerotic plaques.
METHODS Twenty-four New Zealand white rabbits (8-week-old) were randomly assigned to the normal control group, the atherosclerosis experimental group and the trypsin inhibitor aprotinin group, with eight rats in each group. The control group was given standard rabbit chow, while the experimental and aprotinin groups were fed with high-fat diet. At the 13th week of feeding, the rabbits in the aprotinin group were treated with aprotinin via the ear vein at a dose of 5 mg/kg/day for 4 weeks, whereas the experimental group was injected with the same amount of saline. At the end of the 16th week, the rabbits were sacrificed and their heart and aortic tissues were taken for pathological and biochemical examinations.
RESULTS Compared with the experimental group, the lipid deposition in the aortic root cross sections and the aortic wall was significantly reduced in the aprotinin-treated group. Western immunoblotting and immunohistochemical analysis showed that the expression of ectopic trypsin and matrix metalloproteinase-9 in the aortic tissues were significantly up-regulated in the experimental group compared to the control group, and were consistently distributed in atheroma plaques. The high-fat diet also increased the expression of pro-inflammatory cytokines such as IL-6, IL-1β, and TNFα in aortic tissues. Aprotinin treatment significantly inhibited the expression of trypsin and matrix metalloproteinase-9, as well as the production of pro-inflammatory cytokines.
CONCLUSIONS As a potent inhibitor of trypsin, aprotinin can alleviate the inflammatory response of atherosclerotic plaque by inhibiting the expression of ectopic trypsin and matrix metalloproteinase-9 in atherosclerotic plaque tissues, thereby impeding the progression of atherosclerosis.
[GW30-e0756]
Chunyan KONG 1,2,3 , Zhenguo Ma 1,2,3 , Qizhu Tang 1,2,3
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, RP China
2Cardiovascular Research Institute of Wuhan University, Wuhan 430060, RP China
3Hubei Key Laboratory of Cardiology, Wuhan 430060, RP China
OBJECTIVES Doxorubicin (DOX) is an effective antineoplastic drug, but its clinical application is limited by cardiovascular toxic effects. Oxidative stress, inflammation and cardiomyocyte apoptosis play critical roles in DOX-induced cardiotoxicity. Toll-like receptor 5 (TLR5) is a member of TLR family expressed on immune cells and cardiac tissues. However, whether TLR5 is involved in doxorubicin-induced cardiotoxicity and its underlying mechanisms remain unclear.
METHODS Global TLR5-deficient mice and wild-type littermates were subjected to a single intraperitoneal injection of DOX (15 mg/kg) for an acute model. Body weight (BW), heart weight (HW), and tibial length (TL) were measured to reflect cardiac injury. Echocardiographic parameters including ejection fraction (EF) and fractional shortening (FS) were collected to assess heart phenotype.
RESULTS The data in our study demonstrated that DOX resulted in significant weight loss and cardiac atrophy, and these pathological alterations were blocked after TLR5 deficiency. TLR5 deficiency also improved cardiac function in mice with DOX treatment. TLR5 deficiency protected the mice from oxidative stress and apoptosis induced by DOX. TLR5 deficiency cannot affect the acute inflammatory reaction in mice with DOX. Western blotting demonstrated that the activation of p38 in hearts caused by DOX was suppressed in TLR5-deficient mice. CBLB502, an agonist of TLR5, aggravated DOX-related cardiac injury, as indicated by the decreased HW/BW, EF and FS, CBLB502 also further enhanced the phosphorylation of p38 in DOX-treated mice. The rat cardiomyocyte-derived cell line H9c2 was cultured with DOX (1μM). CCK8 assay showed a significant decrease in cell viability after DOX treatment and TLR5 deficiency could largely improve cell viability in vitro. TLR5 deficiency also attenuated DOX-induced oxidative stress in cardiomyocytes.
CONCLUSIONS These findings suggest that TLR5 deficiency attenuated doxorubicin-induced cardiotoxicity in mice.
[GW30-e0757]
Nan Tang, Qizhu Tang
Renmin Hospital of Wuhan University
OBJECTIVES Doxorubicin, as a representative of anthracycline drugs, is widely used in the clinical treatment. However, cardiotoxicity is a serious and fatal side effect of doxorubicin, which limits its application in cancer treatment. This study aims to explore the effect and mechanism of TLR9 on doxorubicin-induced cardiotoxicity in vivo and in vitro by genetic or pharmacological interference with TLR9.
METHODS Male C57/BL6 and TLR9-KO mice were divided into four groups randomly, WT+ Saline, WT+DOX, KO+ Saline, KO+DOX. DOX groups were injected intraperitoneally with DOX (5 mg/kg, once a week, the total cumulative dose is 15 mg/kg) for 3 times. Body weight and food consumption were monitored. Plasma CK-MB and LDH from tail vein were collected and detected. For further research, another four groups of mice were treated with 3-MA (10 mg/kg/d, i.p.) after each injection of DOX. Four weeks after the first injection, animals were anesthetized and echocardiographic measurements and hemodynamic analysis were performed. Then mice were sacrificed for molecular biology and histopathology use.
H9C2 cells were treated with 1 μm DOX or PBS for 24 hours, alone or with the TLR9 inhibitor ODN2088 (0.2 μM), or with agonist ODN1826 (0.2 μM). For Further research, H9C2 cells treated with DOX or PBS were treated in combination with ODN2088 and 3-MA (10 mM). The cells were collected for western blot analysis and fluorescence staining.
RESULTS The results show that TLR9 deficiency protects against DOX-induced cardiotoxicity both in vivo and in vitro. It alleviates DOX-induced cardiomyocyte apoptosis, oxidative stress, myocardial atrophy, cardiac fibrosis and improved cardiac function. DOX-treated TLR9-KO mice exhibits enhanced autophagy compared with corresponding control group. 3-MA, an inhibitor of autophagy, abrogates the protection of TLR9 deficiency against DOX-induced cardiotoxicity. Collectively, we demonstrate that TLR9 deficiency alleviates doxorubicin-induced cardiotoxicity via enhancing autophagy and it suggests a potential target for clinical treatment of DOX-induced cardiotoxicity.
CONCLUSIONS Our present study implies that TLR9 deficiency protects against doxorubicin-induced cardiotoxicity, accompanied by alleviated cardiomyocyte apoptosis, oxidative stress, myocardial atrophy, cardiac fibrosis and improved cardiac function. However, inhibition of autophagy abrogates the protection of TLR9 deficiency both in vivo and in vitro.
[GW30-e0776]
Yanjing Feng, Min Xu, Dengfeng Gao
The Second Affiliated Hospital, Xi’an Jiaotong University
OBJECTIVES After acute myocardial infarction (AMI), the loss of a large number of cardiomyocytes will be results in the necrotic cardiac tissue, which is eventually replaced by scar formation. Cardiac patches have emerged as a potential regenerative strategy for MI. In this study, we fabricated reduced graphene oxide (rGO)/silk fibroin modified nanofibrous biomaterials as a cardiac patch to improve the heart function and prevent the ventricular remodeling post-MI. Furthermore, we have investigated the effect of rGO on cardiac fibroblasts (CFs) and potential mechanisms.
METHODS We fabricated reduced graphene oxide (rGO)/silk conductive biomaterials through fabricating electrospun silk scaffolds and vacuum filtration. A rat model of acute myocardial infarction was used to investigate the ability of rGO/silk fibroin modified nanofibrous patches to improve heart function in the injured heart in vivo. Echocardiography (ECHO) was used to evaluate heart function 4 weeks after MI. Immunofluorescence staining was used to visualize the expression of cardiac-specific markers. Western blot analysis was used to illustrate the expression of biomarkers for myocardial fibrosis of cardiac tissue. CFs were obtained and treated in different conditions, the secretion levels of type I (Col1) and type III collagen (Col3) in CFs supernatant were measured by ELISA assay. Cellular proliferation of CFs after treatment of rGO was measured by Cell Counting Kit-8 (CCK8). The mRNA expression levels of type I and type III collagen and TGF-β1 were detected by Real-time PCR; the protein expression levels of Yap/Taz-TGFβ1/Smads signaling pathways and type I collagen were also detected by Western blot.
RESULTS Echocardiography demonstrated less ventricular remodeling in rGO/silk fibroin modified nanofibrous group, with an increase in the ejection fraction and fractional shortening compared with the MI group. Histopathological staining demonstrated that cardiac fibrosis was attenuated in rGO/silk fibroin modified nanofibrous group. The expression level of Col1 of myocardial tissues in in rGO/silk fibroin modified nanofibrous group was lower than the MI group. Western blot analysis illustrated that the expression level of Yap/Taz-TGFβ1/Smads signaling pathways was decreased in rGO/silk fibroin modified nanofibrous patches treated hearts.
rGO inhibited proliferation of CFs in a dose-dependent manner (P<0.05). The secretion levels of type I (Col1) and type III collagen (Col3) in CFs supernatant induced by Ang II was downregulated by treatment of rGO. Real-time PCR results indicated that the gene expression levels of c Col1, Col3 and TGF-β1 in CFs by exposure to Ang II were significantly increased as compared with those in control group (P<0.05). However, Ang II-induced Col1, Col3 and TGF-β1 mRNA upregulation was inhibited by rGO treatment (P<0.05). Western blot analysis illustrated that the protein expression of Yap/Taz-TGFβ1/Smads signaling pathways and Col1 was decreased after the treatment of rGO (P<0.05).
CONCLUSIONS This study suggests that rGO/silk modified nanofibrous patches improve the heart function and attenuate myocardial fibrosis of infraction area. Reduced graphene oxide inhibits the expressions of type I and type III collagen induced by Ang II in cardiac fibroblasts through regulating the Yap/Taz-TGFβ1/Smads signaling pathways.
[GW30-e0796]
Qingyuan Gao 1,2 , Yangxin Chen 1,2 , Haifeng Zhang 1,2 , Wenhao Liu 1,2 , Zhiteng Chen 1,2 , Chengzhang Xu 1,2 , Jingfeng Wang 1,2
1Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China
2Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou 510120, China
OBJECTIVES Cardiac fibrosis is a considerable global health problem that derived from many forms of heart diseases all over the world currently. The aims of this study are to elucidate the interaction between ncRNAs and mRNAs via construction of ceRNA network and validate correlation among genes and correlation between genes and clinical features to further understand molucular mechanisms of cardiac fibrosis.
METHODS The expression profile of mRNA and lncRNA and the miRNA expression profile in human cardiac fibroblast are obtained from NCBI GEO. The different expressed genes (DEGs) were identified using the limma package in R. The Gene Ontology (GO) analysis and KEGG pathway analysis was Performed to idenfity function of DEMs and further indentify enriched signal pathway of DEMs using DAVID. The specific lncRNAs and mRNAs targeted by miRNAs were identified based on starbase, miRcode, miRTarbase, Targetscan databases to construct lncRNA-miRNA-mRNA ceRNA network. We performed WGCNA Using WGCNA package in R to discover the relationship among different genes. Further, the outcome was input into Cytoscape to visualize the gene coexpression network. Different expressed lncRNA and miR were qRT-PCR confirmed. All the statistical analysis were performed using R statistical software package Version 3.5.1. P<0.05 was considered to be statistically significant.
RESULTS Total 420 differentially expressed mRNAs (DEMs), 30 different expressed miRNAs (DEMis) and 34 different expressed LncRNAs (DELs) were screened. Depended on GO and KEGG analysis, there are 81 significant enriched biological processes, 21 significant enriched cellular components, 23 significant Enriched molucular functions and 17 significant enriched pathways among these DEMs. For ceRNA network, the lncRNA-miRNA-mRNA network included 398 mRNA nodes, 30 miRNA nodes and 6 lncRNA nodes and 3256 edges. LncRNA XIST, as a hub lncRNA, was linked with 5 miRNAs, 351 mRNAs and 839 edges in the subnetwork. According to the results of DAVID analysis, these 352 mRNAs were enriched into 64 biological processes like most significant enriched inflammatory response (GO: 0006954). Moreover, the genes can be identified into 4 Network modules and module turquiose is most correlated with cardiac fibrosis phenotype. Most genes in module turquiose are also involved in ceRNA network of cardiac fibrosis.
CONCLUSIONS Three hundred ninety-eight mRNAs are in directly regulated by 6 lncRNA via 30 miRNAs are involved in initiation and development of cardiac fibrosis. More importantly, lncRNA XIST play a critical role in cardiac fibrosis, possibly throughout inflammatory response.
[GW30-e0807]
Mengyue Yang 1,2 , Hou Jingbo 1,2
1The Key Laboratory of Myocardial Ischemia Organization, Chinese Ministry of Education, Harbin, China
2Division Department of Cardiology Organization, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
OBJECTIVES Cholesterol crystals-induced endothelial cell inflammation and pyroptosis plays an important role in the development of cardiovascular diseases, especially in atherosclerosis. As a classical non-specific anti-inflammatory drug, colchicine has been widely used in the treatment of acute gout. However, whether colchicine could alleviate cholesterol crystals-induced endothelial cell injury and the related mechanisms remains to be addressed. Hence, we tested the hypothesis that colchicine limits cholesterol crystals-induced endothelial cell pyroptosis via the activation of AMPK/SIRT1 pathway.
METHODS We synthesized cholesterol crystals in vitro, then treated endothelial cells with cholesterol crystals (0.5 mg/mL) and different concentrations of colchicine (0.1–10 nM) and Si RNA targeting AMPK/SIRT1. We assessed the cell viability using CCK8, and the pyroptotic cell death was evaluated with LDH release assay, Hoechst 33342/PI staining and scanning electron microscopy. We also detected the accumulation of ROS and mitochondrial membrane potential energy using the assay kit. The expression of NLRP3 inflammasome-related proteins (NLRP3, ASC-1, Caspase-1) and AMPK pathway-related proteins (p-AMPKα, AMPKα, SIRT1, SOD-2, SOD-1, HO-1) were assessed by western blotting. Moreover, the mRNA levels of various inflammatory factors such as IL-1β, IL-18, IL-6, IL-8, MCP-1 and GSDMD were examined through quantitative RT-PCR approaches.
RESULTS In this study, the protective effect of colchicine on endothelial cells was confirmed. Our results revealed that after co-treatment with colchicine and cholesterol crystal in endothelial cells, the uptake of cholesterol crystal was reduced, and the expression of intracellular lipoprotein receptor was significantly decreased; the cell viability was obviously increased, the release of LDH and the number of pyroptotic cells decreased significantly; then the expression of NLRP3 inflammasome-related proteins and various inflammatory factors were also visibly suppressed; moreover, as a potent activator of NLRP3 inflammasome, intracellular ROS level was clearly reduced, and the mitochondrial membrane potential energy was significantly improved. However, the above effects of colchicine were completely offset by the treatment of SiRNA targeting AMPK and SIRT1.
CONCLUSIONS Therefore, we conclude that colchicine plays a crucial role in inhibiting the intracellular inflammatory response and NLRP3 inflammation activation, cellular oxidative stress and pyroptosis in endothelial cells via regulating AMPK/SIRT1 signaling, which may be a concrete mechanism for the secondary prevention of cardiovascular diseases.
[GW30-e0818]
Gao Xiaoming 1,2 , Yidan Su 1 , Shirley Moore 1 , Han Li Ping 1 , Helen Kiriazis 1 , Qun Lu 1 , Wei Bo Zhao 1 , Amanguli Ruze 2 , Bin Fang 2 , Ming Jun Duan 2 , Du Xiaojun 1
1Baker Heart and Diabetes Institute, Melbourne, Australia,
2State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, China
OBJECTIVES Microvascular obstruction (MVO) and leakage (MVL) forms a pivotal part of microvascular damage following cardiac ischemia-reperfusion (I/R). We tested the effect of relaxin on MVO and MVL in mice following cardiac I/R injury.
METHODS Male mice were subjected to cardiac I/R and then treated with relaxin (50 μg/kg) or vehicle. The severity of MVO and MVL, infarct size, regional inflammation and opening capillaries in the heart were determined. A microvascular permeability tracer, Evans blue (20 mg/kg), was given to allow for identification of myocardial MVL while the tissue Evans blue content was measured chromatographically. Echocardiography was performed to assess cardiac function and remodeling. Using cultured endothelial cell monolayer, effect of relaxin on hyper-permeability induced by simulated I/R conditions was examined.
RESULTS Compared to vehicle group, relaxin treatment reduced both no-reflow area by 38% (43±3% vs. 27±3% of LV) and Evans blue content in jeopardized myocardium by 56% (0.054±0.001 vs. 0.124±0.014 μg/mg, both P<0.05), effects associated with increased opening capillaries (19±1% vs. 38±2%, all P<0.05). Relaxin also decreased leukocyte density (465±33 vs. 696±64 No./mm2), gene expression of IL-1β and IL-6, and mitigated I/R-induced decrease in protein content of VE-cadherin and relaxin receptor. Infarct size was comparable between the two groups. At 2 weeks post-IR, relaxin treatment partially preserved cardiac contractile function and limited chamber dilatation versus untreated controls by echocardiography. Endothelial cell permeability assay demonstrated that relaxin attenuated leakage induced by hypoxia-reoxygenation, H 2 O 2 , or cytokines, action that was independent of nitric oxide but associated with preservation of VE-cadherin.
CONCLUSIONS Relaxin therapy attenuates I/R-induced MVO and MVL and endothelial leakage both in vivo and ex vivo. This protection was associated with reduced regional inflammatory responses and consequently led to alleviated adverse cardiac remodeling.
[GW30-e0820]
Dilare Adi, Liu Fen, Xie Xiang, Yang Yining, Fu Zhenyan, Ma Yitong
Heart Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang, China
OBJECTIVES The E3MD negatively regulates low-density lipoprotein receptor (LDLR) abundance. The aim of this study was to define the mechanism that how E3MD mutant affected cholesterol level in circulating LDL.
METHODS Using whole-exome sequencing, we identified a nonsynonymous variant in E3MD gene that causes Gly51 to Ser mutation from a Chinese Uygur family.
RESULTS Large cohort analysis revealed +/G51S carriers displayed predominantly higher LDL-C levels. Mechanistically, the Gly51 residue is critical for the maintenance of E3MD protein level. G51S mutant E3MD exhibited reduced dimerization, autoubiquitination and enhanced protein stability. The G51S was more potent to ubiquitinate and degrade LDLR. In vivo hepatic expression of E3MD -G51S mutant in mice caused liver LDLR attenuation and subsequent serum LDL-C elevation.
CONCLUSIONS Our study demonstrates that E3MD (G51S) is a gain-of-function variant responsible for high LDL-C in both humans and mice. These results suggest that E3MD is a key player regulating cholesterol level in humans and required for metabolic homeostasis.
[GW30-e0825]
Xianming Chu 1,2 , Jing Tian 1,3 , Haichu Yu 1,2 , Xianming Chu 1,2
1The Affiliated Hospital of Qingdao University
2The Affiliated Cardiovascular Hospital of Qingdao University
3Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES To evaluate the protective effects of hydroxysafflor yellow A (HSYA) on the injured human coronary artery endothelial cells (HCAECs) induced by High ox-LDL, and related molecular mechanisms.
METHODS Four groups of HCAECs were cultured individually: the control group, High ox-LDL group, High ox-LDL+HSYA group, and HSYA group. After 24 hours of injury induction, the survival rate of each group was measured by colorimetric method with MTT, and the optimal dose of High ox-LDL and HSYA in the test conditions were selected. NO and LDH released from HCAECs in each group were detected by nitrate reduction and lactate dehydrogenase colorimetry method, respectively; and cell apoptosis was analyzed by flow cytometry. The expression of LOX-1 and eNOS genes in transcription levels were detected by reverse transcription-polymerase chain reaction (RT-PCR), and Western blot (WB) was employed to detect the expression in protein levels of LOX-1, eNOS and Bcl-2/Bax.
RESULTS Compared with the control group, High ox-LDL (20 μg/mL) group behaved lower survival rate (99.39±0.66 vs 67.26±2.68, P<0.05); NO content was decreased, and the expression of eNOS mRNA and protein decreased (P<0.05); conversely, LDH content was increased (P<0.05), either the expression of LOX-1 mRNA and protein levels (P<0.05); the number of apoptotic cells increased significantly (16.28%, P<0.001), the proportion of Bcl-2/Bax protein decreased similarly (P<0.001). Compared with High ox-LDL (20 μg/mL) group, High ox-LDL (20 μg/mL)+HSYA (0.2 mM) increased the cell viability (67.26±2.68 vs 86.63±3.29, P<0.05), promoted NO release (P<0.05); the mRNA expression of eNOS was restored, and then was upregulated in protein level (P<0.05); besides, suppressed LDH secretion (P<0.05), and the expressions of LOX-1 mRNA and protein were decreased (P<0.05); inhibited the cell apoptosis significantly (12.04%, P<0.001), the Bcl-2/Bax protein expression also increased (P<0.05).
CONCLUSIONS Endothelial damage could be induced by the lipid peroxidation, such as addition of High ox-LDL. HSYA displayed a protective effect through up-regulating the expression of eNOS mRNA and protein and then improvement of NO content. In contrast, it could inhibit LDH releasement by down-regulating the expression of LOX-1 mRNA and protein. Treatment of HSYA restored the apoptosis of HCAECs by up-regulating Bcl-2/Bax expression.
[GW30-e0846]
Biao Li, Baojian Zhang, Fan Bai, Jiayi Li, Fen Qin, Na Liu, Chao Sun, Yichao Xiao, Tao Tu, Shenghua Zhou, Qiming Liu
Department of Cardiology/Cardiac Catheterization Lab, Second Xiangya Hospital, Central South University, Changsha City, Hunan Province, China
OBJECTIVES Epicardial adipose tissue (EAT) remodeling is important for the pathogenesis of atrial fibrillation (AF). We investigated if metformin (MET) prevents AF-dependent EAT remodeling and AF vulnerability in dogs.
METHODS Eighteen male beagle dogs were randomly divided into three groups: (i) sham-operated (normal diet without pacing, n=6), (ii) RAP (Rapid atrial pacing, n=6), and (iii) RAP+MET (RAP with MET). AF model was induced by rapid atria pacing (RAP) at 400 bpm for 4 weeks with a programmable pacemaker. Daily oral administration of MET (100 mg/kg) was initiated 1 week before surgery and continued throughout the study period. The electrophysiological parameters including effective refractory period (ERP), window of vulnerability induced window (WOV) and AF duration, AF inducibility were measured before and after 6 weeks RAP. The content of ROS, inflammatory factor APN and related signaling pathway protein in LA and EAT were detected. To detect the effect of MET on the interactions between HL-1 atrial myocytes and 3T3-L1 mature adipocytes, HL-1 were indirectly co-cultured with LPS-treated 3T3-L1 via an exchange medium.
RESULTS In vivo, MET attenuated the RAP-induced decrease in effective refractory periods (ERP) and increase in ERP dispersion, cumulative window of vulnerability, AF inducibility, and AF duration. RAP increased ROS production and NF-κB phosphorylation, upregulated IL-6, TNF-α, and TGF-β1 levels in LA and EAT, decreased PPARγ and adiponectin (APN) expression in EAT, and were accompanied by atrial fibrosis and adipose infiltration. MET was shown to reverse the alterations described above. In vitro, LPS stimulated 3T3-L1 adipocytes inflammatory factor expression and decreased APN expression. Indirect coculture HL-1 cells with LPS-stimulated 3T3-L1 conditioned medium (CM) significantly increased inflammatory response and decreased SERCA2a and p-PLN expression, while LPS+MET CM and APN treatment alleviated the inflammatory factor expression and SR Ca2+ handling dysfunction.
CONCLUSIONS MET attenuated RAP-induced increase in AF vulnerability and remodeling of atria and EAT adipokine production profiles and APN may play a key role in MET breaking the vicious “AF begets AF” cycle.
[GW30-e0869]
Yonghui Yu, Jinghui Sun, Jiangang Liu, Peili Wang, Chenglong Wang
Xiyuan Hospital, China Academy of Chinese Medical Science
OBJECTIVES To analyze the components of ECM proteins and the interaction mechanisms within the differential proteins in fibrotic myocardium of CFMI rats model by label-free proteomics.
METHODS CFMI rats model was established by ligation of the left anterior descending coronary artery, then were randomly divided into four groups: Sham after 2 weeks (Sham 2W), Sham after 4 weeks (Sham 4W), CFMI after 2 weeks (Model 2W) and CFMI after 4 weeks (Model 4W), with 10 rats in each group. ECM proteins were extracted using Mary-three-steps. Changes in ECM differential proteins were analyzed by lable-free proteomics. GO analysis was used to describe the characteristics of cellular component, molecular functions and biological processes of ECM proteins. KEGG analysis was used to find the potential underline pathways in regulating expressions of these ECM differential proteins. Finally, the screened out ECM differential proteins were verified by Western Blot (WB).
RESULTS (1) A total of 243 ECM differential proteins were identified. Compared with Sham 2W, Osteoglycin was up-regulated and Nidogen-1 was down-regulated in Model 2W. Compared with Sham 4W, Lumican and Collagen type VI alpha 2 chain (Collagen 6A2) were up-regulated while Nidogen-1 was down-regulated in Model 4W. Compared with Model 2W, Nidogen-1 and Talin-1 were down-regulated in Model 4W (P<0.05). Bio-informatics analysis showed that the cellular component of ECM differential proteins were significantly enriched in extracellular regions, extracellular matrix and other cell components. Molecular functions such as receptor binding, metal ion binding and Integrin binding were enriched. Biological processes such as immune regulation, protein transportation, membrane organization, intercellular signal transduction and cell adhesion were enriched. KEGG analysis showed that focal adhesion kinase (FAK), phosphatidylinositol-3-hydroxykinase (PI3K)/protein kinase B (Akt) and interaction between Integrin and ECM receptor pathways were significantly regulated.
(2) WB results showed that expressions of Collagen 6A2, Lumican and Talin-1 were up-regulated in Model 2W group when compared with Sham 2W group (P<0.05); Collagen 6A2 and Lumican were significantly increased and Nidogen-1 was significantly decreased in Model 4W group when compared with Sham 4W group (P<0.05). When compared with Model 2W group, the expressions of Nidogen-1, Lumican and Talin-1 were down-regulated in Model 4W group (P<0.05). The results involving Collagen 6A2 and Lumican were up-regulated while Nidogen-1 was down-regulated in Model 4W group when compared with Sham 4W group, Nidogen-1 and Talin-1 were down-regulated in Model 4W group when compared with Model 2W group, were coincident between label-free proteomics and WB detection.
CONCLUSIONS The ECM differential proteins including Collagen 6A2, Nidogen-1, Lumican, Talin-1 and Osteoglycin might be the possible targets of CFMI. The mechanisms of regulation in deposition of these ECM differential proteins may relate to FAK, PI3K/Akt and Integrin signaling pathways.
[GW30-e0883]
Yonghui Yu, Jinghui Sun, Jiangang Liu, Peili Wang, Chenglong Wang
Xiyuan Hospital, China Academy of Chinese Medical Science
OBJECTIVES To observe the effects and mechanisms of Hirudin intervention on cardiac function and myocardial pathology in Cardiac fibrosis after myocardial infraction (CFMI) rats and Ang II induced neonatal rat cardiac fibroblasts (NRCFs).
METHODS CFMI rats were established by ligating the left anterior -descending coronary artery of Wistar rats, which were randomly divided into four groups: Sham group (Sham, normal saline), Model group (Model, normal saline), Valsartan group (Valsartan, 144 mg/kg/d) and Hirudin group (Hirudin, 270 mg/kg/d). Twenty rats in each group were treated once a day for four weeks. Echocardiography parameters, peripheral markers and pathological staining were measured. The expression of AMPK, Integrin β1, FAK, PI3K p110α, PI3K p110β, Akt, TGF-β1 and Smad2/3 in fibrotic signaling pathways were measured by WB. NRCFs were separated, extracted, cultivated and lastly identified via vimentin (+)/vWF (–) immunofluorescence staining in vitro. Then NRCFs were randomly divided into four groups: Control group (Control), Model group (Ang II), Valsartan group (Valsartan) and Hirudin group (Hirudin). After 30 min of pre-intervention with corresponding treatment, 10-6M Ang II was employed to induce fibrotic NRCFs for 24 h. Cell proliferation, phenotypic differentiation, cell migration and cell secretion were measured. The protein expression levels of AMPK α1/α2, Integrin β1, FAK, TGF-β1, and Smad2/3 were detected by WB.
RESULTS (1) Compared with the Model group, IVSTs, LVPWT and LVEF were increased, while LVD, EDV and ESV were decreased in Hirudin group; Serum levels of CK-MB, cTnT, ANP, BNP, Ang II and MDA were decreased, while SOD was increased significantly in Valsartan group and Hirudin group; Infarction area and collagen volume fraction were significantly reduced in Valsartan group and Hirudin group; The protein levels of AMPK, FAK, PI3K p110α and Akt were up-regulated, while Integrin β1, TGF-β1 and Smad2/3 were significantly down-regulated in Valsartan group and Hirudin group (all P<0.05). PI3K p110β protein expression showed no significant difference among groups (P>0.05).
(2) After 24 h culture of NRCFs, the ratio of NRCFs with vimentin (+)/vWF (–) was (98.09±1.03) %. Compared with the Ang II group, the percentage of cells in quiescent G0G1 phase was significantly increased, cells in proliferative S phase was significantly decreased; the number of cells with positive immunofluorescence staining of α-SMA and migrating through the Transwell chamber were significantly reduced, moreover the scratch width was significantly extended; The contents of HYP in supernate was reduced, and protein levels of AMPKα1/α2 and FAK were up-regulated, while Integrin β1 was down-regulated in Valsartan group and Hirudin group (all P<0.05). While expressions of TGF-β1 and Smad2/3 in Hirudin group showed no statistical difference with Ang II group (P>0.05).
CONCLUSIONS Hirudin can relieve left ventricle dilation, improve cardiac function, reduce myocardial injury, decrease infarction area and interstitial collagen deposition in CFMI rats. Meanwhile, Hirudin can inhibit Ang II-induced pro-fibrotic changes in NRCFs, involving cell proliferation, phenotypic differentiation, cell migration and secretion of ECM differential proteins. These mechanisms of optimized abilities in dealing with cardiac fibrogenesis is related to the Hirudin regulation of AMPK/Integrin β1/FAK, PI3K/Akt and TGF-β1/Smad2/3 signaling pathways.
[GW30-e0888]
Zhang Jian, Xu Feng
Qilu Hospital of Shandong University
OBJECTIVES Several studies have confirmed that aldehyde dehydrogenase 2(ALDH2) rs671 polymorphism is a susceptibility gene for atherosclerotic cardiovascular disease, due to its Glu504Lys replacement eliminating ALDH2 activity in both heterozygotes and mutation homozygotes to 1-6%. We hypothesized that deletion of ALDH2 in myeloid cells may affect plaque stability via efferocytosis.
METHODS Irradiated apolipoprotein E knockout mice were transplanted with bone marrow from wild type or ALDH2 knockout mice and fed a high cholesterol Western diet. Atherosclerosis, efferocytosis and inflammatory response is to be characterized. We examined whether ALDH2 deletion could affect efferocytic capacity of peritoneal macrophage by coculturing with apoptotic smooth muscle cells. Lipopolysaccharide and liquid supernatant from apoptotic cells were used to stimulate ALDH2–/– and wild type peritoneal macrophage and expression of MerTK, one kind of surface efferocytosis receptor were analyzed.
RESULTS After coculturing peritoneal macrophage with apoptotic smooth muscle cells, ALDH2–/– macrophage displayed significantly decreased efferocytic capacity comparing to wild type macrophage. Myeloid cells from chimeric mice received ALDH2–/– bone marrow expressed significant less ALDH2 protein compared with those received wild type bone marrow.
CONCLUSIONS Our results demonstrated that ALDH2 may stabilize plaque through regulation of efferocytosis.
[GW30-e0910]
Donglu Liu, Yinglong Hou
Qianfoshan Hospital
OBJECTIVES Atrial fibrillation is the most common persistent tachyarrhythmia in clinical practice. Radiofrequency ablation has become an important treatment for atrial fibrillation but this therapy has high recurrence rate because of cardic intrinsic autonomic neural remodeling. In this context, this study further explored the molecular mechanisms of neural remodeling after radiofrequency ablation and provided a new explanation for nerve remodeling after cather ablation.
METHODS Twelve adult beagle dogs were divided into 1 month control group,1 month ablation group,6 month control group, 6 month ablation group (n=3 in each group). The control groups only underwent thoracotomy, and the experimental groups ablated the right-sided ganglionated plexi. They were sacrificed after 1 month and 6 months respectively. We defined 1 cm of tissue awat from the ganglionated plexi as the target atrial tissue and these tissues were taken for high-throughput sequencing. The differentially expressed target genes related to neural remodeling were screened. To predict target gene of lncRNA that differentially expressed and choose lncRNA which target gene related to neural remodeling. After analysis, we confirmed that lncRNA-GAP43 is used for subsequent studies. The correlation between lncRNA56298 and GAP43 was verified by interfering with lncRNA56298 by qRT-PCR.
RESULTS KEGG analysis and GO analysis were performed on differentially expressed target genes by high-throughput sequencing, KEGG analysis showed that differentially expressed genes were involved in neural growth and axon formation; GO analysis showed that differentially expressed genes were related to neurodevelopment and cardiovascular disease. Western blot and qRT-PCR for tissues, the result of western blot revealed that the expression level of GAP43 is higher in 6 months ablation group than another groups and the result of qRT-PCR showed that lncRNA56298 and GAP43 of 6 months ablation group is highest in all groups,1 month ablation group is higher than 1 month control group, 6 months control group has no significant difference with 1 month control group. The FISH assay of lncRNA56298 contirmed that its subcellular localization revealed that lncRNA56298 located in the cytoplasm and nucleus. 5′RACE and 3′RACE were conducted to verify the complete nucleotide sequences of lncRNA56298. Isolation and extraction of canine primary cardiomyocytes, interference with lncRNA56298 followed by qRT-PCR and western blot showed that after the decline of lncRNA56298, both the gene and protein levels of GAP43 decreased revealed that the lncRNA56298 and GAP43 were correlated. We further demonstrated lncRNA56298 how to influence GAP43.
CONCLUSIONS The occurrence of neural remodeling after radiofrequency ablation of atrial fibrillation may be related to lncRNAs and lncRNA56298 may influence the level of GAP43 to affect the reccurrence of atrial fibrillation after radiofrequency ablation.
[GW30-e0949]
Guohua Li, Jia Li, Xing Zhang, Feng Gao
School of Aerospace Medicine, Fourth Military Medical University, Xi’an 710032, China
OBJECTIVES Epidemiological studies have revealed the potential associations between genetic variations of the mitochondrial dynamics-regulating gene and hypertension. Mitochondrial fission of smooth muscle cells has been demonstrated to be involved in vasoconstriction. However, less information is available about the pathophysiological role of endothelial mitochondrial dynamics in the regulation of vascular tone. The present study was aimed to investigate the alterations of endothelial mitochondrial dynamics and its functional consequences in hypertension.
METHODS Mitochondrial networks in the vascular endothelium of hypertensive human subjects, as well as spontaneously hypertensive rats (SHRs) and AngII-induced hypertensive mice, were assessed using transmission electron microscope. In vitro, mitochondrial morphology in human aortic endothelial cells exposed to AngII (10–7 M, 48 h) were evaluated with laser confocal after labeling with MitoTracker Green. Six-week-old SHRs or age-matched WKYs were administrated with Mito-TEMPO or Mdivi-1 by intraperitoneal injection for four weeks. Systolic blood pressure was measured by either tail-cuff or catheterization method, and vasodilatory functions were determined in isolated mesenteric artery rings.
RESULTS Mitochondrial fragmentation and stronger Drp1 staining were observed in the aortic endothelium of AngII-induced hypertensive mice and SHRs. In cultured endothelial cells exposed to AngII, we observed a similar loss of mitochondrial networks and increased Drp1 expression. The observed mitochondrial fragmentation was associated with enhanced mitochondrial ROS production, impaired ACh-stimulated eNOS activation and NO production, all of which were blunted by the Drp1 specific inhibitor Mdivi-1 or Drp1 siRNA treatment. Furthermore, Mdivi-1 pretreatment improved endothelium-dependent vasorelaxation to ACh in isolated mesenteric arteries from SHRs, while four-week intraperitoneal Mdivi-1 administration or six-week swimming training ameliorated endothelial mitochondrial fragmentation, vascular endothelial dysfunction and blood pressure elevation in SHRs. Finally, mitochondrial fragmentation was also observed in the endothelium from mesenteric arteries isolated from human hypertensive subjects.
CONCLUSIONS These findings suggest that Drp1-mediated endothelial mitochondrial fragmentation promotes endothelial dysfunction by increasing mitochondrial ROS production, impairing eNOS activation and nitric oxide bioavilability in hypertension, which implicate increased endothelial mitochondrial fission as a contributing mechanism for hypertension.
[GW30-e0952]
Xiaojun Huang 1 , Jing Jin 2 , Liemin Hu 1 , Jilin Li 1
1Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
2Cardiovascular Surgery Center, Asia Heart hospital, Wuhan, Hubei 430022, China
OBJECTIVES Thoracic aortic dissection (TAD), which caused by the disruption of the intima and blood entering the tear to extend into the media of the aortic walls, is a life-threatening cardiovascular disease. Although previous studies have reported TAD is associated with hypertension, pathogenesis of TAD is not investigated. Endothelial-to-mesenchymal transition (EndMT) has been showed to be involved in cardiac development and a variety of diseases processes like cardiac fibrosis. We collected aortic specimens from patients underwent surgical repair. More and more findings indicated that angiotensin II (AngII) could induce aortic diseases such as aortic aneurysms and dissection. However, what role are endothelial cells (ECs) play in and the molecular mechanism(s) underlying aortic dissection remains incompletely understood. Hence, the aim of this experiment is to define a methodology for the isolation of aortic endothelial cells and investigate whether AngII induce aortic endothelial cells to undergo EndMT.
METHODS Aortic specimens were obtained from patients undergoing vascular replacement surgery at the Cardiovascular Surgery Unit of the first affiliated hospital of shantou university medical college. Tissues were collected in saline and processed after surgery, The single primary ECs were isolated from the intima using collagenase and pancreatin, then incubated in a 5% CO 2.37°C incubator. Cell morphology was observed using microscope. Flow cytometry to detect CD31 to identify endothelial cells. Normal human aortic endothelial cells (HAECs) purchased from the company were cultured in complete medium (ECM medium with 5%FBS, 1% ECGS and 1% penicillin and streptomycin). Cells from passages 4-6 were used in experiments. HAECs were divided into two groups: control group, and AngII (10–7, 10–6, 10–5, 10–4 mol/L)-treated for 24 h group. The expressions of VE-cadherin, Vimentin, CD31, α-SMA were detected by Western blot.
RESULTS The extracted vascular endothelial cells by this methodology showed a polygonal, cobblestone-like shape. Flow cytometry findings indicated positive expression of CD31. Throughout the culture, after one or two round(s) of expansion, we harvested a population of more than 90% pure ECs. The treatment of HAECs in the AngII group resulted in significant increases in the expressions of Vimentin and angiotensin II in dose-dependent manner. The expressions of Vimentin and α-SMA were significantly increased but Ve-cadherin were markedly decreased in the Ang II group. Thus, treatment with Ang II induced the EndMT, particularly at a dose of 10-4mol/L.
CONCLUSIONS This simple and reproducible isolation method provides pure primary cultures of human aortic endothelial cells, thus allowing us to do further research about aortic diseases. The HAECs with Ang II-treated showed increased expression of the fibroblast marker and decreased expression of the EC marker, manifesting that the ECs underwent EndMT. Further, EndMT was enhanced with the increase of AngII concentration. These findings that angiotensin II could induce endothelial-to-mesenchymal transition in human aortic endothelial cells may help us understand the mechanism of how endothelial cells involved in aortic dissection. And the study of normal HAECs may propose to the study of isolated aortic endothelial cells.
[GW30-e0957]
Jinzhu Hu, Menglu Liu, Xin Zhu, Jinyan Xie, Jianhua Yu, Kui Hong
Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University
OBJECTIVES We evaluate the role of sodium channel gene (SCN5A) variant in SQTS, and characterize the biophysical properties of this channe mutation to determine whether changes are consistent with cardiac defects.
METHODS A female with recurrent syncope, and electrocardiogram (ECG) characterized by short QT interval (QTc 270 ms) and ventricular tachyarrhythmias was identified. The SCN5A gene and the known disease-causing genes (KCNH2, KCNQ1, KCNJ2, CACNA1C, CACNB2b, CACNA2D1) of SQTS were sequenced. Mutated SCN5A channel (Nav1.5) plasmid was constructed by site-directed mutagenesis system and transfected to Human embryo kidney (HEK) 293 cells. Electrophysiological analysis was evaluated by the whole-cell patch clamp recordings. Both proteins from the whole cell and plasma membrane were extracted to evaluate the expression of mutated and WT Nav1.5 respectively.
RESULTS The patient was completely consistent with the diagnosis of SQTS, according to current guideline. A novel heterozygous missense mutaiton p.E428G (c.1283A>G; p.Glu428Gly) was identified. The patient was completely consistent with the diagnosis of SQTS, according to current guideline. A novel heterozygous missense mutaiton p.E428G (c.1283A>G; p.Glu428Gly) was identified. The mutation was at the highly conservative site and not detected in the 400 healthy control chromosomes of the same ethnic background. Biophysical properties analysis showed that p.E428G significantly decreased depolarizing late sodium current (INaL), compared with WT (P<0.05). In addition, both the voltage dependence of steady-state inactivation (SSI) and steady-state activation (SSA) of p.E428G were significantly shifted to the hyperpolarization direction (P<0.05). P.E428G displayed increased peak sodium current density (INa), compared with WT (P<0.05). There was no significant difference of Nav1.5 expression in the whole cell level between p.E428G and WT. However, p.E428G showed significantly increased expression of Nav1.5 in the plasma membrane (P<0.01).
CONCLUSIONS We for the first time report the discovery of a novel SCN5A mutation- p.E428G in a strong phentoype of SQTS. The mutation leads to the loss-of-function of I NaL , which may underly the potential basis of SQTS.
[GW30-e0964]
Luo Dan, Li Fang, He Rongfang, Zhang Juan, Li Miaoling
Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiology Key Lab of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China
OBJECTIVES Fibroblasts proliferation and migration are central in atrial fibrillation (AF) promoting structure remodeling, which is strong associated with aging and Hypertension. Transient receptor potential canonical-3 channel (TRPC3) is a key mediator of cardiac fibrosis and the pathogenesis of AF. Here, we have observed the increased TRPC3 expression that induced atrial fibrosis which possibly either mediated by the aging process or related to hypertensive progression.
METHODS In this study, we measured the pathological structure remodeling by H&E staining, Masson staining and Transmission Electron Microscope (TEM). The protein expression levels of fibrotic biomakers and TRPC3 were measured by Western blotting with atrial tissues from normotensive Wistar-kyoto rats (WKY 4m-o, 4-months old), old WKY (WKY 24m-o, 24-months old), spontaueously hypertensive rat (SHR 4 m-o, 4-months old) and old SHR (SHR 24m-o, 24-months old). To illuminate the molecular mechanism of TRPC3 in atrial fibrosis of aging and SHR rats, we detected the inhibited role of TRPC3 selective blocker Ethyl-1-(4-(2,3,3-trichloroacrylamide) phenyl)-5-(trifluoromethyl) -1H-pyrazole-4-carboxylate, pyrazole 3 (Pyr3) on Angiotensin II (Ang II) induced fibrosis in neonatal rat atrial fibroblasts.
RESULTS The pathological examination showed that the Extracellular matrix (ECM) and intercellular collagen fibrils were markerly increased in aged and hypertensive rats. The proteins of atrial fibrotic biomarkers (collagen I, collagen III, transforming growth factor-β1 (TGF-β1)) were significantly upregulated in atrial tissues from WKY 24m-o group, SHR 4m-o and SHR 24m-o groups compared with WKY 4m-o group. Meanwhile, the expression level of TRPC3 was significantly upregulated in WKY 24m-o and both SHR atrial tissues compared to WKY 4m-o rats. In isolated and cultured neonatal rat atrial fibroblasts, Ang II induced the atrial fibroblast migration and proliferation, upregulated the expression levles of TRPC3 and fibrotic biomarkers. TRPC3 selected blocker Pyr3 attenuated the migration and proliferation in neonatal rat atrial fibroblasts. Furthermore, Pyr3 significantly alleviated Ang II-induced upregulation of TRPC3, Collegen I, Collegen III and TGF-β1 through the molecular mechanism of TGFβ-Smad signaling pathway. And that AT1R is involved in Ang II-induced TRPC3 upregulation.
CONCLUSIONS Hence, upregulation of TRPC3 in aging and Hypertension is involved in atrial fibrosis process. Inhibition the upregulation of TRPC3 contributes to reverse Ang II induced fibrosis. TRPC3 may be a potential therapeutic targets for preventing aging and hypertension caused fibrosis.
[GW30-e0969]
Zhenguo Ma, Qizhu Tang
Department of Cardiology, Renmin Hospital of Wuhan University
OBJECTIVES Previous studies have demonstrated that Notch1 and Notch3 protect against pressure overload-induced cardiac remodeling. However, the effect of Notch4 on cardiac remodeling remains completely unknown. Here, our study aimed to investigate the role of Notch4 in cardiac remodeling and to clarify the underlying mechanism.
METHODS Notch4 gene knockout mice were used. Cardiomyocyte-specific overexpression of the activated form of Notch4, intracellular domain (NICD), was achieved by using adeno-associated virus 9. All the mice were subjected to aortic banding to generate pressure overload-induced cardiac remodeling. Echocardiography and hemodynamics were used to assess the cardiac function. After that, hearts of mice were dissected for further pathological examination and molecular biological detection.
RESULTS Our results showed that the knockout of Notch4 markedly inhibited hypertrophic response induced by pressure overload, as indicated by the ratio of heart weight and tibia length and cross-sectional area of cardiomyocytes. Notch4 deficiency decreased ventricle wall thickness and improved cardiac function in mice with aortic banding. Notch4 deficiency also decreased the mRNA expression of brain natriuretic peptide and β-myosin heavy chain. Further detection demonstrated cardiac fibrosis was also suppressed by Notch4 deficiency. Conversely, overexpression of NICD aggravated cardiac hypertrophy and fibrosis, leading to decreased survival rate. The results of western blot revealed the protective effects of Notch4 knockout were mediated by the suppression of protein kinase B (PKB/AKT) pathway in vivo. Using neonatal rat cardiomyocytes, we found that Notch4 depletion caused a significant decrease in the cell surface area and the mRNA expression levels of hypertrophic markers, whereas NICD overexpression led to an increase in these hypertrophic phenotypes.
CONCLUSIONS These findings identified that Notch4 promoted cardiac remodeling due to its regulation of the AKT pathway.
[GW30-e0973]
Zhenguo Ma, Qizhu Tang
Department of Cardiology, Renmin Hospital of Wuhan University
OBJECTIVES Doxorubicin (DOX) is an effective anti-neoplastic drug, but its clinical application is limited by cardiovascular toxic effects. Oxidative stress, inflammation and cardiomyocyte apoptosis play critical roles in DOX-induced cardiotoxicity. Toll-like receptor 5 (TLR5) mainly expressed in immune cells and cardiac tissues. However, whether TLR5 is involved in doxorubicin-induced cardiotoxicity and its underlying mechanisms remain unclear.
METHODS Global TLR5-deficient mice and wild-type littermates were subjected to a single intraperitoneal injection of DOX (15 mg/kg) for an acute model. Body weight (BW), heart weight (HW), and tibial length (TL) were measured to reflect cardiac injury. Echocardiographic parameters including ejection fraction (EF) and fractional shortening (FS) were collected to assess heart phenotype.
RESULTS The data in our study demonstrated that DOX resulted in significant weight loss and cardiac atrophy, and these pathological alterations were blocked after TLR5 deficiency. TLR5 deficiency also improved cardiac function in mice with DOX treatment. TLR5 deficiency protected the mice from oxidative stress and apoptosis induced by DOX. TLR5 deficiency cannot affect the acute inflammatory reaction in mice with DOX. Western blotting demonstrated that the activation of p38 in hearts caused by DOX was suppressed in TLR5-deficient mice. CBLB502, an agonist of TLR5, aggravated DOX-related cardiac injury, as indicated by the decreased HW/BW, EF and FS. CBLB502 also further enhanced the phosphorylation of p38 in DOX-treated mice. TLR5 deficiency could largely improve cell viability in DOX-treated H9c2 cells. TLR5 deficiency also attenuated DOX-induced oxidative stress in cardiomyocytes.
CONCLUSIONS These findings suggested that TLR5 deficiency attenuated doxorubicin-induced cardiotoxicity in mice.
[GW30-e0975]
Min Wu 1 , Longtao Liu 2 , Longtao Liu 2
1Guang’anmen Hospital, China Academy of Chinese Medical Sciences
2Xiyuan Hospital, China Academy of Chinese Medical Sciences
OBJECTIVES Coptis Chinensis, a Chinese herbal medicine, has been widely used in traditional Chinese medicine for a long time. Berberine, the main alkaloid of Coptis Chinensis, has shown to possess extensive cardiovascular pharmacological activities. In our research, we examined the effects of Berberine on arotic atherosclerosis in ApoE–/– mice and explored whether the anti-atherosclerotic effect of Berberine is related to gut microbiota modulation.
METHODS Forty-five ApoE–/– mice, fed a high fat diet from 6 weeks of age, were randomized into three groups, model group (ApoE–/– group), Berberine in large dose group and Berberine in large dose group. Fifteen 6-week-old C57BL/6 were treated as the control group, fed a basic diet. After 36 weeks, we sacrificed the mice for various measurements.
RESULTS The results showed that treatment with Berberine significantly reduced the arotic atherosclerosis. Berberine could regulate the level of serum lipid and inflammatory factors. Compared with control group, the abundance of Lachnospiranceae increased. After treatment of Berberine with large dose, the abundance of Allbaculum raised.
CONCLUSIONS Berberine has the effects of anti-atherosclerotic and anti-inflammatory effects, which are related to alterations in gut microbiota compositions, indicating the potential therapeutic value of pharmacological approaches that may modulate the gut microbiota in treating atherosclerosis.
[GW30-e0977]
Hailong Yang, Chunping Liu, Guangning Nie, Lei Wang
The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
OBJECTIVES Danlou Tablet, which based on Zhang Zhongjing’s classical prescription Gualou Xiebai Baijiu Tang, is the representative prescription of Phlegm and Blood Stasis Co-treatment. Previous studies have proved that Danlou Tablet can reduce myocardial ischemia reperfusion injury, while its mechanism is unknown. Therefore, this study is to investigate the effect of Danlou Tablet on autophagy of myocardial cells in mice of ischemia reperfusion injury.
METHODS The mice model of myocardial ischemia reperfusion was induced by left coronary artery ligation (ligation for 30 minutes, reperfusion for 24 hours). Forty male C57BL/6J mice of 8 weeks old were pre-administered for 5 days before modeling. Then randomly divided into 4 groups, 10 in each group, which were sham group, vehicle group, Danlou Tablet group (3g×kg–1×day–1 gavaged in 5 days) and 3MA group (an autophagy inhibitor, 15 mg/kg intraperitoneal injection twice. the first day and 15 min before surgery). Cardiac function was evaluated by small animals’ echocardiography system in 24 hours after reperfusion. Triphenyl Tetrazolium Chloride (TTC) staining method was used to detect myocardial infarct size. The apoptosis of myocardial cells was investigated by TUNEL staining. The protein expression of LC3B and mTOR were analyzed by immunoblotting.
RESULTS Compared to vehicle group, the autophagy related protein expression of LC3B and mTOR were increased after treatment with Danlou Tablet, LVEF and LVFS was improved as well. In addition, the proportion of nucleus in the TUNEL staining positive area and myocardial infarct size was reduced.
CONCLUSIONS Danlou Tablet could improve the heart function of mice with ischemia reperfusion by reducing myocardial cell apoptosis. At the same time, self-degradation of cardiomyocytes was prevented, which may be associated with inhibiting the autophagy of cardiomyocytes.
[GW30-e0983]
Fuqiang Liu, Yong Zhang, Shuang Shi, Ling Zhu, Yujie Xing, Jiang Lei, Shuo Pan, Gongchang Guan, Junkui Wang
Cardiovascular Department, Shaanxi Provincial People’s Hospital
OBJECTIVES Accumulating evidence has indicated that salt sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. Our previous study showed that salt intake could induce tubular EMT and renal injury in Dahl salt-sensitive rats. Quercetin, a classic flavonoid with multiple pharmacological effects has been reported to possess therapeutic efficacy in the management and treatment of renal fibrosis. The aim of this study was to determine whether Quercetin would ameliorate salt-induced renal fibrosis and epithelial-to-mesenchymal transition.
METHODS Twenty-four male SS and consomic SS-13BN rats were randomized to a normal diet or a high-salt diet or Quercetin. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (a-SMA). The pro-fibrotic transcription factor Snail was aslo evaluated using immunohistochemistry and western blot analysis.
RESULTS After 4 weeks, dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of a-SMA in SS rats. The pro-fibrotic transcription factor Snail, a key regulator of epithelial-mesenchymal transition (EMT), was also found to be up-regulated after high salt loading. Furthermore, treatment with quercetin alleviated the decline in renal function, and the elevated expression of snail and a-SMA was inhibited by quercetin.
CONCLUSIONS Our results demonstrate the protective effects of quercetin on salt-induced renal fibrosis and epithelial-to-mesenchymal transition in Dahl salt-sensitive rats, revealing a potential therapeutic agent for salt induced renal impairment treatment.
[GW30-e0985]
Bingyan Guo, Dudafang, Qinxiaoyue, Liyongjun
The Second Hospital of Hebei Medical University
OBJECTIVES Background: NLRP3 inflammasome plays a pivotal role in the development of diabetic cardiac injury. Resveratrol, a natural phytoalexin, has anti-inflammatory properties via inhibition of oxidation, leukocyte priming, and production of inflammatory mediators. In this study, we aimed to investigate the effect of resveratrol on NLRP3 inflammasome in diabetic cardiac injury.
METHODS We used normal C57BL/6 rat to establish type 2 diabetic cardiac injury model. Cardiac structure was investigated with transmission electron microscopy and pathological examination; and gene expression of markers for oxidative stress and inflammation was detected.
RESULTS Resveratrol treatment alleviated the glucose induced cardiac pathological damage. resveratrol also inhibited the glucose-induced NLRP3, ASC, caspase-1 mRNA and protein expression, and NLRP3 inflammasome activation. Moreover, resveratrol administration not only suppressed the NF-kappaB p65 nuclear translocation, NF-kappaB activity and ROS production in the diabetic cardiac tissue. Meanwhile, resveratrol obviously induced SIRT1 mRNA and protein expression in the diabetic rats.
CONCLUSIONS We demonstrate that resveratrol had cardioprotective effects in diabetic rats. Resveratrol is a negative regulator of NLRP3 inflammasome activation through the sirt1 signaling pathway and protects cardiomyocyte against diabetic cardiac injury.
[GW30-e0989]
Bozhi Ye 1 , Yawen Weng 2 , Shuang Lin 1 , Jiahui Lin 3 , Zhouqing Huang 1 , Weijian Huang 1 , Xueli Cai 1
1Department of Cardiology, The Key Lab of Cardiovascular disease of Wenzhou, The First Affiliated Hospital of WenZhou Medical University, WenZhou, ZheJiang, P.R. China
2Department of Pediatrics, The Second School of Medicine, Wenzhou Medical University, Wen Zhou, Zhe Jiang, P.R. China
3The First School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China
OBJECTIVES Bone mesenchymal stem cells (BMSCs) are non-haematopoietic stem cells with multi-directional differentiation and self-replication that can promote angiogenesis and directly induce differentiation into various cells types, such as osteoblasts and chondrocytes. This study aimed to explore the mechanisms and effects of Vitamin D on the angiogenesis of BMSCs.
METHODS BMSCs were isolated from the femurs and tibias of rats and characterized by flow cytometry. After treatment with different concentrations of 1,25-(OH)2-VD3 (Vitamin D), Cell Counting Kit-8 (CCK-8) was used to analyse the proliferation of BMSCs. The proliferation and migration of BMSCs were measured by Transwell assays and the cell scratch test, respectively. We observed the ability of cells to form bureaucratic structures on Matrigel. Western blot was used to detect the protein expression of VEGF, MMP2 and MMP9 secreted by BMSCs under the influence of Vitamin D. Meanwhile, the effect of Vitamin D on the activity of MMP2 and MMP9 secreted by BMSCs was detected by gelatine zymography. Finally, the phosphorylation levels of key kinases in the PI3K/AKT pathways were determined by Western blot.
RESULTS Vitamin D can promote the proliferation and migration of BMSCs and the ability of BMSCs to form a bureau-like structure on Matrigel. There was a significant improvement in the protein expression level of VEGF, MMP2 and MMP9 and in the activity of MMP2 and MMP9 secreted by BMSCs treated with Vitamin D. The phosphorylation level of AKT increased with time after Vitamin D treatment, and the specific PI3K inhibitor LY294002 weakened the phosphorylation.
CONCLUSIONS Vitamin D can strengthen the ability of BMSCs to promote angiogenesis in vitro, and its mechanism may be related to activation of the PI3K/AKT signalling pathway.
[GW30-e0991]
Jinhua Huang 1 , Wuhong Zheng 2 , Enhui Yao 1
1Department of Cardiology, Fujian Medical University Union Hospital, Fujian Institute of Coronary Heart Disease
2Department of Emergency, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University
OBJECTIVES Junctophilin-2 (JP2) is the primary structural protein anchoring the sarcoplasmic reticulum (SR) to T-tubules (TTs), its required for normal excitation-contraction (E-C) coupling. This study aims to identify the effect of hyperlipidemia on the structure of transverse tubule (t-tubule) and expression of junctophilin-2 (JP-2) in mouse cardiomyocytes and to test whether miR-24 suppression can protect the hyperlipidemia-induced cardiomyocytes injury.
METHODS Cardiomyocytes (CMs) were isolated by enzyme digestion and differential adhesion method. CMs were collected and cultured with normal fatty acid or high fatty acid (0.5 mM) medium. The high fatty acid cultured CMs were then divided into two groups; one group was treated with miR-24-ASO (anti-sense oligonucleotide) and the other was treated with miR-24-MM-ASO (control scramble). After 48 hours of culture, miR-24 and JP2 expression analysis, laser confocal microscopy imaging was used to record the calcium sparks and the structure of t-tubule.
RESULTS Hyperlipidemia significantly increased the frequency of spontaneous calcium sparks and the destruction of t-tubules in ventricular myocytes. In addition, hyperlipidemia decreased the expression of JP-2 in t-tubules and miR-24 was up-regulated. The miR-24 inhibitors markedly up-regulated expression of JP-2 mRNA and protein in cardiomyocytes subjected to hyperlipidemia. The frequency of spontaneous calcium sparks were also significantly decreased by miR-24 inhibitors. Moreover, miR-24 suppression protected E-C coupling in cardiomyocytes injury by hyperlipidemia.
CONCLUSIONS Our findings show suppression of MiR-24 up-regulated JP-2 expression, and promotes hyperlipidemia-induced cardiomyocytes injury. Providing a potential strategy for hyperlipidemia-induced heart failure.
[GW30-e0992]
Yongjun Li, Yongjun Li
The Second Hospital of Hebei Medical University
OBJECTIVES This study aimed to investigate the effect of CTRP9 on high glucose-induced cardiomyocyte hypertrophy and the related mechanism.
METHODS A model of high glucose-induced cardiomyocyte hypertrophy was made in vitro. Rat cardiomyocyte were randomly divided into 5 groups: the control group, CTRP9 group, high glucose group, high glucose with CTRP9 (treatment at the same time) group, high glucose with CTRP9 (pretreatment) group. The surface area of cardiomyocyte was determined by professional Image analysis software. The protein expression of ANP, β-MHC, Beclin 1 and Atg 12 in each group was quantified by western blot method. The gene level of Beclin 1 and Atg 12 in each group was determined by real-time PCR.
RESULTS Compared to the high glucose group, the cell surface area and the protein level of ANP and β-MHC decreased significantly than that in high glucose with CTRP9 (treatment at the same time) group and in high glucose with CTRP9 (pretreatment) group, there was significant statistical difference (P<0.05). High glucose suppressed the expression of autophagy related protein. compared to the high glucose group, the gene and protein level of autophagy related protein such as Beclin 1 and Atg 12 increased significantly than that in the high glucose with CTRP9 (treatment at the same time) group and in high glucose with CTRP9 (pretreatment) group, there was significant statistical difference (P<0.05).
CONCLUSIONS CTRP9 can inhibit high glucose-induced cardiomyocyte hypertrophy, and this effect may be mediated by autophagy.
[GW30-e0995]
Can Hu 1,2 , Xin Zhang 1,2 , Qizhu Tang 1,2
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
2Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China
OBJECTIVES Pathological cardiac fibrosis is the common feature in multiple cardiovascular diseases and is associated with increased ventricular stiffness as well as impaired electrical conduction, that contributing to the occurrence of heart failure and life-threatening arrhythmias. Our previous study demonstrated that matrine could attenuate oxidative stress and cardiomyocyte apoptosis, thereby preventing doxorubicin-induced cardiac dysfunction, however, its effect in cardiac fibrosis remains unclear. Thus, the present study aimed to investigate the effect and underlying mechanism of matrine in pathological cardiac fibrosis.
METHODS Mice were subjected to aortic banding (AB) surgery or isoprenaline (ISO) injection to generate pathological cardiac fibrosis and then were exposed to matrine (200 mg/kg/day, po) or equal volume vehicle as the control. Echocardiography, hemodynamic parameters and molecular markers were used to evaluate the effect of matrine on fibrotic remodeling and cardiac dysfunction. To clarify the involvement of P38 and ribosomal protein S5 (RPS5), constitutively active P38 carried by adenovirus or small hairpin RNA against RPS5 were used. Besides, neonatal rat and human cardiac fibroblasts were cultured to assess the anti-fibrotic effect of matrine in vitro.
RESULTS We found that matrine lavage significantly attenuated AB or ISO-induced cardiac dysfunction and fibrotic remodeling in mice. Besides, we also observed that matrine treatment inhibited the proliferation, migration, collagen production and phenotypic transdifferentiation of cardiac fibroblasts. Mechanistically, matrine suppressed P38 activation, and the overexpression of constitutively active P38 completely abolished the protective effect of matrine in vivo and in vitro. We also demonstrated that RPS5 upregulation was responsible for matrine-mediated inhibition of P38 and fibrogenesis. More importantly, matrine was capable of ameliorating pre-existing cardiac fibrosis in mice.
CONCLUSIONS Matrine treatment attenuates cardiac fibrosis via regulating RPS5/P38 signaling in mice. Matrine might be a promising therapeutic agent for treating pathological cardiac fibrosis.
[GW30-e0996]
Fuqiang Liu, Zhiguo Tang, Yong Zhang, Shuang Shi, Ling Zhu, Yujie Xing, Jiang Lei, Shuo Pan, Gongchang Guan, Junkui Wang
Cardiovascular Department, Shaanxi Provincial People’s Hospital
OBJECTIVES Previous studies report that quercetin, an antioxidant flavonol found in apples, berries, and onions, could lowers both systolic and diastolic blood pressure in the Dahl salt-sensitive rats, However, its pharmacological effects have been rarely reported. Striatin is a scaffolding protein that plays a role in vesicular trafficking in neurons. Striatin deficiency is associated with salt sensitivity of blood pressure. The aim of this study was to determine whether Quercetin would ameliorate Striatin deficiency in Dahl salt-sensitive rats.
METHODS Twenty-four male SS and consomic SS-13BN rats were randomized to a normal diet or a high-salt diet or Quercetin. After 4 weeks, PCR amplification to detect Striatin levels of kidney and aorta vessels was performed with TaqMan gene expression assays. The protein expression of Striatin levels was evaluated using immunohistochemistry and western blot analysis.
RESULTS After 4 weeks, compared to SS-13BN rats, dietary salt intake reduced expression of Striatin levels in the kidney and aorta vessels in SS rats. Furthermore, treatment with quercetin elevated expression of Striatin levels in the kidney and aorta vessels in SS rats.
CONCLUSIONS Our results demonstrate Striatin deficiency was associated with salt sensitivity of blood pressure in Dahl rats, and revealing a potential therapeutic agent for salt sensitive hypertension treatment.
[GW30-e1002]
Yunqi Jiang, Yuhui Qiao, Aiju Tian, Zijian Li
Peking University Third Hospital
OBJECTIVES To investigate novel regulatory mechanism of myocardial infarction (MI) injury.
METHODS By microarray analysis, we found a novel signaling protein, HIP-55, associated with myocardial infarction. HIP-55 knockout mice and transgenic mice were constructed by Talent technique. Myocardial infarction model was made by ligating the anterior descending coronary artery. Myocardial infarction area was detected by Evans Blue-TTC double staining method. Apoptosis was detected by TUNEL staining. At cellular level, we performed western blot, Co-IP and GST-pull down to investigate the mechanism of HIP-55 in cell survive.
RESULTS HIP-55 is high expression in heart and increased significantly after myocardial infarction. Genetic deletion of HIP-55 increased cardiomyocyte injury after MI. Cardiac-specific overexpression of HIP-55 alleviated myocardial infarction injury after MI. HIP-55 could inhibit cardiomyocyte apoptosis after myocardial infarction. Mechanism research showed that HIP-55 inhibit HPK1 kinase and its downstream kinase JNK after myocardial infarction. Further studies showed that HIP-55 inhibits HPK1/JNK apoptosis pathway depending on the HIP-55/14-3-3 complex. After the mutation of 14-3-3 binding sites, overexpression of HIP-55 could not inhibit HPK1/JNK pathway. In addition, after the mutation of 14-3-3 binding sites, overexpression of HIP-55 could neither reduce the infarct size after myocardial infarction nor inhibit cardiomyocyte apoptosis after ischemia-hypoxia. We further generated cardiac-specific overexpression of HIP-55 wide-type mouse (interact with 14-3-3) and HIP-55 mutant mouse (not interact with 14-3-3), results showed that HIP-55 wide-type mouse, but not mutant mouse protects against myocardial infarction injury.
CONCLUSIONS The expression of HIP-55 increased significantly after myocardial infarction. Increased HIP-55 recruited 14-3-3 protein to form complex to inhibit HPK1 and its downstream JNK apoptosis signaling pathway, which led to the protective role in myocardial infarction.
[GW30-e1005]
Xin Zhang 1,2 , Can Hu 1,2 , Qizhu Tang 1,2
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
2Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China
OBJECTIVES Cardiac fibrosis is the key pathophysiological process for cardiovascular disease progressing to heart failure, which is essentially characterized by excessive proliferation, activation and phenotypic transformation of cardiac fibroblasts, resulting in collagen overproduction and cardiac dysfunction. In addition to fibroblasts, there are also a large number of endothelial cells in cardiac tissues. Previous studies have shown that endothelial cells play an important role in regulating fibroblasts proliferation, activation and phenotypic transformation. ETS-related gene (ERG) is a member of the ETS transcription factor family. It is the most expressed ETS transcription factor in mature endothelial cells and plays an indispensable role in endothelial cell differentiation and vascular maturity. At present, most of the researches on ERG are confined to the field of development and tumor, whereas its role and mechanisms in cardiac fibrosis have not yet been clarified. Therefore, the purpose of this study is to explore the role and possible mechanisms of ERG in cardiac fibrosis.
METHODS Mice were exposed to an intramyocardial injection of adenovirus carrying small hairpin RNA against Erg to knock down the endogenous ERG expression, collagen deposition, fibrotic markers and fibrosis-related signal pathways were detected to initially verify the role of ERG in cardiac fibrosis. Next, adult mouse or neonatal rat cardiac fibroblasts as well as human umbilical vein endothelial cells were isolated and cultured to further clarify the role of ERG in vitro. And the possible mechanisms of endothelial ERG in regulating fibroblasts proliferation, activation and phenotypic transformation were studied by using endothelial cells-derived condition medium (ConM). Finally, endothelin-1 (ET-1) neutralizing antibody and its receptor blocker were used to determine the role of ET-1 in ERG-mediated paracrine regulation between endothelial cells and fibroblasts in vivo and in vitro.
RESULTS ERG was mainly expressed in endothelial cells of the adult mouse heart, and its protein level was significantly reduced during cardiac fibrosis. Inhibiting endogenous ERG resulted in the occurrence of spontaneous fibrotic remodeling and cardiac dysfunction, accompanied by the activation of various fibrosis-related signal pathways. ERG knockdown in neonatal rat or adult mouse cardiac fibroblasts made no alteration in α-SMA expression, and the mRNA levels of fibrotic markers were also unaffected. Supernatants from ERG deficient-endothelial cells were collected as the ConM for neonatal rat cardiac fibroblasts. Comparing with the control group ConM, ERG-deficient ConM promoted the proliferation, activation and phenotypic transformation of cardiac fibroblasts, as well as the activation of fibrosis-related signal pathways. Besides, we found that ERG knockdown increased the mRNA level of ET-1 in endothelial cells and enhanced its secretion to the ConM. Application of ET-1 neutralizing antibody and its receptor blocker significantly inhibited the proliferation, activation and phenotypic transformation of cardiac fibroblasts, thereby improving ERG knockdown-induced fibrotic remodeling and cardiac dysfunction.
CONCLUSIONS ERG knockdown leads to increased synthesis and secretion of ET-1, which then promotes the proliferation, activation and collagen production of cardiac fibroblasts through a paracrine manner, triggering the occurrence of fibrotic remodeling and cardiac dysfunction.
[GW30-e1008]
Yujie Xing, Shunming Zhu, Meijuan Ma, Junkui Wang
Shannxi Provincial People’s Hospital
OBJECTIVES To explore the effect of the differentiation of bone marrow mesenchymal stem cells (BMMSCs) into cardiomyocyte-like cells by inducing with 5-azacytidine (5-aza) and angiotensin II (Ang II).
METHODS BMMSCs were isolated from bone marrow of Sprague-Dawley mouse by density gradient centrifugation. The third passage cells were divided into four groups: 5-aza combined with Ang II group (0.1 μmol/L and 10 μmol/L), 5-aza group (10 μmol/L), Ang II group (0.1 μmol/L) and control group. After induction for 24 h, the medium was changed to complete culture medium without any inductor and the cells were culture for 4 weeks. The phase contrast microscope was used to observe the morphological changes. The methyl thiazolyl tetrazolium (MTT) assay was used to observe the ability of cell proliferation. The immunofluorescence staining was used to identify the cardiomyogenic cells. The flow cytometer was used to examine the cell differentiation ratio. The transmission electron microscope was used to view the ultrastructure of the induced cells.
RESULTS The primary BMMSCs formed cell colonies at 14 days. The passaged cells were larger than those of primary culture. After induction, the cells presented long spindle, aligned in parallel and formed “muscle island”-like structure. MTT assay showed that the cell proliferation in 5-aza combined with Ang II group was higher than that of in Ang II group or 5-aza group. The expression of specific protein of cardiac troponin I (cTnI) in induced BMMSCs was positive. Flow cytometer showed that the cell differentiation ratio in 5-aza combined with Ang II group, 5-aza group and Ang II group were respectively (30.0±1.7) %, (24.6±1.9) % and (25.3±2.2) %, demonstrating that the cell differentiation ratio in 5-aza combined with Ang II group was higher than that of in 5-aza group or Ang II group (P>0.05). Transmission electron microscopy showed that the induced cells had myofilaments, Z line-like substances.
CONCLUSIONS 5-aza combined with Ang II can promote the differentiation of BMMSCs into cardiomyocytes.
[GW30-e1019]
Wenhao Liu 1,2 , Qian Chen 1,2 , Haifeng Zhang 1,2 , Yangxin Chen 1,2 , Jingfeng Wang 1,2
1Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University
2Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology
OBJECTIVES The frequency of rs9903609 fat mass and obesity associated gene (FTO) variant is about 12% in Chinese population, which means about 156 million Chinese may influence by this FTO variant. There are some studies reveal that this FTO variant is associated with a higher risk of CVD, but much more studies show a negative result. Here we aim to figure out this paradoxical clinical phenomenon by biological methods.
METHODS In vivo, expressions of FTO, macrophage marker CD68 and smooth muscle cell marker SM22-α in arteries of normal diet and high fat diet ApoE–/– mice were detected by Immunohistochemical staining, Immunofluorescence staining, western blot and Q-PCR. Human atherosclerosis arteries surgery tissues were detected by Immunohistochemical staining. In vitro, relations between stimulating concentrations of ox-LDL, lipid up-take related proteins and FTO expression in macrophages and smooth muscle cells were measured by western blot and Q-PCR. Moreover, Lentivirus and small interference-RNA technique were used to perform FTO gene function gain and loss assay in vitro.
RESULTS In atherosclerosis mice model, expressions of FTO were up-regulated in aortic artery of high fat diet ApoE–/– mice by Immunohistochemical staining. Immunofluorescence staining showed that FTO expression was down-regulated in macrophage, but up-regulated in smooth muscle cells. As for human atherosclerosis arteries surgery tissues, FTO expressions were up-regulated compared with non-atherosclerosis artery, same with mice model. In vitro, FTO expressions were up-regulated when ox-LDL concentration was increased in smooth muscle cells. However, it was down-regulated in macrophage when ox-LDL concentration was increased. Moreover, function gain assay and function loss assay showed that FTO promotes lipid accumulation and up-regulates lipid up-take related proteins in smooth muscle cells, but performed opposite effects in macrophage.
CONCLUSIONS FTO may play a paradoxical effect on macrophages and vascular smooth muscle cells during ox-LDL stimulation. This phenomenon may help to explain that FTO variant is not always be a risk factor of CVD in different study populations.
[GW30-e1021]
Chen Liu 1,2,3 , Qing Qing Wu 1,2,3 , Zhulan Cai 1,2,3 , Saiyang Xie 1,2,3 , Mingxia Duan 1,2,3 , Qingwen Xie 1,2,3 , Yuan Yuan 1,2,3 , Wei Deng 1,2,3 , Qizhu Tang 1,2,3
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China
2Cardiovascular Research Institute of Wuhan University, Wuhan 430060, PR China
3Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China
OBJECTIVES To explored the role of zingerone in cardiac remodelling.
METHODS Mice were subjected to aortic banding (AB) or sham surgery and then received intragastric administration of zingerone or saline for 25 days. In vitro, neonatal rat cardiomyocytes (NRCMs) were treated with zingerone (50 and 250 μM) when challenged with phenylephrine (PE).
RESULTS We observed that zingerone effectively suppressed cardiac hypertrophy, fibrosis, oxidative stress and inflammation. Mechanistically, Zingerone enhanced the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) activation via increasing the phosphorylation of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production. Additionally, we used Nrf2-knockout (KO) and eNOS-KO mice, and found that Nrf2 or eNOS deficiency counteracts these cardioprotective effects of zingerone in vivo.
CONCLUSIONS we concluded that zingerone may be a potent treatment for cardiac remodelling that suppresses oxidative stress via the eNOS/Nrf2 pathway.
[GW30-e1025]
Yujie Xing, Zhongwei Liu, Junkui Wang
Shannxi Provincial People’s Hospital
OBJECTIVES To explore the effect of down-regulation of microRNA-374 on the cardiac function of rats with selenium deficiency.
METHODS Sixty SD rats were randomly divided into control group, selenium deficiency group and down-regulation of microRNA-374 group, with 20 rats in each group. Rats in the control group were fed with standard diet. Rats in the selenium deficiency group were fed with low selenium diet. Rats in the down-regulation of microRNA-374 group were fed with low selenium diet and then injected interference with microRNA-374 by adeno-associated virus 9 through caudal vein. The rats were fed for 17 weeks. Then the blood selenium and BNP level of the rats were measured. The cardiac function of the rats was detected by echocardiography. The expression of microRNA-374 was detected by Real-time Quantitative PCR. The expression level of c-myc and caspase-3 protein were detected by Western Blotting.
RESULTS The blood selenium levels in selenium deficiency group and down-regulation of microRNA-374 group were significantly lower than that of control group. BNP level of down-regulation of microRNA-374 group was lower than that of selenium deficiency group. The echocardiography displayed that the cardiac function of the down-regulation of microRNA-374 group was higher than that of the selenium deficiency group. The expression of microRNA-374 in down-regulation of microRNA-374 group was lower than that of selenium deficiency group. Western Blot displayed lower expression of c-myc and caspase-3 in down-regulation of microRNA-374 group than that of selenium deficiency group.
CONCLUSIONS The down-regulation of microRNA-374 by adeno--associated virus 9 can improve the cardiac function of rats with selenium deficiency.
[GW30-e1026]
Chao Zhou 1 , Quan He 1 , Qiao Liu 1 , Tingting Zeng 1 , Xiongzhong Ruan 3,4 , Nan Ouyang 2
1Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China
2Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China
3John Moorhead Research Laboratory, Centre for Nephrology, University College London (UCL) Medical School, Royal Free Campus, London NW32PF, United Kingdom
4Centre for Lipid Research and Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, 400016 Chongqing, PR. China
OBJECTIVES Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in chronic kidney disease (CKD) patients. Compelling evidence indicates that hyperphosphatemia is linked to cholesterol metabolism and ASCVD. However, the molecular mechanisms underlying hyperphosphatemia accelerated atherosclerosis is unknown.
METHODS We performed a cross-sectional study to examine the correlation between hyperphosphatemia and ASCVD risk in Chinese CKD population. We also produced hyperphosphatemic ApoE–/– mice model with a high-phosphate diet. Finally, we cultured human primary vascular smooth muscle cells.
RESULTS Serum phosphorus levels in Chinese CKD patients correlated positively with increased ASCVD risk. The atheroma burden in the aorta of hyperphosphatemic ApoE–/– mice was increased when compared with control while the severity of atheroma lesion paralleled the serum phosphorus level. Hyperphosphatemia elevated SCAP protein levels and the expression of its downstream signaling molecules in the arteries of ApoE–/– mice. In vitro, excessive phosphate increased smooth muscle cell SCAP protein levels and HMGCR expression in a dose and time-dependent manner, aggravating intracellular cholesterol accumulation, which was quenched by phosphonoformic acid (PFA) or SCAP and SREBP2 silencing. Excessive phosphate enhanced a complex-type conversion of SCAP N-glycans, delaying SCAP degradation, which facilitated transactivation of SREBP2. Excessive phosphate raised the activity of α-mannosidase 2A1 and 2A2. Blocking phosphorus uptake by PFA or enzyme gene silencing abrogated the effects of excessive phosphate on α-mannosidase II activity, SCAP degradation, HMGCR expression, and therefore intracellular cholesterol accumulation. Elevated α-mannosidase II activity was observed in the artery of both ApoE–/– mice and uremic patients with hyperphosphatemia.
CONCLUSIONS Hyperphosphatemia increased the activity of both α-mannosidase 2A1 and 2A2, which promoted complex-type conversion of SCAP N-glycans. SCAP with complex glycans degrades slower and over-activates SREBP2, leading to increased de-novo cholesterol synthesis, and thereby intracellular cholesterol accumulation and atherosclerotic foam cell formation, which explains why hyperphosphatemia accelerates atherosclerosis in CKD population.
[GW30-e1035]
Yingyu Xie 1 , Zihan Fang 1 , Mingyang Wang 1 , Yanan Wang 1 , Yuanfang Li 1 , Junping Zhang 2
1Tianjin University of Traditional Chinese Medicine
2First Teaching Hospital, Tianjin University of Traditional Chinese Medicine
OBJECTIVES To observe the effect of Yiqi Huoxue recipe on heart failure, and to explore the mechanism and target of action based on the change of mitochondrial function.
METHODS The left coronary artery ligator model of SD rats was divided into false operation group, model group, low, middle and high dose groups of Yiqi Huoxue recipe, and the intervention was given for 8 weeks. The cardiac structure and cardiac function, NT-proBNP level, HE, Masson staining, myocardial inflammation, fibrosis and other pathological changes were observed, and the effect of Yiqi Huoxue recipe on heart failure model after myocardial infarction in SD rats was discussed. The structure and morphology of mitochondria in myocardial tissue were observed by transmission electron microscope, and the function of mitochondria was detected. RT-PCR and Western Blotting methods were used to observe the structure and morphology of mitochondria. The expression of autophagy proteins LC3B and PINK1, Parkin genes and proteins were detected by mtDNA fusion, mitotic gene and protein levels.
RESULTS Yiqi Huoxue recipe could significantly improve cardiac contractile function, improve EF and FS, to decrease serum NT-proBNP level, reduce myocardial fiber thickening, breakage and arrangement disorder, and reduce myocardial fibrosis and collagen formation. Yiqi Huoxue recipe can significantly improve the disorder of myocardial mitochondria arrangement, swelling of mitochondria and rupture of mitochondrial crest in rats with heart failure, increase the membrane potential of myocardial mitochondria, decrease the opening degree of mPTP, increase the content of ATP in myocardial energy metabolism, decrease the content of ROS and the further damage of mitochondria caused by myocardial energy metabolism in rats with heart failure. Yiqi Huoxue recipe. It can up-regulate the expression of Mfn1, Mfn2 and Opa1, down-regulate the expression of Drp1, Fis, improve the balance of fusion and division of mitochondria, and up-regulate the expression of LC3B, PINK1, Parkin and regulate the autophagy of mitochondria.
CONCLUSIONS The method of invigorating qi and activating blood circulation can maintain the stability of mitochondrial kinetics, improve the “energy hunger” and “oxidative stress”, improve the state of cardiomyocytes and delay the progress of myocardial energy metabolism and remodeling by regulating the classical pathway of mitochondrial autophagy.
[GW30-e1041]
Menglong Wang, Jishou Zhang, Jun Wan
Department of Cardiology, Renmin Hospital of Wuhan University
OBJECTIVES It has been demonstrated that increased inflammation is the key mechanism that mediates sepsis induced cardiac injury. The resolution of inflammation induced by specialized pro-resolving mediators (SPMs) can attenuate the severity of many inflammatory related diseases. However, the protective role of SPMs in sepsis induced cardiac injury remains unclear.
METHODS Resolvin D1 (RvD1), a member of SPMs, was used to evaluate the protective effects of SPMs in sepsis induced cardiac injury. The mice were randomly divided into three groups: Control group, LPS group and RvD1+LPS group (RvD1 group). LPS (10 mg/kg, i.p.) was used to induce the sepsis induced cardiac injury model. RvD1 (5 μg/kg, i.p.) was injected 30 min before LPS injection. Echocardiography was applied to evaluate the cardiac function 6 h after LPS injection. Then the mice were sacrificed and the heart tissue were harvested for biological experiments.
RESULTS LPS administration significantly deteriorated cardiac contractile function, as evidenced by the decreased left ventricular ejection fraction, which was significantly attenuated by RvD1 injection. TUNEL staining showed that LPS injection results in myocytes apoptosis, while RvD1 injection markedly attenuated the severity of myocytes apoptosis. Increased inflammatory response was found in the heart after LPS injection, as evidenced by the increased expression of inflammatory cytokines and increased infiltration of inflammatory cells in the heart. While these inflammatory responses were significantly attenuated by RvD1injection. In addition, the activated NK-κB signaling and MAPKs signaling induced by LPS injection were significantly attenuated by RvD1 injection.
CONCLUSIONS RvD1 can protect the heart against LPS induced cardiac injuries through attenuating the inflammatory response, highlighting the role of inflammation resolution as a potential therapeutic target in sepsis-induced cardiac injury.
[GW30-e1043]
Sixu Chen, Yangxin Chen
Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
OBJECTIVES Long non-coding RNAs (lncRNAs) were characterized as one of the key causes of cardiovascular diseases. However, our understanding of the importance of lncRNAs in cardiac fibrosis is limited. Here, we aims to identify the role of a novel lncRNA, known as linc00312, in cardiac fibrosis.
METHODS Global lncRNA profiling revealed that linc00312 was upregulated in cardiac fibroblasts (CFs) stimulated by TGF-beta 1. In vitro, we identified the function of linc00312 by loss-of-function approaches. Modified antisense oligonucleotides (ASOs) was used to deplete linc00312 in both the nucleus and cytoplasm. Western blotting was used to detect the expression level of collagen 1,α-SMA and CTGF. Additionally, Cell Counting Kit-8 (CCK-8) and EdU assays were performed to assess the proliferation of CFs.
RESULTS The expression of linc00312 was markedly upregualted in CFs treated with TGF-beta1. Knockdown of linc00312 in CFs inhibited the expression of collagen 1,α-SMA and CTGF, as well as suppressed the proliferation of CFs.
CONCLUSIONS Together, our findings uncover a critical role for linc00312 in the activation of CFs, which may be a new player in the development of cardiac fibrosis, and offer a new target for the prevention of cardiac remodeling.
[GW30-e1055]
Guohua Ni 1 , Meifang Chen 2
1The First Affiliated Hospital of Xinjiang Medical University
2Xiangya Hospital of Central South University
OBJECTIVES Asymmetric dimethylarginine (ADMA), a methylated amino acid derived from L-arginine, is inhibits the production of nitric oxide (NO) synthesis in vivo. It has been shown that plasma ADMA level is significantly elevated in patients with cardiovascular disorders associated with reduction of nitric oxide (NO) synthesis. Exogenous ADMA has been found to stimulate the proliferation of VSMC in a time and concentration-dependent manner as a competitive inhibitor of NO synthase. Profilin-1, a small actin-binding protein, has been documented to be involved in endothelial injury and the proliferation of vascular smooth muscle cells (VSMCs) in hypertension. It has been shown that the knockdown of profilin-1 was protective against endothelial dysfunction in the cultured aortic endothelial cells. Profilin-1 activates hypertrophic signaling cascades which contributes to vascular hypertrophy and hypertension. To investigate the relationship between ADMA and profilin-1 in hypertensive individuals and in cultured VSMCs.
METHODS Twelve male spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs) were used four the investigation. Rats were randomly assigned to three groups (n=8). L-Losartan group, SHR were treated with losartan (15 mg/kg/day) orally for 8 weeks. H-Losartan group, SHR were treated with losartan (30 mg/kg/day) orally for 8 weeks. WKYs (n=8) and SHR were treated with saline (1 mL/kg) orally for 8 weeks. Systolic blood pressure (SBP) was measured by tail-cuff sphygmomanometer. RASMCs were treated with different concentrations of ADMA as indicated for 24 h or 30 μM ADMA for different periods of time. RASMCs were transfected with profilin-1 shRNA to interrupt expression of profilin-1 protein. profilin-1 expression in RASMCs was tested through real time-PCR and western blot analysis respectively. RASMCs were treated with ADMA, pretreatment with AG490 (5×10–5 M) or rapamycin (10–8 M) were used. The level and expression of profilin-1 in RASMCs were tested by real time-PCR and Western blot analysis respectively. Cell proliferation was measured via flow cytometry analysis and MTT assay.
RESULTS Compared with healthy subjects, the levels of ADMA, profilin-1, vWF, interleukin-8 (IL-8) and tumor necrosis factor (TNF-α) were markedly elevated and the levels of nitric oxide (NO) were significantly decreased in hypertensive individuals. ADMA-induced protein expression of profilin-1 in RASMCs in a concentration- and time-dependent manner. Moreover, ADMA induced proliferation of RASCMs in a concentration- and time-dependent manner, which was in keeping with previous study. Profilin-1 siRNA knocked down both profilin-1 mRNA and protein levels in RASCMs successfully. Furthermore, compared with negative group, the stimulation of cell proliferation induced by ADMA (30 μM, 24 h) was blunted profilin-1 siRNA with a remarkable decline in the formazan absorbance and the proportion of cells in the S+G2/M phase of RASCMs. Profilin-1 shRNA successfully declined profilin-1 mRNA and protein expression. Furthermore, pretreatment with AG490 (5×10–5 M) or rapamycin (10–8 M) suppressed ADMA-mediated profilin-1expression and RASMCs proliferation determined by MTT and flow cytometry. Rapamycin inhibited the proliferation of RASMCs. ADMA-induced proliferation of RASMCs and profilin-1 expression were inhibited by blockade of JAK2/STAT3 pathway.
CONCLUSIONS Profilin-1 may be involved in ADMA-mediated vascular lesion in hypertension.
[GW30-e1057]
Thach Nguyen 1,2 , Nguyen Nhat Bao Anh 1 , Thi Truc Anh Nguyen 2 , Duy Duc Nguyen 2 , Tarneem Darwish 3 , Gianluca Rigatelli 4
1Tan Tao University, School of Medicine, Long An, Vietnam
2Methodist Hospital, Merrillville, IN, USA
3UCLA David Geffen School of Medicine, Los Angeles, CA, USA
4Rovigo General Hospital, Rovigo, Italy
OBJECTIVES Coronary injuries are hypothesized to be caused by the cavitation phenomenon (explosion of air bubbles) which is seen frequently in domestic or industrial pipes. Following hydraulics principle, with distal negative suctioning in diastole, if the coronary dynamic pressure decreases below the vapor pressure (VP) most likely of nitrogen in the blood, bubbles will form. They explode when the coronary dynamic pressure recovers>the VP during systole. These explosions create jet waves weakening and rupturing the cap of the plaque, triggering acute coronary syndrome (ACS). If because of many reasons, there was only laminar flow, without collision between antegrade and retrograde flow, could the plaques appear?
METHODS Angiograms of patient with stable angina having mild to moderate lesions were selected. The comparisons were the flow between the arteries with and without lesion. (Figure 1A (baseline) and B (flow) The left coronary arteries were recorded in the right anterior oblique caudal view and the right coronary artery in the left anterior oblique view (at 15 frames per second) Then the angiograms were viewed off line frame by frame. The first frame was the angiogram of an artery completely filled with contrast. The following frames showed the blood moving in, seen in white. The flow could be LAMINAR, TURBULENT (mixing of blood in white and contrast in black) (Figure 2A and B) or RETROGRADE (black column traveling backward). The turbulent flow reflects the collision between antegrade and retrograde flow. The LOCATION and the length in TIME of laminar, retrograde and mainly turbulent flow were recorded. The flow of the arteries without lesions was compared with the flow of the arteries with lesion.
RESULTS The results of 50 angiograms with stable CAD showed that after being laminar (85%) at the beginning of diastole, the flow became turbulent with diffuse mixing of black (contrast) and white (blood) at the MID SEGMENT of the LAD, LCX or RCA. This observation matched with the location of 82% of plaques. The length of the time of retrograde flow lasted more than 30 frames encompassing 2 systoles.
CONCLUSIONS This is the first time, the matching of location of plaques and turbulent flow representing the collision between antegrade flow in diastole and retrograde flow in systole was confirmed. These results may help to find the precise measures preventing the genesis of coronary artery disease.
[GW30-e1065]
Syed Abrar Ahmad 1 , Chandrakant Chavan 2 , Rajesh Badani 3 , Varsha Wankhade 1
1Department of Zoology, Savitribai Phule Pune University, Pune
2Department of Cardiology, Bharati Hospital, Pune
3Department of Cardiology, Aditya Birla Hospital, Pune
OBJECTIVES Mutations in MYL2 and MYL3 gene are present in <1% of hypertrophic cardiomyopathy and the phenotypic expression may vary with respect to the mutation. Objective of the present study is to investigate the genetic variations in MYL2 and MYL3 genes in hypertrophic cardiomyopathy patients of Indian origin.
METHODS Institutional Human Ethics Committee Savitribai Phule Pune University and Bharti Hospital, Pune approved the present study protocol (DCG1 Reg. no. ECR518). HCM patients were recruited from Cath lab of Bharti Hospital, Pune. 2-D echocardiography and ECG were performed by cardiologists. HCM was determined on the basis of size of interventricular septum (12 mm and above). DNA was extracted by phenol: chloroform: isoamylalchol and PCR optimization was done for all the exons. SSCP was done for study of mutations and mutations were confirmed by Sanger sequencing.
RESULTS Study of all the exons of MYL2 revealed a C>T transition (rs2233260) which is of intron variant at g.7528 located in exon 07 of MYL2 gene. SSCP analysis shows a band shift in exon 7 of proband 16 and no band shift was observed in control and other HCM positive samples. Mutant shows less free energy (–116 Kcal/mol) as compared to control (–118.4 Kcal/mol). This change in free energy results in less stability of mutant as compared to control. Screening of all the exons of MYL3 gene by SSCP technique reveals a band shift in proband 06 of exon 03. Samples were forwarded for Sanger sequencing and bi-directional sequencing reveals a G>C transversion at chromosomal position 46902336. This polymorphism is of “novel status” as confirmed on dbSNP, 1000 genomes and ExAC Browser.
CONCLUSIONS Genotypic variations in MYL2 and MYL3 genes show an effect on phenotypic expression in the probands such as Slit like left ventricular cavity, LV cavity obliteration during systole, LV diastolic dysfunction, sclerotic aortic valve, trivial aortic regurgitation, Minimal and tricuspid mitral regurgitation, Mild pulmonary hypertension, etc.
[GW30-e1068]
Xiaoxiao Zhao 1 , Like Guan 2 , Kyung Hye Lee 3 , Weon Kim 3
1Taizhou Hospital, Linhai, zhejiang, China
2Yanbian university hospital, Jilin, China
3Kyung Hee University Medical Center Hospital Center Cardiological Lab, Souel, Korea
OBJECTIVES The critical mechanism of doxorubicin (DOX) mediated cardiotoxicity has been previously attributed to a theory of “iron and ROS”. Recent study reports which associated with inhibition of autophagic degradation and mitochondrial respiration defection, what’s more, defected respiratory chain could inhibit lysosomal hydrolysis. The present study investigates the effect of mitochondrial ferritin (MtFt), a mitochondrial iron-storage protein, on autophagosomes formation in DOX treated cardiomyocytes.
METHODS H9c2 cardiomyoblasts were treated with DOX (0.5–10 μM), with or without pre-treated 10 μM Bay 60–2770, an activator of oxidized and deactivated soluble guanylate cyclase (sGC), which up-regulated the level of MtFt expression significantly in our previous DOX rats model and attenuated DOX induced cardiomyopathy. Cell viability and DCFH-DA were measured. We constructed MtFt knock down (MtFt-KD) cells by using siRNA, subsequently did Cyto-ID autophagy detection. Also, MitoSOX RED and TMRE fluorescence under DOX exposure were examined. Proteins expression levels were examined by western blot analysis.
RESULTS DOX induced mitochondrial ROS increasement significantly, and many autophagosomes formation. DOX decreased TMRE fluorescence in H9c2 cells, induced mitochondrial membrane potential loss. High level MtFt expression associated with decreased intracellular ROS and mitochondrial ROS, and increased TMRE fluorescence with more abundant autophagosomes. But there’re no significant on the levels of LC3 II, LC3 I, Becline1 and P62 expression level except for significantly increased autophay-related protein 5 (ATG5). However, siMtFt induced decrease of autophagosomes in DOX H9c2 cells significantly.
CONCLUSIONS MtFt participated in autophagosomes formation. MtFt could protect mitochondrial respiration against DOX cardiotoxicity and improve autophagic degradation process potentially.
TRANSLATIONAL RESEARCH OF CARDIOVASCULAR DISEASE
[GW30-e0025]
Xianglan Liu 1,2 , Guosheng Fu 1 , Jian Wu 2 , Yong Sun 2 , Bo Yu 2
1Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
2Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
OBJECTIVES The long non-coding RNA antisense non-coding RNA in the INK4 locus (ANRIL) plays a critical role in atherosclerosis development. However, the precise effect of ANRIL on endothelial dysfunction remains unclear. In this study, we investigated the expression of ANRIL in patients with coronary artery disease (CAD) and the regulatory influence of ANRIL on the proliferation, apoptosis, inflammatory activation and tube formation of human umbilical vein endothelial cells (HUVECs) and elucidated the underlying molecular mechanism.
METHODS In this study, 111 CAD patients were included and detected the expression of ANRIL in coronary sinus blood plasma. We analysis the correction between ANRIL and endothelial dysfunction markers. Downregulation the expression of ANRIL in HUVECs and examine the role of ANRIL in regulating endothelial endothelial dysfunction which participates in AS. We also elucidated the underlying molecular mechanism.
RESULTS Levels of ANRIL were elevated in acute coronary syndrome patients. The expression of ANRIL is associate with inflammation cytokines MCP-1 and IL-10 which secreted by endothelial dysfunction. Knockdown of ANRIL significantly promotion the proliferation and tube formation, inhibited of inflammatory activation and apoptosis of HUVECs, significantly increased the levels of TGF-βR1 and p-Smad signalling pathway members and enhanced the expression of let-7b. ANRIL-mediated inhibition of let-7b regulates HUVEC dysfunction by targeting the TGF-βR1 signalling pathway.
CONCLUSIONS We investigated the expression of ANRIL in ACS patients and identified a crucial role of ANRIL in regulating endothelial dysfunction through targeting let-7b-TGFβR1 signalling pathway. This study highlights a new therapeutic strategy for preventing endothelial dysfunction associated with cardiovascular disease.
[GW30-e0040]
Changlong Zheng, Yongmei Fu, Xiaoqin Chen, Yanling Li, Yongmei Fu
Department of Emergency, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
OBJECTIVES Sarcoplasmic reticulum Ca2-ATPase 2a (SERCA2a) modulates calcium homeostasis in vascular smooth muscle cells, which is downregulated in pulmonary artery smooth muscle cells isolated from in pulmonary arterial hypertension (PAH) patients and animal models of PAH. The purpose of the study was to evaluate the effects of overexpression of SERCA2a on hypoxia-induced PAH in rats.
METHODS Forty Sprague-Dawley rats weighing 250 to 300 g were randomly divided into normal control (control) group, hypoxia (hypoxia) group, hypoxia+AAV-GFP (hypoxia+GFP) group and hypoxia+AAV-SERCA2a (hypoxia+SERCA2a) group. Adeno-associated virus (AAV-GFP or AAV-SERCA2a) was delivered intratracheally via tracheal catheter in a hypoxia-induced PAH model. The right ventricular systolic pressure (RVSP) and the right ventricular hypertrophy index (RVHI) were detected. The lung tissue sections were stained with van Geison staining. Percentage of wall thickness (WT%) and wall area (WA%) of pulmonary arterioles was measured. Right ventricular wall thickness (RVWT), right ventricular internal diameter (RVID), cardiac output (CO) and pulmonary artery acceleration time (PAAT) were measured by transthoracic echocardiography. The expression of SERCA2a was detected by western blotting.
RESULTS SERCA2a expression was signifcantly decreased in the hypoxia treated rats in comparison with the controls. RVSP and RVHI in the hypoxia group and hypoxia+GFP group were significantly elevated compared with those in the control group. However, overexpression of SERCA2a significantly inhibited the elevation of RVSP and RVHI. Compared with the control group, these parameters of WT%, WA%, RVWT and RVID were significantly increased while CO and PAAT were significantly decreased in the hypoxia and hypoxia+GFP group. Gene transfer of SERCA2a obviously decreased WT%, WA%, RVWT and RVID, restored CO and PAAT to nearly normal level compared with the hypoxia+GFP group.
CONCLUSIONS Our data suggested that overexpression of SERCA2a attenuated pulmonary artery pressure and improves heart function in hypoxia-induced PAH by alleviating lung vascular and right ventricular remodeling.
[GW30-e0229]
Lily Chen
The China-Japan Union Hospital of Jilin University
OBJECTIVES FORS blood group system, which expresses Fossman antigen on the surface of red blood cells, is newly discovered by human, and its coding gene in human is GBGT1. The mutation c.887G>a [p.arg296gln] in A few ABO subgroup members of does allow FS antigen to be expressed on the surface of red blood cells. However, in recent years, we have also found that most human erythrocytes have negative Fossman antigen expression, and single nucleotide mutations such as c.688G>a, c.887A>G and c.363C>A can explain this conclusion. In addition, our understanding of the function of GBGT1 is limited, so we did this study.
METHODS We compared the expression levels of blood lipidemia and GBGT1 in the peripheral blood of 89 patients with acute myocardial infarction and 89 patients with stable angina pectoris who had no vascular stenosis from May 2016 to October 2016. Meanwhile, gene transfection technology was applied to set the experimental group with GBGT1 gene and the control group with negative vector to compare the triglyceride and cholesterol levels of the two groups. In addition, PT-PCR experiments were conducted to observe whether the experimental group had an effect on the expression of lipid-metabolism-related genes, such as HMGCR and LDLR etc.
RESULTS Clinical experiments showed that the expression level of GBGT1 mRNA in the myocardial infarction group was significantly higher than that in the stable angina pectoris group, and the expression level was represented by, which were 3.180×10–3 (2.613×10–3, 4.613×10–3) and 2.794×10–3 (1.708×10–3, 4.771×10–3), respectively, with statistically significant differences. At the cellular level, the triglyceride concentration in the GBGT1 group was higher than that in the negative control group, 2.543×10–3±0.037×10–3, 2.044×10–3±0.017×10–3, respectively. Rt-PCR found that the mRNA levels of SREBP1 and SCAP in GBGT1 group were significantly increased.
CONCLUSIONS GBGT1 gene may affect lipid metabolism by increasing the expressions of SREBP1 and SCAP, and serve as one of the molecular markers for identifying coronary heart disease.
[GW30-e0245]
Xiaoqun Wang, Chang Li, Jiawei Chen, Zhuhui Liu, Ying Shen, Ruiyan Zhang, Weifeng Shen, Lin Lu, Xiaoqun Wang
Department of Cardiology, Rui Jin Hospital, Shanghai Jiao-Tong University School of Medicine
OBJECTIVES Increased transcytosis of low-density lipoprotein (LDL) across the endothelium and oxidation of LDL deposited within the subendothelial space are crucial early events in atherogenesis. C1q/TNF-related protein (CTRP) 5 is a novel secreted glycoprotein and its biological functions are largely undefined.
METHODS In this study, we analyzed CTRP5 levels in sera of patients with coronary artery disease (CAD, n=288) and non-CAD controls (n=264). In this study, we analyzed CTRP5 levels in sera of patients with coronary artery disease (CAD, n=288) and non-CAD controls (n=264). The role of CTRP5 in LDL transcytosis and oxidative modification was investigated in vivo and in vitro.
RESULTS We found CTRP5 serum levels were higher in patients with than without CAD (247.26±61.71 vs. 167.81±68.08 ng/mL, P<0.001), and were positively correlated to the number of diseased vessels (Spearman’s r=0.611, P<0.001). Increased expression of CTRP5 was detected in human coronary endarterectomy specimens as compared to non-atherosclerotic arteries. Immunofluorescence showed that CTRP5 was predominantly localized in endothelium and macrophages in human atherosclerotic lesions. In vivo and in vitro experiments demonstrated that CTRP5 promoted transcytosis of LDL across endothelial monolayers, as well as the oxidative modification of LDL in endothelial cells. Inhibition of CTRP5 with a neutralizing antibody dramatically attenuated the deposition of oxidized lipids in the aortic wall of ApoE–/– mice. Mechanistically, we found that CTRP5 up-regulated 12/15-lipoxygenase (LOX), a key enzyme in mediating LDL trafficking and oxidation, through STAT6 signaling. Genetic or pharmacological inhibition of 12/15-LOX dramatically attenuated the deposition of oxidized LDL in subendothelial space and the development of atherosclerosis.
CONCLUSIONS These data indicate that CTPR5 is a novel pro-atherogenic cytokine and promotes transcytosis and oxidation of LDL in endothelium through up-regulating 12/15-LOX.
[GW30-e0631]
Jiangning Yang, Yahor Tratsiakovich, Jiao Tong, Michaela Sundqvist, Ali Mahdi, Zhichao Zhou, MaiLis Hellenius, Eddie Weitzberg, Jon Lundberg, John Pernow
Karolinska Institutet
OBJECTIVES Existing evidences suggest that dietary nitrate improves endothelial function and ischemic tolerance via an NO-dependent mechanism. Recent data indicate that red blood cells (RBCs) are an important source of NO bioactivity that protects the heart from ischemia-reperfusion injury. It is unknown whether dietary nitrate exerts cardioprotection during myocardial ischemia-reperfusion by increasing export of RBC NO bioactivity. Objective: To investigate whether dietary nitrate protects the heart against ischemia-reperfusion injury via a mechanism mediated by RBCs.
METHODS Mice on nitrate-free chow were treated with vehicle or nitrate (1 mM) in the drinking water for 4 weeks. RBCs were collected and isolated by the end of the forth week. Patients with mild hypertension (systolic blood pressure >130, ≤159 mmHg) were randomly assigned to one of three groups after a 2-week run-in period on a diet low in nitrate: group 1 received nitrate-rich vegetables (green leafy, ∼150 g/day) plus pill with placebo salt (KCl), group 2 received low nitrate vegetables (cherry tomato, sweet corn, capsicum, carrot, ∼150 g/day) and capsules with nitrate salt (KNO3, 300 mg) and group 3 received low nitrate vegetables and placebo capsules for 5 weeks. The nitrate content of the pills and nitrate-rich vegetables were precisely matched. As a pre-specified substudy, RBCs were collected blindly from 48 subjects before (baseline) and after the 5-week treatment (follow-up). The effect of the RBCs from the mice and human subjects were investigated in isolated Langendorff-perfused mouse and rat hearts, respectively. The hearts were subjected to global ischemia (mouse hearts 25 min, rat hearts 30 min) followed by reperfusion (60 min). The RBCs were administered into the coronary circulation at the onset of ischemia with and without the soluble guanylyl cyclase (sGC) inhibitor (1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one, ODQ). Left ventricular developed pressure (LVDP) was recorded as an indicator of cardiac function.
RESULTS RBCs from nitrate-treated mice improved post-ischemic recovery of LVDP in comparison with RBCs from vehicle-treated mice. The protective effect was abolished by pre-incubation of the RBCs with the sGC inhibitor ODQ (Fig. A). By contrast, pretreatment of the isolated hearts with ODQ failed to block the protective effect of RBCs from nitrate-treated mice (Fig A) indicating that sGC in the RBC but not in the heart is critical for nitrate-induced cardiac protection. The post-ischemic recovery of rat hearts given RBCs collected from the hypertensive patients at baseline was similar in the three groups (Fig. B). Notably, post-ischemic recovery of LVDP was significantly improved by administration of RBCs from patients randomized to high nitrate vegetables or nitrate capsule compared to the group randomized to low nitrate and placebo (Fig. C). There was no difference in LVDP recovery between the groups receiving high nitrate vegetables or nitrate capsule (Fig. B). The nitrate-induced improvement in post-ischemic cardiac recovery was completely abolished by the sGC inhibitor ODQ (Fig. D), indicating that the protective effect induced by RBCs from subjects given nitrate is NO-sGC dependent.
CONCLUSIONS Dietary nitrate induces export of RBC NO activity and protects the heart against ischemia–reperfusion injury via an RBC NO-sGC pathway.
[GW30-e0826]
Yonggang Zhang 1,2 , Lan Cheng 1,2 , Yunzhang Zhangm 1,2 , GuoXing Wan 1,2 , LiHua Ji 1,2 , JinYao Zhong 1,2 , WenBin Xia 1,2 , YuQiang Cui 1,2 , HaiLun Qin 1,2 , LingYu Wang 1,2 , Piao Ouyang 1,2 , yonggang Zhang 1,2
1Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, China
2Ardiovascular Laboratory, Centre for Translational Medicine and Clinical Research, Shantou University Medical College, Shantou 515041, China
OBJECTIVES Aim: Urotensin II (UII) is a potent of vasoactive peptides. We previously found that UII was involved in diabetes cardiomyopathy. The aim of this study was to explore whether UII gene knock-out could ameliorate cardiac fibrosis in type 2 diabetic mice.
METHODS Sixteen male six-week-old UII(–/–) C57BL/6J mouse (17–20 g) and 16 age matched male wild type C57BL/6J mouse (17–20 g) were randomly divided into wild type control group (WT), wild type diabetes group (WT+DM), UII(–/–) control group and UII(–/–) diabetes group (UII–/– +DM). UII gene knockout model of mice was established with TALEN. Diabetic mice were induced by feeding high fat diet for six weeks and a one-time intraperitoneal injection of STZ (120 mg/kg), followed by an 8-week of high fat diet. Cardiac function and pathological changes, immunoreactivity of UII/UT (UII receptor), mRNA expression of TGF-β1, IL-6, TGF-βRII, CTGF and Col I, and protein expression of TGF-βRII, CD31, α-SMA were determined by echocardiography, HE staining and Sirius red staining, Real time RT-PCR, immunohistochemistry and Western blotting, respectively.
RESULTS At the 15th weekend, the WT+DM group showed significantly increases of fasting blood glucose and TG, TC and LDL-C levels, lower of Left ventricular ejection fraction and short axis shortening rate, marked myocardial disarray and fibrosis compared with the WT control group. In addition, weaker CD31 immunoreactivity while marked UII/UT, α-SMA immunoreactivity were shown in heart in WT+DM group. Compared with WT control group, the mRNA expression of TGF-β1, TGF-βRII, COLI, CTGF and the protein expression of TGF-βRII, and interstitial cell marker α-SMA were significantly increased while endothelial cell marker CD31 protein expression was significantly decreased in WT+DM group. There were no significant differences about these changes between UII–/– and WT control group except for lower of TGF-β1 and higher of cd31 mRNA expression in the UII–/– control group. Importantly, UII gene knockout can significantly decrease fasting blood glucose and the TG, TC and LDL-C levels, improve Glucose Tolerance and insulin sensitivity by glucose and insulin tolerance tests, and improve cardiac functions in diabetic mice. Compared with the WT+DM group, the degree of myocardial fibrosis in the UII–/– +DM group was significantly alleviated. The immunoreactivity of UII/UT was decreased, CD31 was increased, and the expression of α-SMA was decreased in UII–/– +DM group compared with the WT+DM group. The mRNA expression of TGF-β1, TGFβ-RII, CTGF, IL-6, and the protein expression of TGF-βRII and α-SMA were significantly lower while CD31 protein expression was significantly higher in UII–/– +DM group than that of WT+DM group.
CONCLUSIONS This study suggested that knockout UII gene might reduce fasting blood glucose levels, improve insulin resistance, reduce myocardial fibrosis and improve cardiac function, probably via inhibition of microvascular endothelial mesenchymal transition and inflammation.
[GW30-e0842]
Guo Li, Jingfeng Wang
Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
OBJECTIVES Although patients of acute myocardial infarction (AMI) performed primary PCI (PPCI) within 12 hours, 30% still progress to irreversibly ventricular remodeling. The mechanism of this phenomenon is still unclear. The aim of this study was to explore the effects of monocytes cells in peripheral blood on ventricular remodeling by single-cell RNA sequencing.
METHODS We perform scRNA-seq 10X Genomics on 43567 single peripheral blood mononuclear cells (PBMC) from 6 male patients with AMI undergoing PPCI within 12 h and accepted ACEI/ARB, β-Block, and aldosterone standard medicine treatment over 1 year, which including 3 patients with LVEF≥55% as preserved LVEF (Pre-LVEF) group and 3 with LVEF≤40% as reduced LVEF (Re-LVEF) group. Another 3 male healthy people were selected as healthy control. Cell Ranger, Seurat and other R packages are used to normalize data and analyze differentially expressed genes. The scRNA-seq results are verified by flow cytometry and qPCR in PBMC from patients.
RESULTS The clinical marker NT-proBNP and TNT-HS increased significantly in Re-LVEF group compared to Pre-LVEF group and healthy control. Unbiased clustering identified 21 clusters which were singled out with top 20 upregulated markers, including: 8 clusters for T cells, 3 clusters for B cells, 3 clusters for NK cells, 3 clusters for monocytes, 1 cluster for NKT cells, 1 cluster for megakaryocytes, 1 cluster for plasmacytoid dendritic cells, 1 cluster for mixed cells. Compared to the healthy control and Pre-LVEF group, the proportion of classical monocytes, KLRC2+ adaptive NK cells, CD4+ Treg cells and plasmacytoid dendritic cellsare upregulated in Re-LVEF group, which show no significant difference in proportion between healthy control and Pre-LVEF group, and the proportion of CD8+ cytotoxic T cellssubset increases moderately in Pre-LVEF group, and increases significantly in Re-LVEF group, compared to healthy control, respectively. The upregulated genes of different subsets are all involved in several inflammatory pathways through KO and GO enrichment analysis. CCL3L3 and CCL4L2 show similar expression in healthy control and Pre-LVEF group, but significantly upregulated in Re-LVEF group almost in all clusters. Through t-SNE distribution diagram, CCL3L3 and CCL4L2 show extreme enrichment and upregulation in classical monocytes and non-classical monocytes. Cell trajectoryanalysis of monocytes shows S100A family and CCL3L3, CCL4L2 are the key genes in the branch point from classical monocytes to non-classical monocytes. Flow cytometry verified the presence of classical monocytes and non-classical monocytes and show the same proportion compared to the scRNA-seq results.
CONCLUSIONS Classical monocytes, KLRC2+ adaptive NK cells, CD4+ Treg cells, plasmacytoid dendritic cells and CD8+ cytotoxic T cells promote ventricular remodeling after AMI with PPCI through various inflammatory pathways. Classical monocytes promote ventricular remodeling by secreting CCL3L3, CCL4L2 into peripheral blood, meanwhile activating the chemokine family inflammatory pathways and might be a new predict marker of ventricular remodeling in the future. The cell subsets defined by scRNA-seq show the heterogeneous view of peripheral blood immune cells from myocardial infarction after PPCI and provide new therapy targets for ventricular remodeling.
[GW30-e0950]
Thach Nguyen 1,2 , Vu Tri Loc, Cao Tien Dung 3 , Nguyen Hong Thao 4 , Tran Anh Tuan 5 , Gianluca Rigatelli 6 , Tarneem Darwish 7
1Tan Tao University, School of Medicine, Long An, Vietnam
2Methodist Hospital, Merrillville IN, USA
3Tan Tao University, School of Engineering, Long An, Vietnam
4FPT University, Ho Chi Minh City, Vietnam
5Vietnam National University, University of Sciences, Ho Chi Minh City, Vietnam
6Rovigo General Hospital, Rovigo, Italy
7UCLA, David Geffen School of Medicine, Los Angeles, CA, USA
OBJECTIVES Coronary artery disease (CAD) is hypothesized to be caused by cavitation (explosion of air bubbles) which is seen frequently in domestic or industrial pipes. With distal negative suctioning in diastole, if the coronary dynamic pressure decreases below the vapor pressure (VP), bubbles will form. They explode when the coronary dynamic pressure recovers>the VP in systole and create jet waves weakening, rupturing the cap of plaques, triggering acute coronary syndrome (ACS). How could these events be located and tabulated by Machine Learning of artificial intelligence (AI) program compared to the results of human investigators?
METHODS Angiograms with culprit lesions (recorded at 15 frames/second) were reviewed frame by frame. The first frame was of the artery completely filled with contrast. The following frames showed the (white) blood moving in. The flow could be LAMINAR, TURBULENT (mixing of blood in white and contrast in black) or RETROGRADE (black column traveling backward). The turbulent flow reflects the collision between antegrade and retrograde flow. The investigations included the direction and duration of flows. The intensity of turbulence was measured by (1) length of coronary segment with turbulence (2) length of the stagnant retrograde flow. The AI programs were trained to use the U-Net deep learning for medical image segmentation and then build the UNet model based on the previous dataset (Images, ImageMask).
RESULTS Angiograms of 20 patients showed laminar flow (85%) in diastole. The flow became turbulent at systole with diffuse coarse mixing of black (contrast) and white (blood) at the MID SEGMENT of the left circumflex artery (LCX) or the right coronary artery (RCA). The presence of turbulence matched the location of 86% of ruptured plaques. The time of retrograde flow lasted more than 2 systoles. Special protocols were used successfully to train AI to recognize the lesions, antegrade, retrograde flow, turbulence and the persisting retrograde stagnant area.
CONCLUSIONS This is the first time, the matching of location of ruptured plaques and turbulent flow representing the collision between antegrade flow in diastole and retrograde flow in systole was confirmed and compared between humans and AI These results may help to understand the genesis and offer precise prevention and treatment in ACS.
[GW30-e1070]
Nanchao Hong, Erge Zhang, Yu Yu, Kun Sun
Department of Pediatric Cardiology, Xinhua hospital, Affiliated to Shanghai Jiao Tong University School of Medicine
OBJECTIVES Disruption in cardiac cushion formation can lead to septal and valvular malformations, which account for the largest proportion in congenital heart defects. The transcription factor Sox7 has critical functions in the differentiation of multiple mesodermal lineages. However, its effect on cardiac cushion development has not been explored. This study aims to clarified the role of Sox7 in cardiac cushion development and the underlying mechanisms.
METHODS Whole exome sequencing was performed in 100 atrioventricular septal defect (AVSD) patients and 100 controls. Sox7 in a patient with 8p23.1 deletion was thought to be the candidate gene of this AVSD patient. Then, Sox7 endocardial lineage specific loss-of-function (Sox7 EnKO) and gain-of-function (Sox7 EnKI), pan-endothelial cells specific and cardiac progenitor cells specific loss-of-function (Sox7 EcKO and Sox7 CpcKO respectively) mice were generated. Transcriptome analysis was performed. Sox7 downstream target genes BMP2 and Wnt4 were confirmed by luciferase, ChIP assays and rescue experiments. Finally, Sox7 EnKI embryos were carefully screened for the changes of EndMT process.
RESULTS Ten rare copy number variants (CNVs) were identified among 100 AVSD patients. Among the 10 rare CNVs, deletion of 8p23.1 had been reported to be associated with congenital heart defects, particularly in the form of AVSD, and we verified the 8p23.1 deletion by qPCR. Interestingly, the known AVSD-related genes were not identified in the patient with 8p23.1 deletion. Sox7 EnKO embryos exhibited delay in fusion of ventricular septum with cardiac cushion and partial AVSD, the cardiac cushion endothelial to mesenchymal transition (EndMT) process of Sox7 EnKO, Sox7 EcKO and Sox7 CpcKO embryos were also severely impaired. To identify altered signaling pathways involved in the impaired EndMT process of Sox7 EnKO, we used AVCs of E9.5 Sox7 EnKO and control embryos to perform RNA-sequencing. Ingenuity pathway analysis identified 15 altered pathways relevant to this study, and BMP signaling pathway was significantly downregulated in Sox7 EnKO embryos. We found that the expressions of BMP2, pSMAD1/5/8 and downstream target gene Tbx2 were significantly reduced in Sox7 EnKO embryo. In addition, endocardial deletion of Sox7 reduced the endocardial Wnt4 expression, which could also downregulated the AVC myocardium BMP2 expression, leading to impaired EndMT process. In vitro, overexpression of Sox7 in mouse embryonic endocardial cells (MEEC) and human umbilical vein endothelial cells (HUVEC) can increase the expression of Wnt4, BMP2, pSMAD1/5/8 and Tbx2. Luciferase and ChIP assays showed that Sox7 could activate Wnt4 and BMP2 by directly bind to Sox7 binding sites in the prompter regions of them. Furthermore, Wnt4 and BMP2 protein can rescue the impaired EndMT process caused by Sox7 deficiency, and the BMP2 signaling inhibitor Noggin can block the effect of Wnt4 protein on Sox7 EnKO AVC explant. Finally, Sox7 EnKI embryos exhibit increased EndMT process in cardiac cushion, and we also found the evidence of ectopic EndMT in the ventricle of Sox7 EnKI embryo.
CONCLUSIONS Sox7 regulates the Wnt4-BMP2 pathway to modulate EndMT process and cardiac cushion formation. Notably, this study identifies a novel gene and clarifies the underlying mechanism involved in cardiac cushion development, provides new strategy for the diagnosis and treatment of congenital heart defect.
CLINICAL RESEARCH ON -CARDIOVASCULAR DISEASES
CORONARY HEART DISEASE
[GW30-e0012]
Yunjie Yin, Liang Xu, Song Yang, Yanchun Chen
Department of Cardiology, Yixing People’s Hospital, Yixing, Jiangsu Province 214200, P.R. China
OBJECTIVES Percutaneous coronary intervention (PCI) is one of the dominant methods for revascularization in patients with coronary heart disease (CHD). However, periprocedural myocardial injury (PMI) is a frequent complication following PCI and is known to be a predictor of postprocedural cardiovascular morbidity and mortality. Although several studies try to identify the serum markers to predict the PMI, there is a little information about the role of lipoprotein-associated phospholipase A2 (Lp-PLA2) as a predictor of PMI. Therefore, we aimed to investigate the relationship between lipoprotein-associated phospholipase A2 levels and PMI in patients undergoing elective PCI.
METHODS This study included 265 consecutive patients with normal preprocedural cardiac troponin T (cTNT) who received elective PCI. The samples for cTNT were collected at 8, 16, and 24 hours after PCI to assess perioperative myocardial injury. The Lp-PLA2 and other serum lipid parameters were measured after 12 fasting hours before PCI.
RESULTS The data suggested that the patients with preprocedural high Lp-PLA2 were strongly and independently correlated with the risk of PMI. Pearson correlation analysis showed that preprocedural Lp-PLA2 was significantly positively correlated with postprocedural cTnT elevation (R=0.549, P<0.05). Logistic regression analysis was used to analyze the risk factors of postprocedural cTnT elevation, we found that smoking, hs-CRP (OR=1.126, P<0.05) and Lp-PLA2 (OR=2.348, P<0.05) are independent risk factors for postprocedural cTnT elevation.
CONCLUSIONS Our study demonstrated that Lp-PLA2 was associated with postprocedural cTnT elevation, and high Lp-PLA2 levels were the independent risk factor of PMI.
[GW30-e0078]
Tianxiang Li, Xiangyu Hao, Zhibo Zhu, Jianqiang Guo
Department of Cardiology, The Affiliated Hospital of Inner Mongolia Medical University
OBJECTIVES To explore the role of Angiotensin II type 1 receptor (AT1) in the instability of atherosclerotic plaques caused by Homocysteine (HCY).
METHODS Twenty-one 6-week-old male ApoE–/– mice were weighed and divided into three groups according to the random number table: control group (CTL), Hyperhomocysteinemia group (HHCY), HHCY telmisartan treatment (TLM) group (10 mg/kg gavage treatment). Weight and blood pressure were measured before and after 12 weeks of feeding. The blood specimen was retained by removing the eyeball. Plasma HCY was detected by using cyclic enzyme method. Oil red “O” staining was used to measure the area of aortic root plaque, and immunohistochemical SP method was used to detect plaque inflammatory factor interleukin-6 (IL-6), Monocytes chemoprotein-1 (MCP-1), macrophage surface molecules (mac-3), matrix metalloproteinase-9 (MMP-9), and collagen was stained by Masson staining.
RESULTS T The plaque area of HHCY group was significant larger than that of control group. The expression levels of IL-6, MCP-1, mac-3 and MMP-9 in plaque were higher in HHCY group than control group, but collagen content of plaque was reduced in HHCY group. After 12 weeks of treatment, the area of aortic root plaque, the expression levels of IL-6, MCP-1, mac-3 and MMP-9 macrophage infiltration were significantly lower in telmisartan treatment group than in HHCY group, but collagen content of plaque was significantly higher in telmisartan treatment group than in HHCY group. We also noted that the blood pressure and body weight of the telmisartan group were lower than those of the HHCY group.
CONCLUSIONS Homocysteine promotes the development of atherosclerosis and leads to plaque instability, blocking At1 receptor by telmisartan improved atherosclerosis and promoted plaque stabilization, indicating that its mechanism may be through the At1 receptor.
[GW30-e0079]
Jindong Wan, Sen Liu, Dan Wang, Yi Yang, Fei Ran, Siwei Xia, Peng Zhou, Peijian Wang
The First Affiliated Hospital of Chengdu Medical College
OBJECTIVES Although the replacement of bare-metal stents with drug-eluting stents has led to a significant reduction in the rate of angiogenic in-stent restenosis (ISR), ISR occurs in 3%–20% of patients with a drug-eluting stent, depending on lesion characteristics and patient risk factors. High-mobility group box 2 (HMGB2) is a novel inflammatory protein that has been positively related to cardiovascular disease. However, information regarding the role of HMGB2 in spontaneous reperfusion (SR) of infarct-related artery in patients with ST-segment elevation myocardial infarction (STEMI) is limited. The present study was designed to evaluate the association of serum HMGB2 levels with SR of infarct-related artery in this high-risk population.
METHODS We measured serum HMGB2 in 1080 consecutive STEMI patients who were recruited between October 2014 and October 2018 using an enzyme-linked immunosorbent assay kit. Blood samples were obtained on admission and before primary percutaneous coronary intervention (pPCI). According to thrombolysis in myocardial infarction (TIMI) results, patients were divided into SR (TIMI 2-3, n=248) and non-SR (TIMI 0-1, n=832) groups. Logistic regression analysis was performed to define the independent predictors of SR.
RESULTS Serum HMGB2 was significantly lower in patients with SR compared to patients with non-SR ([3.01±1.24] ng/mL vs. [6.36±1.32] ng/mL, P=0.013). A cut off HMGB2 value of 2.75 ng/mL had a predictive value of 83% to identify patients with SR (sensitivity=87%). Logistic regression analysis showed that serum HMGB2 level is an independent predictor of SR (odds ratio=4.25, 95% confidence interval: 1.58 to 7.69, P=0.005) for STEMI patients.
CONCLUSIONS Serum HMGB2 levels were associated with ISR in patients. Lower serum HMGB2 level is an independent and novel predictor of SR for STEMI patients. Detection of serum HMGB2 level is promoted to predict SR in STEMI patients. These findings support the use of HMGB2 as a biomarker of atherosclerosis in this high-risk group.
[GW30-e0084]
Yuanyuan Pei, Wen Chen, Xue Mao, Jihong Zhu
Peking University People’s Hospital
OBJECTIVES Patients with acute myocardial infarction (AMI) are at high risk for acute kidney injury (AKI). Studies indicated several biomarkers of early structural kidney injury such as cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and Klotho have been identified that may predict early AKI before a significant increase in serum creatinine (SCr) level. However, limited researches were executed in AKI after AMI. These novel biomarkers potentially allow timely intervention in high risk patients of AKI when damage is still reversible. Therefore, we performed a prospective study with AMI patients in order to explore early biomarkers for AKI prediction at hospital admission.
METHODS The study included consecutive patients between May 2016 and November 2017 diagnosed with AMI in emergency department of Peking University People’s Hospital. Patients with end stage renal disease, septic shock and who died or discharged within 48 h of admission were excluded. AKI were diagnosed according to KDIGO definition. Serum sample for NGAL, cystatin C and Klotho were taken instantly when diagnosed AMI. SCr was measured on the first, third and seven days. All biomarkers were measured in duplicate by a single enzyme-linked immunosorbent assay (ELISA). Baseline characteristics were collected. The primary analysis compared the AKI group with the non-AKI group. P<0.05 was considered statistically significant. All variables were tested for a normal distribution through the Kolmogorov-Smirnov test. Continuous variables and normal distribution data were compared using independent sample t tests. Categorical data were tested by the Chi-square test or Fisher’s exact test. Discrimination was assessed using the area under a receiver operating characteristic curve (AUROC). The analysis for AUROC was also conducted to estimate the cut-off values, sensitivity and specificity were calculated by determining the best Youden index.
RESULTS Overall, 285 patients were included. In our study, 17.5% (50/285) patients developed AKI. Compared to non-AKI group, the length of hospital stay of the AKI group was obviously longer (17d vs. 11d, P<0.01) and mortality was higher either (20.0 vs. 0.4%, P<0.001). Clinical data were displayed in Table 1. Cystatin C, NGAL and Klotho both increased significantly in AKI group (Table 2). The ROC curves of biomarkers and SCr on admission were displayed in predicting development of AKI after AMI in Table 3 and Figure 1, areas showed that serum levels of cystatin C had modest discriminative powers in prediction of AKI than SCr (0.899, 95% confidence interval, 0.855 to 0.944, P<0.001 and 0.734, 95% confidence interval, 0.649 to 0.819, P<0.001, respectively). The cut-off values for cystatin C in predicting AKI were 2362.9 ng/mL, sensitivity and specificity value of cystatin C in predicting AKI in AMI patients was 0.880 and 0.791. NGAL and Klotho didn’t display preferable diagnostic values compared with SCr. There was no difference between the discrimination performances of SCr, NGAL and Klotho.
CONCLUSIONS In this cohort of patients with AMI, serum cystatin C maybe a more reliable and earlier diagnostic biomarker for AKI associated with AMI. Meanwhile, serum NGAL and Klotho did not provide additional value regarding AKI prediction compared with baseline creatinine.
[GW30-e0090]
Tianxiang Li, Zhibo Zhu, Xiangyu Hao, Jianqiang Guo
Department of Cardiology, The Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia Medical University
OBJECTIVES Trimethylamine N-oxide (TMAO), a gut microbiota metabolites, has recently been found to promote atherosclerosis. Here, we examined the effect of angiotensin II type 1 receptor blockers (ARB) telmisartan on plasma levels of TMAO in apolipoprotein E-deficient (ApoE–/–) mice.
METHODS Sixteen ApoE–/–mice were randomly divided into two groups: control group and telmisartan (10 mg/kg, intragastric administration) treatment group. All mice were fed a high-fat diet. After 12 weeks, the mice were sacrificed. Venous blood was collected from the retro-orbital sinus to detect TMAO using high performance liquid phase chromatography-tandem mass spectrometry. Severity of atherosclerosis was determined by measuring the area of the plaques. Stability of atherosclerotic plaques were determined by analyzing the expression of inflammatory factors interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), matrix metalloproteinase-9 (MMP-9), the infiltration of macrophages and the morphology of plaques at the root of the aorta.
RESULTS Compared with the control group, the plaque area of the telmisartan treatment group decreased significantly, and the expression of IL-6, MCP-1, MMP-9 and the infiltration of macrophages also decreased significantly. The plaque of the telmisartan treatment group had thicker fiber caps, a few foam cells, and a reduced lipid/necrotic core. Plasma TMAO levels were significantly lower in the telmisartan-treated group than in the control group. Meanwhile, the blood pressure and body weight of the mice treated with telmisartan were lower than those of the control group.
CONCLUSIONS That ARB telmisartan lower plasma TMAO levels may be one of the mechanisms by which it improves atherosclerosis, which may indicate a certain intrinsic association between At1 receptor and gut microbiota.
[GW30-e0094]
Wenduo Zhang, Wenduo Zhang
Beijing Hospital
OBJECTIVES The best strategy to treat ostial coronary lesions (OCLs) is controversial. Hypothesis: A drug-coated balloon (DCB)-only strategy for OCLs is safe and efficacious.
METHODS Forty-four patients (55 OCLs) with typical angina symptoms were treated with DCBs. After pre-dilatation, a paclitaxel-eluting balloon was inflated for ≥30 s. Primary outcome was target-lesion revascularization. Secondary endpoints were post-interventional lumen gain and late lumen loss (LLL) at the longest available follow-up.
RESULTS Mean age was 64.35±10.8 years; 25% of patients had diabetes mellitus, and 25.5% presented with in-stent restenosis. We treated OCLs of the left main coronary artery, left anterior descending artery, left circumflex artery, and right coronary artery (first diagonal, marginal, posterior descending and posterolateral branches). Pre-dilatation with a cutting balloon was used in 16.4% of cases. At the longest available clinical follow-up (mean of 15.60±8.7 months), the prevalence of major cardiac adverse events was 14.5%. There was no thrombosis but three OCLs showed total occlusion. LLL was 0.074±0.63 mm.
CONCLUSIONS DCBs are a safe and technically easy therapeutic option, and associated with acceptable long-term clinical outcomes.
[GW30-e0095]
Xing Luo 1,2 , Xiuzhu Weng 1,2 , Ying Lv 1,2 , Shan Zhang 1,2 , Chunyang Zhe 1,2 , Chen Zhao 1,2 , Xiaoxuan Bai 1,2 , Ming Zeng 1,2 , Haibo Jia 1,2 , Bo Yu 1,2
1Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University
2The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education
OBJECTIVES Plaque erosion and plaque rupture are the main pathological mechanisms of acute coronary syndrome (ACS). They have different pathological characteristics. plaque rupture (PR), characteristic with a large necrotic lipid core and thin fibrous cap with discontinued endothelial layer, which accounts for about two-thirds of ACS; Plaque erosion, is rich of smooth muscle cell (SMC) and extracellular matrix, such as hyaluronic acid (HA), but less of macrophage compared to PR, PE accounts about one-thirds of ACS. Because of the different pathological characteristics, The EROSION study (Effective Anti-Thrombotic Therapy Without Stenting: Intravascular Optical Coherence Tomography-Based Management in Plaque Erosion) suggested that in patients with acute coronary syndrome presenting with plaque erosion, conservative treatment with antithrombotic therapy may be a reasonable option instead of stent implantation. And the follow-up results for one month and one year demonstrate that effective anti-thrombotic therapy is safe. Because the different pathological characteristic and clinical treatment. Some researches demonstrated that the mechanism of the two subset maybe different, and some researches claimed that the two subsets have inflammatory status in culprit lesion, Our study is aim to compare the inflammatory status of local white blood cell which is near to culprit lesion between plaque erosion and plaque rupture.
METHODS Fifty-one ST-segment elevation myocardial infarction patients (21 erosion patients and 30 rupture patients) with <6 hours of chest pain were classified as plaque erosion or plaque rupture using optical coherence tomography. During the PCI time, the blood near to culprit lesion was collected, and separated the white blood cell immediately in trizol reagent and kept −80°C in in for RNA extraction. And reversed transcription to cDNA for quantitative real-time polymerase chain reaction (Rt-PCR). We compared the anti-inflammatory cytokine (IL-4, IL-10) and pro-inflammatory factor (IL-1β, TNF-α, IL-8) mRNA expression level in the two groups.
RESULTS Between erosion and rupture patients, there is no significant anti-inflammatory cytokine (IL-4, IL-10) mRNA different expression in the two groups. But erosion patients show elevated mRNA expression of pro-inflammatory factor than rupture patients: IL-1β, (P=0.026), IL-8 (P=0.021), TNF-α, (P=0.028).
CONCLUSIONS These results demonstrate differential pro-inflammatory factor expression in local erosion and rupture culprit lesion. To our surprised, although there is less inflammatory cell in eroded plaque, the local white blood cell in eroded plaque show elevated pro-inflammatory factor (IL-1β, TNF-α, IL-8) mRNA expression than rupture plaque, but no significant different expression anti-inflammatory cytokine (IL-4, IL-10) mRNA expression in the two groups.
[GW30-e0104]
Jia Su, Xiaomin Chen
Department of Cardiology, Ningbo No. 1 Hospital, Ningbo, Zhejiang, P.R. China
OBJECTIVES The CAD patients with clopidogrel resistance were more likely to get cardiovascular events and the diabetes mellitus may be a risk of clopidogrel resistance.
METHODS The platelet function of CAD patients after PCI was evaluated by VerifyNow P2Y12, and the fasting and 2 h postprandial level of insulin, glucose, and C peptide were tested for examining the glucose control affecting on CR.
RESULTS Compared with NCR patients, incidence rate of CR was higher in DM patients (50.9 vs. 32.4%). Meanwhile, fasting and 2 h postprandial level of insulin and C peptide might affect the clopidogrel response (fasting insulin, CR group vs. NCR group: 56.5±12.2 pmol/L vs. 114.3±42.2 pmol/L; fasting C peptide, CR group vs. NCR group: 10.12±1.89 nmol/L vs. 7.25±2.21 nmol/L). If the glucose could be controlled better, the clopidogrel response would be improved.
CONCLUSIONS The DM and the condition of glucose controlment might be the risks of clopidogrel resistance.
[GW30-e0107]
Muhammad Akhlaq
Taishan Medical University, Taishan, China
OBJECTIVES Aims to: (1) Review the literature for best initial management approach for Non-ST-Elevated Acute Coronary Syndromes (NSTE-ACS), (2) Minimise the Conflicting Strength with the better understanding of Heterogeneity or Differences between the Trials and Meta-analyses, (3) To collect the relevant Mega-data for a specific topic, our is early invasive strategy or initial conservative strategy; what strategy is best as initial management for NSTE-ACS?, (4) Evaluation of the most Prognostic and Influential factors for the early invasive approach, (5) Posit directions for future research.
METHODS We conducted a computer-based search in representative databases by Medline, Embase, Cochrane database and Google Scholar from 1985 to 2017 using key words of relevant subject headings for randomized controlled trials, meta-analyses and included some standard observational studies that met eligibility criteria for each mentioned topic of our research included 10 influential factors headings. We independently reviewed searches and selected trials that compared early invasive strategy with initial conservative strategy covered many dimensions of our research requirements with prognostic values.
RESULTS We screened more than 500 abstracts, evaluated more than 200 full-text articles. By which included more than 300 Randomised Control Trials and their Meta-Analyses with more than 300 observational but standard studies. As per theme of our type of research, we have collected vast data to cover the almost all aspects of our topic related issues or factors. We corresponded with experts in the field, After focus studying, opinions and discussions with researchers, we extracted and evaluated that there are some influential and prognostic factors regarding early invasive approach for NSTE-ACS patients, which have to be understand, dealing and approach first for the cause of better outcome with early invasive strategy. These most influential factors are: (1) Diagnosis Accuracy, (2) Significance of Early Risk Stratification, (3) Individualised Patient Assessment: Co-Morbidities (Age Factor, DM, CKD, Gender, HTN, etc), (4) Timing of EIS, (5) Radial vs Femoral Approach, (6) Prognostic Value of Peri-Procedural and Long-term Drugs, (7) Peri-Procedural Major Bleeding, (8) Peri-Procedural and Spontaneous MI, (9) Stent Type with two Major Complications: Stent Thrombosis & Stent Re-Stenosis and (10) Peri-Procedural Kidney Injury.
CONCLUSIONS (1) In respect to early invasive strategy for the management of NSTE-ACS, with proper diagnosis, better early risk stratification approach, skilful individualise patient assessment, through proper-site approach, with better understanding of the individualized timing for patients, with administration of proper and recommended pre-and-post procedures, short & long term drugs, and especially the choice and type of stents according to patient co-morbidities, anatomical lesion and clinical condition, we can reduce the mortality hazard complications like peri-procedural major bleeding, peri-procedural & spontaneous MIs, procedural-induced AKI, stent thrombosis and in-stent re-stenosis, all these leads to decreasing mortality indirectly. (2) With the better understanding of some prognostic and influential factors related to the approach of early invasive strategy, for patients with NSTE-ACS, an early invasive strategy should be strongly considered during initial hospitalisation in all-risk-level patients.
[GW30-e0108]
Jiaqi Yang, Yujie Zhou
Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
OBJECTIVES HCM is associated with poor prognosis. In our previous study, it has been reported that patients with AMI with HCM exhibited worse long-term outcomes than those patients with AMI without HCM and patients with HCM without AMI. In this article, we aimed to assess the impact of BMI on the long-term outcomes of HCM patients with AMI.
METHODS Seventy-eight consecutive patients with HCM and AMI were included. The endpoints were major adverse cardiac events (MACEs) and secondary endpoints.
RESULTS There were no differences in observed in-hospital mortality or 5-year mortality between the two groups of HCM and AMI patients divided by BMI. However, significantly increased incidences of re-PCI and stroke were observed in the group of obesity (re-PCI: 0.0 vs. 21.4%, P=0.007; stroke: 5.6 vs. 28.6%, P=0.042). The 5-year outcomes of MACEs were inferior in the obese group (log-rank P=0.020 and 0.001).
CONCLUSIONS AMI and HCM patients who were obese exhibited worse long-term outcomes than patients without obesity.
[GW30-e0109]
Tingyu Zhang, Kang Meng
Beijing Anzhen Hospital
OBJECTIVES To investigate the relationship between monocyte-to-lymphocyte ratio (MLR) and plaque vulnerability assessed by optical coherence tomography in patients with acute coronary syndrome.
METHODS Seventy-two patients with acute coronary syndrome were enrolled in Beijing Anzhen hospital and received coronary angiography and optical coherence tomography test.
RESULTS The coronary plaques in high MLR group exhibited thinner fibrous cap thickness (FCT) (112.37±60.24 vs. 153.49±110.29 μm, P=0.013), greater maximum lipid arc (167.36±62.33 vs. 138.79±56.37°, P=0.010) and longer lipid plaque length (6.34±6.12 vs. 4.50±3.21 mm, P=0.041). Besides, the incidence of vulnerable plaque (TCFA) (44.7 vs. 18.4%, P=0.014) and plaque rupture (36.8 vs. 13.2%, P=0.017) were higher in high MLR group. Meanwhile, MLR was negatively associated with FCT (R=0.225, P=0.005). Furthermore, MLR (OR=3.316, 95% CI: 1.448–7.593, P=0.005) was found to be an independent risk factor of TCFA.
CONCLUSIONS MLR level has potential value in assessing coronary plaque vulnerability in patients with acute coronary syndrome.
[GW30-e0113]
Yanguo Xin, Xiaojing Liu
West China Hospital of Sichuan University
OBJECTIVES In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) has been the cornerstone strategy. Several studies, however, have shown that a clopidogrel loading dose >300 mg resulted in high platelet inhibition, a faster onset of action, and fewer poor responders in both clopidogrel-naïve and clopidogrel-treated patients. Ticagrelor provides faster and more consistent platelet inhibition than that of clopidogrel. Most patients with ACS have comorbidities and risk factors that greatly increase their risk of ischemic or bleeding events. We compared ticagrelor and clopidogrel for the prevention of cardiovascular events and safety in high ischemic and bleeding risk patients who presented with ACS and underwent a percutaneous coronary intervention (PCI).
METHODS One thousand nine hundred and thirty-nine patients with high ischemic and bleeding risk were enrolled into three groups according to their antiplatelet strategy: standard antiplatelet therapy (clopidogrel 75 mg daily plus aspirin 100 mg daily, the Standard group), double-dose clopidogrel (clopidogrel 150 mg daily plus aspirin 100 mg daily, the Double group) and ticagrelor therapy (ticagrelor 90 mg twice daily plus aspirin 100 mg daily, the Ticagrelor group).
RESULTS Clinical outcomes: The primary endpoint of MACCE events at 24 months post-PCI occurred in 134 patients (19.5%) in the Standard group, 73 patients (13.7%) in the Double group, and 87 patients (12.0%) in the Ticagrelor group. The difference in the 24-month MACCE rates in the Ticagrelor group was lower than that in the Standard group (hazard ratio [HR]: 0.558, 95% CI: 0.427–0.731), demonstrating the superiority of the ticagrelor strategy over that of standard DAPT. Regarding the Double group, the MACCE rate was lower than that of the Standard group (HR: 0.649, 95% CI: 0.489–0.861). The risks of cardiovascular death and MI did show a significant difference among the three groups. A significantly decreased risk of NACCE could be detected in the Ticagrelor group (HR: 0.646, 95% CI: 0.488–0.856) compared to that of the Standard group.
Subgroup analysis of endpoints: For the efficacy endpoints, we first identified the potential clinical factors associated with MACCE using a COX multivariate analysis; three factors, including renal function, history of MI, and triple vessel artery disease, were revealed to be associated with MACCE. The stratified analyses revealed that participants with an eGFR<90 mL/min/1.73 m2 had a lower ischemic rate in the Ticagrelor group than that in the Standard group (HR: 0.616, 95% CI: 0.387–0.981, P=0.01). In addition, patients with a previous MI could benefit from stronger antiplatelet treatments (P=0.027). Similar results were also observed in patients with triple vessel artery disease (P=0.019). For the safety endpoints, seven factors were identified to be related with bleeding events, and among these factors, participants aged >70 years accounted for a higher bleeding rate in the Double group than that in the Standard group (HR: 2.264, 95% CI: 1.553–3.30, P<0.001).
CONCLUSIONS In East Asian PCI patients with high ischemic and bleeding risk, the ticagrelor antiplatelet strategy significantly reduced the MACCE rate without increasing the risk of major bleeding. A decreased rate of MACCE was observed in patients with double dosage of clopidogrel, but the bleeding risk was higher than that in the standard group.
[GW30-e0125]
Run Guo, Jun Zhang
Cardovascular Department, Cangzhou Central Hospital
OBJECTIVES The aims were to investigate the sensitivity of inflammatory factor PTX3 in early forecast of the coronary artery damage in ACS patients accepted PCI by testing the levels of PTX3 and hs-CRP in patients during perioperative period, and to observe the influence of different dose of pitavastatin and atorvastatin on the inflammatory factors, providing theory basis for management of patients with ACS and assessment of the disease prognosis.
METHODS One hundred and twenty-one patients diagnosed as ACS in Cangzhou central hospital were selected from January 2015 to October 2015, and divided into 3 groups randomly: Conventional dose of pitavastatin group (38 cases) took pitavastatin 2 mg before sleep (qn). Conventional atorvastatin group (40 cases) took atorvastatin 20 mg before sleep. Intensive pitavastatin group (43 cases) was given pitavastatin 4 mg before sleep on preoperative and postoperative day, then maintained 2 mg later. Observe all patients: the levels of PTX3 and hs-CRP at preoperative day, 24 h and 72 h after PCI. The major adverse cardiac events (MACE) in 121 patients during 6 months, including cardiac death, target vascular remodeling and nonfatal myocardial infarction.
RESULTS (1) The basic clinical date of 121 patients before PCI showed no statistical difference (P>0.05); (2) There was no statistical difference in levels of hs-CRP among 3 groups in preoperative period (P>0.05); intra-group comparison, the levels of hs-CRP at 24 h, 72 h after PCI showed no statistical difference in each group (P>0.05); compared with preoperative, the levels of hs-CRP at postoperative 24 h, 72 h among 3 groups showed no statistical difference (P>0.05); (3) The levels of PTX3 among 3 groups during preoperative period were no statistical difference (P>0.05); and at 24 h after PCI were higher than preoperative, but at 72 h the levels of PTX3 is decreased compared with 24 h, though the concentrations was still higher than preoperative (P<0.05); comparison between the 2 conventional dose groups, the levels of PTX3 at postoperative 24 h, 72 h was no statistical difference (P>0.05), but the levels of PTX3 in intensive pitavastatin group at 24, 72 h postoperative was lower than conventional groups (P<0.05); (4) There was no cardiac death within 6 months after PCI in 3 groups. In normal dose pitavastatin group, there were 0 MI cases happened, and 4 patients accepted target vessel revascularization; in normal dose atorvastatin group, there was 0 MI cases happened, and 4 patients accepted target vessel revascularization; in intensive pitavastatin group, there was 0 MACE happened; between the 2 conventional dose groups, the total incidence of MACE during 6 months showed no statistical difference (P>0.05); compared with conventional group, the total incidence of MACE in the intensive group was obviously lower (P<0.05).
CONCLUSIONS (1) The sensitivity of PTX3 in early prediction of the blood vessel damage in ACS patients accepted PCI is better than hs-CRP. (2) For ACS patients who accept PCI, PCI itself will damage the vascular wall, cause inflammation and increase the levels of PTX3. (3) There was no significant difference between normal dose pitavastatin and normal dose atorvastatin therapy in reducing inflammation. Intensive pitavastatin therapy can reduce inflammation better than normal dose pitavastatin and atorvastatin therapy. (4) Using intensive pitavastatin therapy at perioperative PCI period can reduce the incidence of MACE within 6 months, improving the prognosis in the near future, and the benefit is superior to conventional therapy.
[GW30-e0127]
Jie Yang, Yujie Zhou
Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES To explore the correlation between fasting blood glucose (FBG) and inflammatory level and severe coronary artery lesions in patients with prediabetes (HbA1c 5.7–6.4%) undergoing elective PCI.
METHODS We consecutively enrolled 885 pre-diabetes (HbA1c 5.7–6.4%) undergoing elective PCI in our hospital. Subjects were divided into two groups, one group was IFG group (5.6£FBG<7.0 mmol/L), another was NFG group (FBG<5.6 mmol/L), We recorded and compared the baseline characteristics, inflammation index (white blood cells, hypersensitive c-reactive protein, neutrophil lymphocyte ratio, platelet lymphocyte ratio) and characteristics of coronary artery disease.
RESULTS Compared with the NFG group, the patients in the IFG group had higher BMI (P=0.028), more patients with hypertension (P=0.049), higher TG (P=0.005) and higher LDL-C (P=0.001). After comparing the inflammatory index of the two groups, WBC (P=0.028), NLR (P=0.005), PLR (P=0.013) and hs-CRP (P=0.028) in the IFG group were significantly higher than those in the NFG group. In addition, compared with the NFG group, the proportion of three-vessel disease (P=0.040), the GENSINI score (P=0.014) and the SYNTAX score (P=0.008) were higher in the IFG group.
CONCLUSIONS In patients with elective PCI complicated with pre-diabetes mellitus (HbA1c 5.7–6.4%), IFG patients have higher levels of subclinical inflammation and more severe coronary artery lesions.
[GW30-e0139]
Wuyang He, Li Chunqiu, Chen Qingwei
The Second Affiliated Hospital of Chongqing Medical University
OBJECTIVES Recently, sclerostin, a bone-derivedprotein, has been shown to play a key role in the progression of atherosclerosis. However, few studies have investigated the influence of sclerostin on the prognosis of cardiovascular disease. We investigated the relationship betweenserum sclerostin levels and adverse outcomesin elderly patients with stable coronary artery disease (SCAD) who are undergoing percutaneous coronary intervention (PCI).
METHODS A total of 310 elderly SCAD patients who underwent PCI were enrolled in this study, with a follow-up of 3 years. According to the median serum sclerostin levels, subjects were stratified into a low sclerostin (low scl) group (n=144) and a high sclerostin (high scl) group (n=166). Time-to-event analyses were performed by the Kaplan-Meier method. The associations between sclerostin levels and main the adverse cardiovascular and cerebrovascular events (MACCEs) and mortality were evaluated by Cox multivariate regression analysis.
RESULTS Kaplan-Meier curves showed thatthehigh scl group had a significantly higher MACCE-free rate (log rank P<0.001) and better survival (log rank both P<0.05) than the low scl group did. Serum sclerostin was an independent predictor of MACCEs and all-cause mortality. In addition, serum sclerostin levels were significantly associated with N-MID (β=−0.357, P<0.001), β-CTX (β=0.200, P=0.012), and PINP (β=0.207, P=0.006) levels, a lower presence of multivessel disease (β=−0.223, P=0.005) and lower CCS angina class (β=−0.160, P=0.017).
CONCLUSIONS Serum sclerostin is a prognostic parameter for predicting and intervening in the adverse outcomesof elderly SCAD patients undergoing PCI, which may be explained by its potential role in thebone-vascular axis.
[GW30-e0140]
Jishou Zhang, Jun Wan
Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan 430060, China
OBJECTIVES Previous studies have demonstrated that interleukin 20 (IL-20) is associated with several inflammatory diseases, such as experimental arthritis, osteoporotic bone loss and atherosclerotic plaque formation in mice. However, the expression and clinical significance of IL-20 in coronary artery diseases (CAD) is still unknown.
METHODS Coronary artery tissue samples from normal donors and ischemic cardiomyopathy (ICM) patients who underwent heart transplantation were collected. The expression of IL-20 and its receptors, including IL-20 receptor I (IL-20R I) and IL-20R II, were analyzed in coronary artery tissues. Blood samples were collected from consecutive patients with chest pain who subsequently underwent coronary angiography. Patients were divided into the control group (n=28), stable angina pectoris (SAP) group (n=84) and acute myocardial infarction (AMI) group (n=28). The plasma IL-20 concentrations were evaluated with ELISA kits.
RESULTS The expression levels of IL-20 and its receptors were higher in coronary artery stenosis tissues from ICM patients than in tissues from control patients. Double immunofluorescence showed that CD3+ T lymphocytes were the main source of IL-20. In addition, IL-20 receptors were mainly expressed in T lymphocytes and macrophages in coronary artery tissues. In plasma samples, the plasma IL-20 concentrations were significantly higher in AMI patients than in controls. However, there was no significant difference between the controls and SAP patients. Spearman’s correlation analysis showed that plasma IL-20 was positively correlated with cardiac troponin I, cholesterol, LDL cholesterol, systolic blood pressure and diastolic blood pressure. Multiple linear regression revealed that IL-20 was independently associated with the presence of AMI.
CONCLUSIONS Plasma IL-20 levels were significantly increased in AMI patients but not in SAP patients. IL-20 may be involved in the progression of coronary artery stenosis and plaque vulnerability through regulating CD3+ T lymphocytes and macrophages via binding with its receptors and further participating in the onset of AMI. IL-20 signaling may be a promising biomarker and therapeutic target for AMI.
[GW30-e0141]
Jianqing She 1,2 , Bowen Lou 1,2 , Yangyang Deng 1,2 , Zuyi Yuan 1,2
1Cardiology Department, First Affiliated Hospital of Xi‘an Jiaotong University, Xi‘an, 710048, PR China
2Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi‘an 710048, P.R. China
OBJECTIVES The coexistence of atrial fibrillation and coronary artery disease is commonly found in clinical practice. So far, three RCT trials have evaluated the utilization of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with acute coronary syndrome (ACS) or undergoing percuraneous coronary intervention (PCI). The aim of this meta-analysis is to compare the efficacy and safety of NOACs versus VKA in combination with antiplatelet therapy in AF patients with ACS or undergoing PCI, based on PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS trials.
METHODS We included three phase 3 RCT trials comparing the efficacy and safety of NOACs versus VKA, the PIONEER AF-PCI trial, RE-DUAL PCI trial, and the AUGUSTUS trial. The risk ratios (RR) were extracted from each study. Pooled estimates with corresponding 95% confidence intervals were estimated by a fixed or random-effects model.
RESULTS Three studies involving a total of 9532 patients with AF were included in this meta-analysis. 3995 participants received antiplatelet therapy together with VKA and 5537 together with NOACs. The NOACs group was associated with a significantly lower incidence of all bleeding (RR 1.22, P<0.001), TIMI major (RR 1.60, P=0.004), ISTH major (RR 1.63, P<0.001) bleeding events and intracranial hemorrhage events (RR 3.33, P=0.002) but no difference with regard to ischemic vascular events and mortality rate.
CONCLUSIONS NOACs with either a P2Y12 inhibitor or DAPT has significantly reduced the bleeding events, and similar efficacy were observed in terms of outcomes including stroke, myocardial infarction, in-stent thrombosis, all cause and cardiovascular mortality.
[GW30-e0144]
Jianqing She 1,2 , Bowen Lou 1,2 , Zuyi Yuan 1,2
1Cardiovascular Department, First Affiliated Hospital of Medical College, Xi‘an Jiaotong University, Xi‘an, 710048, P. R. China
2Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi‘an
OBJECTIVES Myocardial free wall rupture (MFWR) refers to laceration of heart ventricle or atria, which is a rare but fatal complication of acute -myocardial infarction (AMI). In this study, we aim to identify clinical characteristics and protective factors of free wall rupture after myocardial infarction.
METHODS This is a single center, retrospective observational analysis. The study screened all patients admitted to the cardiology department of the First Affiliated Hospital of Xi’an Jiaotong University between January 2013 and April 2018. The biochemical, clinical, angiographic and echocardiographic features of these patients were then collected and analyzed.
RESULTS Among 5946 AMI patients screened, 23 patients with the diagnose of MFWR after AMI were enrolled in the present study. 18 (78.3%) patients were diagnosed with acute ST-segment elevated myocardial infarction (STEMI) and the rest 5 (21.74%) have acute non-ST-segment elevated myocardial infarction (NSTEMI). Early phase MFWR happened in 12 (52.2%) and late phase accounted for 8 (34.8%) in total. Late phase MFWR had lower left ventricle ejection fraction value (45.75±5.55% vs. 63.00±3.81%, P<0.001) as compared to early phase. Patients survived from MFWR has higher ACEI/ARB and β-Blocker coverage in the in-hospital treatment of AMI (ACEI/ARB: 100 vs. 35.3%, P=0.014; β-Blocker: 100 vs. 47.1%, P=0.048).
CONCLUSIONS The present study provides evidence for better understanding of clinical characteristics and protective functions in MFWR after AMI. Reduced cardiac function is correlated to higher incidence of later phase FWR. And higher ACEI/ARB and β-Blocker coverage in the AMI treatment strategy is associated with less MFWR incidence.
[GW30-e0146]
Jingxiu LI, Xueqi Li, Yang Li, Shujun Yan, XueYan Zhang, Yingnan Dai, Zhaoyan Song, ShiHao Liu, Xin Li, Yeping Chen, DeJun Xia, Enze Jin
Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China
OBJECTIVES Although impaired platelet responsiveness to clopidogrel is strong predictors of unfavorable outcome after percutaneous coronary intervention (PCI), the impact of high post-treatment platelet reactivity (HPPR) to 600 mg loading dose clopidogrel in Chinese patients with ACS undergoing PCI is still unknown. We sought to determine whether HPPR to 600 mg loading dose clopidogrel affects outcomes in Chinese patients with the acute coronary syndrome (ACS) following the PCI. To investigate whether there might exist a correlation between platelet reactivity unite (PRU) and the character of the patients such as age, gender, diabetes, hemoglobin, AST, ALT, BUN, Crea, Ccr, BMI.
METHODS We did observational research about 134 unselected patients with ACS undergoing urgent or planned PCI with 600 mg loading dose clopidogrel. The platelet activation expressed as the PRU by VerifyNow assay.
RESULTS Among 134 patients (mean age 60.62±9.13, 60.4% male), there were 46 patients with HPR (34.3%) and 88 patients without HPR (65.7%). The univariate analysis revealed a significant inverse correlation between PRU and hemoglobin (r=–0.291, P<0.05). The multivariate linear analysis -identified hemoglobin and gender are independent predictors of PRU (y=456.355–1.736X 1 –31.880X 2 , X 1 : Hemoglobin, X 2 : male). At a mean follow-up of 6±1 months, cardiac death, unstable angina, and rehospitalization for target lesion revascular (TLR) and bleeding events were higher in the HPPR group (19.5 vs. 6.8%, P=0.026). For the logistic regression model, the only independent variables for the incidence of ischemic events were PRU and angiographic characteristics extent of disease (Z=–21.135+0.014X 1 +2.529X 2 , X 1 : PRU, X 2 : angiographic characteristics extent of disease). A receiver-operating characteristic curve analysis, PRU values could significantly discriminate between with and without cardiac death, unstable angina, and rehospitalization for TLR (area under the curve [AUC]: 0.758, 95% confidence interval: 0.62–0.85, P<0.001). By ROC analysis the optimum PRU cutoff for definitely-probable was 176, providing a sensitivity 0.933, specificity 0.602.
CONCLUSIONS In patients with ACS following PCI, the presence of HPPR with clopidogrel 600 mg loading dose is associated with worse outcomes after PCI. There is close correlation between the PRU and hemoglobin and gender. The result of PRU can predict the prognosis such as cardiac death, unstable angina, and rehospitalization for TLR.
[GW30-e0147]
Meng Jiang, Lianna Xie
Zhongshan Hospital Affiliated to Danlian University
OBJECTIVES The primary purpose of this study is to evaluate whether RIC participates in myocardial protection by increasing serum stromal cell-derived factor-1α (SDF-1α) levels in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI)
METHODS Two hundred patients with AMI including acute ST-segment elevation myocardial infarction (STEMI) and acute non-ST-segment elevation myocardial infarction (NSTEMI) were random divided into limb RIC (n=100) group and control group (n=100). AMI patients arrive at the catheterization laboratory, a blood pressure cuff is placed on their right lower limbs by one of the researchers. The limb RIC group underwent 3 cycles of ischemia induced, the control group only underwent PCI. Serum SDF-1α was measured preoperative and postoperative PCI evaluation of during hospitalization and long-term clinical outcomes by echocardiography and major adverse cardiac events (MACE)
RESULTS Compared with the control group, patients in the limb RIC group had a higher postoperative serum SDF-1α (5.04 vs. 8.80%, P=0.006) and left ventricular ejection fraction (LVEF) during hospitalization ((52.48±7.12) vs. (55.74±9.22)%, P=0.007)), whereas long-term MACE was lower (HR=0.45, 95% CI: 0.22–0.87, P=0.020). Postoperative serum SDF-1α levels were negatively correlated with left ventricular end-diastolic diameter (LVDD) (r=–0.346, P=0.006.
CONCLUSIONS This study showed that RIC improved the clinical outcome of patients with AMI undergoing PCI, and that SDF-1α may be involved in the cardioprotective effects of RIC.
[GW30-e0156]
Na Jia, Ruisheng Zhang, Baoyi Liu, Bing Liu, Xin Qi, Ming Lan, Junmeng Liu, Congxia Chen, Wenchan Li, Yue Guo, Zhiming Yao, Qing He
Beijing Hospital
OBJECTIVES Coronary artery disease (CAD) is a challenging affliction which has a high annual morbidity rate in China and the worldwide. Some end-stage CAD patients are not beneficial enough from traditional treatments. Cardiac shock wave therapy (CSWT) is a relatively new therapy for severe CAD patients. Many countries run this program, but rare studies to show the efficacy and safety in elderly patients. Our study is to evaluate the efficacy and safety of CSWT in elderly patients with CAD.
METHODS Patients whose age over 65 years old with multiple or diffused coronary artery lesions and refractory angina were enrolled into this study. They were evaluated by myocardial perfusion imaging (MPI), Canadian Cardiovascular Society (CCS) classification, NYHA classification, nitroglycerin (NTG) usage, 6 minutes’ walk test (6MWT) and Seattle Angina Questionnaire (SAQ) before and after CSWT. The improvement of MPI score in target segments were collected and analyzed. Manual MPI score was evaluated by two nuclear medicine physicians, while automatic MPI score was given by software. All outcomes were assessed at baseline evaluation and 4 months after the initiation of CSWT. Data were compared using paired t-tests. P<0.05 was considered to indicate a statistically significant difference.
RESULTS A total of 32 elderly CAD patients were enrolled. There were 20 males and 12 females. The mean age was 72.81±6.78 years with a range of 65–88 years. 11 patients underwent CABG previously. CCS classification (2.28–1.18, P=0.003), NYHA classification (2.16–1.90, P=0.003), NTG usage (1.48–0.41 pill/day, P=0.03), physical limitation of SAQ (60.07–66.16, P=0.018), angina frequency of SAQ (76.21–84.63, P=0.04), treatment satisfaction of SAQ (74.14–80.13, P=0.005), manual MPI score in stress (2.68–2.12, P=0.01), automatic MPI score in stress (3.14–2.50, P=0.013) and ischemic area in stress (96.43–64.27%, P=0.000) was shown significantly improved after CSWT. The level of TNT, CKMB and BNP was not different before and after treatment.
CONCLUSIONS CSWT is an effective and safe treatment in elderly patients with severe CAD.
[GW30-e0204]
Linying Xue 1 , Zhebin You 1 , Kaiyang Lin 2 , Weiping Zheng 1 , Chunjin Lin 1 , Fan Lin 1 , Yansong Guo 2 , Pengli Zhu 1
1Departments of Geriatric Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Geriatrics, Fujian Medical University, Fuzhou, China
2Department of Cardiology, Fujian Provincial Hospital, Fujian Medical University, Fujian Cardiovascular Institute, Fuzhou, China
OBJECTIVES Inflammatory factors play a critical role in contrast-induced acute kidney injury (CI-AKI). Prealbumin, a nutritional and inflammatory indicator, is a well-established predictor of short- and long-term outcomes in numerous clinical conditions. The present study investigated the association of pre-procedural prealbumin levels with CI-AKI and long-term outcomes in geriatric patients after elective percutaneous coronary intervention (PCI).
METHODS A total of 558 patients aged ≥75 years, who underwent elective PCI between January 2012 and December 2015, were selected for the present study. Pre-procedural prealbumin levels were measured before PCI. Multivariable logistic regression and Cox proportional hazards regression analyses were performed to identify the independent risk factors for CI-AKI and long- term mortality.
RESULTS 54/558 patients developed CI-AKI. The optimal cutoff value of prealbumin for detecting CI-AKI was 185.5 mg/L with 62.7% sensitivity and 70.4% specificity based on the receiver operating characteristic analysis [C statistic=0.710, 95% confidence interval (CI): 0.673–0.751). Multivariable analysis demonstrated that prealbumin ≤185.5 mg/L was significantly associated with CI-AKI [odds ratio (OR)=0.397; 95% CI: 0.195–0.808; P=0.011). Cox regression analysis demonstrated that prealbumin ≤185.5 mg/L was associated with long-term mortality (adjusted hazard ratio (HR)=0.525; 95% CI: 0.289–0.952; P=0.034) during follow-up.
CONCLUSIONS Pre-procedural levels of prealbumin were independently associated with an increased risk of CI-AKI and long-term mortality in elderly patients undergoing elective PCI.
[GW30-e0217]
Liang Geng, Guo Wei, Gao Limin, Li Jiming, Wang Yunkai, Chen Yi Han, Zhang Qi
Shanghai East Hospital
OBJECTIVES The management of intermediate coronary lesions remains a daily challenge for interventional cardiologists. Intravascular ultrasound help achieve better vascular profiling of lumen area and plaque burden, which are related to future outcomes. IVUS also provide vascular geological characteristics such as remodeling index. But the impact of lesion site remodeling on clinical outcomes is still poorly understood.
METHODS We consecutively enrolled 162 patients with coronary heart disease who had at least one intermediate lesion without PCI between August 2011 and January 2015. A total of 212 lesions were assessed by IVUS. The intermediate lesions were divided into 3 groups: RI<0.88 as negative remodeling; 0.88≤RI≤1.0 as intermediate remodeling; RI>1.0 as positive remodeling. The IVUS characteristics and MACE events (cardiac death, myocardial infarction, TLR or rehospitalization due to angina) were compared between 3 groups.
RESULTS Negative remodeling group have the smallest MLA (4.16 mm2 vs. 5.05 mm2; 4.16 mm2 vs. 4.85 mm2; P<0.01) and highest area stenosis rate (59.32±10.15% vs. 54.61±9.09%; 59.32±10.15% vs. 51.67±12.96%; P<0.01) among three groups. During a median follow-up of 5.2 years, the MACE occurred most frequently in the negative remodeling group (41.7 vs. 4.6%; 41.7 vs. 10.5%; P<0.001). After adjusting for multiple covariates, negative remodeling independently predicted future worse clinical outcomes (HR: 4.716; 2.146–10.632; P<0.001).
CONCLUSIONS IVUS derived negative remodeling (RI<0.88) independently predict future MACE of intermediated lesions.
[GW30-e0219]
Li Lei 1,2 , Jin Liu 1 , S. Chen 1 , W. Guo 1 , F. Song 1 , G. Sun 1 , Y. He 1 , Z. Guo 1 , B. Liu 1 , L. He 1 , L. Liu 1,2 , G. Chen 1 , Yong Liu 1
1Department of Cardiology, Provincial Key Laboratory of Coronary Heart Disease, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China
2The Second School of Clinical Medicine, Southern Medical University
OBJECTIVES Percutaneous coronary intervention (PCI) is one of the most commonly performed therapeutic interventions worldwide. However, for relatively stable non-acute myocardial infarction (non-AMI) patients with chronic kidney disease (CKD), the benefits of PCI remain unknown. Therefore we aim to investigate whether myocardial revascularization will lead to decreased mortality in non-AMI patients with CKD.
METHODS A total of 2713 consecutive non-AMI patients with CKD undergoing coronary angiography (CAG) or PCI were divided into a PCI group (n=1604) and a non-PCI group (n=1609) depending on whether they had PCI or not. CKD was defined as estimated glomerular filtration rate (eGFR <90 mL/min/1.73 m2). The endpoint was all cause mortality, which was defined as any death recorded after the date of enrollment. Multivariable logistic regression and Cox proportional hazards regression analyses were performed to identify the association between myocardial revascularization and long-term mortality.
RESULTS Overall, during the mean follow-up of 3.34±0.02 years, mortality was 5.1% (n=49) and 5.7% (n=27) in PCI group and non-PCI group, respectively. Multivariable logistic regression analysis showed that PCI, CKD G4 (eGFR 15–30 mL/min/1.73 m2), age>75 years, pre-procedure hypotension and the use of diuretics were significantly associated with worse long-term mortality [HR of 1.462 (95% CI: 1.035–2.063), HR of 5.488 (95% CI: 3.258–9.245), HR of 1.557 (95% CI: 1.105–2.195), HR of 2.335 (95% CI: 1.153–4.729), and HR of 1.737 (95% CI: 1.239–2.435), respectively]. Log-rank analyses showed that there was no difference in all-cause mortality between PCI group and non-PCI group (P=0.095). Patients with worse renal function were less likely to obtain benefit and may even get harm from PCI. (P<0.05).
CONCLUSIONS Myocardial revascularization is not associated with decreased mortality in non-AMI patients with CKD. Further investigation is needed to evaluate whether such patients will obtain benefit from PCI.
[GW30-e0255]
Tong Yin 1 , Dandan Li 1 , Zheng Wan 2 , Zhanquan Li 3 , Hongliang Cong 4 , Tao Hong 5 , Wei Dong 1 , Yundai Chen 1
1The Chinese PLA General Hospital (301 Hospital)
2Tianjin Medical University General Hospital
3The People’s Hospital of Liaoning Province
4Tianjin Chest Hospital
5Peking University First Hospital
OBJECTIVES To explore and compare pharmacodynamic profile of ticagrelor and clopidogrel in Chinese patients with ACS.
METHODS This multicentre, open-label, phase IV, randomized trial was conducted between May, 2013 and March, 2014 in China with 6 weeks follow-up period. Patients with ACS were randomized (1:1) to receive ticagrelor (180 mg loading dose, later 90 mg twice daily) or clopidogrel (600 mg loading dose, later 75 mg once daily [QD]), along with background aspirin therapy (300 mg loading dose, later by 100 mg QD). The primary outcome was P2Y12 reaction unit (PRU) measured by VerifyNow at 2 h post-loading dose. Secondary outcomes included PRU, inhibition of platelet aggregation (IPA%: 100×[PA predosing–PA postdosing/PA predosing]; PA: platelet aggregation) and percentage of patients with.
RESULTS A total of 60 patients (mean age: 58.7±10.3 years; 82.5% males; FAS, n%: 96.55%; PPS, n%: 89.66%) with comparable baseline features were randomized to ticagrelor (n=29) and clopidogrel (n=31) treatment arms. PRU at 2 h after loading dose was significantly better in ticagrelor arm (130.9±111.3 vs. 228.83±74.1; P=0.0002). After 2 h of loading dose, ticagrelor caused rapid and significantly higher IPA% (2 h: 51.6±45.4 vs. 8.4±25; 8 h: 67.9±34.9 vs. 25.4±32.7, 24 h: 79.2±17.9 vs. 28.8±26.9; 6 weeks: 82.8±13.9 vs. 24.22±33.5) and reduced PRU (8 h: 84±87.6 vs. 190.3±86.8; 24 h: 57.2±50.4 vs. 183.7±79.4; 6 weeks: 45.2±42 vs. 187.6±82.8) than clopidogrel (P≤0.0001 for all). Higher proportion of ticagrelor-treated patients had PRU <0.0001; PRU: P=0.0002).
CONCLUSIONS Ticagrelor induced faster and better antiplatelet effect than clopidogrel in Chinese patients with ACS; however, the effect was lower in STEMI patients as compared to that in NSTEACS patients. The safety profiles of both the drugs were comparable.
[GW30-e0310]
Wendong Tang, Pan Li, Xiaxian Shen, Hailing Li, Yuan Bai, Ni Zhu, Bili Zhang, Zhifu Guo, Hong Wu, Xianxian Zhao
Department of Cardiology, Changhai Hospital, Second Military Medical University
OBJECTIVES Carotid ultrasound has been widely used in the risk assessment of coronary artery disease (CAD). Data regarding the relationship between carotid plaque length (CPL) and CAD are lacking. We evaluated whether CPL had independent and incremental predictive value for the presence or severity of CAD.
METHODS We prospectively enrolled 2149 consecutive patients who underwent both first coronary angiography (CAG) and carotid ultrasound with measurements of mean intima-media thickness (mean-IMT), plaque score (PS), and maximal CPL (max-CPL). The severity of CAD was measured by the Gensini score (GS), and it was divided into tertiles: low, intermediate, and high GS. Ultrasound parameters were tested for their incremental value to predict CAD or high GS over traditional risk factors (TRF). Logistic regression analysis was used to evaluate the association between the three parameters and coronary stenosis. We calculated the area under the curve (AUC) and net reclassification improvement (NRI) to determine the predictive value of different models.
RESULTS The prevalences of CAD and high-GS patients were 65.5% (n=1408) and 33.5% (n=719), respectively. Patients with CAD had longer max-CPL than those without CAD (mean 8.31±6.12 vs. 3.05±4.13 mm, P<0.001). The GS was closely correlated with max-CPL, followed by PS and mean-IMT (P<0.001). Multivariate analysis demonstrated that max-CPL remained independently associated with both CAD (odds ratio: 1.19, P<0.001) and high-GS (odds ratio: 1.23, P<0.001) after adjusting for TRF. Compared with PS or mean-IMT, max-CPL had significantly higher discrimination value for predicting CAD (AUC 0.767 vs. 0.738 vs. 0.642, P<0.001) and high-GS (AUC 0.819 vs. 0.769 vs. 0.634, P<0.001). At a cut-off value for the max-CPL of 6.3 mm, the sensitivity and negative predictive value for high-GS were 84.6 and 89.1%, respectively. Moreover, max-CPL demonstrated significant incremental prediction for high GS over mean-IMT; this was true for both discrimination (AUC 0.821 vs. 0.634, P<0.001) and reclassification (NRI=0.474, P<0.001). When added to TRF, max-CPL showed the highest incremental predictive value for CAD (AUC=0.823, NRI=0.208, P<0.001 for both), and the same was true for high-GS (AUC=0.832, NRI=0.431, P<0.001 for both).
CONCLUSIONS Ultrasound max-CPL had independent and incremental predictive value over TRF for the presence and severity of CAD. And max-CPL had higher incremental value than mean-IMT for detecting CAD and high GS. Furthermore, max-CPL could improve CAD risk prediction when added to mean-IMT. Thus, max-CPL measured by carotid ultrasound seemed to be an effective marker of high-risk patients to refer to CAG.
[GW30-e0357]
Xiaojuan Fan, Ping Liu
Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi, China
OBJECTIVES There is no definite recommendation of reperfusion time for inferior ST-elevation myocardial infarction (STEMI) patients presenting later than 12 h from symptom onset when complicating new atrioventricular block (AVB) on admission. It is not clear whether the percutaneous coronary intervention (PCI) could facilitate the recovery of AVB or not.
METHODS We conducted a retrospective study including 52 consecutive inferior wall STEMI patients with presenting time >12 h and complicating second or third-degree AVB on admission. All of them underwent PCI. The clinical characteristics, time to PCI after symptom onset, procedural data, and time to AVB improvement were studied.
RESULTS There were 42 males and the mean age was 61±10 yrs. Median presenting time from symptom onset was 36 h (ranging 13–192 h). Median time to PCI after MI was 6.0 days (ranging 1–15 days) and median time course of AVB improvement from symptom onset was 5.0 days (ranging 1–15 days). 24 patients got AVB improvement before PCI procedure (defined as preoperative group) and 28 patients got AVB improvement after PCI procedure (defined as postoperative group). The median time of AVB getting improvement was 5.0 days vs. 5.5 days (P=0.367) in preoperative and postoperative group respectively. In the postoperative group, there was a strong association between time to PCI and time to AVB improvement (r s =0.869, P=0.000) by Spearman correlation analysis. No adverse PCI procedure-related complications or death occurred and all the patients got complete AVB recovery at discharge.
CONCLUSIONS Early PCI was safe and should be recommended as the priority strategy for late presentation inferior STEMI patients when complicating new onset of AVB. Successful reperfusion of the infarct-related artery was helpful to facilitate AVB improvement in this situation.
[GW30-e0359]
Gao Yang 1 , Dalin Jia 1
1First Affiliated Hospital, China Medical University
2Central Hospital, Shenyang Medical College
OBJECTIVES Mechanism of lycopene in alleviating endoplasmic reticulum stress induced by hypoxia/reoxygenation in H9C2 cardiomyocytes.
METHODS H9C2 cardiomyocytes were randomly divided into control group, lycopene group, H/R group, lycopene+H/R group, 4-phenyl butyric acid (4-PBA)+H/R group, thapsigargin (TG) group, and lycopene+TG group. The apoptosis ratio of H9C2 cardiomyocytes was detected and the expressions of protein of glucoseregulated proteins 78 (GRP78), C/EBP homologous protein (CHOP), c-Jun-N-terminal protein kinase (JNK), phosphorylation of JNK (p-JNK) and caspase-12 were detected by Western blot.
RESULTS The apoptosis ratio and the expressions of protein of GRP78, CHOP, JNK, p-JNK and caspase-12 increased markedly in H/R group and TG group in comparison with those in the control group (P<0.01). They decreased markedly in lycopene+H/R group and 4-PBA+H/R group compared with those in H/R group (P<0.01) and in lycopene+TG group compared with those in TG group (P<0.01). No statistically significant difference was found between lycopene+H/R group and 4-PBA+H/R group. No significant difference was found in the changes of the expression of protein of JNK.
CONCLUSIONS Lycopene may exert its protective effect on H/R H9C2 cardiomyocytes through inhibiting the key signaling pathways of CHOP, p-JNK and caspase-12 to reduce ERS.
[GW30-e0360]
Li Xiaoyan, Dalin Jia
The First Affiliated Hospital of China Medical University
OBJECTIVES Celastrol, a major active constituent of Tripterygium wilfordii, has antioxidant, anti-inflammatory, and anticancer effects. However, whether celastrol can exert protective effect on myocardial ischemia–reperfusion injury (MIRI) is unknown. The aim of this study was to test the protective effect of celastrol on MIRI and elucidate its underlying mechanism.
METHODS Cardiomyocytes (H9C2 cells) were subjected to hypoxia for 8 h followed by reoxygenation for 4 h to create hypoxia/reoxygenation (H/R) model, an in vitro MIRI model. Celastrol was added to the medium 60 min before the H/R process. Cell viability was detected using MTT assay. Myocardial injury was evaluated by measuring lactate dehydrogenase (LDH) and creatine kinase MB isoenzyme (CK-MB) activity. Changes in mRNA and protein expression of TNF-α, IL-1β, and nuclear factor-KB (NF-KB) were measured with RT-qPCR assay and western blot analysis.
RESULTS Results showed that low-dose celastrol (20 and 50 nM) treatment significantly increased cell viability and decreased LDH and CK-MB activity in the condition of H/R, but high-dose celastrol (200 and 400 nM) resulted in extra injury to cardiomyocytes. Moreover, treatment with 50 nM celastrol significantly downregulated mRNA and protein expression of TNF-α and IL-1β. Meanwhile, NF-KB mRNA and protein in the nucleus were also correspondingly reduced.
CONCLUSIONS Our study demonstrated that low-dose celastrol could prevent MIRI in cardiomyocytes by inhibiting the activation of NF-KB, and celastrol may be a potential therapeutic agent for preventing MIRI.
[GW30-e0380]
Jieyun You, Qi Zhang, Qi Zhang
Department of Cardiology, Shanghai East Hospital, Tongji University
OBJECTIVES Dual antiplatelet therapy (DAPT) with aspirin and P2Y12 antagonists has become the standard therapy for preventing adverse cardiovascular events after percutaneous coronary intervention (PCI). Evidence for platelet function testing (PFT)-based antiplatelet therapy is limited for patients with acute myocardial infarction (AMI) and left ventricular dysfunction underwent contemporary PCI.
METHODS We prospectively enrolled 824 consecutive patients subjected to AMI with left ventricular ejection fraction (LVEF) <0.5 undergoing PCI based on the Shanghai East Hospital PCI database since 2012. All these patients received loading dose DAPT with aspirin and a P2Y12 inhibitor (clopidogrel or ticagrelor). Platelet function was assessed more than 72 h post-PCI by vasodilator-stimulated phosphoprotein (VASP) assay. In total, 212 patients (25.73%) were identified with HPR on P2Y12 antagonists, among whom 102 patients (48.11%) adjusted antiplatelet therapy based on PFT. The primary endpoint was major adverse cardiac events (MACE) and the secondary endpoint was major bleeding (BARC grade≥3) 1 year after PCI.
RESULTS Kaplan-Meier survival analysis demonstrated higher mortality in the HPR group during the 1-year follow-up (HR 0.11, 95% CI 0.04–0.28, P<0.01). MACE at 1 year post-PCI was significantly higher in the HPR group (44.81 vs. 21.24%, P<0.01; OR: 3.01, 95% CI: 2.16–4.20), mainly driven by the higher risk of cardiac death, cardiac shock, malignant arrhythmia, stent thrombosis, nonfatal myocardial infarction, target vessel revascularization (TVR) and ischemic stroke (P<0.05). For patients with HPR on P2Y12 antagonists, the intensified antiplatelet strategy by switching from clopidogrel to ticagrelor, but not double-dose clopidogrel, significantly reduce the incidence of MACE when compared with continuing maintenance dose of DAPT (12.00 vs. 60.00%, P<0.01; OR: 0.09, 95% CI: 0.04–0.23). The incidence of major bleeding (BARC grade≥3) was comparable among all groups (P>0.05).
CONCLUSIONS For post-AMI patients with left ventricular dysfunction undergoing PCI, PFT-guided intensified antiplatelet therapy with ticagrelor reduced major cardiovascular events without increasing the risk of bleeding.
[GW30-e0381]
Diljan Mansoor, Liang Long Chen, Professor Dr.
Fujian Medical University Union Hospital
OBJECTIVES This study aims: (1) to set up a method to detect BFC/POC shape and to its dimension in different bifurcation types and locations; (2) to validate the four models base on the coronary bifurcation measurements from normal population; (3) to investigate potential relevance of the BFC/POC morphology in CBLs interventions.
METHODS Inclusions criteria: (1) subjects with unknown chest discomfort in whom coronary artey disease could be finally excluded clinically, (2) subjects underwent CCTA with normal or negative findings either by CCTA or invasive coronary angiography if obtainable, (3) images of CCTA with high quality.
RESULTS Normal coronary segmentation of a normal case took 20–25 minutes for centerlines and 7 minutes for the mesh computation. Registration time was approximately 40 seconds for the rigid part and 3 minutes for the non rigid on a macbook pro 1-14.3 system with 8 GB of memory and 2.3 GHz intel core i5 processors. Average normal minimum lumen area within the LM were mainly located within POC (51 and 71%). Distal LM proximal to the carina (to include DLM and POC) positively correlated with the normal coronary bifurcation MLA within the POC (r=0.283, P=0.02; BFC within the POC less than 6.1 mm± 2.1 mm (2). The approximate median registration error was 0.29 mm with a median standard deviation of 0.19 mm and a median maximum error of 1.39 mm. Maximum error occurred in areas of high deformation such as large or curved ostium shape. In total where n=330 bifurcations models as follow LMB=100, D1=55, LAD=40, OM1=40, POC=25, LCX=20 and 50 cruxes. Having removed isotropic size (scaling factor), the average model and first three models of variation.
CONCLUSIONS Clinically very important insights and information concluded from normal coronary bifurcation anatomy such as defining normal range and distribution of shape. This method is more like computational which confirms in a quantifiable and computational fashion. This is far superior over a long standing questions of statistically significant shape differences among the major coronary bifurcation in interventional cardiology. The model support and applicable to any collection of shape and can be applied to create a probability model of the major coronary bifurcations. The BFC/POC within the bifurcation was a good surrogate reflecting the overall normal shape of LM bifurcation including ostial LCX and the ability to measure normal distal LM shape as well as final ostial LCX lumen area. Information about the size (and future shape), clinical doctors will have great stent designs and benefits and can span the populations size. According to individual specific patient geometry within the statistical shape, individual stent can be designed or selected, which will reduce the burden of choosing random stent.
[GW30-e0410]
N.A. Musikhina, I.S. Bessonov, N.A. Galeeva, T.I. Petelina, E.A. Gorbatenko, L.I. Gapon
Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia
OBJECTIVES To carry out a comparative analysis of the dynamics of biochemical markers of vascular wall inflammatory response in patients with stable coronary artery disease (CAD) after angioplasty of BS and stents coated with everolimus.
METHODS Forty-one patients (mean age 62.7±8.6 years) with stable CAD and single-vessel coronary lesion were examined according to coronary angiography and indications for percutaneous coronary intervention (PCI). The study did not include patients who underwent PCI or coronary artery bypass grafting in the previous year, with the presence of restenosis in the stent. Group 1 included 21 patients with an implanted stent coated with everolimus (Xince Prime); group 2 included 20 people with an implanted BS (Absorb). Randomization was carried out by the random number method. All patients received optimal medical treatment that included statins and dual antiplatelet therapy. Endothelial dysfunction markers (endothelin-1, nitrites); inflammatory markers (hs-CRP, TNF-alpha, homocysteine, interleukine 1β, 6, 8, 16; sCD40 L, MMP-9, TIMP-1) were measured. The parameters were evaluated at baseline, 1, 4 days and 1, 6, 12 months after PCI.
RESULTS In the studied groups no undesirable atherothrombotic events were revealed during the follow-up. Initially, the groups did not differ in biochemical parameters before PCI. In both groups, 1 day after PCI, the increase in cytokines was registered, followed by a decrease in 4 days to the initial level and MMP-9, while maintaining a high concentration for 1 month. In both groups, 1 month after PCI, an increase in IL-8 was registered as a response to damage to the vascular wall, followed by an increase to the maximum values in 12 months. In dynamics, the maximum increase in CD40L after 6 months without reaching the initial level after 12 months was observed only in group 2. In the compared groups, after 12 months, the maximum values of endothelin-1 as a marker of vascular endothelial dysfunction were registered in group 1, while in group 2 this figure decreased to the initial level. Both groups maintained a high level of hs-CRP.
CONCLUSIONS Patients with stable CAD after implantation of BS and stents coated with everolimus did not show any differences in the dynamics of the mediators of the acute phase of inflammation during the 1 month. High levels of pro-inflammatory factors of instability of the atherosclerotic plaque IL-8 and CD40L, as well as a persistent increase in the concentration of hs-CRP within 1 year after PCI suggest a continuing high risk of thrombosis, more pronounced in the group with implanted BS.
[GW30-e0426]
Pan Li, Wendong Tang, Xianxian Zhao
Department of Cardiology, Changhai Hospital, Second Military Medical University
OBJECTIVES Carotid ultrasound parameters, such as intima-media thickness (IMT) and carotid plaque thickness have been proven to be associated with the prevalence of coronary artery disease (CAD), whereas they are far from optimal for clinical utility, due to small differences among individuals and slight annual changes. So far, data regarding the relationship between carotid plaque length (CPL) and the presence and severity of CAD are lacking. The aim of the study was to evaluate the emerging role of CPL as an effective marker of CAD risk.
METHODS We prospectively enrolled 2149 consecutive patients who underwent both first coronary angiography (CAG) and carotid ultrasonography with measurements of intima-media thickness (IMT), plaque score (PS), and CPL.
RESULTS In total, 1408 (65.5%) had CAD (defined as stenosis ≥50%), and 741 (34.5%) had no CAD. Patients with CAD had longer maximal CPL than those without CAD (mean 8.31±6.12 vs. 3.05±4.13 mm, P<0.001). The severity of CAD, measured by the Gensini score (GS), was closely correlated with max-CPL, followed by PS and mean-IMT. After adjustment for traditional risk factors, max-CPL remained independently associated with CAD and high-GS. Max-CPL, compared with PS or mean-IMT, had significantly higher discrimination value for predicting high-GS (area under the curve 0.819 vs. 0.769 vs. 0.634, P<0.001). At a cut-off value for the max-CPL of 6.3 mm, the sensitivity and negative predictive value for high-GS were 84.6 and 89.1%, respectively. Furthermore, the addition of max-CPL improved the discrimination (AUC 0.821 vs. 0.634, P<0.001) and reclassification (net reclassification improvement [NRI]=0.474, P<0.001) over mean-IMT.
CONCLUSIONS Ultrasound max-CPL has independent and incremental value for predicting the presence and severity of CAD. Max-CPL seems useful to identify high-risk patients to refer to CAG.
[GW30-e0472]
Yuehua Ruan, Renqiang Yang
The Second Affiliated Hospital of Nanchang University
OBJECTIVES To investigate the clinical, characteristics of lesion procedural characteristics and prognoses of coronary stent fracture (CSF).
METHODS From January 2012 to December 2017, 14,717 patients underwent drug-eluting stents implantation in the Department of Cardiology, the Second Affiliated Hospital of Nanchang University. The angiograms of all 2098 patients who underwent repeat angiography or more advanced imaging examination were studied to identify the presence of stent fracture, then to count the detection rate of coronary stent fracture. The clinical, characteristics of lesion procedural characteristics and prognoses which might predispose to stent fracture were systematically analyzed. The symptoms, vital signs and main adverse cardiac events (MACE) of patients with stent fracture were followed up regularly and analyzed in combination with the relevant literature.
RESULTS The patients of coronary stent fracture was found in 9 patients during the period 2012–2017, with a detection of 0.4%. Open-loop design, alloy material, sirolimus eluting stent, angulated lesions and the right conorary are risk factors that leading to the coronary stent fracture. Follow-up as of December 31, 2018, 2 cases of 9 patients follow-up results in death, more than 3 cases of unstable angina in patients, 2 cases of stable angina, 2 cases of chest has no obvious symptoms such as chest pain. 9 cases of major adverse cardiac events in patients with follow-up, there are 4 cases with routine target-vessel revascularization (TVR). There have no patient with cardiac death, myocardial infarction and in-stent thrombosis, all patients with coronary stent fracture can be found in varying degrees of coronary stent hyperplasia.
CONCLUSIONS There is low detection rate of coronary stent fracture by using the coronary angiography. Predisposing factors of stent fracture may be associated with the open-loop design, alloy material, sirolimus eluting stent, angulated lesions and the right conorary. The main adverse cardiac events that affect coronary stent fracture are target lesion revascularization (TLR).
[GW30-e0486]
Ying-Ying Zheng 1,2 , Xie Xiang 1,2 , Xie Xiang 2
1Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P.R. China
2Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, P.R. China
OBJECTIVES The present study aimed to investigate the efficacy and safety of long-term DAPT (>18 months) after PCI.
METHODS A total of 4447 CAD patients after PCI from CORFCHD-PCI, aretrospective cohort study (Identifier: ChiCTR-INR-16010153) were divided into 3 groups (No antiplatelet therapy group [NAPT group, n=1242], Monotherapy of aspirin or clopidogrel group [SAPT group, n=2188], and DAPT group, n=1017) according to antiplatelet therapy situation after administration of 18-month DAPT. All the patients were followed up for at least 24 months and the longest follow-up time is 120 months. The primary endpoint was the mortality and the secondary endpoints were the major adverse cardiac events (MACEs) and bleeding events.
RESULTS The all-cause mortality (ACM) and cardiac mortality (CM) were significantly increased in the NAPT group compared to that in the DAPT group (15.6 vs. 0.6%, P<0.001; and 12.1 vs. 0.3%, P<0.001, respectively) or in the SAPT group (15.6 vs. 0.6%, P<0.001; and 12.1 vs. 0.5%, P<0.001, respectively). We did not found significant difference in mortality (ACM or CM) between the SAPT group and the DAPT group (P=0.611 or P=0.328). The incidence of MACEs was significantly increased in the DAPT group compared to SAPT group (16.3 vs. 9.4%, P<0.001). We also found DAPT increased the bleeding events compared to SAPT (4.6 vs. 2.4%, P<0.001).
CONCLUSIONS The present study suggests that long-term dual antiplatelet therapy longer than 18 months significantly increased the incidence of MACEs and bleeding events after PCI.
[GW30-e0487]
Ying-Ying Zheng 1,2 , Xie Xiang 2
1Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P.R. China
2Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, P.R. China
OBJECTIVES The relation between GGT and outcomes of coronary artery disease (CAD) patients underwent PCI remains controversial. The present study aimed to investigate the association of physiological serum GGT with the long-term up to 10-year follow-up mortality of CAD patient after percutaneous coronary intervention (PCI).
METHODS A total of 6050 CAD patients after PCI from CORFCHD-PCI, a retrospective cohort study (Identifier: ChiCTR-INR-16010153) were evaluated. 412 patients were excluded due to no GGT data available, acute infections, malignancies, hepatobiliary disease or alcohol abuse. 614 patients were further excluded for abnormal high activity of GGT (GGT>60 U/L). Finally, 5024 patients with physiological concentration of GGT were enrolled. The primary outcome was long-term mortality after PCI. The main secondary endpoints were stroke, readmission, and major adverse cardiovascular events (MACEs) defined as the combination of cardiac death, stent thrombosis, recurrent myocardial infarction, and target vessel reconstruction.
RESULTS Patients were divided into 3 groups according to GGT tertiles: 1st tertile (GGT<19.6 U/L; n=1865), 2nd tertile (GGT≥19.6 U/L–32.9 U/L; n=1880) and 3rd tertile (GGT>32.9 U/L; n=1269). Overall, there were 264 all-cause mortality (ACM) during the following up. The incidence of ACM in the 1st tertile is 111 (5.9%), 2nd tertile is 100 (5.3%), and 3rd tertile is 53 (4.2%). The ACM incidence was significantly lower in 3rd tertile compared to that in the 1st tertile (P=0.031). Cardiac mortality (CM) occurred in 212 patients: 92 (4.9%) in the 1st tertile group, 80 (4.3%) in the 2nd tertile and 40 (3.2%) in the 3rd tertile group. There was significant difference in the CM incidence between the 1st tertile group and 3rd tertile group (P=0.016). The multivariate Cox proportional hazards model showed that decreased serum GGT level was independently correlated with the ACM (adjusted HR=1.431 [1.025–1.998], P=0.035) and CM (adjusted HR=1.553[1.064–2.267], P=0.023), We did not found significant difference in the incidence of MACEs, stroke, bleeding events and readmission among these three groups.
CONCLUSIONS The present study indicated that decreased physiological serum GGT concentration was independently associated with long-term mortality in CAD patients underwent PCI.
[GW30-e0489]
Ying-Ying Zheng 1,2 , Xie Xiang 2 , Xie Xiang 2
1Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P.R. China
2Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, P.R. China
OBJECTIVES Both gamma-glutamyl transferase (GGT) and albumin have been reported to be associated the risk and mortality of coronary artery diseased (CAD) with or without percutaneous coronary intervention (PCI). GGT is an important enzyme in glutathione (GSH) metabolism and has been found to be involved in the pathogenesis of CAD. Albumin is the major protein in human plasma and has generally been used as a quantitative measure of nutritional status. Recently, serum albumin concentrations were reported to be associated with increased risk for the development of myocardial infarction (MI), CAD and stroke. Therefore, the ratio of GGT to albumin (GAR) may be a powerful predictor for outcomes in cardiovascular disease. However, the relation between GGT to albumin ratio (GAR) and outcomes in CAD patients after PCI has not been investigated.
METHODS In the present study, we enrolled 5638 CAD patients underwent PCI who were from the Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI (CORFCHD-PCI) study. The patients with serious heart failure, rheumatic heart disease, valvular heart disease, congenital heart disease, pulmonary heart disease, and serious dysfunction of liver or kidney were excluded from the present study. 5638 patients were divided into two groups according to GAR (GAR<0.62, n=2712 and GAR≥0.62, n=2926). The primary outcome was long-term mortality including all-cause mortality (ACM) and cardiac mortality (CM) after PCI. The average follow-up time is 35.9±22.6 months.
RESULTS We found there was significant difference between the two groups in the incidence of all-cause mortality (P=0.016) and bleeding events (P=0.010). Multivariate Cox regression analyses suggested that compared to the patients in the lower GAR, the risk of ACM and bleeding events were decreased 23.8% (Hazard risk [HR]=0.762 95% CI: 0.601–0.966, P=0.025), and 39.4% (HR=00.616, 95% CI: 0.446–0.852, P=0.003) in the higher GAR group, respectively, during the long-term follow-up.
CONCLUSIONS The present study indicated that GAR is an independent and novel predictor of mortality and bleeding events in CAD patients underwent PCI.
[GW30-e0496]
C. Richard Conti, MD
University of Florida
OBJECTIVES Ventriculography done in the catheterization laboratory provides more information than ultrasound ventriculography.
METHODS Catheter based ventriculography vs. Ultrasound ventriculography performed in a single laboratory.
RESULTS One observational study of myocardial infarction patients, prior to PCI/stent revealed an increasing 30-day mortality related to poor LV function determined by cardiac ultrasound Advantages of Catheter Based Ventriculography Catheter base Left Ventriculography provides data on wall motion, volume, ejection fraction, chamber size, valvular regurgitation and helps predict the outcome of patients with coronary artery disease. It is the only method to accurately evaluate LVEDP, and LV Systolic pressure. LV angiography can also identify regional LV wall motion abnormalities consistent with abnormalities found in the epicardial coronaries and coronary microcirculation. LV angiography can also identify regional LV wall motion abnormalities consistent with abnormalities found in the epicardial coronary arteries. Limitations of catheter based LV angiography include: There are no specific guidelines, from ACC, AHA, ESC or SCAI for the performance of left ventriculography at the time of coronary angiography or left heart catheterization. Radiation exposure, contrast-induced AKI and invasive procedure. Advantages of Ultra Sound Readily available, relatively inexpensive, and portable. Can be easily repeated no radiation exposure. Limitations of Ultrasound Studies have shown that quantitative assessment of LV function by 2D TTE is suboptimal in up to 20 percent of patients. Foreshortening of the heart sometimes seen with ultrasound makes interpretation of LV function difficult. Ultrasound may be performed by an experienced sonographer, who does not know the patient’s physiology or anatomy and, not by a physician who knows the state of the coronary artery pathology. If Echo is used to assess L V function then the Cath Lab operator should be aware of the quality of the Echo and the findings of ventricular function before the patient enters the catheter laboratory and include in the Cath lab report the reason for not doing an LV angiogram.
CONCLUSIONS All things considered I favor catheter based ventriculography.
[GW30-e0497]
Heyu Meng, Xue Wang, FanBo Meng
Department of Cardiology China-Japan Union Hospital of Jilin University
OBJECTIVES Suppressor of cytokine signaling 3 (SOCS3) is a member of the suppressor of cytokine signaling (SOCS) family. SOCS regulates cells’ responses to external stimuli through a common molecular mechanism. The disorder of SOCS3-mediated cytokine signaling can cause many diseases, including allergies, autoimmune diseases, inflammation and cancer. In addition, the pathogenesis of acute myocardial infarction (AMI) and coronary atherosclerosis is increased vascular responses to inflammation, and a considerable amount of research shows that atherosclerosis is an inflammatory disease. The aim of this study was to evaluate the possibility of using SOCS3 gene expression as a biomarker for predicting the risk of AMI.
METHODS Peripheral white blood cells were collected from 113 patients with AMI and 85 patients with stable coronary artery disease (SCAD). The SOCS3 mRNA expression in peripheral blood was detected by real-time quantitative polymerase chain reaction. Western-blot was used to detect the differences in SOCS3 gene expression at the protein level.
RESULTS The expression level of SOCS3 mRNA in peripheral blood of patients with AMI was 1.33 times higher than that of patients with SCAD, and the expression of SOCS3 genes at the protein level was 1.250 times higher than that of patients with SCAD (both P<0.05). Bivariate logistic regression analysis showed that the high expression of SOCS3 gene was an independent risk factor for AMI, which increased the risk of AMI by 3.197 times. It was also found that there was no correlation between the high expression of SOCS3 genes and fasting blood glucose level, high-density lipoprotein, low-density lipoprotein and cardiac troponin level.
CONCLUSIONS The expression level of SOCS3 genes in patients with AMI was significantly higher than that in patients with SCAD. High expression of SOCS3 genes is an independent risk factor for AMI. It is probable that the high expression of SOCS3 genes increases the risk of AMI by increasing inflammatory responses. High expression of SOCS3 genes may serve as a potential biomarker for predicting the risk of AMI.
[GW30-e0518]
Mengli Zhou, Hong Yuan
The Third Xiangya Hospital of Central South University
OBJECTIVES Anti-hypertension drugs together with DAPT are widely used in ACS patients to reduce the incidence of ischemic events. Bleeding is the most common non-cardiac complication in ACS patients with DAPT. However, the impact of anti-hypertension drugs on bleeding events in ACS patients with DAPT is still unclear. The study is to investigate the association between anti-hypertension drugs and bleeding events in ACS patients with DAPT.
METHODS This retrospective study involved 2017 ACS patients with hypertension in Third XiangYa Hospital of Central South University from April 2007 to July 2017. The patients were divided into two groups: bleeding group (n=154) and non-bleeding group (n=1863). Logistic regression was used to examine the association between anti-hypertension drugs use and bleeding events in ACS patients.
RESULTS Baseline characteristics between bleeding and non-bleeding groups: Totally, 2017 patients were included in the study; 154 patients (7.6%) did not have bleeding events (non-bleeding group), 1863 patients (92.4%) had bleeding events (bleeding group).
Demographic data: The SBP, DBP and female people were similar between the two groups (P>0.05). The people were older and the HR was greater in the bleeding group than in the non-bleeding group.
Past history: The number of patients whose Killip grades>1 and the number of smokers were similar between the two groups (P>0.05).
Baseline Laboratory Examination: The Hg, CCr, TP and ALB were lower in the bleeding group than in the non-bleeding group (P<0.05). The AST was higher in the bleeding group than in the non-bleeding group (P<0.05). The RDW, PLT, ALT and Hct were similar between the two groups (P>0.05).
Immediate therapy: The use of β-blocker, ACEI, ARB or CCB in bleeding group was significantly less than that in the non-bleeding group (P<0.05). There were no differences in the number of patients with diuretics, vasodilators, statin, anticoagulant, PPI or PCI between the bleeding group and the non-bleeding group (P>0.05).
The association between anti-hypertension drugs and bleeding events: The incidence of bleeding events was lower in patients with the anti-hypertension drugs of β-blocker, ACEI, ARB and CCB (P<0.05). The incidence of bleeding events was similar in patients with the anti-hypertension drugs of diuretics and vasodilators (P>0.05). After adjustment for covariates, patients with β-blocker, ACEI, ARB have lower bleeding incidence. ((β-blocker OR 0.48, 95% CI (0.31, 0.72), P<0.001; ACEI OR 0.48, 95% CI (0.31, 0.74), P=0.001; ARB OR 0.54, 95% CI (0.31, 0.95), P=0.020).
Independent predictors of bleeding events: The following baseline characteristics were independent predictors of increased bleeding events: no treatment with β-blocker, ACEI, ARB, greater HR and lower ALB.
CONCLUSIONS We studied the association between bleeding events and the use of anti-hypertension drugs in 2017 ACS patients with hypertension in XiangYa third hospital from April 2007 to July 2017. The use of β-blocker, ACEI and ARB could reduce the incidence of bleeding events among ACS patients with hypertension (P<0.05).
[GW30-e0543]
Zheng Ying-Ying 1,2 , Xie Xiang 1 , Xie Xiang 1
1Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P.R. China
2Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, P.R. China
OBJECTIVES Inflammation-related immune cell and acute phase reactive protein are the bio-markers of systematic inflammation, and the levels of them can reflect the degree of chronic inflammation in the patient. A novel AFR–Alb-derived neutrophil/lymphocyte ratio (dNLR) score (ADS) were reported to associate with clinical outcome in various malignancies, However, the relation between the ADS score and outcomes in CAD patients after percutaneous coronary intervention (PCI) has not been investigated.
METHODS Six thousand fifty patients were divided into 2 groups according to ADS score: Low group (ADS score <2; n=2508) and High group (ADS score ≥2; n=3542). Overall, there were 309 all-cause mortality (ACM) during the following up.
RESULTS The incidence of ACM in the low group is 156 (4.4%) and high group is 153 (6.1%). The ACM incidence was significantly higher in high group compared to that in the low group (P=0.004). Cardiac mortality (CM) occurred in 251 patients: 119 (3.4%) in the low group and 132 (5.3%) in the high group. There was significant difference in the CM incidence between the low group and high group (P<0.001). Major adverse cardiac and cerebrovascular events (MACCE) occurred in 862 patients: 422 (11.9%) in the low group and 398 (15.9%) in the high group. There was significant difference in the MACCE incidence between the low group and high group (P=0.002). Major adverse cardiac and events (MACE) occurred in 785 patients: 422 (11.9%) in the low group and 363 (14.5%) in the high group. There was significant difference in the MACCE incidence between the low group and high group (P=0.004). The multivariate Cox proportional hazards model showed that ADS score was independently correlated with the ACM (adjusted HR=1.520 [1.919–1.204], P<0.001); CM (adjusted HR=1.743 [2.264–1.341], P<0.001); MACCE (adjusted HR=1.296 [1.491–1.127], P<0.001) and MACE (adjusted HR=1.303 [1.509–1.125], P<0.001).
CONCLUSIONS The present study indicated that the ADS score was associated with long-term mortality, the MACCE and the MACE in CAD patients underwent PCI.
[GW30-e0548]
Shengjun Liu, Jinzhou Zhu, Weiwei Quan, Yi Sun, Ruiyan Zhang
Ruijin Hospital, Shanghai Jiaotong School of Medicine
OBJECTIVES The aim of this study was to evaluate the relationship between uric acid, creatinine, glomerular filtration rate and coronary in-stent stenosis (ISR) in patients with drug eluting stent (DES), and provide evidence on management of renal function in patients who receive revascularization with DES.
METHODS A retrospective analysis was made for patients who underwent coronary arteriography after receiving revascularization with drug eluting stent for 12–24 months. Medical history, baseline and follow-up laboratory examination and imaging data was collected. In-stent stenosis (ISR) is defined as more than 50% stenosis of minimum coronary inner diameter in follow up coronary arteriography than that of baseline coronary arteriography. Variance analysis, univariate and multivariate analyses were used to identify the risk factors of renal function for in-stent stenosis.
RESULTS One thousand seven hundred and ninety patients averaged 63.4 years old, with 475 (26.5%) woman, 200 (11.2%) with ISR, with medium coronary arteriography interval 406 days (IQR 378–488 days) were included in this study. There is no significant difference in gender, BMI, history of smoke, diabetes, CKI, hyperlipidemia, baseline and follow-up blood pressure, serum triglyceride, cholesterol, HDL and LDL among ISR and No-ISR group. Independent-samples t-test revealed that there were significant differences between the patients with ISR and No-ISR in baseline creatinine (86.91±60.14 mmol/L vs. 80.11±38.67 mmol/L, P=0.030), follow up creatinine (92.40±92.18 mmol/L vs. 81.29±44.85 mmol/L, P=0.005) and follow up estimated glomerular filtration rate [86.50±25.69 mmol/L vs. 90.70±26.49 mL/(min−1×1.73 m2), P=0.035]. Binary logistic regression indicated higher baseline creatinine level was the independent and significant risk factor for ISR (OR=1.00240, 95% CI: 1.00047–1.00433, P=0.015).
CONCLUSIONS For patients who receive DES treatment, higher baseline creatinine level could increase the incidence of ISR.
[GW30-e0560]
Yun He 1 , Jin Jun 2
1Chongqing Kanghua Zhonglian Cardiovascular Hospital
2Institute of Cardiovascular Disease of People’s Liberation Army
OBJECTIVES To investigate the predictive value of SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SS) combined with reactive hyperemia index (RHI) in predicting 2-year major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).
METHODS We undertook a prospective study in 401 ACS patients that underwent PCI. The RHI-SYNTAX score (RSS) was calculated by categorizing and summing up the RHI and SS of individual patients. Patients with RHI<1.67 are given 1 point, RHI≥1.67 given 0 points; and those with SS≤22 scored as 0, and >22 as 1 point. Patients were classified into 3 groups: Low RSS (Group 0), moderate RSS (Group 1) and high RSS (Group 2).
RESULTS Among patients in the low, moderate and high groups, the 2-year rates of MACE were 5.50%, 10.66% and 23.33% respectively (P<0.0001). Total revascularization rates were 1.83%, 2.54%, and 8.89% respectively (P=0.015). Ischemic stroke rates were 0.00%, 3.67%, and 5.56% respectively (P=0.031). By multivariate analysis, the RSS was an independent predictor of 2-year MACE (hazard ratio [HR]: 2.09, 95% CI: 1.36 to 3.21, P=0.001). ROC analysis indicated that the area under the curve significantly improved from 0.63 to 0.69 when RHI was added to SS (P<0.0001).
CONCLUSIONS RSS is correlated with 2-year MACE in patients presenting with ACS undergoing PCI.
[GW30-e0561]
Muhina Nadezhda Vladimirovna, Komarova Irina Sevastyanovna, Dyatlov Nikita Vyacheslavovich, Zhelnov Vladimir Vasilievich
I.M. Sechenov First Moscow State Medical University (Sechenov University)
OBJECTIVES To study the incidence of long-term cardiac events in patients with acute myocardial infarction (AMI) depending on the type of coronary bed lesion.
METHODS The study comprised 1240 patients admitted to the resuscitation and intensive care unit for patients with myocardial infarction between 2016 and 2017 in S.S. Yudin Moscow city hospital. The diagnosis was established based on the III Universal Definition of MI. All enrolled patients underwent cardioangiography (CAG). CA damage was considered non-obstructive, if a detected CA obstruction was less than 50%, regardless of the number of affected arteries. Following the CAG Results, the patients were divided into 3 groups: group 1 included patients with multivessel obstructive arterial sclerotic disease of the CA according to the CAG data – 664 (53.5%) patients, group 2 included patients with non-obstructive arterial sclerotic disease of the CA – 96 (7.7%) patients, the third comparison group included patients with single-vessel obstructive arterial sclerotic disease with total acute occlusion of the CA – 272 (21.9%) patients. Patients with a hemodynamically relevant disease of the trunk of the left CA – 208 (16.8%) were not enrolled. In one year after discharge, the prospective follow-up was conducted over the phone. The loss in monitoring amounted to 19%.
RESULTS The age of patients in groups 1 and 2 was 66.14±11.8 years and 67.9±11.5 years (P>0.05), the median age of patients in group 3 was 56.59±11.6 years, and was significantly different from the median age of patients in groups 1 and 2 (P<0.001). When analyzing gender distribution between the groups, significant statistical differences were found between groups 1 and 2 (P><0.01) and between groups 2 and 3 (P>0.05), and in the group with single-vessel obstructive arterial sclerotic disease no effort angina was observed in any of the patients.
CONCLUSIONS During the first year after the old MI, patients with non-obstructive coronary atherosclerosis did not develop recurrent coronary events; CAG, XRD and CABG were not performed, as opposed to the patients with obstructive disease of the CA. This bears record to rapid progression of arterial sclerotic disease of the CA in patients with obstructive disease of the CA.
[GW30-e0570]
Chenkai Wu, Zhaowei Zhu, Qiming Liu, Zhenfei Fang, Xinqun Hu, Shenghua Zhou
Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University
OBJECTIVES Percutaneous coronary intervention (PCI) is a well-established technique used to treat coronary artery disease (CAD), while the risk of coronary artery in-stent restenosis (ISR) following PCI is still high. Previous study revealed that High-Mobility-Group-Protein B1 (HMGB1) plays critical role in neointimal formation. In this study, we aim to investigate the role of glycyrrhizic acid (GA), a HMGB1 inhibitor, in the process of neointima formation and the potential mechanisms.
METHODS We investigated the role of GA on neointima formation through iliac artery balloon injury model in rabbits. Proliferation, migration and phenotype transformation of vascular smooth muscle cell (hVSMCs) were observed. Besides, inflammation and RAGE/P38/ERK signaling pathways were tested.
RESULTS The results indicated that GA attenuated neointima formation and down-regulated HMGB1 expression in injured artery in rabbits. HMGB1 promoted proliferation, migration and phenotype transformation through the activation of RAGE signaling pathways in VSMCs and blockade of HMGB1 by GA (1, 10 and 100 μM) could attenuate those process and alleviate hVSMCs proliferation.
CONCLUSIONS In conclusion, HMGB1 inhibitor GA might be useful to treat proliferative vascular diseases via down regulating RAGE signaling pathways. Our results indicated a new and promising therapeutic agent for restenosis.
[GW30-e0595]
Fuqiang Liu, Shuang Shi, Qingyu Wang, Ling Zhu, Yujie Xing, Jiang Lei, Weifeng Tian, Gongchang Guan, Junkui Wang
Cardiovascular Department, Shaanxi Provincial People’s Hospital
OBJECTIVES The ear lobe crease is a common body surface marker. This simple and easy-to-recovery sign has been closely related to coronary heart disease after extensive screening. However, the mechanism of earlobe creases is not yet clear, and may be related to endothelial dysfunction. This study aimed to investigate the role of Adropin disorder in the formation of earlobe creases and to explore the potential mechanism of coronary heart disease.
METHODS A total of 135 patients ranging from ages 40–68 years who underwent coronary angiography were enrolled. Patients were categorized into three groups based on the presence or absence of coronary artery disease (CAD) and DELC: patients with CAD and DELC (ELC group, n=45); patients without ELC (no-ELC group, n=45); control patients without ELC and CAD (control group, n=45). The Serum Adropin concentration was acquired through enzyme-linked immunosorbnent assay (ELISA).
RESULTS Adropin levels were significantly lower in the earlobe crease-positive group than in the Ear-lobe negative group (168.85±101.25 pg/mL vs. 349.00±189.43 pg/mL). There was a statistically significant difference (P<0.05). Coronary heart disease was diagnosed in the positive group of ear lobe creases in this study. In subjects without ear lobes, serum Adropin levels were lower in coronary heart disease patients than in those without coronary heart disease (P<0.05); in patients with coronary heart disease, The serum Adropin level in the earlobe crease-positive group was lower than that in the earlobe crease-negative group (P<0.05), with statistically significant differences.
CONCLUSIONS The earlobe crease sign is one of the independent risk factors of coronary heart disease; moreover, endothelial dysfunction mediated by the decrease of Adropin level may be one of the reasons for the occurrence of coronary heart disease.
[GW30-e0614]
Ekaterina Kreneva, Nikolai Nelassov, Dmitry Safonov, Maxim Morgunov, Olga Eroshenko, Roman Sidorov, Natalja Doltmurzieva, Emil Arzumanjan, Anna Nechaeva
Rostov State Medical University
OBJECTIVES It was demonstrated previously that vasodilatory effects of adenosine triphosphate (ATP) and adenosine are nearly equal. Therefore, ATP is widely utilized in stress-Echo and stress cardiac MRI, CT and PET imaging in the countries of Eastern Asia and Russia instead of adenosine. The recommended algorithm of ATP infusion during stress-test is monotonous intravenous infusion of vasodilator at a dose of 140–160 μg/kg/min without the evaluation of blood pressure level. However, administration of adenosine or ATP in traditional manner in nearly 1/5 of cases did not lead to adequate hemodynamic response systolic blood pressure (SBP) decrease. So in this subgroup of patients submaximal myocardial hyperemia presumably is not achieved. In this study we decided to: 1) develop and test a new algorithm of ATP infusion during stress-Echo with a step-by-step increase in the dosage of vasodilator; 2) analyze if 4D strain-stress-Echo with new algorithm of ATP infusion is helpful in detection of left ventricular (LV) myocardial segments with hidden ischemia in patients with coronary artery disease (CAD).
METHODS Twenty-six patients with CAD (male 24, mean age 63.1±7.5 years, multivessel disease 19) underwent ATP 4D strain-stress-Echo of LV (Vivid E95, AFI technology). Complications and adverse effects registered during modified stress-test were analyzed. 4D Echo data sets of patients were used for detection of myocardial segments with hidden ischemia.
RESULTS The key points of new algorithm of stress Echo with ATP are as follows: 1) Algorithm includes three stages: registration of Echo data sets before, at the time of ATP infusion and after 5 minutes. 2) Registration of Echo data at the second stage should begin only when adequate myocardial hyperemia is generated. Main criterion is stable decrease in SBP by 5 mmHg or more. 3) Initial dose of ATP is 140 μg/kg/min. If after 2 min of ATP infusion SBP do not diminish the infusion rate should be increased at first to 175 and then to 210 μg/kg/min. Using new algorithm of ATP infusion we managed in all cases to achieve effective vasodilation and register interpretable LV 4D Echo data sets for visual analysis of segmental contractility and automatic strain analysis. In 2 (7.6%) patients SBP decreased below 90 mmHg but simple reduction in speed of infusion immediately elevated SBP up to 95 mmHg. In 1 patient drop in SBP was accompanied by appearance of a–v block 2 degree; this conduction disorder was transient and disappeared with increase of SBP. No major complications were registered at all. Visual assessment of LV contractility during ATP stress-test has revealed the expansion of existing hypokinetic zones and the appearance of new ones in 11 patients (42.3%). Application of AFI technology has led to the identification of appearance of new areas of myocardial deformation disturbances in 21 patients (80.7%; P=0.0044).
CONCLUSIONS (1) New algorithm of ATP infusion during stress-Echo with a step-by-step increase in the dosage of vasodilator in cases of inadequate myocardial hyperemia was developed. New algorithm is safety and well-tolerated by patients. (2) LV myocardial segments with hidden ischemia can be determined 1.9 times more often using 4D AFI technology with longitudinal strain analysis than traditional technology of myocardial contractility visual assessment.
[GW30-e0617]
Jianjun Ruan, Heyu Meng, Fanbo Meng
Department of Cardiology China-Japan Union Hospital of Jilin University
OBJECTIVES In order to search for molecular marker for diagnosis of acute myocardial infarction (AMI), the relation between FFAR2 gene and AMI is further analyzed in this study by expanding the sample size in accordance with earlier microarray results.
METHODS The leukocytes in peripheral venous blood of 113 patients with AMI and 94 patients with non-coronary artery disease are collected as case group and control group respectively. The relative mRNA expression level of FFAR2 gene is detected by real-time fluorescent quantitative PCR. The clinical data of patients with AMI and patients with non-coronary artery disease are analyzed and compared.
RESULTS The mRNA expression level of FFAR2 gene in peripheral blood shows that the relative mRNA expression level of FFAR2 gene in AMI group is 0.33 (0.04–1.08), while that in control group is 0.62 (0.07–1.86), indicating that there is a statistically significant difference between the two groups. The relative mRNA expression level of FFAR2 gene in peripheral blood of patients with AMI is significantly lower than that in control group, which is 0.53 of the latter. The clinical data of subjects indicate that there is no significant difference between the two groups in the gender, history of hypertension, smoking history, and the level of serum triglyceride, total cholesterol and low density lipoprotein cholesterol (P>0.05). However, compared with control group, the patients in AMI group are significantly older, P<0.01; the number of patients with type 2 diabetes is larger, P=0.02; the fasting blood glucose level is higher, P<0.01; the total number of leucocytes is higher, P<0.01; and the high density lipoprotein cholesterol level is lower, P=0.03. The mRNA expression level of FFAR2 gene has no correlation with age (P=0.121), type 2 diabetes (P=0.836), fasting blood glucose level (P=0.339) and total number of leucocytes (P=0.502), while it has a correlation with high density lipoprotein cholesterol level (P<0.001). The results of logistic regression analysis show that low expression of FFAR2 gene in peripheral blood is an AMI risk factor which is independent of age, total number of leucocytes, history of diabetes, fasting blood glucose level and high density lipoprotein cholesterol level (P=0.025). Compared with high expression of FFAR2, the risk of AMI in low FFAR2 gene expression group is increased by 6.308 times; high number of leucocytes is an AMI independent risk factor (P=0.014), which increases the AMI risk by 14.316 times; high fasting blood glucose level is also an AMI independent risk factor (P=0.008), which increases the AMI risk by 3.132 times.
CONCLUSIONS The expression level of FFAR2 gene in peripheral blood of patients with AMI is significantly lower than that in control group. Low expression of FFAR2 gene in peripheral blood is an AMI independent risk factor, which may be used as a potential biomarker for predicting the occurrence risk of AMI.
[GW30-e0622]
Wei Liu 1 , Fang Wei 1 , Zongzhuang Li 1 , Nina Peng 2 , Wei Liu 1
1Guizhou Provincial People’s Hospital
2Guizhou Orthopedics Hospital
OBJECTIVES The efficiency and safety of Drug-coated balloons (DCB) and everolimus-eluting stents (EES) is still unknown for the treatment of in-stent restenosis (ISR). The present pair-wise meta-analysis was to compare DCB with EES for the treatment of ISR.
METHODS A systematic literature search was conducted using the online databases PubMed and EMBASE to identify all relevant studies. Angiographic results and clinical events were separately assessed. Risk ratio (RR) and mean difference (MD) with the 95% confidence interval (CI) were calculated as the effect size for endpoints with categorical and continuous data, respectively. Subgroup meta-analyses were performed according to the type of restenosed stent.
RESULTS Six randomized trials with 1134 patients were included. The overall pooled outcomes indicated that DCB was associated with lower minimum lumen diameter (MD=–0.17, 95% CI=–0.29 to –0.05, P=0.006) and higher target lesion revascularization (RR=2.38, 95% CI=1.36 to 4.18, P=0.002) compared with EES. But subgroup meta-analyses showed DCB was inferior to EES only in patients with DES-ISR, with lower minimum lumen diameter (MD=–0.25, 95% CI=–0.37 to –0.14, P<0.001), higher percent diameter stenosis (MD=5.37, 95% CI=1.33 to 9.42, P=0.009), more binary restenosis (RR=2.01, 95% CI=1.16 to 3.49, P=0.01) and higher incidence of TVR (RR=2.01, 95% CI=1.19 to 3.41, P=0.009) and TLR (RR=2.37, 95% CI=1.24 to 4.52, P=0.009). There were no differences between DCB and EES in patients with BMS-ISR on angiographic results and clinical events.
CONCLUSIONS In patients with DES-ISR, DCB was inferior to EES on angiographic results and clinical events. But for BMS-ISR, the two strategies were comparable. More high-quality randomized trials was needed to further evaluate the role of DCB for the treatment of ISR, especially in patients with DES-ISR. The potential mechanisms of the different efficacy between BMS-ISR and DES-ISR for DCB were also necessary to be explored in the future.
[GW30-e0623]
BuChun Zhang, YanFeng Ma, BuChun Zhang
Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University
OBJECTIVES The aims of this study was to summarize the clinical characteristics and risk factors of acute myocardial infarction (AMI) patients treated with percutaneous coronary intervention (PCI) developing major adverse cardiovascular events (MACEs) within 1 year. We then build a nomogram and confirmed its utilities using decision curve analysis (DCA).
METHODS One hundred and three AMI subjects (cases) who underwent PCI experienced MACEs within 1 year of their index admission were included in this retrospective study. Cases were matched for age, sex and presentation with 225 controls who did not have MACEs. An analysis was performed to investigate the clinical characteristics and risk factors for MACEs in AMI patients and to subsequently develop a nomogram for MACEs based on multivariate logistic regression. C-index, calibration curves, and DCA were conducted to validate the model.
RESULTS After uni- and multivariate analysis, a nomogram was built based on age, low-density-lipoprotein (LDL)-cholesterol, lipoprotein (a) (Lp(a)), left ventricular ejection fraction (LVEF), serum brain natriuretic peptide (BNP), syntax score, and serum bile acid level. A C-index of 0.819 and the calibration curve demonstrated good concordance. Decision curve analysis demonstrated satisfactory positive net benefits.
CONCLUSIONS The proposed nomogram resulted in more-accurate prognostic prediction for 1-year MACEs in AMI patients treated with PCI. To ensure generalizability, this model needs to be externally validated.
[GW30-e0625]
BuChun Zhang, YanFeng Ma, BuChun Zhang
Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University
OBJECTIVES Bile acid metabolism is reported to be associated with cardiovascular diseases. It is unknown whether serum bile acid level is associated with atherosclerotic plaque. We investigated whether elevated serum bile acid level predict coronary high risk plaque in asymptomatic populations as detected by coronary CT angiography (CTA).
METHODS A total of 194 patients who have suspected coronary artery disease (CAD) and underwent coronary CTA were retrospectively reviewed. Serum bile acid level was quantified by enzyme-linked immunosorbent assay (ELISA). The predictive value of serum bile acid for high risk plaque was determined using multivariate logistic regression model and receiver-operating characteristic (ROC) curves.
RESULTS Serum bile acid level was significantly higher in patients with high risk plaque than in controls (6.18; interquartile range [IQR] 5.29–7.30) vs. 3.16; IQR 2.18–4.01) umol/L, P<0.001). Multivariate regression revealed that serum total bile acid level (OR=6.854, 95% CI: 3.948–11.901, P<0.001) and body mass index (BMI) (OR=1.941, 95% CI: 1.055–3.569, P=0.033) were independently associated with occurrence of high-risk coronary plaque. After adjustment for potential confounding factors, subgroup with high serum total bile acid level was more likely to have high-risk coronary plaque than low bile acid level at multivariate analysis (P for trend <0.001). The area under receiver operating characteristic (ROC) curve for serum total bile acid level was 0.876, with a sensitivity of 87.13% and a specificity of 86.02% for high-risk coronary plaque patients.
CONCLUSIONS We concluded that high level of serum total bile acid appeared to be an independent predictor for the high-risk coronary plaque.
[GW30-e0651]
Qiaoyu Wu 1,2 , Xinyao Liu 1,2 , Yao Lu 1,2 , Hong Yuan 1,2
1The Third Xiangya Hospital of Central South University
2Hunan Provincial Institution of Hypertension Research
OBJECTIVES Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist has been shown to increase the risk of bleeding. It is reported that age and sex are risk factors of long-term outcomes of DAPT-related bleeding. However, whether age and sex affect the short-term bleeding outcomes of DAPT is unclear.
METHODS A total of 3853 subjects were enrolled in the study of the patients who received DAPT after ACS events in the 3rd Xiangya Hospital between April 2007 and July 2017, including 281 patients with bleeding (bleeding group) and 3572 patients without bleeding (nonbleeding group). Bleeding was defined by Thrombolysis In Myocardial Infarction (TIMI) standards and included all four types of non-CABG-related bleeding during hospitalization which equal or less than 30 days. Multivariate regressions were performed to determine age’s association with DAPT-related bleeding.
RESULTS There were 2625 men and 1228 in the study. The rate of bleeding was the same in the two groups, 7.3% in men (191 patients occurred bleeding) and 7.3% in women (90 patients occurred bleeding). Old age was associated with increased bleeding outcomes in men (OR=1.778, 95% CI=1.323–2.390, P<0.001), while no difference was found in women (OR=1.446, 95% CI=0.907–2.305, P=0.121). And adjusted for the confounding factors, old age was still associated with increased bleeding outcomes in men (OR=1.712, 95% CI=1.076–2.723, P=0.023).
CONCLUSIONS Old age is associated with increased short-term bleeding events in men who received DAPT post of acute coronary syndromes (ACSs).
[GW30-e0675]
Thach Nguyen 1,2 , Vu Tri Loc 1 , Nguyen Van Lanh 1 , Khang M. Nguyen 2 , Duy D Nguyen 2 , Thi Truc Anh Nguyen 2 , Anthony Kim 3,4 , Gianluca Rigatelli 5
1Tan Tao University, School of Medicine, Long An Vietnam
2Methodist Hospital, Merrillville IN, USA
3Purdue University Northwest, Westville IN USA
4Oak Street Health, Munster IN USA
5Rovigo General Hospital, Rovigo, Italy
OBJECTIVES Coronary injuries are hypothesized to be caused by the cavitation phenomenon (explosion of air bubbles) which is seen frequently in domestic or industrial pipes. Following hydraulics principle, with distal negative suctioning in diastole, if the coronary dynamic pressure decreases below the vapor pressure (VP) most likely of nitrogen in the blood, bubbles will form. They explode when the coronary dynamic pressure recovers > the VP during systole. These explosions create jet waves weakening and rupturing the cap of the plaque, triggering acute coronary syndrome (ACS). How could these events be located, recorded and tabulated?
METHODS Angiograms with ACS culprit lesions were selected. The left coronary arteries were recorded in the right anterior oblique caudal view and the right coronary artery in the left anterior oblique view (at 15 frames per second). Then the angiograms were viewed off line frame by frame. The first frame was the angiogram of an artery completely filled with contrast. The following frames showed the blood moving in, seen in white. The flow could be LAMINAR, TURBULENT (mixing of blood in white and contrast in black) or RETROGRADE (black column traveling backward). The turbulent flow reflects the collision between antegrade and retrograde flow. The LOCATION and the length in TIME of laminar, retrograde and mainly turbulent flow were recorded. The intensity of turbulent flow was measured by (1) the length of coronary segment with mixing contrast and blood (2) the length of the stagnant retrograde flow.
RESULTS The results of 50 angiograms with ACS showed that after being laminar (85%) at the beginning of diastole, the flow became turbulent with diffuse mixing of black (contrast) and white (blood) at the MID SEGMENT of the LAD, LCX or RCA. This observation matched with the location of 82% of ruptured plaques. The length of the time of retrograde flow lasted more than 30 frames encompassing 2 systoles.
CONCLUSIONS This is the first time, the matching of location of ruptured plaques and turbulent flow representing the collision between antegrade flow in diastole and retrograde flow in systole was confirmed. These results may help to find the precise measures preventing ACS.
[GW30-e0703]
Guangyao Zang, Jinchuan Yan
Department of Cardiology, Affiliated Hospital of Jiangsu University
OBJECTIVES Myocardial ischemia-reperfusion injury (IRI) after acute myocardial infraction (AMI) is a major cause of worldwide mortality. Various studies have demonstrated that CD137 (4-1BB) promotes atherosclerosis and vascular inflammation via interactions with CD137 ligand (CD137L). However, the exact role of CD137 in myocardial ischemia reperfusion injury remains unknow. In this study, we used a murine model of acute myocardial ischemia reperfusion injury to examine whether the interactions of costimulatory receptor CD137 and its ligand (CD137L) are involved in the early phase of acute myocardial inflammation caused by IRI.
METHODS Myocardial ischemia reperfusion injury murine model was induced with 30 min of left anterior descending (LAD) occlusion followed by 4 h of reperfusion. We analyzed the changes of CD137 expression on heart in the mouse I/R model, as well as alternation of cardiac function, infract size and myocardial inflammatory status after activation or inhibition of the CD137/CD137L pathway using CD137L-Fc or anti-CD137L Monoclonal Antibody. Infract size was detected by Evans Blue and triphenyl tetrazolium chloride (TTC) staining while CCK8 assay was used to analyze the pyroptosis in heart. Meanwhile, the levels of aspartate transaminase (AST), creatine phosphokinase-isoenzyme (CKMB) and lactate dehydrogenase (LDH) in serum were used to analyze the cardiac function. Moreover, the contents of interleukin-1β (IL-1β), interleukin-18 (IL-18) and tumor necrosis factor (TNF-α) were used to analyze the myocardial inflammatory status. Besides, the HL-1 cells were stimulated with H/R protocol in the presence or absence of CD137L-Fc to find the changes of apoptosis-associated speck-like protein containing CARD (ASC), Caspase-1 and NLRP3 inflammasome while the Tunel and CCK8 assay were used to analyze the cardiomyocytes pyroptosis.
RESULTS Firstly, we found that I/R mice showed elevated expression of CD137 in heart tissue during the early phase of acute myocardial inflammation. Remarkably, blockade of the CD137/CD137L pathway ameliorated the myocardial I/R injury and cardiomyocyte H/R as evidenced by Evans blue and TTC staining and CCK8 assay respectively. Secondly, injection of CD137-Fc into I/R mice was founded to increase the level of AST, CKMB and LDH in serum as well as the contents of IL-1β, IL-18 and TNF-α in serum of mice and supernatant of HL-1 cells were increased. In addition, blockade of CD137 signaling remarkably downregulated the expression of toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-kB). Interestingly, we also found that blockade of CD137 signaling inhibited the upregulations of inflammasome components, such as NLRP3, ASC and Caspase-1 in I/R-induced mice and I/R-induced HL-1 cells with the use of western blot and RT-PCR. In vitro, we also found that blockade of CD137 signaling inhibited inflammasome activation in macrophages, cardiomyocytes, and cardiac fibroblasts via TLR4 and NF-kB signaling.
CONCLUSIONS Our findings indicate that enhanced CD137 costimulation occurs in the early phase of acute myocardial inflammation caused by IRI and promotes the activation of NLRP3 inflammasome, which in turn upregulates cardiac inflammatory response. The CD137 signaling pathway in cardiomyocytes therefore may represent a new target for blocking the initial stage of inflammatory diseases like myocardial IRI.
[GW30-e0720]
Chen Zhao, Chunyang Zhe, Ying Lv, Hongxia Gao, Shan Zhang, Sining Hu, Bo Yu, Haibo Jia
Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
OBJECTIVES ST-segment elevation myocardial infarction (STEMI) is one of the most significant emergency types of acute coronary syndrome (ACS). Stent implantation was the most widely accepted treatment measure in ACS. Three underlying mechanisms for ACS include plaque rupture, plaque erosion, and calcified nodule. Although plaque rupture is the most common cause (60%) of ACS, plaque erosion is responsible for 22–44% of patients. However, at one-year follow-up, partly of the patients with conservative treatment implanted stents in the infarct related arteries. In this study, we retrospectively analysed the baseline clinical and imaging angiography and optical coherence tomography (OCT) data to access which factors may contributed to this phenomenon.
METHODS We assessed plaque characteristics of plaque erosion by OCT in 212 STEMI undergoing emergency procedures and 88 patients were excluded in this research for losing to follow-up. Stent were Implanted in 47 patients immediately, and 77 patients were enrolled in this research finally. All the patients were divided into two groups according to the stent implantation or not: stent implantation (SI) and no stent implantation (nSI).
RESULTS Baseline clinical data didn’t show significant difference among two groups expect for the diabetes mellitus. The patients with diabetes mellitus appeared more frequency in SI compared with nSI (25 vs. 3.8%, P=0.01). And the diameter stenosis was similar (65 [41–83] vs. 60% [23%–82%], P=0.259) between SI and nSI. OCT results revealed that the minimum fibrous cap thickness was thinner in SI compared with nSI (50 μm [20 μm–190 μm] vs. 70 μm [20 μm–280 μm], P=0.008). SI had a higher prevalence of thin-cap fibroatheroma (TCFA) (54.2 vs. 26.4%, P=0.018), macrophage accumulation (75.0 vs. 37.7%, P=0.002) and intimal vasculature (41.7 vs. 20.8%, P=0.056) in the culprit lesion compared with nSI.
CONCLUSIONS Despite some studies showed conservative treatment with anti-thrombotic therapy without stenting may be an option for patients with STEMI caused by plaque erosion, the diabetes mellitus and plaque vulnerability were also needed full consideration before selection of treatment strategy.
[GW30-e0737]
Li Lei 1,2 , Feier Song 1 , Jin Liu 1 , Shiqun Chen 1 , Wei Guo 1 , Guoli Sun 1 , Yibo He 1 , Zhaodong Guo 1 , Bowen Liu 1 , Lihao He 1 , Liwei Liu 1,2 , Guanzhong Chen 1 , Yong Liu 1
1Department of Cardiology, Provincial Key Laboratory of Coronary Heart Disease, Guangdong Cardiovascular Institute, Guangdong Provincial people`s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China
2The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
OBJECTIVES Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are widely prescribed drugs for patients with coronary artery disease (CAD), despite their nephrotoxicity in acute setting. It is recommended by the guidelines that ACEI/ARB treatment should be discontinued if serum creatinine (SCr) increase by 30% or more after initiation. However, there is no data on whether patients with CAD and contrast-induced nephropathy (CIN) after angiography should be prescribed ACEI/ARB at discharge. Therefore, we aim to explore the association between prescription of ACEI/ARB at discharge and long-term mortality in patients with CAD and CIN after angiography.
METHODS This prospective observational study included consecutive patients with confirmed CAD and CIN after angiography. CIN was defined as a >25% or 0.5 mg/dL increase in SCr from baseline during the first 48 to 72 hours after contrast exposure. The endpoint was all-cause mortality. Comparison of mortality between groups were conducted, and survival analysis and multivariable cox proportional hazards regression analysis were performed to identify the association between ACEI/ARB and long-term mortality.
RESULTS Overall, 349 patients were divided into ACEI/ARB group (n=312) and non-ACEI/ARB group (n=37). During the mean follow-up of 7.16±1.50 years, mortality was 18.27% (n=57) in ACEI/ARB group and 21.62% (n=8) in non-ACEI/ARB group, respectively. Multivariable cox proportional hazards regression analyses showed that the prescription of ACEI/ARB at discharge was not associated with long-term mortality HR of 1.02 (95% CI: 0.40–2.56). Survival analyses revealed no difference in long-term mortality between groups (P=0.97).
CONCLUSIONS The ACEI/ARB may not be associated with long-term mortality in patients with CAD and CIN after angiography.
[GW30-e0753]
Jingjia Wang, Chunli Shao, Jing Chen, Mou Mu, Wenjia Zhang, Fang Luo, Shaodong Ye, Min Yang, Ping Li, Jian Tian, Yida Tang
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
OBJECTIVES The Coronary artery disease Optimal clinical therapeutic regimen Experience (COE) project aims to improve the understanding and clinical practice of Chinese clinicians on standardized treatment of coronary artery disease (CAD). The present cross-sectional survey was conducted on the application of β-blockers (BB) in hospitalized patients with acute coronary syndrome (ACS) or stable angina pectoris in order to understand the current status of BB use in ACS and stable CAD (SCAD) by cardiovascular specialists in China and to improve patient prognosis.
METHODS The study data are from the COE project, conducted between 11/2017 and 05/2018 in 67 hospitals from 24 cities in China. The frequency of BB use and initial dose within 24 h after admission, transition rate to sustained-release dosage forms, dose titration, patient clinical condition during hospitalization, BB prescription at discharge, and safety of BB were examined in hospitalized patients with ACS or SCAD. The 2013 ACCF/AHA Guideline for the Management of ST-elevation myocardial infarction (STEMI) and 2015 CSC/CMA Guideline for diagnosis and treatment of STEMI were used as references for analysis.
RESULTS There were 13,375 patients with ACS or SCAD, including 1854 with STEMI (14%), 3520 with non-STEMI (NSTEMI; 26%), 3398 with unstable angina (UA; 25%) and 460 with SCAD. The frequency of regular BB use before hospitalization was 17.0%. A total of 12,761 (95.4%) patients received BB within 24 h of admission, with metoprolol tartrate (84.5%) as the most commonly used of all BBs. The overall transition rate of metoprolol tartrate to metoprolol succinate was 68.3% in all patients, with a relatively low rate of 37.0% in patients with SCAD. The heart rates at admission and discharge were 83.9±14.6 vs. 70.7±8.6 bpm for STEMI, 85±16.5 vs. 72.6±11.7 bpm for NSTEMI, 79.9±13.9 vs. 69.9±8.7 bpm for UA, and 81.3±15.1 vs. 71.8±9.5 bpm for SCAD (all P<0.05); the systolic blood pressure were 139.5±20.0 vs. 125.2±13.1 mmHg for STEMI, 139.4±19.7 vs. 124.6±14.1 mmHg for NSTEMI, 140.5±19.6 vs. 127.6±13.4 mmHg for UA, and 138.7±21.2 vs. 126.7±15.3 for mmHg SCAD. The frequencies of BB use at discharge was 35.0, 16.8, 24.9 and 18.9% for STEMI, NSTEMI and UA and SCAD, respectively. At discharge, a total of 39 (1.0%) patients received the target dose of ≥190 mg/day metoprolol and 4419 (33.0%) patients received a high dose of ≥95 mg/day. During hospitalization, 7425 (55.5%) patients had no dose adjustment, 4438 (33.2%) had one dose adjustment, 1076 (8.0%) had two, and 436 (3.3%) had three. A total of 396 (3.0%) events were reported: one patient died, 41 (0.3%) had resting heart rate <45 bpm, 261 (2.0%) had systolic pressure <100 mmHg, 15 (0.1%) had atrioventricular block, 53 (0.4%) had unstable decompensated heart failure, and 26 (0.2%) had cardiogenic shock.
CONCLUSIONS The present study suggests that, despite an adequate initial BB use, the dose form transition rate, time of dose titration and the maintenance dose of BB at discharge were low for hospitalized patients with ACS and SCAD in China. Compared with developed western countries, the BB use in CAD has room for improvement. It is necessary to strengthen the education of Chinese cardiovascular specialists on the application of BB, to gradually narrow the gap between the present situation and the recommended standard by the Chinese and international guidelines and ultimately to improve patient prognosis.
[GW30-e0816]
Fangcheng Wu 1 , Pengyang Li 2 , Ying Ning 2 , Bin Wang 3
1Memorial Hospital West, 703 N Flamingo Rd, Pembroke Pines, FL 33028, USA
2Saint Vincent hospital, 123 Summer Street, Worcester, MA 01608, USA
3Department of Cardiology, the first Affiliated Hospital of Shantou University Medical College, Shantou 515041, China
OBJECTIVES Coronary artery dissection is a nonatherosclerotic acute coronary syndrome for which optimal management remains controversial. Our study aimed to compare the inpatient outcomes in coronary artery dissection treated with conservative therapy vs. revascularization (including interventional and surgical).
METHODS We conducted a retrospective cohort analysis of the National Inpatient Sample (HCUP-NIS) 2016 database. Patients hospitalized with a major diagnosis of coronary artery dissection were identified using the ICD-10 codes. Multivariate logistic regression was performed after adjust for patient baseline characteristics, hospital demographics and relevant comorbidities. Inpatient mortality and length of hospital stay (LOS) were compared between the patients who received conservative management and revascularization.
RESULTS A total of 7475 hospitalizations with coronary artery dissection were identified. Of these, 2065 (27.63%) received conservative therapy and 5410 (72.37%) received revascularization. Multivariate logistic regression analysis after adjustment showed that there was no significant difference in in-hospital mortality (conservative 3.16 vs. revascularization 6.96%, OR 95% CI 0.71–3.25, P=0.282) or LOS (5.23 vs. 5.63 days, P=0.717) between the two groups. Further analysis of the revascularization subgroups revealed that 4705 (86.97%) patients received interventional (PCI/PTCA) and 705 (13.03%) patients received surgical revascularization (CABG). Strategies of revascularization had no impact on inpatient mortality (OR 95% CI 0.36–1.32, P=0.263). However, patients who received interventional therapy had shorter LOS compared to those who received CABG (4.96 vs. 10.14 days, P<0.001). Furthermore, patients with cardiogenic shock (OR 3.48, P><0.001), respiratory failure (OR 2.19, P><0.001), or acute kidney failure (OR 1.86, P=0.001) were more likely to receive revascularization.
CONCLUSIONS Methods of treatment (conservative therapy vs. revascularization) and strategies of revascularization (PCI/PTCA vs. CABG) had no impact on inpatient mortality in coronary artery dissection patients.
[GW30-e0843]
Selcuk Kucukseymen
Antalya Training and Research Hospital, Department of Cardiology, Antalya, Turkey
OBJECTIVES Usage of fibrinolytic therapy is suggested in patients with ST-elevation myocardial infarction (STEMI) upon which a primary percutaneous coronary intervention (PCI) cannot be performed on time or at all. Despite this, the treatment procedure for patients with a high thrombus burden who cannot achieve patency of the infarct-related artery through a primary PCI is not yet clear. In this study, we planned to evaluate the clinical and angiographic findings of patients with a heavy thrombus burden who were firstly given fibrinolytic therapy instead of PCI and according to the findings of the following angiography were performed PCI or not.
METHODS Total of 65 consecutive patients with STEMI, who applied at the emergency room and were subjected to fibrinolytic therapy following heavy thrombus burden detection in coronary angiography, were included in this study. Tissue plasminogen activator (t-PA) was used as a fibrinolytic agent. The fibrinolytic therapy was followed by a control coronary angiography. According to the obstruction degree of the artery affected by the infarction, a PCI procedure was performed. The patients were investigated concerning patency rates for the affected artery, 30-day mortality rates and bleeding-related complications.
RESULTS A total of 65 patients, of which 58 males (89.2%) and seven females (10.8%) were included in the study. The mean age was 56±11. 52 patients (80%) who were subjected to this kind of therapy had a TIMI 3-grade flow at the end of it. The angiographic blood vessel patency rate was 84.6%. The in-hospital mortality rate was found to be 7.7% (5 patients). One of these patients had intracranial bleeding while the others had complications related to the myocardial infarction. Another patient had GI bleeding that required a blood transfusion.
CONCLUSIONS Providing coronary patency through a PCI in STEMI patients with a heavy thrombus burden is a procedure that implies a certain amount of difficulty for the operator. Our study shows that patients presenting with a heavy thrombus burden can also be treated by using fibrinolytic therapy. By lightening the thrombus burden through this procedure, a better angiographic result and a TIMI 3 (Thrombolysis in Myocardial Infarction) grade flow can be obtained while avoiding the development of adverse events.
[GW30-e0899]
Mengmeng Gong, Yidong Wei
Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine
OBJECTIVES We sought several parameters on admission to develop the GRACE scoring system for predicting long-term the composite endpoint of all-cause mortality and MACE events for MI patients with arrhythmia.
METHODS A total of 2150 patients treated for MI between 2014 and 2018 were included. Patients were classified into groups according to the new-onset atrial fibrillation (NOAF) or not. We applied multivariate logistic regression model to select the independent predictors that were added to the GRACE scores to additive prognostic value significantly. The prognostic performance were evaluated by receiver operating characteristic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).
RESULTS At 3 years follow-up 376 (17.5%) reach the composite endpoint: 274 (14.3%) with Non-NOAF and 102 (44.5%) with NOAF. Eight variables were included in the multivariate logistic regression model: NOAF, Hyperlipidemia, Prior stroke, GRACE scores, hemoglobin (HBA1C), eGFR, left ventricular systolic ejection fraction (LVESD), left ventricular ejection fraction (LVEF). Area under the curve (ROC) of predicting long-term MACE events increased significantly in the extended GRACE score model comparing GRACE score only in both groups. (0.719 vs. 0.798; Z=–6.4085, P<0.001). Furthermore, NRI and IDI improved by new model. (NRI 0.231, 95% CI 0.105 to 0.357, P<0.001; IDI 0.157, 95% CI 0.107–0.207, P<0.001). Though, the AUC of predicting long-term mortality was not be improved in MI patients with NOAF (0.728 vs. 0.773, Z=–1.6779, P=0.093), NRI and IDI were increased significantly. (NRI 0.345, 95% CI 0.150–0.540, P<0.001; IDI 0.122, 95% CI 0.064–0.181, P=0.027).
CONCLUSIONS The several parameters at admission are possible indicators to increase the ability of the GRACE score for detecting MI patients with arrhythmia at high risk for long-term MACE events or mortality.
[GW30-e0930]
Xue Wang, Jianjun Ruan, Fanbo Meng
Department of Cardiology China-Japan Union Hospital of Jilin University
OBJECTIVES The study aimed to assess whether the expression of G0S2 gene in peripheral blood can be used as a biomarker to predict the risk of acute myocardial infarction, and to further investigate the role of G0S2 gene in acute myocardial infarction by analyzing the clinical data of the subjects.
METHODS In this study, 92 patients with acute myocardial infarction (AMI) were enrolled in the case group, and 75 patients with coronary heart disease were enrolled in the control group. The diagnosis of both groups was confirmed by coronary angiography. Clinical data of the two groups were analyzed and compared. Peripheral venous blood was collected, and real-time fluorescence quantitative PCR was adopted to detect the expression level of G0S2 gene mRNA in peripheral blood.
RESULTS After analyzing the relative expression level of G0S2 gene mRNA between patients with acute myocardial infarction and patients with coronary heart disease, the result showed that there was a significant difference in the relative expression level of G0S2 gene mRNA in peripheral blood of AMI patients. The relative expression level of G0S2 gene mRNA in peripheral blood of AMI patients was significantly lower than that of the control group, and its relative expression level was 0.413 times that of the patients with coronary heart disease.
The clinical data analysis results of the study objects indicated that there was no significant difference between the two groups in terms of age, smoking history, triglyceride level, total cholesterol level, low-density lipoprotein cholesterol level, high-density lipoprotein cholesterol level, hypertension diagnosis, type-II diabetes diagnosis.
Further analysis of the clinical data and the expression level of the G0S2 gene suggested that the relative expression level of G0S2 gene mRNA was independent of age (P=0.872), triglyceride level (P=0.525), total cholesterol level (P=0.997), high-density lipoprotein cholesterol level (P=0.823), and low density lipoprotein cholesterol level (P=0.542).
The binary Logistic regression analysis showed that the low expression level of the G0S2 gene was an independent risk factor for the development of coronary heart disease towards acute myocardial infarction. Compared with the group with a high level of G0S2 expression, the group with low expression had a 2.098-fold increased risk in developing AMI.
CONCLUSIONS The expression level of the G0S2 gene is significantly lower in the peripheral blood of patients with acute myocardial infarction, and it is an independent risk factor for acute myocardial infarction. The G0S2 gene could be used as a genetic marker to assess the risk of acute myocardial infarction.
[GW30-e0934]
Minghui Piao 1,2 , Changbin Sun 1,2 , Bo Yu 1,2
1Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
2The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
OBJECTIVES Diabetes mellitus has been acknowledged as a prominent risk factor for coronary artery disease (CAD) and characterized by poor prognosis, which may be due to atherosclerotic plaque characteristics. However, in vivo data are lacking. Optical coherence tomography (OCT) is an intravascular imaging modality that could qualitatively and quantitatively evaluate fibrous cap thickness (FCT), maximum lipid arc and the appearance of microphage. We assessed atherosclerotic plaque characteristics by OCT imaging in coronary heart disease patients with Diabetes mellitus compared with a sex- and age-matched control group. The present study aimed to investigate the effect of diabetes mellitus on the changes of characteristics of coronary culprit lesions measured by OCT.
METHODS We randomly recruited 211 patients with symptomatic or asymptomatic coronary artery disease and objective evidence of myocardial ischaemia who underwent OCT images during coronary angiography (CAG). Patients with incomplete clinical histories or laboratory data were excluded. We divided the population into two groups: One group is DM group (n=45, patients with diabetes) and another group is NDM group (n=166, patients without diabetes). OCT was used to assess FCT, maximum lipid arc and the appearance of microphage of the two groups respectively. FCT of lipid plaque was measured at its thinnest part 3 times, and the average value was calculated. Lipid arc was measured on the cross-section with largest lipid pool. Macrophage accumulation on the OCT images was defined as increased signal intensity within the plaque, accompanied by heterogeneous backward shadows. All OCT images were analyzed using the previously validated criteria for plaque characterization and were then compared between DM and NDM groups. Statistical methods were used to assess the relationship between diabetes mellitus and coronary plaque characteristics.
RESULTS The mean age of the patients was 56.8±10.7, 162 (76.8%) were male. Patients with diabetes showed lower frequency of thrombus (86.7 vs. 95.8%, P=0.024) when compared with NDM group. The maximum lipid arc was comparable in DM group compared with NDM group (322.9±55.5° vs. 293.7±66.2°, P=0.019). However, there is no evident difference of fibrous cap thickness (FCT) between the two groups (54.0±26.0 μm vs. 57.4±28.5 μm, P=0.528). Likewise, no significant distinction in the appearance of microphage can be seen in both groups (91.1 vs. 86.6%, P=0.415).
CONCLUSIONS Diabetes mellitus can affect the maximum lipid arc and the formation of thrombus, but has no significant effect on FCT and the appearance of microphage. Clinically, diabetes and thrombosis may not have a direct relationship, because the impact of diabetes mellitus on atherosclerosis was affected by many factors. Furthermore, in the present study, the small sample size may not objectively reflect the experimental results, which need to be verified in a research with a lot of samples. We cannot determine the occurrence and the treatment of thrombosis based solely on whether we have diabetes or not. However, our research results still provide significant evidence for the diagnosis and treatment of vulnerable plaques in patients with diabetes mellitus complicated with coronary heart disease.
[GW30-e0940]
Jiaqi Liang 1 , Min Wu 2 , Min Wu 2
1Beijing Longfu Hospital
2Guang’anmen Hospital, China academy of Chinese Medical Sciences
OBJECTIVES Modern Chinese medical studies indicate that blood stasis caused toxicity is the key pathogenesis of unstable angina pectoris. The combination of traditional Chinese medicine components of toxicity-removing and blood-activating can play an effective role in treating unstable angina pectoris by regulating the balance between pro-inflammatory and anti-inflammatory networks. The purpose of this study is to observe the efficacy of traditional Chinese herbal medicine polygonum cuspidatum and hawthorn for the intervention of unstable angina pectoris with syndrome of toxin and blood stasis, and to explain its mechanism by observing the change of pro and anti-inflammatory network in patients, so as to provide evidence for clinical application.
METHODS Sixty participants with unstable angina pectoris were randomly divided into control group and intervention group. Control group was given conventional basis western medicine treatment, while intervention group was given in addition to conventional basic western medicine treatment with Chinese medical formula of granule polygonum cuspidatum and hawthorn. Each dose of traditional Chinese medicine formula contains 15 g of polygonum cuspidatum and 10 g of hawthorn. Participants were directed to take one dose per day in a course of treatment for 4 weeks. Before and after the treatment, the participants’ symptoms were evaluated by scale, and their serum pro-inflammatory factors including Hs-CRP, TNF-alpha, IL-6 and anti-inflammatory factors IL-10 and adiponectin were examined. And the ration of pro-inflammatory factors to anti-inflammatory factors was calculated to observe the difference between the two groups before and after treatment.
RESULTS Compared with the control group, the angina pectoris score, TCM syndrome score, Seattle angina questionnaire score and SF-36 score were significantly improved in intervention group (P<0.05). After treatment, TNF-alpha decreased significantly in both groups (P<0.01). In the intervention group, it was observed that Hs-CRP decreased while IL-10 increased after treatment (P<0.05), and the serum adiponectin level was much higher than that in the control group (P<0.01). The ratio of pro-inflammatory and anti-inflammatory factors in the two groups are both changed to different degrees after the treatment. Compared with the control group, the IL-6/adiponectin ratio in the intervention group decreased (P<0.05), while the Hs-CRP/adiponectin ratio decreased significantly (P<0.01).
CONCLUSIONS The combination of traditional Chinese medicine components of toxicity-removing and blood-activating can play a therapeutic role in treating unstable angina pectoris by regulating pro-inflammatory/anti-inflammatory balance of patients.
[GW30-e0945]
Deshan Yuan, Sida Jia, Ce Zhang, Yue Liu, Xiaofang Tang, Ying Song, Ru Liu, Huanhuan Wang, Jingjing Xu, Lijian Gao, Xueyan Zhao, Zhan Gao, Yuejin Yang, Shubin Qiao, Runlin Gao, Bo Xu, Jinqing Yuan
Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College
OBJECTIVES The aim of the present study was to compare the long-term outcomes after three different therapeutic strategies for coronary artery disease patients aged ≥75 years with three-vessel disease (3VD).
METHODS A total of 711 coronary artery disease patients aged ≥75 years with 3VD were consecutively enrolled from April 2004 to February 2011 in Fuwai hospital. Patients were followed up for a median of 7.25 years, and were divided into PCI, CABG, or medical therapy (MT) groups according to the treatment they received. The primary endpoint was all-cause death, and the secondary endpoints included cardiac death and major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction, stroke, and unplanned revascularization.
RESULTS Compared with MT group, patients in PCI and CABG group both had lower incidence of all-cause death and cardiac death (all P<0.05). Especially, CABG group also had lower rate of MACCE (41.1 vs. 53.0%, P=0.023) and higher rate of stroke (12.4 vs. 5.7%, P=0.018). Compared with PCI group, patients in CABG group had lower incidence of cardiac death (7.8 vs. 15.7%, P=0.026), myocardial infarction (1.6 vs. 6.3%, P=0.037) and unplanned revascularization (2.3 vs. 8.4%, P=0.020). Kaplan-Meier survival analysis showed similar results. After adjust for confounding factors using multivariate Cox regression analysis, CABG was independently associated with lower risk of cardiac death (HR 0.475, 95% CI: 0.232–0.974, P=0.042), myocardial infarction (HR 0.196, 95% CI: 0.043–0.892, P=0.035) and unplanned revascularization (HR 0.279, 95% CI: 0.079–0.982, P=0.047) compared with PCI group, while MT group was independently associated with higher risk of cardiac death (HR 1.636, 95% CI: 1.092–2.449, P=0.017) compared with PCI group. Subgroup analysis showed that there was a significant interaction between treatment strategy (PCI vs. CABG) and gender for MACCE (P=0.026).
CONCLUSIONS Among 3VD patients aged ≥75 years, patients undergoing PCI or CABG have lower incidence of long-term all-cause and cardiac death compared with patients receiving MT alone. Compared with PCI group, CABG is independently associated with lower risk of long-term cardiac death, myocardial infarction and unplanned revascularization, while MT group had higher risk of long-term cardiac death.
[GW30-e0953]
Min Wu 1 , Jiaqi Liang 2 , Liang Jiaqi 2
1China Academy of Chinese Medical Sciences
2Beijing Longfu hospital
OBJECTIVES To observe the balance of pro/anti-inflammatory factors in patients with unstable angina.
METHODS Compared with stable angina and fifty cases of healthy people were included. The serum levels of pro-inflammatory and anti-inflammatory factors including hypertensive c-reactive protein (hs-CRP), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin (IL-10) and adiponectin were examined. We calculated the ratio of pro-inflammatory and anti-inflammatory factors.
RESULTS Compared with the healthy group, the serum level of hs-CRP, TNF-α, IL-6, the ratios of pro-inflammatory and anti-inflammatory factors, such as hs-CRP/IL-10, TNF-α/IL-10, IL-6/IL-10, hs-CRP/adiponectin, TNF-α/adiponectin, IL-6/adiponectin, (TNF-α×hs-CRP×IL-6)/(IL-10×adiponectin) significantly elevated in unstable angina group (P is less than 0.05 or 0.01). Compared with the stable angina group. The ratios of pro-inflammatory and anti-inflammatory factors, such as TNF-α/IL-10, IL-6/IL-10 and TNF-α/adiponectin were significantly increased in unstable angina group (P is less than 0.05 or 0.01).
CONCLUSIONS The unstable angina patients have a higher level of pro-inflammatory factors, and a lower level of anti-inflammatory factors. The fluctuation of pro/anti-inflammatory factors is a potential indicator to the severity of coronary heart disease.
[GW30-e0956]
Olim Pulatov, Umida Kamilova, Abror Khamraev
Tashkent Medical Academy
OBJECTIVES The study of indicators of platelet aggregation activity in patients with young myocardial infarction.
METHODS Seventy-four patients with acute Q-wave myocardial infarction (AMI) were examined. The patients were divided into 2 groups: 38 young patients with AMI were 1 group and 36 patients with AMI over 60 were 2 group. Evaluated indicators of platelet aggregation activity. ADP was used as an inducer.
RESULTS Analysis of the obtained data showed that in patients of group I and in patients of group II, the initial indicators of platelet aggregation activity (AAT) were significantly higher than in healthy individuals –1.98±0.36 μmol ADP and 1.99±0.41 μmol ADP versus 4.78±0.22 μmol ADP in healthy individuals (P<0.001) and P><0.005). The rates of platelet aggregation (Vagr) in group I were 1.96±0.27 cm/min and group II was 1.83±0.41 cm/min versus 0.34±.5.5 cm/min in healthy individuals, respectively, P><0.001).
CONCLUSIONS The study of platelet aggregation ability depending on age revealed that the rates of aggregation were significantly higher in patients with AMI at a young age.
[GW30-e0974]
Thach Nguyen 1,2 , Vu Thi Nguyet Hang 1 , Anthony Kim 3 , Hien DN Duong 1 , Thi Truc Anh Nguyen 2 , Duc Duy Nguyen 2 , Tarneem Darwish 4 , Gianluca Rigatelli 5
1Tan Tao University, School of Medicine, Long An Vietnam
2Methodist Hospital, Merrillville IN, USA
3Purdue University Northwest Oak Street Health, LLC, Munster IN, USA
4UCLA David Geffen School of Medicine, Los Angeles CA, USA
5Rovigo General Hospital, Rovigo, Italy
OBJECTIVES Patient with anomalous coronary origin, such as right coronary artery (RCA) originated from the left sinus, can have chest pain and sudden death. How to identify these patients in the prevention of ischemia and sudden death?
METHODS Patients with the RCA originated from the left sinus were selected. At first, they were interviewed for history of chest pain or no chest pain. Then they underwent bilateral coronary angiogram in order to confirm the origin of the RCA from the left sinus. CT coronary angiograms showing the origin of the RCA from the left sinus were also collected. During coronary angiograms, the left coronary arteries were recorded in the right anterior oblique caudal view and the RCA in the left anterior oblique view (at 15 frames per second). Then the angiograms were viewed off line frame by frame. The first frame was the angiogram of an artery completely filled with contrast. The following frames showed the blood moving in, seen in white. The flow could be LAMINAR, TURBULENT (mixing of blood in white and contrast in black) or ANTEGRADE or RETROGRADE (black column traveling backward). The antegrade flow reflected the normal supply of blood to the myocardium in diastole. The turbulent flow represented the collision between the antegrade and retrograde flow. The retrograde flow represented the flow in reversed direction due to contraction of the left ventricle in systole (Figure 1). The speed and the time of retention of contrast reflected the transit time of blood before it reached the myocardium. A slow speed and a prolonged period of retention increase the possibility of ischemia. The presence and time of persistent ejection of contrast from the ostium into the coronary sinus were evidence of persistent constriction of the proximal RCA squeezed between the aortic root and pulmonary artery (Figure 2).
RESULTS A total of 20 patients with the RCA anomalous origin from the left sinus and patent coronary arteries was selected. The results showed 90% of patient with chest pain had persistent reversed flow with ejection of contrast from the RCA to the right coronary sinus. In these patients, there were significant slow or no flow in the distal coronary segment lasting more than 8 seconds (120 frames) even the arteries were patent. There was also persistent reversed flow in the proximal coronary segment (>90%) and persistent ejection of contrast into the coronary sinus. These 3 above observations (No flow in distal, reversed flow in the proximal coronary arteries and ejection of contrast into the coronary sinus) were the mechanisms of ischemia in patients with RCA having its anomalous ostium originated from the left sinus.
CONCLUSIONS This technique is innovative in the diagnosis (or identification) of patients with possible sudden death due to anomalous origin of the artery crossing between the aorta and pulmonary artery.
[GW30-e0978]
Yan Xue, Ying Shi, Ling Liu, Yingzhong Lin
Department of Cardiology, People’s Hospital of Guangxi Zhuang Autonomous Region
OBJECTIVES Inflammatory cytokines polymorphism plays an important role in the pathogenesis of cardiovascular disease. So far, few studies had investigated the association between interleukin-12RB1 (IL-12RB1) and interleukin-12RB2 (IL-12RB2) genetic variants and coronary heart disease (CHD). We sought to explore the association between IL-12RB1 and IL-12RB2 polymorphisms and CHD in Chinese Zhuang population.
METHODS Six hundred and twenty CHD patients and 705 age- and sex-frequency match controls were enrolled in our case-control study. Genotypes of the single nucleotide polymorphisms (SNPs) were examined by MassArray (Sequenom) in those subjects. The multivariate logistic regression model was used to evaluate the association between SNPs and CHD risk.
RESULTS Comparing with AA genotype of IL-12RB1 rs11575934, the individuals with GG genotype has 1.62 (95% CI: 1.02–4.12, P=0.042) increasing risk of CHD in Chinese Zhuang population, after adjusting for risk factors, those with GG genotype subjects still had a higher risk of CHD than AA genotype of rs11575934 (OR=1.39, 95% CI: 1.07–5.10, P=0.046). Another SNP of IL-12RB1 rs393548 and all SNPs of IL-12RB2 include rs375947, rs401502, rs3790567 and rs12131065 were not significantly associated with the risk of coronary heart disease.
CONCLUSIONS IL-12RB1 rs11575934 polymorphism was related to the risk of CHD in Chinese Zhuang population.
[GW30-e0990]
Thach Nguyen 1,2 , Nguyen Trong Hoang 1 , Anthony Kim 3 , Hien DH Duong 1 , Thi Truc Anh Nguyen 2 , Duc Duy Nguyen 2 , Tarneem Darwish 4 , Gianluca Rigatelli 5
1Tan Tao University, School of Medicine, Long An Vietnam
2Methodist Hospital, Merrillville IN, USA
3Purdue University Northwest Oak Street Health, LLC, Munster IN, USA
4UCLA David Geffen School of Medicine, Los Angeles CA, USA
5Tan Tao University, School of Medicine, Long An Vietnam; Methodist Hospital, Merrillville IN, USA, Purdue University Northwest Oak StRovigo General Hospital, Rovigo, Italy
OBJECTIVES New onset of heart failure (HF) is an indication for investigation for coronary artery disease (CAD). In many cases, the angiogram results showed mild CAD with normal left ventricular (LV) function or mild to moderate LV dysfunction. Management was to continue medical treatment without percutaneous or surgical interventions. Whether CAD causes HF or HF causes ischemic changes on the EKG as well as the chest pain is not clear. Theoretically an elevation of the left ventricular (LV) end diastolic pressure (LVEDP) representing the systolic and diastolic dysfunction) might cause EKG changes suggestive of ischemia. The aim of this study was to clarify the mechanistic causes of new onset HF associated with ischemic EKG changes, chest pain in patients with patent or minimally diseased coronary arteries
METHODS In group A, 20 patients were consecutively selected using the following criteria: (1) history of new onset of HF on presentation to the emergency room, (2) having chest pain on the index admission, (3) EKG changes indicating ischemia (ST depression (Figure 1) or T wave inversion (Figure 2) and no ST segment elevation), AND (4) negative coronary angiogram. Group B (control) included 15 patients with patent coronary arteries and elevated LVEDP (chronic diastolic HF). The aortic systolic (AOS), aortic diastolic (AOD), aortic mean pressure (AOM), pulse pressure, and ejection fraction (EF) were recorded. CPP using the formula CPP=AOD-LVEDP was calculated in both groups.
RESULTS The results showed that both groups had a similar percentage of chest pain and SOB (P>0.05). All patients had a negative coronary angiogram. The majority of patients in group A had a higher LVEDP than the control group (B) (P<0.05). However, the AO Diastolic (AOD) pressure was lower in group A than in group B (P><0.05). In patients with elevated LVEDP and low AOD, with CPP><20 mmHg, the EKG changes (type 3) with deep T wave inversion were more frequently seen in more chest and limb leads (Figure 2). If the CPP was between 20¡§C30 mmHg, the EKG changes were more of type 2 (mild ST depression) (P><0.5%). If the CPP>30 mmHg, there were normal EKG readings or only type 1 changes (P<0.05%). It was strongly suggested that CPP><20 mmHg was associated with chest pain and ischemia on the EKG. Once the elevated LVEDP was reduced to a lower level or when the OAD pressure improved (no more diastolic hypotension), the ST segment abnormalities improved.
CONCLUSIONS In patients with HF and EKG changes suggestive of ischemia, a lower AOD could aggravate ischemia in patients with elevated LVEDP. The reason is that the coronary perfusion pressure (CPP) is the difference between AOD and LVEDP; the CPP could then decrease and cause ischemia (due to low perfusion pressure) even though the coronary arteries are patent. As result, LV dysfunction could cause ischemia in selected patients, and could be the cause of death in patients with elevated LVEDP (e.g., CAD with LV dysfunction or aortic stenosis) undergoing PCI.
[GW30-e0998]
Thach Nguyen 5 , Marco Zuin 1,2 , Gianluca Rigatelli 2 , Fiorenzo Scaranello 3 , Loris Roncon 4 , Nguyen Khanh Duy 6
1Section of Internal and Cardiopulmonary Medicine, University of Ferrara, Faculty of Medicine Ferrara, Italy
2Department of Cardiovascular Diagnosis and Endoluminal Interventions, Santa Maria della Misericordia Hospital, Rovigo, Italy
3Department of Radiological Sciences, Santa Maria Della Misericordia Hospital, Rovigo, Italy
4Division of Cardiology, Santa Maria Della Misericordia Hospital, Rovigo, Italy
5Tan Tao university, School of Medicine, Long An Vietnam
6Vo Truong Toan University, School of Medicine, Can Tho Vietnam
OBJECTIVES Wall shear stress (WSS) plays a pivotal role on plaque progression in coronary artery bifurcation disease. Left main (LM) bifurcation is the most clinically relevant bifurcation in humans. To assess the prognostic role of baseline mean WSS in developing a bifurcation-located myocardial infarction (B-MI) over the following three years in angiographically non-significant LM bifurcation disease.
METHODS We reconstructed 32 LM bifurcation with an angiographically non-significant LM bifurcation disease based on the patient-specific geometries derived from the coronary computed tomography angiography (CCTA). A steady flow simulation using the patient-specific diastolic blood pressure assessed during the imaging acquisition was then carried out.
RESULTS Among 32 patients, (20 males, mean age 70.4±12.0 years old, 12 (37.5%) had a B-MI over the following three years after the CCTA; the remaining 20 subjects were used as controls. B-MI patients had a higher significant mean WSS values of the proximal stenotic segments (WSSprox) and of entire lesion (WSSentire_lesion) compared to controls. Both the mean WSSprox and the mean of WSSentire_lesion of each vessel, adjusted for the related mean lesions lengths and 3-dimensional percentage of stenosis (DS%) resulted independent predictors of 3-year B-MI. A mean WSSentire_model ≥5.05 Pa correlated with the risk of B-MI over 3-year follow-up Log-rank (Mantel-Cox analysis) P=0.001). The multivariate Cox-regression analysis confirmed that a baseline means WSSentire_model ≥5.05 Pa (HR 1.98, 95% CI 1.83–2.10, P=0.001) was a predictor of 3-year B-MI independently from the entire mean lesions lengths (HR 1.56. 95% CI 1.43.1.68, P=0.002) and DS% (HR 1.26, 95% CI 1.18–1.37, P=0.03).
CONCLUSIONS In patients with an angiographically non-significant LM 1,1,1 Medina disease, both the mean WSSprox and WSSentire_lesion of each stenotic vessel predicted B- over 3-year follow-up. Moreover, a WSSentire_bifurcation ≥5.05 Pa resulted MI a predictor of 3-year B-MI independently from the DS% and lesions lengths.
[GW30-e1015]
Yao XU, Jun Wan
Renmin Hospital of Wuhan University
OBJECTIVES Acute aortic dissection (AAD) is known as one of the most life-threatening diseases in cardiovascular system which has reported to be associated with inflammatory reaction. But little is known about interleukin (IL) 25 expression and roles in AAD. In present study, we detected levels of IL-25 in serum and aorta and attempted to reveal the potential relationships between inflammatory factor IL-25 and AAD.
METHODS The expression of IL-25 in aorta of AAD was simultaneously measured by immunofluorescence. In addition, we compared and analyzed serum levels of IL-25 in patients including hypertension patients excluded AAD (n=30, we named it NAD group) and AAD patients of Stanford A (n=45) and Stanford B (n=41) by the enzyme-linked immune sorbent assay (ELISA) kits. And the levels of IL-6 and TNF- were also evaluated in those serum samples.
RESULTS Analysis of tissue samples from aorta showed that IL-25 mainly located in macrophages and also up-regulated in tissues of AAD. Furthermore, compared with NAD group, levels of IL-25 in AAD serum were significantly increased. Moreover, both IL-6 and TNF- were markedly elevated in serum of AAD patients. Serum IL-25 levels were positively correlated with IL-6 and TNF- levels in AAD patients. Furthermore, IL-25 was correlated with the occurrence of AAD which was identified by simple linear regression analysis and binary logistic regression analysis.
CONCLUSIONS Higher levels of IL-25 were found in serum and aorta of AAD patients, which suggested that IL-25 may associated with the occurrence and development of AAD.
[GW30-e1017]
Qian Chen 1,2 , Jingfeng Wang 1,2 , Wenhua Ling 3,4
1Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China
2Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, Guangdong 510120, China
3Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
4Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong Province 510080, China
OBJECTIVES Irreversible liver fibrosis in coronary artery disease (CAD) contribute to adverse progression. Whether baseline liver fibrosis scores (LFSs) provide predictive value for long-term mortality among CAD patients requires investigation.
METHODS The analysis was conducted based on a prospective cohort study among 3263 CAD patients, followed to the end of September, 2016. We used Cox models to assess the association of baseline LFSs, including non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis 4 (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), gamma-glutamyltransferase to platelet ratio (GPR) and Forns score, with the risk of all-cause and cardiovascular mortality among patients with CAD. All the LFSs were categorized into low, intermediate and high levels according to their originally developed cut-offs.
RESULTS During a median of 5.63 years follow-up, 357 deaths were identified, 230 of those were cardiovascular-related. Compared with patients in the lowest score levels, multivariable-adjusted hazard ratios (95% CI) for the highest levels of NFS, FIB-4, APRI, GPR and Forns score were 3.19 (2.20–4.64), 3.39 (2.35–4.88), 2.01 (1.43–2.82), 1.60 (1.22–2.09) and 3.34 (1.79–6.26) for all-cause mortality, and 3.74 (2.31–6.06), 3.63 (2.29–5.75), 2.05 (1.36–3.10), 1.86 (1.33–2.60), and 2.48 (1.15–5.35) for cardiovascular mortality, respectively. These associations were consistent when participants were stratified by sex, age (<65 vs. ≥65 years), type of CAD, diabetes status and BMI (<24 vs. ≥24 kg/m2).
CONCLUSIONS Higher NFS, FIB-4, APRI, GPR and Forns score were associated with increased risks of all-cause and cardiovascular mortality among Chinese patients with CAD. These LFSs might play an important role on prognosis prediction in CAD patients.
[GW30-e1018]
Wenjie Zuo, Mingming Yang, Xiaoguo Zhang, Zhenjun Ji, Yifan Chen, Rui Zhang, Yamin Su, Genshan Ma
Department of Cardiology, Zhongda Hospital, Southeast University
OBJECTIVES Angiographic evaluation remains the cornerstone for decision-making regarding revascularization and fractional flow reserve (FFR) is still underutilized in routine clinical care. Thus, we aimed to develop a simple, practical and angiography-based diagnostic protocol to discriminate the intermediate stenosis with functional ischemia.
METHODS Consecutive patients who underwent both invasive coronary angiography and lesion-specific FFR measurement were screened in this retrospective analysis. Percent diameter stenosis (%DS), percent area stenosis (%AS), lesion length (LL), and minimal lumen diameter (MLD) were calculated by the operator-independent software. The ratio of LL to the fourth power of MLD (LL/MLD4), derived from the Poiseuille equation, was also assessed in the present study. The C statistics of VE and QCA, also known as area under the receiver-operating characteristic curves, were calculated and the Youden index was used to determine the optimal cut-off values. An FFR value ≤0.80 was considered to indicate the physiological significance of stenosis.
RESULTS In total, 351 patients with 366 lesions were included. The positive FFR results were identified in 71 lesions (19%) and the median of FFR values was 0.87. There was a significant but modest correlation between %DS and FFR in VE (ρ=–0.303; P<0.001) and QCA (ρ=–0.245; P<0.001). VE had a greater %DS than QCA with the mean difference (standard deviation) of 21.7% (9.7%). The best cutoff values for predicting FFR≤0.80 were >65% for VE, >48% for %DS by QCA, >73% for %AS, ≤1.66 mm for MLD, >13.53 mm for LL, and >2.42 mm–3 for LL/MLD4. C statistic was revealed as 0.72 for VE, significantly greater than %DS by QCA (0.60; P=0.005), %AS (0.60; P=0.007) and LL (0.58; P=0.009) with comparable to MLD (0.67; P=0.328) and LL/MLD4 (0.70; P=0.651). In our protocol, any positive of the two parameters (VE>65% or LL/MLD4>2.42 mm–3) is regarded as a positive result, requiring further FFR measurement. In contrast, the protocol is negative if the two parameters are all negative (VE≤65% and LL/MLD4 ≤2.42 mm–3). Compared with single variables including VE, %DS by QCA, %AS, LL, MLD, and LL/MLD4, the protocol yielded a higher sensitivity (88.7%; 95% CI 79.0–95.0; P<0.001 for all) and negative predictive value (94.2%; 95% CI 88.8–97.5), but a lower specificity (43.7%; 95% CI 38.0–49.6; P<0.001 for all besides P=0.001 for LL).
CONCLUSIONS Overall, VE demonstrated a better diagnostic performance than %DS by QCA to predict physiological significance in borderline stenosis. This protocol could be a simple and easy-to-access screening tool to identify those high-risk lesions which need further FFR confirmation, improving risk stratification and clinical outcomes with limited resources.
[GW30-e1023]
Di Ye, Zhen Wang, Jing Ye, Menglong Wang, Jianfang Liu, Yao Xu, Huimin Jiang, Jun Wan
Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan 430060, China
OBJECTIVES Interleukin (IL)-5 is an anti-inflammatory cytokine which has been demonstrated to be involved in cardiovascular diseases, including aortic aneurysm and heart failure. This study aimed to investigate the involvement of IL-5 in coronary artery disease (CAD) and possible mechanisms.
METHODS The expression of IL-5 in human coronary artery specimens collected from CAD patients and normal donors (we name it Normal) was analyzed. In addition, the plasma IL-5, IL-17, and interferon (IFN)-γ levels in CAD patients were detected using ELISA kits, with samples from chest pain patients (non-CAD, hereafter referred as NCAD) as controls. Mouse CD4+ T helper (Th) cells were separated, and the effect of IL-5 on Th1, Treg and Th17 differentiation and the mRNA levels of their characteristic cytokines were detected using flow cytometry and RT-PCR, respectively.
RESULTS IL-5 was significantly decreased in the coronary plaque of CAD patients when compared with the Normal group, and IL-5 was mainly derived from macrophages in the coronary artery plaque. In addition, compared with the NCAD group, plasma IL-5 levels in the CAD groups were significantly lower, and the sequence from high to low is stable angina pectoris (SAP), unstable angina pectoris (UAP), and acute myocardial infarction (AMI). Binary linear regression analysis showed that IL-5 was independently correlated with the occurrence of CAD. In addition, the recombinant mouse IL-5 (rIL-5) treatment decreased Th1, Th17 levels and the mRNA expression of their characteristic cytokines in oxidized low-density lipoprotein (OX-LDL)-treated CD4+ Th cells.
CONCLUSIONS The IL-5 levels were decreased in CAD patients and inhibits ox-LDL-induced Th1 and Th17 differentiation in vitro.
[GW30-e1031]
Luping He, Sining Hu, Yuhan Qin, Yishuo Xu, Xue Feng, Zhaoyue Li, Shaosong Zhang, Jingbo Hou, Haibo Jia, Bo Yu
Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150086, China
OBJECTIVES Histology studies have illustrated that different thrombus had distinct characteristics and mechanisms. However, there was no in-vivo study to focus on thrombus type and its morphology. Intravascular imaging, especially optical coherence tomography (OCT), enables us to detect and evaluate thrombus in vivo accurately. In this study, we sought to evaluate the relationship between thrombus type and residual thrombus after thrombus aspiration among STEMI patients using intravascular optical coherence tomography (IVOCT).
METHODS A total of 79 consecutive STEMI patients who did pre-PCI OCT were enrolled into this study. According to thrombus type, patients were divided into two groups: red thrombus (erythrocyte-rich, highly backscattering with high attenuation) group and white thrombus (platelet-rich, less backscattering, and homogeneous with low attenuation) group. Manual thrombus aspiration was performed at the operator’s discretion. Thrombus was defined as an irregular mass protruding into the lumen. Other characteristics of residual thrombus and the quantitative method for thrombus analysis were defined with established criteria in previous papers.
RESULTS Among all the 79 patients, 31(39.2%) patients had red thrombus and 48 (60.8%) patients had white thrombus. The frequency of thrombus aspiration 51 (100%) vs. 17 (100%), P=1.000 had no significant difference between the two cohorts. When it came to IVOCT vessel morphology analysing, we found that patients with red thrombus showed a bigger vessel when compared with white thrombus group, including proximal reference area [15.28 (11.03–17.33) vs. 10.99 (9.85–14.34), P=0.024], distal reference area [13.35 (10.69–15.12) vs. 9.98 (7.77–11.92), P=0.003], mean lumen area [3.30 (2.45–5.15) vs. 2.41 (1.79–3.14), P=0.003] and mean flow area [2.39 (1.89–3.97) vs. 1.91 (1.45–2.59), P=0.012]. However, red thrombus cohort had significantly bigger residual thrombus than the white thrombus cohort, including mean thrombus area [0.51 (0.36–1.28) vs. 0.34 (0.20–0.67), P=0.002], maximal thrombus area [1.20 (0.59–2.82) vs. 0.73 (0.40–1.44), P=0.011] and thombus volume [2.54 (1.25–8.33) vs. 1.32 (0.58–2.93), P=0.004]. In plaque components, patients with red thrombus had a bigger lipid arc than white thrombus group [204.0 (145.7–236.7) vs. 152.3 (100.7–199.8), P=0.012].
CONCLUSIONS There were distinct differences between the two cohorts. Patients with red thrombus had a more vulnerable plaque phenotype and much more residual thrombus. However, the red thrombus group had a much bigger lumen and flow area than the white. Further studies should be done to illuminate the underlying mechanisms and to access their impact on long-term prognosis.
[GW30-e1040]
Thach Nguyen 1,2 , Vu Ngoc Phuong Thao 1 , Thi Truc Anh Nguyen 2 , Duy Duc Nguyen 1 , Tarneem Darwish 3 , Gianluca Rigatelli 4
1Tan Tao University, School of Medicine, Long An Vietnam
2Methodist Hospital, Merrillville, IN, USA
3UCLA David Geffen School of Medicine, Los Angeles, CA, USA
4Rovigo General Hospital, Rovigo, Italy
OBJECTIVES Coronary injuries are hypothesized to be caused by the cavitation phenomenon (explosion of air bubbles) which is seen frequently in domestic or industrial pipes. Following hydraulics principle, with distal negative suctioning in diastole, if the coronary dynamic pressure decreases below the vapor pressure (VP) most likely of nitrogen in the blood, bubbles will form. They explode when the coronary dynamic pressure recovers > the VP during systole. These explosions create jet waves damaging the integrity of the endothelium, allowing infiltration of the LDL molecule into the subintimal space, starting the formation of coronary plaques. How could these events be located and tabulated by Machine Learning (artificial intelligence) program?
METHODS Angiograms of patients with stable angina were selected. The left coronary arteries were recorded in the right anterior oblique caudal view and the right coronary artery in the left anterior oblique view (at 15 frames per second). Then the angiograms were viewed off line frame by frame. The first frame was the angiogram of an artery completely filled with contrast. The following frames showed the blood moving in, seen in white. The flow could be LAMINAR (Figure 1), TURBULENT (mixing of blood in white and contrast in black) (Figure 2) or RETROGRADE (black column traveling backward) (Figure 3). The turbulent flow reflects the collision between antegrade and retrograde flow. The LOCATION and the length in TIME of laminar, retrograde and mainly turbulent flow were recorded. The intensity of turbulent flow was measured by (1) the length of coronary segment with mixing contrast and blood (2) the length of the stagnant retrograde flow. The AI programs were trained to Use the U-Net deep learning for medical image segmentation and then build the UNet model based on the previous dataset (Images, ImageMask) (Figure 4).
RESULTS Angiograms of 50 patients showed laminar flow (85%) in diastole. The flow became turbulent at systole with diffuse coarse mixing of black (contrast) and white (blood) at the MID SEGMENT of the left circumflex artery (LCX) or the right coronary artery (RCA). The presence of turbulence matched the location of 86% of ruptured plaques. The time of retrograde flow lasted more than 2 systoles. Special protocols were used successfully to train AI to recognize the lesions, antegrade, retrograde flow, turbulence and the persisting retrograde stagnant area.
CONCLUSIONS In patients with stable angina, the location of plaques and turbulent flow representing the collision between antegrade flow in diastole and retrograde flow in systole was confirmed. These results may help to find the precise measures preventing formation of de nova coronary plaques.
[GW30-e1054]
Xiaodong Wang, wang
Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine
OBJECTIVES In patients with ST-elevation myocardial infarction (STEMI), residual platelet reactivity soon after a loading dose (LD) of clopidogrel or ticagrelor is higher in healthy volunteers than that in patients with stable coronary artery disease, and the majority of primary percutaneous coronary intervention (PCI) procedures with dual anti-platelet therapy (DAPT) are performed without proper platelet inhibition. However, ticagrelor LD (180 mg once) is just the daily dose (90 mg twice per day), whereas clopidogrel LD is 4 or 8-fold the long-term daily dose. We hypothesized that a vasodilator-stimulated phosphoprotein (VASP)-guided ticagrelor LD may achieve platelet inhibition more effectively, and decrease the rate of major adverse cardiac events (MACE) as compared the standard ticagrelor LD.
METHODS This monocenter prospective randomized trial included 374 patients with a low ticagrelor response after a 180 mg ticagrelor LD undergoing PCI. Patients were randomly assigned into a control group (n=186) and a vasodilator-stimulated phosphoprotein (VASP)-guided group (n=188) (Figure 1). In the VASP-guided group, patients received up to 3 different LD of ticagrelor (180 mg, 270 mg, 360 mg) to achieve platelet reaction index (PRI) less than 50% before PCI. The primary endpoint was the MACE at 1 month. Secondary endpoints were Thrombolysis in Myocardial Infarction (TIMI) major and minor bleeding.
RESULTS Demographic data and clinical characteristics were similar in two groups (Table 1). PCI was performed in all patients. The PRI before ticagrelor LD in two groups was not different (85.4±16.2 vs. 79.3%±13.1%; P=0.22). After totally 180 mg, 270 mg and 360 mg LD of ticagrelor, PRI decreased from 79.3±13.1 to 50.5%±9.4%, 36.9±5.8 and 21.0%±6.9%, respectively (P<0.01) and 98.2% of patients reached PRI<50% in the VASP-guided group; whereas in the control group, PRI decreased from 85.4±16.2 to 45.3%±10.0%, 42.8±9.7 and 39.6%±5.5%, respectively (P>0.05) and 62.4% of patients reached PRI<50%. The adenosine concentration in VASP-guided group increased from 94.3±10.5 to 125.6±19.7, 147.2±15.8 and 177.3±21.2 μg/L (P<0.01), whereas in the control group, the adenosine level fluctuated among 92.6±11.7, 98.4±17.5, 108.4±14.1 and 105.6±10.8 μg/L (P>0.05) (Table 2). The rate of MACE was significantly lower in the VASP-guided group compared to the control group (6.9 vs. 14.5%, P=0.007). There was no major hemorrhagic complication in either group (Table 3). The rate of minor bleeding in the VASP-guided group was higher than that in the control group, but the difference was not significant (12.8 vs. 8.6%, P=0.06) (Figure 2).
CONCLUSIONS The individualized ticagrelor loading dose guided by VASP decreases the rate of major adverse cardiovascular events after PCI without increasing major bleeding.
[GW30-e1060]
Baxrom Alyavi, Akbar Abdullaev, Jamol Uzokov
Republican Specialized Scientific Practical Medical Center of Therapy and Medical Rehabilitation
OBJECTIVES Clopidogrel is an antiplatelet medication used to prevent stent re-thrombosis in patients with coronary artery disease (CAD). Despite using of the standard therapy after implanting DES stents in patients with CAD, some patients may suffer from stent thrombus. Aim of the study was to estimate the impact of clopidogrel gene polymorphisms, including those of CYP2C19*1, CYP2C19*2, CYP2C19*3 and CYP2C19*17 on clopidogrel antiplatelet activity in patients CAD after DES implantation.
METHODS Forty-nine patients undergoing percutaneous intervention with DES implantation in patients with CAD were enrolled in the study. All patients were admitted for elective coronary intervention (aged 43–68 years; mean age 53±12.0; male n=29). Blood samples for platelet function testing were collected before clopidogrel administration (baseline) and at the 36 hours after the loading dose. Platelet aggregation (PA) was performed in a two-channel aggregometer and assessed by inhibition of platelet aggregation (IPA). Genetic polymorphisms was performed using polymerase chain reaction (PCR).
RESULTS Among 49 patients, 45% of patients had CYP2C19*1, 22% CYP2C19*2, 7% CYP2C19*3 and 26% CYP2C19*17 genetic polymorphisms. Only 84% of patients had a response to clopidogerel. Most of the non--responders were subjects with CYP2C19*2 and CYP2C19*3 genotypes. IPA significantly increased in 36 hours after loading dose in CYP2C19*17 genotype with 5 mmol/L and 20 mmol/L ADP (P<0.01), and normal increased in 36 hours after loading dose in CYP2C19*1 genotyping subjects (P><0.05) whereas IPA did not changed significantly in subjects with CYP2C19*2 and CYP2C19*3 genotypes with 5 mmol/L and 20 mmol/L ADP (P>0.05).
CONCLUSIONS CYP2C19*2 and CYP2C19*3 genetic polymorphisms are the predictor of the clopidogrel non-responders whereas CYP2C19*17 polymorphisms are strong responders in the population.
[GW30-e1062]
Baxrom Alyavi, Akbar Abdullaev, Jamol Uzokov
Republican Specialized Scientific Practical Medical Center of Therapy and Medical Rehabilitation
OBJECTIVES Aim of the study was to establish the prognostic value of post-infarction (PI) cardiac remodeling and cytokine imbalance for the development of chronic heart failure (CHF) in patients with coronary artery disease (CAD).
METHODS Fifty-five patients with the history of Q wave myocardial infarction (MI) were enrolled in this study. All laboratory, instrumental and anthropometric data were obtained and the quality of life was assessed by using the University of Minnesota questionnaire.
RESULTS Men prevailed in this group of patients (67.2% of men and 32.7% of women). Analysis of central hemodynamic parameters in patients with various types of myocardial remodeling showed that in all studied groups there was a decrease in the ejection fraction, systolic shortening of left ventricle (LV), end-diastolic LV pressure and high systolic and diastolic myocardial stress. In patients with the history of Q MI, cardiac remodeling is characterized by the formation of eccentric hypertrophy with dilatation of 27.5% and without LV dilatation of 23.5%; normal heart geometry in 25% and concentric hypertrophy in 24% of cases. Multivariate regression analysis revealed that the decrease in EF <40%, eccentric hypertrophy with dilation, systolic and diastolic dysfunction of the LV, increase in TNF α and IL-6 were the most significant prognostic factors for the CHF in patients of FC III (P>0.05).
CONCLUSIONS For of development of CHF in patients with PI myocardial remodeling the clinical picture, cardio hemodynamic indicators and laboratory markers will allow to identify the maladjusted LV model in the early stages of the disease and to develop new pathogenically based treatment methods for this pathology.
[GW30-e1064]
Baxrom Alyavi, Jamol Uzokov, Sherzod Iskhakov
Republican Specialized Scientific Practical Medical Center of Therapy and Medical Rehabilitation
OBJECTIVES Aspiring along with prasugrel widely used in patients undergoing percutaneous interventions (PCI). Aim of the study was to estimate functional platelet recovery and platelet function after the loading dose of prasugrel.
METHODS Thirty-two patients who underwent loading dose of prasugrel with maintenance dose of aspirin were enrolled in the study. Platelet function was assessed by optical aggregation in the presence of collagen, arachidonic acid (aspirin) and ADP (prasugrel). Platelet-leukocyte complex (PLC) level was quantified at each time-point. Before treatment and after the loading dose of prasugrel, bleeding time and fibrinogen plasma concentration were also evaluated.
RESULTS Platelet function was efficiently inhibited by aspirin and prasugrel at baseline and after the loading dose of prasugrel whilst PLC levels were significantly higher after the loading dose of prosugrel than baseline (+4±10%; P=0.016), in line with an effective platelet inhibition. Prasugrel treatment was associated with variable platelet inhibition and its withdrawal led to variable functional recovery. PLC levels were significantly increased five days after prasugrel reintroduction (+12±18%; P=0.02), compared to baseline. There was a reduction in 5-μM ADP-induced platelet aggregation of after 6 (47±33.8%, P<0.05) and 12 weeks (58±38.5%, P><0.05) in patients with coronary artery disease; 35±41% and 29±59% in the cerebral vascular disease group; and 36±36% and 35±49% in the total group (P>0.05). Plasma fibrinogen levels did not vary during treatment (P>0.05). Bleeding time was significantly prolonged in all studied groups.
CONCLUSIONS Prasugrel along with aspirin significantly reduced inhibition of platelet aggregation in patients with coronary artery disease who underwent percutaneous intervention.
[GW30-e1067]
Akbar Abdullaev, Baxrom Alyavi, Jamol Uzokov, Bekzod Karimov
Republican Specialized Scientific and Practical Medical Center of Therapy and Medical Rehabilitation
OBJECTIVES Quantitative and qualitative analyses of the inflammatory biomarkers play a crucial role to prognosis of the ischemic heart disease. Aim of the study was to conduct a comparative analysis of inflammatory markers in patients with coronary heart disease of stable and unstable flow.
METHODS Ninety-two patients with coronary heart disease (CHD) aged 35–79 years were enrolled in this study (mean age 57.4±13.8 years; male=43%). Laboratory and instrumental data were obtained and assessed. IL-6, TNF-α in blood plasma was carried out by the method of enzyme immunoassay on a solid-phase analyzer ‘Humareader Single’. Statistical processing of the obtained results was carried out using vibrational statistics methods recommended for biomedical research on the IBM PC AT Pentium IV.
RESULTS In patients with unstable angina (UA), the frequency of elevated levels of C-reactive protein (CRP), TNF-α, and leukocytes was higher than in the group with stable ischemic heart disease (P<0.05). The mean levels of these markers were greater in patients with UA compared with patients with stable form of CHD (P><0.05), CRP (4.4±2.3 and 2.8±2.4 mg/L, P><0.05, respectively), TNF-α (10.7±2.3 and 7.6±3.6 pg/mL, P><0.05) and leukocytes (9.1±2.6 vs. 6.6±2.1×109/L, P><0.05). The level of IL-6 in patients with UA was higher in comparison in patients with stable angina (3.3±1.8 vs. 2.7±0.4 pg/mL), but the difference was not significant (P>0.05). There were no significant differences in the level of fibrinogen and sedimentation rate between patients with UA and stable angina.
CONCLUSIONS It was noted that the inflammatory biomarkers were detected both group of patients with unstable forms and stable form of CHD, but the degree of inflammation in patients with UA (level of TNF-α, CRP and leukocytes) is higher than those patients with stable ischemic heart disease.
HYPERTENSION
[GW30-e0013]
Demikhova Nadiia, Kovalenko Yeugen, Melekhovets Oksana, Melekhovets Yuriy
Sumy State University, Ukraine
OBJECTIVES Among the population of Eastern Europe, hyperuricemia (HU) prevalence is 28% in female and 23% in male. Patients with comorbidity of HU and arterial hypertension more often suffer from metabolic syndrome, chronic kidney disease and diabetes mellitus. Aim: to study the relationship between the rate of the morning blood pressure increasing and hyperuricemia in hypertensive patients.
METHODS Total of the 60 hypertensive persons, 30 with uric acid level (SUA) 400 μmol/L (2nd group), were included in study. The groups were comparable in age and sex. SUA level was measured on a biochemical analyzer RT-9800. A 24-hour ambulatory blood pressure monitoring was performed by using of a 24-hour blood pressure monitor ABMP-50 HEACO. The strength of association between two variables was determined by Spearman’s correlation coefficient.
RESULTS At the baseline daytime SBP and DBP was for 1st group: 146±5 mmHg and 92±2 mmHg; for 2nd group: 152±7 mmHg and 96±5 mmHg. The rate of morning increase in SBP and DBP was for 1st group: 22±3 mmHg/h and 14±2 mmHg/h, for 2nd group: 28±4 mmHg/h and 18±3 mmHg/h. The rate of SBP morning increase was higher by 21.4% in the 2nd group, and DBP – by 22.2% compared with the 1st group. Correlation between rate of morning increase in SBP and serum uric acid were discovered in hypertensive patients. The rate of SBP morning increase was correlated with uric acid level: in 1st group r+0.32 and in 2nd group r+0.63 (P<0.05). The rate of DBP morning increase had a low correlation power with SUA level in the 1st group r+0.26 (P>0.05) and in 2nd group r+0.28 (P<0.05).
CONCLUSIONS Higher level of SUA has a stronger effect on rate of morning increase in SBP in hypertensive patients when the level of SUA>400 μmol/L. The rate of morning increase in SBP was correlated with SUA level (r+0.63), but DBP morning increase had low power correlation without statistical significance meaning.
[GW30-e0018]
Min Wang, Shujie Yu, Xianguan Yu, Bin Zhou, Dinghui Liu, Lin Wu, Xiaoxian Qian
The Third Affiliated Hospital of Sun Yat-sen University
OBJECTIVES To study the plasma level of pigment epithelium-derived factor (PEDF) and endothelial inflammation in patients with essential hypertension (EH).
METHODS A total of 602 EH patients were divided into 3 groups: Grade I group, n=154, Grade II group, n=252 and Grade III group, n=196. There was a Control group containing 150 healthy subjects. Plasma levels of PEDF, MCP-1 and IL-6 level were tested and compared among different groups.
RESULTS The plasma PEDF level and inflammation level were different between Control group and EH patients, P<0.001. With the increased severity of hypertension, the PEDF level and inflammation level were elevated accordingly. The PEDF level with higher inflammation level is higher than that in lower blood pressure group, P<0.001.
CONCLUSIONS Plasma PEDF is closely related to EH development, and PEDF level may reflect the inflammation level in EH patients.
[GW30-e0019]
Min Wang, Xianguan Yu, Zhenda Zheng, Shujie Yu, Bin Zhou, Dinghui Liu, Lin Wu, Xiaoxian Qian
The Third Affiliated Hospital of Sun Yat-sen University
OBJECTIVES To study the plasma level of pigment epithelium-derived factor (PEDF) and artery stiffness in patients with essential hypertension (EH).
METHODS A total of 602 EH patients were divided into 3 groups: Grade I group, n=154, Grade II group, n=252 and Grade III group, n=196. There was a Control group containing 150 healthy subjects. Plasma levels of PEDF were tested by ELISA, artery stiffness level were tested by the brachial-ankle pulse wave velocity (baPWV), and compared among different groups.
RESULTS The plasma PEDF level and artery stiffness were different between Control group and EH patients, P<0.001. With the increased severity of hypertension, the PEDF level and artery stiffness level were changed accordingly. The PEDF level with lower artery stiffness level is higher than that in lower blood pressure group, P<0.001.
CONCLUSIONS Plasma PEDF is closely related to EH development, and PEDF level may reflect the artery stiffness level in EH patients.
[GW30-e0036]
Shuting Cheng 1 , Fei Rui 2 , Fei Yu 3
1Department of Radiology, Jilin University
2Department of Cell Biology, College of Basic Medical Sciences, Jilin University
3Department of Cardiology, the Second Hospital, Jilin University
OBJECTIVES Previous studies showed that acupuncture may treat hypertension (HT) and reduce the side effects caused by using western medicine. However, the systemic evaluate effectiveness of acupuncture in the treatment of systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) has not been reported.
METHODS Needling or armature or prod or acupuncture or acupuncture therapy and hypertension or HT are retrieved from PubMed, Elsevier science, Cochrane library, China Sino Med, China National Knowledge Infrastructure, China Science Periodical Database and Chinese Evidence-Based Medicine Database. Evaluate according to Cochrane System Evaluation Manual 4.2 standard. Data were extracted by two reviewers, with disagreement resolved by third party examiners either by consensus or by arbitration. Inclusion criteria: (1) adult HT patients. HT was defined as blood pressure SBP >140 mmHg (1 mmHg=0.133 kPa) and/or DBP>90 mmHg measured 3 times not the same day within a week without the use of antihypertensive drugs. Patients with previous history of HT, currently using anti-HT drugs, although lower than 140/90 mmHg blood pressure should also be diagnosed as HT; (2) treatment group on the basis of western medicine to give acupuncture treatment, acupuncture (including acupuncture, electro-acupuncture). Techniques, needle retention time, treatment, TCM syndrome is not limited; (3) clear control group; (4) the effectiveness of treatment of blood pressure, adverse reaction; and (5) randomized controlled study (RCT). Exclusion criteria: (1) reviews, dissertations and republished papers; (2) animal experiments; and 3) dissertation. RevMan5.3 software provided by Cochrane Collaboration was used for data analysis. The risk ratio (RR) and weighted mean differences (MDs) were used in outcome measures between the end of the final intervention. 95% confidence intervals (CIs) were calculated in the meta-analysis. We pooled data using a fixed-effect model (I2<50%, P>0.05), otherwise we using random effects model (I2>50%, P<0.05); The result is expressed in the forest plot. Bias analysis applied by the funnel plot. Statistically significant differences was P<0.05.
RESULTS Of the 13 Chinese literatures, there were 1062 cases, including 528 of the experimental group, 534 of the control group. Compare to control group, total effective rate is significant increased (RR=1.18, 95% CI=1.12–1.24, P<0.05), and reduced blood pressure (SBP: MD=–10.59, 95% CI=–13.89 to –7.29; DBP: MD=–6.83, 95% CI=–13.46 to –0.19, all P<0.05), among the most obvious in lowering DBP in experimental group (MD=15.91, 95% CI=9.82 to 21.99), acupuncturing Taichong points has statistically significant difference in reducing DBP (I2=84.7%, P<0.05). Adverse reactions has no significant difference between two groups (RR=0.60, 95% CI=0.23 to 1.58, P>0.05).
CONCLUSIONS Acupuncture treatment of HT is safe and effective, especially, reducing DBP by acupuncturing Taichong points, which is worthy of clinical promotion.
[GW30-e0132]
Chaolei Chen, Yingqing Feng
Guangdong Cardiovascular Institute
OBJECTIVES The aim of this retrospective cohort study was to explore the relationship between diastolic blood pressure and first ischemic stroke in community elderly hypertensive patients from China.
METHODS We enrolled 3315 consecutive elderly hypertensive patients including 1475 men and 1840 women from community between January 2010 and December 2011 in China. Patients were divided into four groups according to diastolic blood pressure at 10 mmHg intervals. Multivariate COX regression analysis, subgroup stratified and interaction analysis were preformed to evaluate the relationship between diastolic blood pressure and first ischemic stroke.
RESULTS During a median 5.5 years follow-up perriod, 206 patients were identified as first ischemic stroke. After adjustment for potential confounders, using the first group (diastolic blood pressure less than 70 mmHg) as the reference, the hazard ratio (HR) (95% CI) for the first ischemic stroke of extra three DBP groups were 1.323(95% CI, 0.730–2.397; P=0.35658), 1.519(95% CI, 1.039–2.752; P=0.01678), and 2.348(95% CI, 1.152–4.782; P=0.01875), respectively (P=0.018 for trend). Subgroup and interaction analysis showed there was no interactive effect on diastolic blood pressure and the first ischemic stroke.
CONCLUSIONS Our findings suggested that higher diastolic blood pressure was associated with a higher risk of first ischemic stroke. Diastolic blood pressure was an independent risk factor for the first ischemic stroke among Chinese elderly hypertensive patients.
[GW30-e0133]
Chaolei Chen, Jiyan Chen
Guangdong Cardiovascular Institute
OBJECTIVES We aim to explore the association of diastolic blood pressure and stroke in community hypertensive population.
METHODS This is a cross-sectional study which obtained a total of 8179 hypertensive patients coming from Dongguan Liaobu community from January 2013 to December 2013. We divided these subjects into five groups according to DBP at 10 mmHg intervals and collected information (values) including demographic characteristics, blood pressure and other clinical variables. Univariable and multivariate logistic regression was performed to detect connection between DBP and stroke. Restricted cubic spline and a two-piecewise linear regression model were also used for further exploration.
RESULTS A total of 8139 subjects were recruited and selected and eventually 8130 were left for data analysis. The average age of them is 64.01 years, and male accounted for 48.6%. Among all the participants, 310 suffered from stroke. There is no connection detected in univariate analysis and in different multivariate logistic regression models. Thus, after adjusting for potential confounders (age, sex, BMI, SBP, smoking, drinking, eGFR, heart rate, FBG, TC, TG, LDL-C, HDL-C, DM and antihypertensive drugs), a non-linear relationship was discovered between DBP and stroke, which had an inflection point of 80. The odd ratios and the 95% confidence intervals on the left and right sides of the inflection point were 0.969 (0.948–0.991) and 1.008 (0.991–1.027), respectively.
CONCLUSIONS The relationship between DBP and stroke risk is non-linear. DBP was positively correlated with risk of stroke when less than 80 mmHg.
[GW30-e0134]
Kyeongmin Jang 1,3 , Hack Lyoung Kim 2 , Miri Park 1
1Department of Nursing, SMG-SNU Boramae Medical Center
2Division of Cardiology, Boramae Medical Center, Seoul National University College of Medicine
3Department of Nursing, Chung-Ang University
OBJECTIVES In spite of the clinical importance of orthostatic hypotension (OH), time point of blood pressure (BP) drop in the diagnosis of OH is still under debate. The purpose of this study was to identify the time of BP drop of OH test, and to propose a realistic and appropriate duration in OH test.
METHODS A total of 879 consecutive patients (61-year old and 44% female) with positive on OH test in the emergency room (ER) were retrospectively reviewed. OH was defined as drop in standing systolic BP of at least 20 mmHg or standing diastolic BP of at least 10 mmHg from their supine values after standing for 5 minutes. BP measurement was performed at 1, 3, and 5 minutes after standing.
RESULTS 684 patients (77.8%) had BP drop at 1 minute, and 152 patients (17.3%) had BP drop at 3 minutes after standing. Only 43 patients (4.9%) had BP drop at 5 minutes. As compared to patients with BP drop at 1 or 3 minute, patients with BP drop at 5 minute were significantly younger (39 vs. 62 years, P<0.001), female dominant (65 vs. 43%, P=0.004), had more syncopal events (61 vs. 41%, P=0.035) and had less cardiovascular risk factors including hypertension (14 vs. 46%, P><0.001), diabetes (7 vs. 23%, P=0.006) and coronary artery disease (0 vs. 12%, P=0.005). In blood tests, estimated glomerular filtration rate (100 vs. 77 mL/min/1.73 m2, P><0.001) and albumin (4.2 vs. 4.0 mg/dL, P=0.033) levels were higher, and glucose (114 vs. 141 mg/dL, P><0.001) and blood urea nitrogen (13 vs. 19 mg/dL, P><0.001) level was lower in patients with BP drop at 5 minute as compared to those with BP drop at 1 or 3 minute. Less patients with BP drop at 5 minute took vasoactive medications (14 vs. 45%, P><0.001). In multivariable logistic regression analysis, younger age (>
CONCLUSIONS Most of the patients with OH (95.1%) in ER showed BP drop within 3 minutes of standing. Younger age (
[GW30-e0202]
Haoyu Wang 1,2 , Yingxian Sun 2 , Haoyu Wang 1,2
1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2Department of Cardiology, the First Hospital of China Medical University
OBJECTIVES Adiposity, defined by higher cardiometabolic index (CMI), lipid accumulation product (LAP), and body adiposity index (BAI), has conferred increased metabolic risk. However, the incremental utility of CMI, LAP, and BAI in association with prevalent hypertension has not been well described in a population-based setting. We hypothesized that CMI, LAP, and BAI would provide important insight into hypertension risk.
METHODS Blood pressure (BP), fasting lipid profiles, and anthropometric parameters were recorded in a cross-sectional study of 11,400 participants (mean age, 54 years; 53% women) from China. Logistic regression models were used to assess associations of CMI, LAP, and BAI with prevalent hypertension. BAI was evaluated according to hip (cm)/[height (m) 1.5]–18; LAP was calculated separately for men [(WC-65)×TG] and women [(WC-58)×TG]; and CMI was defined by TG/HDL-C×waist-to-height ratio.
RESULTS CMI, LAP, and BAI were independently correlated with higher SBP and DBP, with nonstandardized (B) coefficients ranging from 1.827 to 4.590 mmHg and 1.475 to 2.210 mmHg (all P<0.001). After adjustment for hypertension risk factors and potential confounders, CMI, LAP, and BAI, modeled as continuous measures, carried hypertension odds (95% CI) of 1.356 (1.259–1.459), 1.631 (1.501–1.771), and 1.555 (1.454–1.662) in women, respectively, per SD increment. In men, each SD increase in CMI, LAP, and BAI experienced a 31%, 65%, and 53% higher hypertension risk, respectively. Moreover, among women, the odds ratio (95% CI) for hypertension were 2.318 (1.956–2.745), 3.548 (2.985–4.217), and 3.004 (2.537–3.557) in the 4th quartile vs. the first quartile of CMI, LAP, and BAI, respectively. For men, the corresponding figures were 2.200 (1.838–2.635), 3.892 (3.238–4.677), and 3.288 (2.754–3.927), respectively.
CONCLUSIONS: Measurements of CMI, LAP, and BAI provide a more complete understanding of hypertension risk related to variation in body fat distribution and pinpoint hypertensive participants in great risk of cardiovascular disease in the future.
[GW30-e0214]
Haoyu Wang 1,2 , Yingxian Sun 2 , Haoyu Wang 1,2
1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2Department of Cardiology, the First Hospital of China Medical University
OBJECTIVES Despite current interest in the unfavourable impact of non-traditional lipid profiles on cardiovascular disease, information regarding its relations to reduced glomerular filtration rate (GFR) in H-type hypertension population has not been systemically elucidated.
METHODS Analyses were based upon a cross-sectional study of 3259 participants with H-type hypertension who underwent assessment of biochemical, anthropometric and blood pressure values. Reduced GFR was considered if meeting estimated GFR <60 mL/min/1.73 m2.
RESULTS A stepwise multivariate regression analysis indicated that non-traditional lipid parameters remained as independent determinants of estimated GFR (all P<0.001). In multivariable models, we observed a 50, 51, 31, and 24% higher risk for decreased GFR with each SD increment in TC/HDL-C, TG/HDL-C, LDL-C/HDL-C ratios and non-HDL-C levels, respectively. The highest quartile of TC/HDL-C, TG/HDL-C and LDL-C/HDL-C ratios carried reduced GFR odds (confidence intervals) of 5.50 (2.50–12.09), 6.63 (2.58–17.05) and 2.22 (1.15–4.29), respectively.
CONCLUSIONS Non-traditional lipid profiles has been linked with the occurrence of cardiovascular disease, but none of the studies that address the effect of non-traditional lipid profiles on reduced GFR risk in H-type hypertension population has been specifically established. A greater emphasis of this study resided in the intrinsic value of TC/HDL-C, TG/HDL-C, LDL-C/HDL-C ratios and non-HDL-C that integrate atherogenic and anti-atherogenic lipid molecules to predict the risk of reduced GFR among H-type hypertension population and provide insight into the pathophysiology of subsequent cardio-cerebrovascular outcomes. In a large Chinese H-type hypertension adults, the relative independent contribution of non-traditional lipid profiles, as indexed by TC/HDL-C, TG/HDL-C, LDL-C/HDL-C ratios and non-HDL-C, towards reduced GFR putting research evidence at the very heart of lipoprotein-mediated renal injury set a vital example for applying a clinical and public health recommendation for reducing the burden of CKD.
[GW30-e0228]
Yifang Yuan 1 , Tingting Lv 1 , Huijuan Li 3 , Jing Yang 1 , Jiayu Wang 1 , Lingyun Kong 1 , Zhaoguo Zhang 12 , Yanfang Wang 3 , Hua Li 1 , Xingjie Li 4 , Yingxian Sun 5 , Xuewen Li 6 , Zheng Zhang 7 , Xiaoshu Cheng 8 , Lirong Wu 9 , Xuerui Tan 10 , Bing Han 11 , Yangfeng Wu 2 , Jihong Guo 3 , Ping Zhang 1
1Cardiology of Department, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University
2Peking University Clinical Research Institute
3Department of Cardiology, Peking University People’s Hospital
4Jining NO. 1 People’s Hospital
5The First Hospital of China Medical University
6Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital
7The First Hospital of Lanzhou University
8The Second Affiliated Hospital of Nanchang University
9The Affiliated Hospital of Guiyang Medical College
10Department of Cardiology, the First Affiliated Hospital of Shantou University Medical College
11Xuzhou Central Hospital
12Beijing Sijiqing Hospital
OBJECTIVES ECG is a cost-effective tool for screening left ventricular hypertrophy (LVH). Sokolow-Lyon criterion is one of the most widely used criteria in clinical practice. A newly Peguero-Lo Presti ECG criterion was reported with higher sensitivity but lower specificity in Caucasian. However, its performance in general Chinese population was limited. Our study aimed to validate Peguero-Lo Presti ECG criterion in general Chinese adults who enrolled in a large-scale nationwide population study and compare its diagnostic performance with the classical Sokolow-Lyon criterion.
METHODS A multi-stage, stratified cluster sampling across China during 2012–2013 was performed to select the representative Chinese adults aged 18–85 years. A total of 7405 participants without intraventricular conduction defects (53% females, mean age 48±15 years) were analyzed in the study. ECG was collected by GE MAC 5500 and analyzed automatically by using Marquette 12SL algorithm in MUSE® Cardiology Information System. Left ventricular mass (LVM) was estimated by transthoracic echocardiography (echo). LVH was defined as LVM indexed by BSA (LVMI)>115 g/m2 for male or >95 g/m2 for female. Peguero-Lo Presti was defined as the deepest S wave in any single lead (S D )+SV 4 >2.3 mV for women or >2.8 mV for men. Sokolow-Lyon voltage was defined as SV 1 +RV 5 /V 6 ≥3.5 mV or R aVL ≥1.1 mV. Sensitivity, specificity and other statistical measures for contingency table were compared using Fisher’s Exact test. Diagnostic performance of two ECG criteria was compared by receiver operating characteristic (ROC) analysis and Mcnemar test. All continuous single leads for two criteria, including deepest S (S D ), SV 4 , RV 5 , SV 1 , RV 6 and R aVL , were analyzed for linear correlation with LVMI and diagnostic performance for echo-LVH. LVM indexed by height2.7 was used for sensitivity analysis.
RESULTS The overall population, among which 32% were hypertensive, had an average LVMI of 80±18 g/m2 and a mean blood pressure of 126/82 mmHg. Prevalence of echo-LVH was 11% while ECG-LVH ranged from 11–27% (27% for Peguero-Lo Presti, 11% for Sokolow-Lyon). Both Peguero-Lo Presti and Sokolow-Lyon were associated with the severity of LVH (P<0.0001 for both). Peguero-Lo Presti had higher sensitivity (29 vs. 12%, P<0.0001) but lower specificity (73 vs 89%, P<0.0001) and reduced accuracy (68 vs. 80%, P<0.0001) compared with Sokolow-Lyon in overall population. Both two ECG – LVH showed poor diagnostic performance (AUC: 0.51 vs. 0.51, P>0.05). All continuous single leads had weak correlation (r=0.12–0.18) and poor diagnostic performance (AUC: 0.50–0.60). R aVL had relatively higher linear correlation (r=0.18, P<0.0001) and diagnostic ability (AUC=0.60) among all the single leads. While S D , the novel predictor in Peguero-Lo Presti criterion, only showed weak correlation (r=0.12, P<0.0001) and poor diagnostic performance (AUC=0.53). Similar results were observed in sensitivity analysis with LVM indexed by height2.7.
CONCLUSIONS Though with higher sensitivity, Peguero-Lo Presti did not have better diagnostic performance compared with the traditional Sokolow-Lyon criteria for detecting echo-defined LVH in general Chinese population. RaVL may have better diagnostic ability for echo-LVH.
[GW30-e0232]
Zulong Sheng, Chenwei Ju, Zulong Sheng
Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing
OBJECTIVES To investigate the gene polymorphism effect of hypoxia inducible factor 1α in left ventricular hypertrophy of the hypertensive patients.
METHODS The 583 hypertensive patients were divided into two groups, with left ventricular hypertrophy (LVH(+), 198 cases) and without left ventricular hypertrophy (LVH(–), 385 cases). The polymerase chain reaction restriction fragmentlength polymorphism was used in the above groups for the detection of the single nucleotide gene polymorphism of rs11549465, rs11549467, and rs1957757 loci in HIF-1α.
RESULTS The distribution difference of gene frequency of rs11549465, rs11549467, and rs1957757 loci in HIF1A single nucleotide gene polymorphism in LVH(+) and LVH(–) was statistically significant (P<0.05). Thereinto, the T allele of rs11549465 loci and the G allele of rs11549467 loci can increase the risk of LVH, which was related to the increased plasma expression of HIF-1α (P<0.05).
CONCLUSIONS The gene polymorphism of HIF-1α was related to the occurrence of primary hypertension left ventricular hypertrophy, and the rs11549467 loci was correlated with the increasing concentration of plasma HIF-1α.
[GW30-e0262]
Luyun Fan, Huimin Zhang, Jun Cai
Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Childhood Takayasu’s arteritis (c-TA) are scarcely reported but with devastating morbidity and mortality. Our previous study proved revascularization decision at baseline admission as a protective indicator of further clinical outcomes in childhood TA including all cause death, vascular complications and/or disease re-flares. This study aims to investigate the clinical course, endovascular procedure-related outcomes and associated factors of childhood TA undergoing interventions.
METHODS The present study is based on a retrospective analysis of 101 consecutive childhood TA patients fulfilled the 1990 ACR criteria or the 2010 EULAR/PRINTO/PReS criteria and hospitalized in Fuwai Hospital, between 2002 and 2017, including 5 patients prospectively recruited from 2017/01 and 2017/12. Four patients requiring mere open surgery and medications are excluded. Data are compared between patients undergoing endovascular intervention management (n=69) and patients requiring mere medical management (n=28) during the study period.
RESULTS The median ages at c-TA onset and at intervention are 14 (Inter-quartile range, IQR 13–16) years and 15.8 (IQR, 14–17) years in group undergoing intervention. Male sex accounts for 18.8 vs. 39.3% in medical-management group (P=0.034). Body mass index (BMI) in 31.9% patients under intervention is lower than 18.5 kg/m2, vs. 60.7% in medical group (P=0.009). Hypertension (78.3 vs. 57.1%, P=0.035), blood pressure discrepancy (56.5 vs. 21.4%, P=0.37), bruits (52.2 vs. 53.6%, P=0.9) and pulse deficits (37.7 vs. 39.3%, P=0.88) are core baseline presentations and dominating Hata’s angiographic type of disease include type IV (47.8 vs. 17.9%, P=0.006), type V (29 vs. 39.3%, P=0.32) and type I (8.7 vs. 21.4%, P=0.1). Immunosuppressive therapy (89.9 vs. 60.7%, P=0.001) and antiplatelet agents (81.2 vs. 57.1%, P=0.014) are majorly administered. After multivariate logistic regression analysis, male sex (OR=0.20, 95% CI 0.05–0.75, P=0.02), dual antiplatelet therapy (OR=6.64, 95% CI 1.22–36.24, P=0.03), immunosuppressive therapy (OR=12.05, 95% CI 2.57–56.52, P=0.002) and type IV disease (OR=10.69, 95% CI 2.39–47.76, P=0.002) are independent associated factors for intervention in c-TA. Clinical presentations at intervention include hypertension (73.9%), heart failure (21.7%), claudication (21.7%), cerebrovascular symptoms (15.9%), blurred version (7.2%), angina pectoris (2.9%) and pulmonary hypertension (4.3%). Major vascular beds under intervention include renal artery (63.8%), mid-aorta (18.8%) and supra-aortic arch artery (23.2%). Retinopathy (P=0.027), dual platelet therapy (P=0.004), descending thoracic aorta involvement (P=0.003) and time of delay in diagnosis (P=0.016) are independent associated factors for stenting in patients undergoing intervention. At a median 3.1 (IQR 1–6.7) years of follow-up, procedure-related complications including restenosis, bleeding, stroke, dissection, thrombosis and others are observed in 39.1% and re-interventions are observed in 24.6%.
CONCLUSIONS This largest study of c-TA reveals 68.3% patients requiring endovascular procedures during a three-year follow-up, particularly female cases with type IV disease. Immunosuppressive therapy and dual antiplatelet agents are associated with intervention, while baseline retinopathy, descending thoracic aorta involvement and longer delay in diagnosis are related to stenting.
[GW30-e0288]
Guangyu Yan, Hong Yuan
Center of Clinical Pharmacology, the Third Xiangya Hospital, Central South University
OBJECTIVES To explore the gender-dependent association between mean corpuscular hemoglobin concentration (MCHC) and hypertension incidence in prehypertensive patients.
METHODS This was a longitudinal study involving non-elderly prehypertensive adults without any vascular disease such as stroke or diabetes. MCHC, blood pressure, anthropometric data, medical history, and lifestyle were measured or inquired at baseline visit from all patients. Associations between hypertension incidence and M were assessed by a time-dependent, Cox proportional hazard model.
RESULTS During a median follow-up of 5.02 years, 903 male patients and 607 female patients were enrolled in our study, and hypertension incidence was 27.69 and 13.51% respectively. In male patients, MCHC in the fourth quartile (Q4) were significantly related to hypertension incidence. However, such an association was not found in female patients.
CONCLUSIONS There were gender-dependent associations between MCHC and hypertension incidence in the non-elderly prehypertensive population. High MCHC (higher than 338 g/L) were associated with increased risk of hypertension in male prehypertensive patients. Mean corpuscular hemoglobin concentration is a risk factor in prehypertensive male patients.
[GW30-e0335]
Qing Li, Ya Gao, Huiying Liang, Fengxia Duan, Yu Zhao, Yarong Qian, Xurui Zhang, Deli Tian, Zihong Guo
The Fuwai Yunnan Cardiovascular Hospital, Kunming, China
OBJECTIVES Left ventricular hypertrophy (LVH) has been linked with stroke, heart failure and atrial fibrillation, interactions between the left ventricular and the renin-angiotensin-aldosterone system (RAAS) are key determinants of cardiovascular function. However, the effects of Aldosterone/Renin Ratio (ARR) in different postures on the prevalence of electrocardiographic LVH are unclear. The aim of this study was to examine the relationship between effects of ARR in different postures and LVH in hypertensive subjects for primary aldosteronism screening.
METHODS Baseline data, supine and upright level of RAAS in plasma, 24 h-ABP and electrocardiographic parameters were compared between LVH group and control group, Logistic regression analysis was performed to obtain independent predictor of LVH after adjusting for confounding factors.
RESULTS A total of 328 with hypertensive subjects for primary aldosteronism screening admitted to the Department of Hypertension, Fuwai YunNan Cardiovascular Hospital from June 2018 to June 2019. The LVH correlated with the number of variables including LDL (r=0.215, <0.001), upright ARR (r=0.238, P<0.001), supine ARR (r=0.124, P=0.025), NT-pro BNP (r=0.161, P=0.004). In a logistic regression analysis, after adjusting for age, gender, LDL and NT-pro BNP, the upright ARR was an independent risk factor for LVH OR=1.149 (95% CI:1.057–1.249, P=0.001).
CONCLUSIONS We demonstrated that ARR in different postures are associated with the prevalence of electrocardiographic LVH in hypertensive subjects for primary aldosteronism screening. Based on this evidence, future studies should investigate ARR-lowering therapy in hypertensive individuals.
[GW30-e0384]
Wei Zhou, Xiaoshu Cheng
The Second Affiliated Hospital of Nanchang University
OBJECTIVES The association between age at menarche (AAM) and hypertension has been previously been reported with inconsistent results. There are few such studies on the association in underdeveloped areas in China. The aim of this study was to assess the association between AMM an hypertension in southern China.
METHODS Participants in a cross-sectional study were required to complete a standard self-reporting questionnaire and physical measurements, in Jiangxi Province of southern China. Self-reported AMM was assessed from the questionnaire. A history of hypertension was obtained by answering the questionnaire or physical examination. Binary logistic regression analysis was performed to evaluate the association between hypertension and AAM. Multiple linear regression analysis was carried out to evaluate the association between SBP, DBP and AAM, and compute the subgroup analysis for interactions.
RESULTS A total of 5102 women (aged from 15 to 97 years, with a mean±SD of 52.6±17.7 years at enrollment) were included in this study. The mean±SD of AAM (aged from 9 to 24 years) for the total sample was 15.5±2.1 years. After adjustments, continuous AAM was associated with a higher risk of hypertension [OR (95% CI)=1.15 (1.11–1.19)], and ORs (95% CIs) for hypertension across AMM categories (≤13 y, 14–15 y, 16–17 y, ≥18 y) were 1 (referent), 0.95 (0.76, 1.19), 1.68 (1.34, 2.11), 2.01 (1.56, 2.58), respectively (P for trend <0.001). Independently, continuous AAM was positively correlated with SBP [β (95% CI)=0.88 (0.29, 1.46)], as well as DBP [β (95% CI)=0.80 (0.47, 1.13)], and β (95% CIs) for hypertension across AAM categories (≤15 y, 16–17 y, ≥18 y) were respectively 0 (referent), 3.50 (0.72, 6.27), and 5.84 (2.62, 9.05) for SBP (P for trend <0.001), and 0 (referent), 3.35 (1.81, 4.88), and 4.34 (2.53, 6.16) for DBP (P for trend <0.001). ORs for hypertension across AAM in three age subgroups (Tertile 1: 15–44 y, Tertile 2: 45–61 y, Tertile 3: 62–97 y) were respectively 1.37, 1.16 and 1.10, with a decreasing trend (P for interaction <0.05).
CONCLUSIONS The study is the first to report that, in southern China, a late AMM is associated with a high risk of hypertension. Women with a later AMM tend to develop hypertension in younger adulthood. Knowledge of the menarcheal history would be a preventive marker for hypertension.
[GW30-e0387]
Hui Geng, Xiahuan Chen, Yanjun Wang, Meilin Liu
Peking University First Hospital
OBJECTIVES To explore association between orthostatic hypotension (OH) and blood urea nitrogen-to-creatinine ratio in elderly inpatients.
METHODS 180 elderly patients (≥60 years old) who hospitalized during March 2017 to November 2017 in geriatric department of Peking University First Hospital were involved. Continuous Non-invasive Arterial Pressure (CNAP) was used to record the blood pressures and heart rates at the moments of supine, immediately after standing and the first, second, third minute after standing. The gender, age, blood urea nitrogen-to-creatinine ratio, proportions of hypertension, diabetes, coronary heart disease, cerebrovascular disease and medication were compared between OH and non-OH groups immediately and within 3 minutes after standing. Multiple linear regression analysis was used to analyze the correlation between the maximum amplitudes of blood pressure and the age, supine blood pressure, supine heart rates, brachial-ankle pulse wave velocity, left ventricular ejection fraction, and urea nitrogen-to-creatinine ratio.
RESULTS In the 180 elderly inpatients, the proportion of male of OH group immediately after standing was significantly lower than non-OH group (P<0.05); no significant difference in age, urea nitrogen-to-creatinine ratio, proportions of hypertension, diabetes, coronary heart disease, cerebrovascular disease and medication. There was no difference in gender, age, urea nitrogen-to-creatinine ratio, proportions of hypertension, diabetes, coronary heart disease, cerebrovascular disease and medication between OH and non-OH group within 3 minutes after standing. The maximum SBP drops (SBP of supine minus the lowest SBP during postural changes) was positively correlated with brachial-ankle pulse wave velocity and urea nitrogen -to-creatinine ratio [β=0.007 (95% CI 0.001–0.014), 0.673 (95% CI 0.186–1.159); P=0.041, 0.007], while there was no significant correlation with age, supine systolic pressure, supine diastolic pressure, supine heart rate and left ventricular ejection fraction.
CONCLUSIONS OH is very common in elderly inpatients. There may be no correlation between the incidence of OH and blood urea nitrogen-to-creatinine ratio, but maximum decrease in systolic blood pressure during postural changes is positively correlated with blood urea nitrogen-to-creatinine ratio.
[GW30-e0409]
A.M. Vershinina, L.I. Gapon, Yus Reut, N.V. Tretyakova, L.N. Kopylova, E.S. Busarova, S.V. Vdovenko
Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia
OBJECTIVES: To estimate the role of inflammatory markers in vascular damages and their prognostic value in case of arterial hypertension (AH) and metabolic syndrome (MS).
METHODS The study enrolled 70 patients with AH I-III stages (40 males and 30 females) with MS signs (abdominal type of obesity, lipid and carbon metabolism). The MS group had 33.07±2.58 kg/m2 of body mass index (BMI), 6.47±1.18 mmol/L of total cholesterol (LDLP 3.49±0.84 mmol/L). Males and females average age was 47.9±1.14 years. Arterial stiffness was measured by recording pulse wave velocity (PWV), with registration of cardio-ankle vascular index (CAVI) and ankle-brachial index using sphygmography. Measurement of carotid artery intima-media thickness (IMT) was carried out. The following inflammatory response markers were studied: high sensitive C-reactive protein (hs CRP) and homocysteine. Blood lipids profile testing included total cholesterol, low-density lipoproteins, high density lipoproteins and triglycerides.
RESULTS Increase in arterial stiffness parameters was detected in AH and MS patients (increased PWV (P<0.05), decrease of ankle-brachial index (P><0.05) and increase of hs CRP and homocysteine (P≤0.05) and P≤0.05) along with AH progress. Increase of vascular wall stiffness was positively correlated with systolic BP (P><0.01), level of hs CRP and homocysteine (P><0.01, P><0.05) and IMT level (P><0.05). Along with the growth of AH and obesity degree, patients with AH and MS had negative correlation of CAVI with total cholesterol and triglycerides (P><0.05) and hs CRP (P><0.05). Arterial stiffness parameters (PWV) were positively related to BMI, left ventricular hypertrophy, total cholesterol and triglycerides level in blood (P><0.05). In the conditions of lipid metabolism disorders, a separate study of arterial stiffness and inflammatory markers in case of AH I, II and III stages was performed. A reliable correlation between PWV and hs CRP and homocysteine increasing along with AH progress (I stage – P≤0.05; II stage – P≤0.01; III stage – P≤0.0001) was revealed.
CONCLUSIONS In AH and MS patients in conditions of lipid metabolism disorders more significant rise of arterial stiffness associated with inflammatory response markers were observed. The increase of direct correlation between these markers along with AH progress highlights the important role of the inflammatory markers and their prognostic value in the vascular complications progress in case of this pathology.
[GW30-e0413]
A.S. Vetoshkin, N.P. Shurkevich, L.I. Gapon, A.A Simonyan
Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia
OBJECTIVES To estimate structural and functional condition of left ventricular (LV) myocardium with the physical working capacity of AH patients in the Arctic.
METHODS Within the period of 2002–2010, 881 males aged 20–59 years were examined at the medical unit ≪Gazprom dobycha Yamburg≫. Patients were randomized into Gr.1 consisted of 373 males with AH of 1, 2 stage doing the watch work in the Arctic (71°N) and Gr.2 (control group) consisted of 144 males with AH of 1, 2 stage living in Tyumen (57°N). The groups matched in age: 46.0±6.0 (P=0.445), office systolic blood pressure (SBP) /diastolic blood pressure (DBP): 157.5/153.9 (P=0.322); 106.7/100.3 (P=0.0640). All patients had 24-hour BP monitoring, echocardiography, treadmill test, and biochemical blood examination performed.
RESULTS Gr.1 had lower values of SBP24 (P<0.001), higher values of DBP24 (P><0.0001) in comparison with Gr.2; 30% of people with AH (Gr.1) had normotension (SBP24/DBP24><0.001) and heart rate 24 (HR24) (P><0.001). Such metabolic changes as overweight (P=0.0002), elevated level of glucose (P=0.0002) and creatinine (P=0.0001) were observed in Gr.1. Myocardial mass of left ventricle (MMLV) and index of MMLV (P=0.0002), (P=0.0024) were higher in Gr.1. Patients of Gr.1 more often had growth of left atrium (P=0.0088) and concentric LV hypertrophy (P=0.0014) due to thickness of interventricular septum (IVS) and LV posterior wall (P><0.0001); however, LV ejection fraction was reliably higher (P><0.0001) in Gr.1. Disorder of LV diastolic function was observed more often (P=0.0475) in Gr.1 due to slow LV relaxation (P=0.0001). Treadmill test in Gr.1 showed that adaptation mechanism level as per adaptation potential coefficient was in the ≪tension≫ range and ≪unsatisfactory≫ and even ≪failure≫ of adaptation (P=0.0001); threshold level of maximum oxygen consumption was lower in Gr.1 (P=0.0001). Patients of Gr.1 had lower value of specific work and duration of exercise test (χ2=262, P=0.0001). Only 5.7% of patients had positive treadmill test, and 4.8% out of them had positive test according to ECG (with painless myocardial ischemia).
CONCLUSIONS The expressed structural and functional alterations of myocardium in patients with AH and preserved ejection fraction define the risk of unfavorable clinical outcomes in perspective. These results are also an optimal target for medication therapy and confirm the need for a detailed study of pathogenic and prognostic formation of congestive heart failure with preserved ejection fraction in the Arctic watch workers.
[GW30-e0415]
A.S. Vetoshkin, N.P. Shurkevich, L.I. Gapon, A.A. Simonyan
Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia
OBJECTIVES To estimate structural and functional condition of left ventricular (LV) myocardium with the physical working capacity of AH patients in the Arctic.
METHODS Within the period of 2002–2010, 881 males aged 20–59 years were examined at the medical unit ≪Gazprom dobycha Yamburg≫. Patients were randomized into Gr.1 consisted of 373 males with AH of 1, 2 stage doing the watch work in the Arctic (71°N) and Gr.2 (control group) consisted of 144 males with AH of 1, 2 stage living in Tyumen (57°N). The groups matched in age: 46.0±6.0 (P=0.445), office systolic blood pressure (SBP)/diastolic blood pressure (DBP): 157.5/153.9 (P=0.322); 106.7/100.3 (P=0.0640). All patients had 24-hour BP monitoring, echocardiography, treadmill test, and biochemical blood examination performed.
RESULTS Gr.1 had lower values of SBP24 (P<0.001), higher values of DBP24 (P><0.0001) in comparison with Gr.2; 30% of people with AH (Gr.1) had normotension (SBP24/DBP24><0.001) and heart rate 24 (HR24) (P><0.001). Such metabolic changes as overweight (P=0.0002), elevated level of glucose (P=0.0002) and creatinine (P=0.0001) were observed in Gr.1. Myocardial mass of left ventricle (MMLV) and index of MMLV (P=0.0002), (P=0.0024) were higher in Gr.1. Patients of Gr.1 more often had growth of left atrium (P=0.0088) and concentric LV hypertrophy (P=0.0014) due to thickness of interventricular septum (IVS) and LV posterior wall (P><0.0001); however, LV ejection fraction was reliably higher (P><0.0001) in Gr.1. Disorder of LV diastolic function was observed more often (P=0.0475) in Gr.1 due to slow LV relaxation (P=0.0001). Treadmill test in Gr.1 showed that adaptation mechanism level as per adaptation potential coefficient was in the ≪tension≫ range and ≪unsatisfactory≫ and even ≪failure≫ of adaptation (P=0.0001); threshold level of maximum oxygen consumption was lower in Gr.1 (P=0.0001). Patients of Gr.1 had lower value of specific work and duration of exercise test (χ2=262, P=0.0001). Only 5.7% of patients had positive treadmill test, and 4.8% out of them had positive test according to ECG (with painless myocardial ischemia).
CONCLUSIONS The expressed structural and functional alterations of myocardium in patients with AH and preserved ejection fraction define the risk of unfavorable clinical outcomes in perspective. These results are also an optimal target for medication therapy and confirm the need for a detailed study of pathogenic and prognostic formation of congestive heart failure with preserved ejection fraction in the Arctic watch workers.
[GW30-e0416]
N.P. Shurkevich, A.S. Vetoshkin, L.I. Gapon, A.A. Simonyan
Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia
OBJECTIVES To estimate the role of BP in the formation of severe left ventricular (LV) hypertrophy and carotid artery subclinical atherosclerosis (CASA) in patients with AH in conditions of the watch work in the Arctic.
METHODS Within the period of 2002–2010, 715 males were examined at the medical unit ≪Yamburggasdobycha≫ (71°N). Patients were randomized into Gr.1 consisted of 373 males with office BP (157.5±13.7/106.7±8.8 mmHg); and Gr.2 consisted of 173 males with office BP (123.4±7.5/80.5±5.5 mmHg), aged 46.0±6.0 years, (P=0.445), with the watch work duration (11.2±3.8 years). The control group (Gr.3) consisted of 169 patients with normal and elevated BP -living in Tyumen (57°N) matched in age and BP. All patients underwent echocardiography, carotid arteries ultrasound examination, standard and chronobiological analysis of 24-hour BP monitoring.
RESULTS Gr.1 compared to Gr.3 had lower values of systolic BP24 (SBP24) (P<0.001), higher values of diastolic BP24 (DBP24) (P><0.0001); and Gr.1 had high variability of SBP24, DBP24 (P><0.001) and heart rate24 (HR24) (P><0.001); 30% of people with AH (Gr.1) had normotension (SBP24/DBP24).
CONCLUSIONS Thus, one of the reasons of the formation of severe target organ damage and CASA in patients with AH in the Arctic watch is not the office BP level and average daily BP according to 24-hour BP monitoring, but hypersympathicotonia with violation of the chronostructure of the BP daily rhythm.
[GW30-e0567]
Ling Zhu 1 , Fuqiang Liu 1 , Shuo Pan 1 , Yong Zhang 1 , Xin Jiang 1 , Fangfang Yang 2 , Yin Liu 2 , Zhongwei Liu 1 , Junkui Wang 1
1Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, China
2Xi’an Medical College, Xi’an, Shaanxi, China
OBJECTIVES Numerous studies have shown that anxiety is closely related to the occurrence and development of hypertension. Anxiety is one of the important psychological factors affecting hypertension. This study explores the relationship between anxiety and hypertension and the influence of anxiety on the blood pressure control rate.
METHODS A total of 272 patients were enrolled in Shaanxi Provincial People’s Hospital from 2017 to 2018. Exclusion criteria were: age below 30 years or above 80 years, NYHA III or IV, coronary heart disease, atrial fibrillation, frequent arrhythmia, renal failure, serum creatinine above 175 μmol/L, thyroid dysfunction, acute infection, known history of cancer or chronic-immune-mediated disorders, or current use of immunosuppressive agents including corticosteroids.
Hypertension is defined as systolic blood pressure (SBP) higher than 140 mmHg, or a diastolic pressure (DBP) greater than 90 mmHg. The blood pressure goal was SBP lower than 140 mmHg, and a DBP lower than 90 mmHg. All enrolled subjects completed the Hamilton Anxiety Scale (HAMA) which is a rating scale developed to quantify the severity of anxiety. The total score of HAMA ranges from 0 to 56 points. HAM-A score ≥14 was defined as the presence of anxiety. The association between anxiety and hypertension was estimated with univariate and multivariate logistic regression models. Model 1 was unadjusted. Model 2 was adjusted for age, sex, and smoking. Model 3 adjusted for age, sex, smoking, educational level, economic income. Model 4 adjusted for age, sex, smoking, educational level, economic income, family history of hypertension, and hyperlipemia. We also performed psychological or drug interventions and follow-up of patients with hypertension and anxiety.
RESULTS Participants were divided into two groups according to with anxiety or not. Compared with the non-anxiety group, the ratio of hypertension was significantly higher in the anxiety group (69.3 vs. 50.0%, P=0.002). Then, we assessed the association between anxiety scores and blood pressure, anxiety scores levels were significantly positive correlated to the systolic blood pressure (r=0.511, P<0.001).
In univariate logistic regression models (Model 1), compared with patients in non-anxiety group, the odds ratios (OR) for development of hypertension in the anxiety group were 2.33 (95% CI 1.42–3.84, P=0.001). Multivariate analysis showed that anxiety was independently and positively related to the development of hypertension (adjusted OR: 2.22, 95% CI 1.34–3.61, P=0.002, compared with the non-anxiety group) after adjusting for Model 2. With further adjustment for adjusted for Model 3 and Model 4. The OR for the development of hypertension in the anxiety group showed no change (Model 3, OR 2.16, 95% CI 1.29–3.62, P=0.003; Model 4, OR 1.88, 95% CI 1.08–3.28, P=0.026).
In addition, after 2 months follow-up of patients with hypertension and anxiety, We performed the Hamilton Anxiety Scale again. Compared with the control group, the anxiety scores were significantly decreased in the treatment group (P<0.001). The rate of goal blood pressure of treatment group was significantly increased than the control group in patients with hypertension and anxiety (P=0.008) (treatment group: before 60%, after 75%; control group: before 38.9%, after 27.8%).
CONCLUSIONS Our data indicated that anxiety is an independent risk factor for hypertension. Relieving anxiety can increase the rate of goal blood pressure in patients with hypertension and anxiety.
[GW30-e0618]
Tai Huang 1,2 , Xiaoguang Yao 1,2 , Sheng Li 1,2 , Yingchun Wang 1,2 , Lei Wang 1,2 , Nanfang Li 1,2
1Research Center for Hypertension, People’s Hospital of Xinjiang Uygur Autonomous Region
2Xinjiang Institute of Hypertension, Xinjiang Uygur Autonomous Region
OBJECTIVES To explore the diagnostic value of nocturnal blood pressure level for severe OSAS, and establish a simple, economical and effective screening method by combining with the existing scale for OSAS in patients with hypertension.
METHODS Clinical data from 144 patients with hypertension ((45.41±11.13) years old, 102 males), who underwent PSG, ABPM in our hospital from September 2018 to November 2018. Anthropometric index, STOP-Bang questionnaire, NoSAS score, No-Apnea model would be also collected. According to AHI, the patients were divided into non-severe group (AHI<30 times/hour) and severe group (AHI≥30 times/h). The receiver operating characteristics (ROC) curve was used to evaluate the value of predicting severe OSAS, and DeLong method judge that whether there is statistical significance in comparing the difference of ROC curve among each index. Sensitivity, specificity, positive predictive value, negative predictive value, Jordan index, Accuracy and Kappa value were also calculated.
RESULTS The diagnostic value of nocturnal mean systolic blood pressure for OSAS was improved with the increasing of AHI as the cutoff point. When the cutoff point was selected as AHI≥30 times/hour, the AUC of nocturnal mean diastolic blood pressure was 0.793, and the best cutoff point was >86 mmHg (Jordan index 0.533). The sensitivity, specificity, positive predictive value and negative predictive value were 75.8, 77.5, 50.0 and 91.5% respectively, and the Accuracy and Kappa value, 77.1% and 0.451 respectively, were better than the three existing scales mentioned above. After being connected with STOP-Bang questionnaire, the sensitivity, specificity, positive predictive value, negative predictive value, Jordan index, Accuracy and Kappa value were 75.8%, 82.9%, 56.8%, 92.0%, 0.587, 81.3 and 0.525 respectively. All the prediction indexes were higher than before except for the sensitivity.
CONCLUSIONS Nocturnal mean diastolic blood pressure has a good diagnostic value for severe OSAS in hypertensive population, and the ability to diagnosis severe OSAS can be improved after being connected with STOP-Bang questionnaire.
[GW30-e0655]
Li Zhang 1 , Dongsheng Sun 1 , Dibo Lao 1 , Huiling Huang 1 , Ning Zhou 1 , Bingquan Shen 1 , Xuan Zheng 2 , Zhiyan Jiang 2 , Jianhong Xie 1
1Zhejiang Provincial People’s Hospital
2Beijing Novartis Pharma Co., Ltd
OBJECTIVES There are still limited real-world data for the 1-year treatment efficacy and safety of valsartan/amlodipine in elderly patients in China. This study aimed to evaluate the efficacy and safety of 1-year blood pressure (BP) management using valsartan/amlodipine in Chinese elderly patients, and to compare the efficacy and safety between middle-aged and elderly patients.
METHODS This was an ad-hoc analysis of the CHINA SATATUS III study, which was a 1-year registry study of valsartan/amlodipine in patients who had already received valsartan/amlodipine for at least 4 weeks before enrollment. Patients were grouped as the middle-aged (30–64 years) and elderly (over 65 years) subgroups. The primary efficacy endpoints were BP control rate after 12 months of treatment. Safety was examined.
RESULTS A total of 894 patients were included the present analysis. The office BP control rates significantly improved from baseline at 56.9 to 74.4% at 12 months (P<0.001). Compared with the middle-aged group, the control rate in the elderly at baseline was lower (56.9 vs. 68.6%, P<0.001), but not at 12 months (74.4 vs. 74.0%, P=0.902). Office systolic blood pressure (SBP) and diastolic blood pressure (DBP) both significantly reduced at 12 months in the elderly group (P<0.05), with a more pronounced reduction in SBP (–5.0±15.1 vs. –2.0±14.6 mmHg, P=0.014) observed compared with the middle-aged group. The occurrence of serious adverse events was not associated with the age group (odds ratio=1.3, 95% confidence interval: 0.8–2.4).
CONCLUSIONS Valsartan/amlodipine is effective and safe in the 1-year treatment of elderly patients with elevated BP.
[GW30-e0657]
Xintian Cai, Qing Zhu, Nangang Li
Center for Hypertension of the People’s Hospital of Xinjiang Uygur Autonomous Region, Hypertension Institute of Xinjiang
OBJECTIVES DNA microarray and high-throughput sequencing have been widely used to identify the differentially expressed genes (DEGs) in Kawasaki disease (KD). However, the big data from gene microarrays are also challenging to work with in terms of analysis and processing. The presents study combined data from the microarray expression profile (GSE73464) and bioinformatics analysis to identify the key genes and cellular pathways in KD.
METHODS Gene ontology (GO) and cellular pathway enrichment analyses of DEGs were performed to investigate significantly enriched pathways. A protein-protein interaction network was constructed to determine the key genes in the occurrence and development of KD.
RESULTS A total of 418 DEGs were identified in KD, including 418 upregulated genes and 76 downregulated genes. GO analysis revealed that the most significant biological process of DEGs was immune system process. Kyoto Encyclopedia of Genes and Genome pathway analysis showed that these DEGs were enriched in signaling pathways associated with the immune system, including systemic lupus erythematosus, primary immunodeficiency, cell adhesion molecules (CAMs) and T cell receptor signaling pathway. The current study screened the top 3 genes with higher degrees as hub genes, which included G protein-coupled receptor 84, formyl-peptide receptor-2 and complement component 3a receptor 1. Module analysis revealed that these hub genes were also involved in the chemokine signaling pathway, cytokine-cytokine receptor interaction and staphylococcus aureus infection.
CONCLUSIONS Kawasaki disease, differentially expressed genes, pathway enrichment analysis, gene ontology, protein-protein interaction network.
[GW30-e0658]
Xintian Cai, Qing Zh, Nangang Li
Center for Hypertension of the People’s Hospital of Xinjiang Uygur Autonomous Region, Hypertension Institute of Xinjiang
OBJECTIVES The purpose of this meta-analysis is to assess the relationship between circulating blood adipokines levels and Kawasaki disease (KD).
METHODS Articles were identified by searching Web of Science, EMBASE, PubMed, Wanfang and CNKI databases. Studies identified were pooled, and the standardized mean difference (SMD) and its corresponding 95% confidence interval (CI) were calculated. Subgroup analyses and publication bias detection were also conducted. Cochrane Q test and I2 statistic calculated by Review Manager software (version 5.3) to test heterogeneity. To assess publication bias, the STATA software (version 12.0) was used for statistical analysis.
RESULTS The KD group had a higher level of resistin than HC (healthy control) and DC (disease control) (SMD=2.52, 95% CI=1.48–3.56, P<0.001, SMD=1.26, 95% CI=0.49–2.02, P=0.001). Compared with NCAL (non-coronary artery lesions), the CAL (coronary artery lesions) group had higher levels of adiponectin and resistin (SMD=0.29, 95% CI=0.02–0.55, P=0.03, SMD=0.97, 95% CI=0.10–1.85, P=0.03). Compared to the phase, the active group had a higher level of resistin (SMD=2.10, 95% CI=0.77–3.43, P=0.002).
CONCLUSIONS In conclusion, the present meta-analysis indicated that resistin levels were generally elevated in KD patients. Compared with NCAL, the circulating resistin and adiponectin levels in the CAL group were significantly increased. The active group have a higher level of resistin than the inactive group. The results of these meta-analyses suggest that resistin and adiponectin may play an important role in the pathogenesis of KD. Resistin and adiponectin could be used as biomarkers for KD diagnosis.
[GW30-e0719]
Ling Zhu 1 , Fangfang Yang 2 , Yin Liu 2 , Zhongwei Liu 1 , Fuqiang Liu 1 , Shuo Pan 1 , Yong Zhang 1 , Xin Jiang 1 , Junkui Wang 1
1Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, China
2Xi’an Medical College, Xi’an, Shaanxi, China
OBJECTIVES Previous studies have shown that depression is closely related to the occurrence and development of hypertension. Depression is one of the important psychological factors affecting hypertension. Thus, we assessed the impact of depression on the development of hypertension.
METHODS A total of 272 patients were enrolled in Shaanxi Provincial People’s Hospital from 2017 to 2018. Exclusion criteria were: age below 30 years or above 80 years, NYHA III or IV, coronary heart disease, atrial fibrillation, frequent arrhythmia, renal failure, serum creatinine above 175 μmol/L, thyroid dysfunction, acute infection, known history of cancer or chronic-immune-mediated disorders, or current use of immunosuppressive agents including corticosteroids.
Hypertension is defined as systolic blood pressure (SBP) higher than 140 mmHg, or a diastolic pressure (DBP) greater than 90 mmHg. All enrolled subjects completed the Hamilton depression Scale (HAMD) which is a rating scale developed to quantify the severity of depression. HAMD score ≥20 was defined as the presence of depression. The association between depression and hypertension was estimated with univariate and multivariate logistic regression models. Model 1 was unadjusted. Model 2 was adjusted for age, sex, and smoking. Model 3 adjusted for age, sex, smoking, educational level, economic income. Model 4 adjusted for age, sex, smoking, educational level, economic income, family history of hypertension, and hyperlipemia.
RESULTS Participants were divided into two groups according to with depression or not. Compared with the non-depression group, the rate of hypertension was significantly higher in the depression group (70.5 vs. 54.1%, P=0.008). Then, we assessed the association between depression scores and blood pressure, depression scores levels were significantly positive correlated to the systolic blood pressure (r=0.283, P<0.001).
To further evaluate the effect of depression on development of hypertension, we used univariate and multivariate regression models to reveal whether the depression was an independent risk factor for the development of hypertension.
In univariate logistic regression models (Model 1), compared with patients in non-depression group, the odds ratios (OR) for development of hypertension in the depression group were 2.43 (95% CI 1.45–4.06, P=0.001). Multivariate analysis showed that depression was independently and positively related to the development of hypertension (adjusted OR: 2.35, 95% CI 1.40–3.95, P=0.001, compared with the non-depression group) after adjusting for Model 2. With further adjustment for adjusted for Model 3 and Model 4. The OR for the development of hypertension in the depression group showed no change (Model 3, OR 2.36, 95% CI 1.29–4.01, P=0.001; Model 4, OR 2.52, 95% CI 1.43–4.45, P=0.001).
CONCLUSIONS Our data indicated that depression is an independent risk factor for the development of hypertension.
[GW30-e0726]
Nanfang Li, Lin Wang, Mulalibieke Heizhati, Xiaoguang Yao, Gulinuer Duiyimuhan, Nanfang Li
Hypertension Institute of Xinjiang, Center for Hypertension of the People’s Hospital of Xinjiang Uygur Autonomous Region
OBJECTIVES The aim was to determine prevalence, awareness, treatment, control and risk factors associated with hypertension among multi-ethnic population in northwest China.
METHODS We conducted a hypertension screening project covering a third of adults in Emin Xinjiang, northwest China during 2014–2016. All the participants were selected from the hypertension screening project which included health archives, health check-up records and disease registrations with a solid information security system. Hypertension was defined as systolic blood pressure (BP) ≥140 mmHg, and/or diastolic BP≥90 mmHg and/or taking anti-hypertension drugs. Awareness was defined as whether they had a medical diagnosis of hypertension and treatment as whether they were receiving BP-lowering medications. Control was defined as an average SBP and DBP <140/90 mmHg. We compared prevalence, awareness, treatment and control of hypertension and related factors by different regions (agricultural, stock-raising or urban) and by ethnic groups.
RESULTS Totally 47,040 adults were screened with 48.5% women. A total of 54.9% participants (n=25,850, aged 43.6 years) were enrolled from rural setting, 17.0% (n=7994, aged 42.0 years) from stock-raising setting and 28.1% (n=13,196, aged 45.9 years) were from urban setting. 77.4% subjects in stock-raising setting were Kazakh ethnicity, and 53.4% in urban setting were Han ethnicity and 43.3% in rural setting were Han and 45.5% were Kazakh ethnicity. Overall prevalence of hypertension was 26.5%. Among those with hypertension, 64.6% (95% CI, 61.9–67.1%) were aware of their condition, 44.5% (95% CI, 43.7–45.2%) were taking medications to lower their BP, whereas only 15.3% (95% CI, 14.8–15.9%) achieved BP control. Age-gender-adjusted hypertension prevalence was higher in urban (28.2%) than in other regions and in Kazakh (30.3%) than in others. The awareness and treatment rates were lower in patients from agricultural regions than in those from urban or stock-raising settings (awareness rate: 59.7 vs. 66.5 vs. 76.3%; treatment rate: 41.6 vs. 42.3 vs. 58.4%), whereas the control rate in patients from stock-raising setting was lower than that of those from urban and rural setting (13.8 vs. 15.2 vs. 15.8%, P<0.05). The awareness, treatment and control rates of hypertension were lower in Kazakh subjects than in other ethnic groups (P for all <0.001). After adjusting for age, gender, ethnicity and regions, abdominal obesity (OR 1.30; 95% CI, 1.21–1.41), general obesity (OR 1.94; 95% CI, 1.75–2.15), cigarette consumption (OR 2.49; 95% CI, 2.20–2.81), and alcohol intake (OR 4.90; 95% CI, 4.33–5.53) were significantly associated with the presence of hypertension (P<0.05).
CONCLUSIONS Disparities in hypertension control among regions and ethnic groups suggested inadequate screening and treatment, especially in stock-raising regions and Kazakh populations. Control of alcohol intake, smoking and obesity should be at high priority of health promotion. Even though the current project did not collect data on salt intake, it is should be addressed as sodium consumption is high in the region.
[GW30-e0730]
Fengyu Pan, Mulalibieke Heizhati, Lin Wang, Ling Zhou, Jing Hong, Mayila Kamilijiang, Delian Zhang, Guijuan Chang, Qin Luo, Le Sun, Na Yue, Nanfang Li
Hypertension Institute of Xinjiang, Center for Hypertension of the People’s Hospital of Xinjiang Uygur Autonomous Region
OBJECTIVES The aim was to investigate Hcy and folate levels, prevalence of hyperhomocysteinemia (HHcy) and of folate deficiency in population from urban, agricultural and stock-raising regions.
METHODS Multistage stratified random sampling method was used to obtain study population aged ≥15 years. Surveys on health behavior questionnaires and physical examinations were conducted. Blood samples were collected for Hcy and folate measurement. Study subjects were divided into three groups as urban, agricultural and stock-raising population. HHcy was defined as Hcy ≥10 μmol/L and folate deficiency as <3 ng/mL.
RESULTS 1926 participants with 885 (45.9%) from urban, 861 (44.7%) from agricultural and 180 (9.4%) from stock raising regions were evaluated. Although Hcy concentration in the three region showed no significant difference (14.2 vs. 13.3 vs. 13.2 μmol/L, P=0.202), subgroup analysis showed significantly higher Hcy in women, Kazakh, non-drinking subjects, low education takers from stock-raising region than did other two regions. Folate concentration in stock raising region is significantly lower than in other two regions (3.3 vs. 7.2 vs. 6.5 ng/mL, P<0.001); subgroup analysis showed consistent results. Prevalence of HHcy and folate deficiency in stock raising region is the highest (82.2 and 54.8% respectively), followed by agricultural (69.7%, 8.3%) and urban (68.4%, 2.6%) region with statistical significance (P=0.001 for HHcy and P<0.001 for folate). Folate deficiency, stock raising region, older age, and male gender showed higher ORs for HHcy presence.
CONCLUSIONS Prevalence of HHcy and folate deficiency is unacceptably high in stock raisers. Current results is of important reference for the prevention and control of HHcy to Xinjiang, extending to others with approximate lifestyles and dietary habits by folate supplementation and lifestyle modification.
[GW30-e0732]
Sheng Li, Xiaoguang Yao, Tai Huang, Lu Wen, Yingchun Wang, Nanfang Li
Hypertension Institute of Xinjiang, Center for Hypertension of the People’s Hospital of Xinjiang Uygur Autonomous Region
OBJECTIVES The STOP-BANG questionnaire was used widely for detecting patients with obstructive sleep apnea (OSA). However, considering the lower mean level of body mass index (BMI) and neck circumference (NC) of Chinese population, the cut-off point value of these two questions needs to be verified. This study was to assess the diagnostic efficacy of the STOP-BANG questionnaire and establish a more appropriate BMI and NC cutoff value for Chinese patients with hypertension.
METHODS A retrospective analysis of 284 patients admitted to the Hypertension center of People’s Hospital of Xinjiang Uygur Autonomous Region from 2016 to 2017, who underwent 7-hour nighttime polysomnography (PSG) and completed the ESS score, STOP-BANG questionnaire. The diagnostic ability of STOP-Bang questionnaire of severe OSA (AHI≥30 events/h) were assessed and the improved STOP-BANG questionnaire were established.
RESULTS When the BMI cut-off value is set to 28 kg/m2 and the neck circumference cut-off point is set to 42 cm, the area under the ROC curve of the STOP-BANG scale is the largest (0.81, P<0.001). The sensitivity and specificity of the STOP-BANG questionnaire for predicting severe OSA in hypertensive patients were (80.58 and 60.69%), respectively, and the area under the ROC curve was (0.755, P<0.001). In the scale, when the neck circumference was kept and the BMI cutoff value is reduced from 35 to 28, the AUC of the scale increased from 0.755 (0.70–0.80) to 0.784 (0.73–0.83), and the difference is statistically significant (P<0.01). When the neck circumference changed from 40 to 42 in the scale, the AUC of the scale changed from 0.755 (0.70–0.80) to 0.785 (0.73–0.83), and the difference was statistically significant (P<0.01). When the BMI and neck circumference cutoff values were both changed, the area under the curve was 0.81 (0.76–0.85). It was 87.77% (81.1–92.7), the specificity was 62.07% (53.6–70.0), and the Youden index was 0.50.
CONCLUSIONS The STOP-BANG questionnaire has high sensitivity and diagnostic efficacy for screening the population. The improved STOP-BANG questionnaire for this population can improve the diagnostic efficacy of screening. We recommend using BMI (28 kg/m2), neck circumference (42 cm), STOP-BANG score ≥3 is the cut-off value to identify patients with high risk of severe OSA in Chinese patients with hypertension.
[GW30-e0733]
Ying Wang, Xiaoguang Yao, Ling Yao, Nanfang Li
Hypertension Institute of Xinjiang, Center for Hypertension of the People’s Hospital of Xinjiang Uygur Autonomous Region
OBJECTIVES To investigate the effect of diabetes on sleep parameters in postmenopausal women by comparing the nocturnal sleep parameter in menopausal and non-menopausal female with hypertension.
METHODS A total of 549 female patients who underwent polysomonography in the Hypertension Center of People’s Hospital of Xinjiang Autonomous Region were selected from 2005 to 2010. The patients were divided into menopause and non-menopausal group. Differences in sleep parameters between the two groups of patient.
RESULTS 280 menopausal and 269 non-menopausal patients were included in the study. Menopausal women had a higher prevalence of diabetes [23.2 vs. 4.8%], the prevalence of OSA [81.4 vs. 52.4%] and AHI index [13.5 (6.3, 25.8) vs. 6.3 (1.5, 13.4) P<0.001] than non-menopausal women, but the lowest oxygen saturation was lower [77 (70, 82) vs. 79 (74, 83) P=0.008]. The AHI index in patients with diabetes increased compared those without diabetes [11.8 (2.6, 19.1) vs. 8.5 (5.6, 30.2) P=0.008), but the lowest oxygen saturation was lower [79.5 (71.8, 84) vs. 82 (76, 87) P=0.011]. After adjustment, multivariate analysis showed that menopause and poor glycemic control were associated with sleep disturbances and OSA.
CONCLUSIONS Postmenopausal women with diabetes would increase the risk of OSA and the disorder of sleep parameters.
[GW30-e0772]
Yuan Huang 1,2 , Yanjing Feng 1 , Lijun Yang 1 , Xin Xing 1 , Dengfeng Gao 1
1The Second Affiliated Hospital, Xi’an Jiaotong University
2Qinghai Provincial People’s Hospital
OBJECTIVES LVH is a strong predictor of cardiovascular morbidity and mortality because of the increased risk of heart failure and malignant arrhythmia. In the present study, we compared the expression profile of circulating lncRNAs in patients with primary hypertension and LVH, primary hypertension without LVH (NLVH) and normotensive individuals. Illuminating the role of lncRNAs in hypertension-induced cardiac remodeling may help in understanding the underlying molecular mechanism and suggest potential therapeutic targets.
METHODS In this study, venous blood was collected from patients with essential hypertension with and without LVH and healthy controls in a case–control study. Total RNA was extracted from each sample, microarray analysis was used to detect lncRNA expression profiles. The Level of targeted lncRNAs was Confirmed by quantitative real-time PCR. Coding–non-coding gene co-expression network and functional enrichment analysis of lncRNAs with significantly differential expression was conducted. Multivariate logistic regression analysis was used to evaluate the association between LVH and the lncRNAs RP11-327F22.4 and KHSRPP1 in hypertensive patients.
RESULTS A total of 94 differentially expressed lncRNAs was identified by microarray-based screening. The comparison of LVH patients and controls revealed 17 upregulated and 34 downregulated lncRNAs. Among these differentially regulated lncRNAs, we chose two, upregulated RP11-327F22.4 and downregulated KHSRPP1, which agreed with the pattern we expected. We also used RT-PCR to analysis levels of the lncRNAs RP11-327F22.4 and KHSRPP1 in hypertensive patients with LVH or NLVH and matched healthy controls. The two lncRNAs showed a consistent expression pattern on microarray assay, which indicates high reliability of the analysis.
Multivariate logistic regression analysis results showed that LVH in hypertensive patients was associated with upregulated lncRNA RP11-327F22.4 (OR: 1.030; 95% CI: 1.008–1.052; P=0.008) but not downregulated KHSRPP1 (OR: 1.002; 95% CI: 0.998–1.006; P=0.348).
To further explore the interaction between lncRNAs and mRNAs in essential hypertension with LVH, we created a coding–noncoding gene co-expression network. Overall, 13 coding genes were correlated with RP11-327F22.4 (PCC≥0.8), and 29 with KHSRP11 (PCC≥0.8). Notably, these relationships do not indicate a direct interaction between the two molecules. On bioinformatics analysis, the functions of the coding genes for the two lncRNAs were closely related to cell activation, cell chemotaxis and wound healing at the biological process level. On KEGG pathway analysis, the two lncRNA-related coding genes were mainly involved in neuroactive ligand–receptor interaction, calcium signaling and Rap1 signaling pathways.
CONCLUSIONS In conclusion, we have shown that two lncRNAs, RP11-327F22.4 and KHSRPP1, are significantly dysregulated in patients with hypertensive LVH and may be associated with the pathogenesis of cardiac hypertrophy. Although the molecular mechanism and function of these two lncRNAs are still unclear, they might be closely related to hypertensive LVH pathogenesis. These findings encourage future studies to explore the function and mechanism of lncRNAs in the pathogenesis of cardiac hypertrophy.
[GW30-e0847]
F.N. Gasimova 1 , R.M. Alizade 2 , R.N. Mammadova 1 , A.V. Musayeva 1
1Azerbaijan State Advanced Training Institute for Doctors named after A. Aliyev, Department of Therapy, Baku, Azerbaijan
2Republican Clinical Hospital named after M. Mirgasimov, Department of Cardiology, Baku, Azerbaijan
OBJECTIVES Arterial hypertension – one of the most common diseases of the cardiovascular system and its treatment of questions remain urgent problem of preventive cardiology Purpose: To study the comparative characteristics of β-blockers and their impact on the quality of life of patients with arterial hypertension.
METHODS The examination included 130 patients aged 30–59 years with arterial hypertension. Quality of life and compliance to treatment in case of a long-term monotherapy with different β-blockers: propranolol (23 patients), metaprolol (21 patients), nadolol (28 patients), atenolol (18 patients), bioprolol (16 patients) and nebivolol (24 patients) were studied in a comparative aspect. Treatment compliance studied according to the Morisky-Green General questionnaire, and the quality of life according to the General Well Being Questionarie (GWBQ).
RESULTS In general, with monotherapy, all studied β- blockers had a sufficient antihypertensive effect, however, target blood pressure levels were achieved with atenolol, nebivolol and bisoprolol, and a less pronounced antihypertensive effect was observed in propranolol compared with other – β-blockers. The negative chronotron effect was more pronounced in nadolol, the remaining β-adrenoblockers equally reduced the heart rate. A comparative analysis of changes in the quality of life in monotherapy with different β-adrenoblockers showed that the best parameters of the quality of life were found in the treatment with nebivolol (87.5%), then bisoprolol (81.3%), followed by atenolol (72.2%), metaprolol (71.5%), nadolol (67.8) and to a lesser extent, a positive effect the quality of life is observed in -propranolol (43.5%).
CONCLUSIONS Summing up the results of long-term, long-term continuous monotherapy with various β-blokers, it can be stated that, along with stable antihypertensive efficacy and good tolerability with a relatively low incidence of side effects, different β-adrenoblockers have different effects on the quality of life and patient adherence to treatment. The greatest compliance and improvement of the quality of life is observed in patients taking nebivolol, the smallest among those treated with propranolol.
[GW30-e0897]
Pengyang Li 1 , Fangcheng Wu 2 , Lingling Wu 3 , Ying Ning 1 , Mu Li 1 , Peng Cai 4 , Nitish Kumar Sharma 1 , Bin Wang 1
1Saint Vincent Hospital
2Memorial Hospital West
3Mount Sinai St Luke’s
4Worcester Polytechnic Institute
5The First Affiliated Hospital of Shantou University Medical College
OBJECTIVES Hypertension (HTN) is the most common comorbidity in patients with cancer. Meanwhile, chemotherapy and radiotherapy for the cancer treatment were found to be associated with the development or worsening of HTN. This study aimed to investigate the impact of HTN on the in-hospital outcomes of patients admitted for cancer.
METHODS We conducted a retrospective cohort analysis of the National Inpatient Sample 2016 database. Patients hospitalized with a principal diagnosis of cancer were identified using the ICD-10 codes. Multivariate logistic regression was performed after adjustment for patient and hospital demographics, and relevant comorbidities. Inpatient mortality was compared between the patients with and without HTN.
RESULTS A total of 1,022,625 hospitalizations with cancer were identified. Of these, 565,430 (55.29%) had HTN. Multivariate logistic regression analysis after adjustment showed that patients with both cancer and HTN had lower in-hospital mortality (4.44 vs. 5.18%, OR 0.71, 95% CI 0.68–0.75, P<0.001) but similar length of stay (LOS) (6.69 vs. 6.32 days, P=0.389) when compared to patients with cancer but no HTN. Further study of the cancer subgroups revealed that HTN was associated with lower mortality than non-HTN in lung cancer (OR 0.73, 95% CI 0.65–0.81, P><0.001), colon cancer (OR 0.81, 95% CI 0.66–0.99, P=0.043), liver cancer (OR 0.67, 95% CI 0.52–0.86, P=0.002), pancreatic cancer (OR 0.79, 95% CI 0.63–0.99, P=0.037), prostate cancer (OR 0.45, 95% CI 0.29–0.70, P><0.001), bladder cancer (OR 0.50, 95% CI 0.35–0.71, P><0.001), kidney cancer (OR 0.43, 95% CI 0.28–0.67, P><0.001), and leukemia (OR 0.71, 95% CI 0.60–0.83, P><0.001), While, the in-hospital mortality in esophageal cancer, stomach cancer, rectal cancer, breast cancer, ovary cancer, lymphoma, melanoma, and brain cancer were similar between patients with and without HTN. Patients with cancer and HTN had higher rate of in-hospital morbidities including ventricular fibrillation/tachycardia (OR 1.83, P><0.001), respiratory failure (OR 1.33, P><0.001), acute kidney injury (OR 2.04, P><0.001), stroke/TIA (OR 2.41, P><0.001), intubation (OR 1.22, P><0.001), major bleeding (intracranial bleeding and acute GI bleeding) (OR 1.22, P><0.001), complete heart block (OR 2.09, P><0.001), red blood cell transfusion (OR 1.22, P><0.001), but less likely to have cardiac tamponade (OR 0.90, P=0.012), and platelet transfusion (OR 0.86, P><0.001).
CONCLUSIONS HTN is associated with lower inpatient mortality in patients hospitalized for cancer. This effect might due to anti-hypertensive medications treatment. Further large prospective studies are needed.
[GW30-e0922]
Lin Liu, Geng Shen, Jiayi Huang, Yuling Yu, Chaolei Chen, Yuqing Huang, Yingqing Feng
Department of Cardiology, Guangdong Cardiovascular Institute, Hypertension Research Laboratory, Guangdong Provincial People’s Hospital, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention Guangdong Academy of Medical Sciences
OBJECTIVES Left ventricular hypertrophy (LVH) is a risk factor of cardiovascular and cerebrovascular diseases, especially in hypertensive patients. We designed this study to investigate the unidentified association between non-high-density lipoprotein cholesterol (non-HDL-C) and new-onset LVH.
METHODS In this retrospective cohort study, we enrolled 834 hypertensive participants with normal echocardiographic left ventricular mass index (LVMI) at baseline and a readable echocardiogram at the end of follow-up. We used multivariable logistic regression to estimate the association between non-HDL-C levels and new-onset LVH.
RESULTS Over a 4-year period, 210 (25.2%) participants progressed to LVH. The incidence of new-onset LVH decreased with increases in non-HDL-C levels from baseline, from the lowest (27.2%) to the middle (25.2%) and the highest (22.7%). After adjustment for confounding factors, the odds ratios (95% confidence interval) of non-HDL-C levels for new-onset LVH in the middle tertile group and the highest tertile group were: 0.840 (0.537–1.313), 0.606 (0.396–0.926), respectively (P trend=0.019). And each 1 mmol/L increase in non-HDL-C levels resulted in a 20.3% lower risk of incident LVH.
CONCLUSIONS In our community-based, retrospective cohort study, non-HDL-C level is negatively related to new-onset LVH.
[GW30-e0981]
Jong Hoon Koh, MinJeong Kang, Mina Yoo
Seoul SeoNam Hospital
OBJECTIVES The aim of this study was to assess if the usefulness of albumin/creatinine ratio (ACR) and plaque in carotid artery (PCA) could be independent from MetS in hypertensive patients
METHODS We identified 100 participants with hypertension with metabolic syndrome. CIMT and PCA were evaluated by ultrasonography. ACR was obtained from first morning urine specimens. MetS was defined according to the National Cholesterol Education Program (USA) Adult Treatment Panel III classification.
RESULTS Hypertensive patients with MetS had a significantly higher prevalence of a CIMT>0.85 mm (P=0.001) and PCA (P<0.001) as compared with participants without MetS. CIMT was significantly correlated with fasting triglycerides and fibrinogen levels both in participants with MetS and in those without MetS (all P<0.01). Univariate linear regression analysis showed a positive relationship between ACR and PCA, Regression models including ACR, showed that only ACR, BMI, hypertension duration and systolic blood pressure (SBP) were independently associated with ACR.
CONCLUSIONS MetS or hypertension are associated with increased risk of subclinical atherosclerosis. Screening for ACR and PCA in hypertensive patients with MetS may identify at high risk subset for cardiac and renal subclinical organ damage.
ARRHYTHMIAS
[GW30-e0034]
Lingyun Kong 1 , Lingling Chen 1 , Ping Zhang 1 , Tiangang Zhu 2 , Fang Liu 1
1Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University
2Cardiology Department, Peking University People’s Hospital
OBJECTIVES Atrial fibrillation (AF) causes turbulence of LV function status and poses challenges for rapid and accurate assessment of myocardial function by echocardiogram. The index beat assessment of LV systolic function has been shown to agree well with the average method. But whether it is applicable to measurement of Doppler LV systolic and diastolic function parameters has not been fully studied. Recently, the dual Doppler technique allows simultaneous demonstration of flow-tissue pulse wave, hence it facilitates the recording of mitral E wave, systolic (s′) and diastolic (e′) mitral annular motion velocity in the same cardiac cycle. Therefore, E/e′ and s′ can be acquired during the same beat in AF patients. The aim of this study was to assess the value of index beat in assessing s′ and E/e′ using dual pulse wave Doppler technique.
METHODS A total of 50 AF patients were prospectively enrolled for a comprehensive echocardiography study. Dual pulse-wave Doppler technique was used to obtain trans-mitral flow and mitral annular motion velocity simultaneously from apical 4-chamber view. Ten beats were acquired for analysis in each patient. The ratio of peak early mitral inflow velocities (E) and septal and lateral mitral annulus velocity (e′), i.e., E/e′, and peak systolic mitral annular motion velocity (s′) were simultaneously acquired at each cardiac cycle. The index beat was determined if the ratio of the preceding RR interval/pre-preceding RR interval equals 1 (0.95~1.06). Difference, correlation and agreement were assessed between the values (s′ and E/e′) at the index beat, the preceding as well as the ensuing beat and the corresponding mean value.
RESULTS The index beat was identified in only 27 patients for septal analysis, and 22 patients for lateral wall analysis. The mean s′ and E/e′ measured by dual Doppler technique showed no significant difference to the value measured by conventional single Doppler average of 5 beats (both P>0.05). The index beat s′ showed the highest correlation (r=0.96 for septal wall and 0.92 for lateral wall, both P=0.000) with the mean value. While E/e′ at the pre-index beat, instead of the index beat initiated cycle had the best correlation with the mean value (r=0.88 for septal wall and 0.97 for lateral wall, both P=0.000). Bland-Altman analysis showed good agreement between index beat s′ and mean s′, and between E/e′ at the pre-index beat and the mean E/e′ across a wide range.
CONCLUSIONS Measurement of LV systolic function in AF patients from the index beat was representative of the mean value from multiple beats. However, it is E/e′ from the pre-index beat, rather than from the index beat, that correlates best with the average value. This finding should improve decision making when choosing a representative beat for assessing LV systolic and diastolic function in patients with AF.
[GW30-e0048]
Yu Fei, Chuang Yang, Jinpeng Liu, Geqing Zhang, Mengyuan Bai, Li Wang
Department of Cardiology, the Second Hospital, Jilin University, Changchun, Jilin 130041, China
OBJECTIVES Recently, some scholars believed that Fumai Decoction (FMD) might cure patients with atrial fibrillation (AF), we systemic evaluated the efficacy and safety of FMD treatment for patients with AF in order to provide the basis for its extensive clinical application.
METHODS “FMD or Integrated traditional Chinese or Fumai Decoction or Chinese herbal medicine” and “atrial fibrillation or AF” were searched from Elsevier Science, Medline, ProQuest, PubMed, VIP, CNKI, Wanfang database. Inclusion criteria: (1) adult AF patients; (2) FMD treatment AF; (3) with definite control groups; (4) total efficacy and drug untoward reaction; and (5) with randomized controlled trials. Exclusion criteria: (1) with one article if the alike literature republished; (2) with animal and basic experimental literature; and (3) conference and essay articles. The extraction and quality assessment was assessed by two reviewers checking independently and crosswise, when differences appears, handle these through discussion or the third party. Evaluate quality according to the 4.2 standard of Cochrane system evaluation manual. The data analysis used for RevMen5.3 software. Dichotomous data were expressed as relative risk (RR) and continuous outcomes as mean differences (MD), while 95% confidence intervals (CI) were calculated for both. The results were shows the forest. Bias analysis applied by the funnel plot. Sensitive maps for sensitivity analysis by stata 15 software. The statistical heterogeneity was presented as significant when the I square (I2) value exceeded 50% or P<0.05, we used random effect mode. When the absence of statistical heterogeneity (I2<50% or P>0.05), we pooled data using the fixed effect mode. The differences were considered significant according to P<0.05.
RESULTS 21 Chinese articles of FMD treating AF patients were selected by screening literature, including 1905 patients totally (treatment group: 999, control group: 906). All the 21 articles mentioned “random”. Three mentioned single blind method, but all literature did not method concealment and so on. Only 2 patients were withdrawed because of pulmonary infection. Quality grade was lower. Compared with control group, (1) the total efficacy of FMD treatment for AF patients were significantly increased (RR=1.23, 95% CI=1.15–1.33); (2) heart rate was significantly decreased (MD=–5.51, 95% CI=–10.25 to –0.76);3) AF cardioversion rate was enhanced in 14 days (RR=5.81, 95% CI=2.40–14.04) and 21 days (RR=3.05, 95% CI=1.69–5.50);4) the untoward reaction were significantly decreased (RR=0.28, 95% CI=0.17–0.46). Two subgroups were not heterogeneity whether or not combined with antiarrhythmic drugs group, whether or not elderly patients group (each I2=0%), except for whether or not including paroxysmal AF groups (I2=87.7%). The experimental results were firm by sensitive analysis. The funnel plot showed little bias.
CONCLUSIONS We believe that FMD has a role in the treatment of AF, It is worth widely using and popularizing in clinic practice.
[GW30-e0049]
Mengyuan Bai 1 , Geqing Zhang 1 , Hongbo Fei 2 , Yu Fei 1
1Department of Cardiology, the Second Hospital, Jilin University
2Hospital of Stomatology, Jilin University
OBJECTIVES Our systemic evaluation of Acehytisine Guan Fu Base A (GFA) treatment for cardiac arrhythmia (CA) is to provide further basis for its wide application clinically.
METHODS “GFA” and “CA” were searched from CNKI, Wanfang database, VIP, PubMed, Medline, ProQuest, Elveset Science. Inclusion criteria: (1) adult patients with CA; (2) using GFA treatment of CA; (3) having control group; (4) observation of therapeutic effect; and (5) randomized controlled trial. Exclusion criteria: (1) case repeated; (2) animal and basic experiments; and (3) evidence-based medical experiments. Independent and cross-checked by two evaluators. When confronted with disagreements, the problem can be resolved through discussion or by inviting the third party to assist. Evaluate quality according to Cochrane System Evaluation Manual 4.2 standard. Dichotomous data were expressed as relative risk (RR), Continuous outcomes as mean differences (MDs), while 95% confidence intervals (CI) were calculated for both. The results was showed forest plot. Bias analysis applied by the funnel plot. The data analyzed by RevMen5.3 software. The statistical heterogeneity was presented as significant when the I square (I2) value exceeded 50% or P<0.05, we used random effect mode. When the absence of statistical heterogeneity (I2<50% or P>0.05), we pooled data using the fixed effect mode. The differences were considered significant according to P<0.05.
RESULTS 7 Chinese documents were included in this study by removing 74 and 9 from 90 relevant literatures, including 421 CA patients (247 cases of GFA group, 174 cases of control group). 7 articles were referred to as “random”, only one article mentioned blindness, but not in other studies, such as blindness, experiment withdrawal and follow-up. One was compared with amiodarone. The others were compared with propafenone. Compared to control group, (1) the total effect of treatment group was significantly increased (RR=1.32, 95% CI=1.16–1.51), which were significant increased in the treatment of supraventricular tachycardia (RR=1.23, 95% CI=1.08–1.40) and ventricular premature beats (RR=2.10, 95% CI=1.22–3.64), they have not homogeneity (I2=71.4%); (2) the CA recovery time of treatment group was significantly shorten (MD=–1.45, 95% CI=–2.79 to –0.11);3) PR intervals, QRS intervals and QTc intervals of treatment group was no significant difference (MD=–0.08, 95% CI=–17.04 to 16.88; MD=–2.87, 95% CI=–12.07 to 6.33; MD=–3.68, 95% CI=–16.05 to 8.69);4) untoward reactions of treatment group was no significant differences (RR=0.90, 95% CI=0.54–1.49). The funnel plot showed symmetry and roughly funnel form, indicating little bias.
CONCLUSIONS These results indicated that GFA has good therapeutic effect on CA, as supraventricular tachycardia and ventricular premature beats, and less adverse reactions and hence it can be used widely clinically.
[GW30-e0088]
Jiaqi Yang, Tienan Sun, Yujie Zhou
Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Patients with atrial fibrillation and dilated cardiomyopathy often exist exhibit cardiac function and poor prognosis. However, the specific reason is unclear. This study aimed to indicate the impact of obesity in patients with AF and DCM.
METHODS 74 consecutive patients with AF and DCM were enrolled in this study and were classified by BMI. The major endpoints were cardiac death, recurrent AF, recurrent atrial tachyarrhythmia (ATa), stroke and secondary endpoints.
RESULTS In multivariate analysis, overweight and obese group presented more incidence of re-AF (0.0 vs. 30.3 vs. 40.0%, log-rank P=0.048) and re-hospitalization (9.1 vs. 36.4 vs. 45.0%, log-rank P=0.035). The five-year outcomes of primary endpoints were inferior in overweight and obese group (18.2 vs. 30.3 vs. 50.0%, log-rank P=0.042). Overweight patients (from 39.1 to 50.0%, P=0.005) exhibited more benefit in LVEF recovery after ablation than normal weight group (from 43.1 to 52.3%, P=0.199) and obese group (from 44.9 to 51.2%, P=0.216).
CONCLUSIONS AF and DCM patients who were overweight or obese exhibited worse long-term outcomes in recurrent AF than patients with normal weight. However, overweight patients benefit most in cardiac function after ablation.
[GW30-e0097]
Tariel Atabekov, Roman Batalov, Sergey Krivolapov, Svetlana Sazonova, Michail Khlynin, Sergey Popov
Cardiology Research Institute, Tomsk National Research Medical Centre, Russian Academy of Sciences, Tomsk, Russia
OBJECTIVES Sudden cardiac death (SCD) remains the leading cause of death. Ventricular tachyarrhythmias (VTA) are the main cause of SCD. The incidence of VTA and SCD in coronary artery disease (CAD) patients still is a hot spot in cardiology. The implantable cardioverter-defibrillator (ICD) is the main method of SCD prevention. However, only 15–25% patients after ICD implantation have VTA events. So, it’s necessary to find out new predictors of VTA. And aim of our research was to study the diagnostic value of left ventricle ejection fraction (LVEF) assessment, myocardial perfusion (MPS) and cardiac 123I-methaiodobenzylguanidine (123I-MIBG) scintigraphy in the VTA prediction in patients with CAD.
METHODS 51 patients (male – 41, average age 65.4±6.9 year) with CAD were examined. All patients were divided into 2 groups according to the ICD implantation indications (primary and secondary SCD prevention). Before ICD implantation, patients underwent echocardiography, MPS with 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) and cardiac 123I-MIBG scintigraphy. During 6th month follow-up, VTA events were documented in each group. Data of LVEF, MPS and cardiac 123I-MIBG scintigraphy before ICD implantation were compared in each group between patients with and without VTA events.
RESULTS The 1st group consisted of 21 (41.1%) patients with primary prevention indications (male – 19, age 63.2±7.7 years), 18 patients of them have VTA (3 patient have successful ventricular antitachypacing and 15 patients have nonsustained VTA) and 3 patients from this group don’t have VTA events. The 2nd group consisted of 30 (58.9%) patients with secondary prevention indications (male – 22, age 6639±8.6 years), 19 patients of them have VTA (1 patient have successful ICD shock therapy, 9 patients have successful ventricular antitachypacing and 9 patients have nonsustained VTA) and 11 patients from this group don’t have VTA events. In 1st group there were significant differences between patients with and without VTA before ICD implantation in terms of: average accumulation defect index of 123I-MIBG on early (SSe%) (29.55±14.97 vs. 11.33±6.35% (P=0.006)) and delayed (SSd%) scintigrams (36.77±14.72 vs. 18.66±4.04% (P=0.03)) and accumulation defect of 99mTc-MIBI – 19.16±12.34 vs. 6.01±3.61% (P=0.01), respectively. In 2nd group there were significant differences between patients with and without VTA before ICD implantation in terms of: LVEF – 50.6±9.2 vs. 64.1±7.9% (P=0.0006), average SSe of 123I-MIBG (31.68±17.71 vs. 7.36±2.24% (P=0.0002)) and SSd (33.05±18.08 vs. 9.36±3.93% (P=0.0001)) and accumulation defect of 99mTc-MIBI – 24.57±15.82 vs. 7.48±7.01% (P=0.001), respectively.
CONCLUSIONS Myocardial perfusion and cardiac sympathetic activity radionuclide assessment, as well as LVEF assessment, can be used for identification of the highest risk group of SCD.
[GW30-e0105]
Yuzhou Xue, Shen Jian, Liu Gang, Zhou Qi, Wen Yi, Zhou Wei, Suxin Luo
The First Affiliated Hospital of Chongqing Medical University
OBJECTIVES The relationship between PR interval prolongation and long-term prognosis in patients with acute ST-segment elevation myocardial -infarction (ASTEMI) has not been elucidated. This study aimed to evaluate the prevalence, predictors and outcomes of PR interval prolongation in a prospective cohort of post-STEMI patients.
This study aimed to evaluate the prevalence, predictors and outcomes of PR interval prolongation in a prospective cohort of post-STEMI patients.
METHODS We measured the PR interval in 915 patients with ASTEMI and classified them into those with (>200 ms) and without (≤200 ms) PR interval prolongation. Among 915 patients with ASTEMI, 87 (9.5%) patients developed PR interval prolongation.
RESULTS Stepwise logistic regression analysis was used for exploring the potential predictors of PR interval prolongation. The mean level of calcium during hospitalization was strongly correlated with development of PR interval prolongation (Hazard Ratio [HR] 0.13; 95% Confidence Interval [CI] 0.027–0.66; P=0.01). During the mean follow-up period of 31 months (interquartile range: 22–39 months), 64 all-cause mortality (endpoint) were registered. After adjustment for confounding covariates in Cox regression analyses, PR interval prolongation was independently associated with worse outcomes (HR 5.37; 95% CI 1.85–15.62; P=0.002).
CONCLUSIONS Serum calcium obviously predicts the occurrence of PR interval prolongation in patients with ASTEMI and the prolongation of PR interval independently improves the prognostic value of long-term mortality.
[GW30-e0112]
Bo Liang 1,2 , Ling Fu 3 , FeiHu Zou 4 , Huiling Liao 1
1The College of Chinese and Western Medicine Hospital (TCM) Affiliated to Southwest Medical University, Sichuan, China
2Department of Cardiology, Nanjing Hospital of T.C.M., Nanjing University of Chinese Medicine, Jiangsu, China
3Chongqing City Traditional Chinese Medicine Hospital, Chongqing, China
4Tongliang Traditional Chinese Medicine Hospital, Chongqing, China
OBJECTIVES Premature ventricular contractions (PVCs) are very common in clinical practice, and currently there is no evidence-based traditional Chinese medicine for treatment. We tested the efficacy and safety of Dingji Fumai Decoction (DFD) in the treatment of patients with PVCs.
METHODS The treatment group (50 patients) received DFD (1200 mg three times daily) combined with metoprolol (12.5 mg twice daily) and the control group (50 other patients) received metoprolol (12.5 mg twice daily) combined with placebo (1200 mg three times daily) for 4 weeks. At the baseline and endpoint, the clinical symptoms, signs, Holter, adverse events, laboratory examination and physical examination were determined in both groups and compared.
RESULTS The groups did not differ significantly in demographic and baseline clinical characteristics. The treatment group significantly decreased the TCM syndrome score (P=0.005) and the number of PVCs (P=0.047) compared with the control group. No adverse events occurred in this trial.
CONCLUSIONS The DFD seems to be safe and ameliorates the TCM syndrome score and the number of PVCs in the patients with PVCs.
[GW30-e0136]
Xiaoyu Wu, Genqing Zhou, Songwen Chen, Yong Wei, Xiaofeng Lu, Juan Xu, Lidong Cai, Shi Peng, Shaowen Liu
Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, No 100, Haining Road, Shanghai 200080, China
OBJECTIVES To compare the long-term efficacy after raidofrequency catheter ablation of paroxysmal atrial fibrillation (PAF) patients with contact force sensing catheter or traditional open- irrigated tip catheter.
METHODS Retrospectively analyze PAF patients who received initial circumferential pulmonary vein isolation (CPVI) in Shanghai General Hospital from January, 2013 to June, 2015. A total of 243 patients were enrolled, of whom 138 patients were divided into contact force sensing open- irrigated tip catheter group (ThermoCool Smarttouch® Catheter, Biosense Webster Inc, CA, USA; ST group) while 105 patients were divided into traditional open- irrigated tip catheter (ThermoCool Navistar; Biosense Webster Inc, CA, USA; TC group). Endpoint of the catheter ablation is bi- directional electrical isolation of left atrium and pulmonary vein. The duration of operation and X-ray exposure, rate of postoperation complications and long-term efficacy remaining in sinus rhythm were compared.
RESULTS Among 243 patients enrolled, the average age was 61.65±10.12 years old, 61.7% were male, 50.6% with hypertension, 12.3% with diabetes, 7.4% had a history of cerebral infarction, and 8.6% with congestive heart failure. There were no statistically significant differences in baseline clinical characteristics between the two groups, including age, gender, comorbidity, left atrial diameter, and left ventricular ejection fraction. All the patients enrolled completed CPVI and were confirmed bi-directional electrical isolation of left atrium and pulmonary vein. Compared ST group with TC group, the duration of operation was shorter and the duration of X-ray exposure was longer, but there was no significantly difference (196.20±52.2 vs. 198.6±36.6 min, P=0.486; 15.81±7.22 vs. 12.50±4.65 min, P=0.231). There were 2 cases of hematoma in the ST group. 1 case of hematoma and 1 case of pericardial tamponade appeared in the TC group. There was no significant difference in the incidence of complications between the two groups (P=0.782). The success rate at 1 year after PVI was significantly higher in the ST group than in the TC group (87.7 vs. 77.1%, P=0.03). After mean 53.0±3.7 follow-up, the success rate in the ST group was significantly higher than that in the TC group (82.6 vs. 71.4%, P=0.038).
CONCLUSIONS Contact force sensing open- irrigated tip catheter is associated with significantly improved long-term success rate after catheter ablation in patients with PAF.
[GW30-e0224]
L.V. Tingting 1 , Yifang Yuan 1 , Huijuan Li 2 , Jing Yang 1,3 , Lingyun Kong 1,3 , Jiayu Wang 3 , Xinjie Li 4 , Yingxian Sun 5 , Xuewen Li 6 , Zheng Zhang 7 , Xiaoshu Cheng 8 , Lirong Wu 9 , Xuerui Tan 10 , Bing Han 11 , Zhaoguo Zhang 1,2 , Hua Li 1 , Yanfang Wang 2 , Yangfeng Wu 2 , Jihong Guo 3 , Ping Zhang 1,3
1Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University
2Peking University Clinical Research Institute
3Department of Cardiology, Peking University People’s Hospital
4Jining NO. 1 People’s Hospital
5The First Hospital of China Medical University
6Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital
7The First hospital of Lanzhou University
8The Second Affiliated Hospital of Nanchang University
9The Affiliated Hospital of Guiyang Medical College
10Department of Cardiology, the First Affiliated Hospital of Shantou University Medical College
11Xuzhou Central Hospital
12Beijing Sijiqing Hospital
OBJECTIVES Electrocardiographic Tpeak-to-Tend interval (Tpe), defined as the time interval between complete epicardial and myocardial repolarization, has been reported as a marker of ventricular arrhythmia and sudden cardiac death. More recently, it has been reported that recently diagnosed, untreated hypertensive outpatients had prolonged Tpe interval than those normotensive ones, which indicates that there might be some potential association between Tpe interval and blood pressure. Therefore, we aimed to examine the association between blood pressure (BP) and Tpe as well as Tpe/QT ratio in a general Chinese population.
METHODS A multi-stage, stratified cluster sampling across China during 2012–2013 was performed to select the representative Chinese adults aged 18–85 years old. 12-lead resting ECG was performed by using GE MAC-5500 with a sampling rate of 1000 Hz and analyzed automatically by utilizing Marquette 12SL algorithm in MUSE Cardiology Information System (GE Healthcare, USA). Only data from leads II, V2, V5 were investigated to limit the amount of statistical tests but cover most of the heart over different axes and planes. Participants were divided into five groups according to the latest hypertension guideline: 1. Optimal: Systolic blood pressure (SBP) was less than 120 mmHg and diastolic blood pressure (DBP) was less than 80 mmHg; 2. Normal: SBP was 120–129 mmHg and/or DBP was 80–84 mmHg; 3. High normal: SBP was 130–139 mmHg and/or DBP was 85–89 mmHg; 4. Grade 1 hypertension: SBP was 140–159 mmHg and/or DBP was 90–99 mmHg; 5. Grade 2 to 3 hypertension: SBP was more than 160 mmHg or and/or DBP was more than 100 mmHg. Generalized linear model adjusted for age, gender, center, smoking and body mass index, was used to assess the association between BP and Tpe (or Tpe/QT ratio).
RESULTS After an exclusion of potential ambiguous Tpe interval, 6251 participants with 47% female and a mean age of 47±14 years old were finally included from the nationwide study. Tpe was normally distributed with a mean of 90±14, 112±16 and 96±11 ms in leads II, V2 and V5, respectively. The average SBP was 125 mmHg and the average DBP was 81 mmHg. The aforementioned five groups had 31, 37, 16, 13 and 3% participants, respectively. After adjustment for age, gender, center, smoking and body mass index, Tpe/QT ratio was positively associated with increased SBP and DBP (P<0.01) while Tpe was not. Furthermore, Tpe/QT ratio increased with elevated BP categories (P<0.0001) while Tpe was associated with neither BP nor BP categories.
CONCLUSIONS Increased BP might relate to prolonged Tpe/QT ratio but not Tpe. Further study is warranted for clear definition of Tpe adjustment and pathophysiological mechanisms between BP and Tpe.
[GW30-e0231]
Kun Li, Jing Yang, Tingting Lv, Shenjie Sun, Fulan Liu, Yuanwei Liu, Fei She, Rong He, Bihe Xu, Yajun Xue, Ping Zhang
Beijing Tsinghua Changgung Hospital
OBJECTIVES Congenital long QT syndrome (LQTS) is a rare inheritable arrhythmic disorder which is linked to at least 15 genes. The clinical characteristics and genetic mutations may be variable among different population groups and they have not yet been studied in Chinese population.
METHODS Clinical characteristics were retrospectively reviewed from patients with congenital long QT syndrome whose blood samples were sent for genotyping during 1998–2018. Whole exome sequencing was used to identify -variants in all other known LQTS genes. Sangers sequencing was used to sequentially identify LQTS-related genetic variants.
RESULTS Of the 87 subjects (60 families), 63% were female, mean QTc was 525.11±77.48 ms and total Schwartz’s score was 4.62±1.39 points. Cardiac events occurred in 61 (70%) patients, and the average age when the first symptoms occurred was 18.08±1.86 years. Genetic studies were performed in all patients, and 74 patients had single pathogenic and likely pathogenic genetic variants (KCNQ1 in 13, KCNH2 in 45, SCN5A in 6, KCNJ2 in 3, KCNE1 in 1, AKAP9 in 4 and KCNJ5 in 2) and 14 patients had multiple LQTS-related mutations (LQTM). Totally 63 genetic variants (9 KCNQ1, 27 KCNH2, 3 SCN5A, 3 KCNJ2, 1 KCNE1, 3 AKAP9 and 1 KCNJ5) were confirmed, including 25 novel LQTS-related mutations. LQT1 patients experienced the majority of their events (99%) during exercise or stress, and only 1% occurred during fever. LQT2 patients developed symptoms under diverse conditions, including emotional stress (23%), noise (19%), arousal (16%), fatigue (16%), urination (6%), fever (3%), hunger (3%), posture change (10%), Menstruation (9%), postpartum (4.5%). LQT3 patients developed symptoms at rest (60%), during sleep (40%) or fever (20%). Cardiac event free survival was lowest in patients with LQTM (P=0.007). Treatment strategies included no active therapy in 36 (41%) patients and beta-blockers in 51 (59%) patients, including 15 (17%) patients combined with implantable cardioverter-defibrillators, 2 (2%) patients combined with pacemaker, 8 (9%) patients combined with left cardiac sympathetic denervation, and 5 (2%) patients combined with mexiletine. Over a median follow-up of 7.14±3.12 years, the annual cardiac event burden after treatment decreased significantly compared before treatment (1.29±1.83 vs. 0.16±0.36, P<0.0001).
CONCLUSIONS LQT2 was the most common subtype in Chinese patients and LQTM was the second most. life-threatening arrhythmias in LQTS patients tended to occur under specific circumstances in a gene-specific manner. Risk factors and outcomes in LQTS patients varied by genotype. Beta-blockers were effective in reducing cardiac events in LQTS patients.
[GW30-e0242]
Wenjia Guo, Fei She, Ping Zhang
Beijing Tsinghua Changgung Hospital
OBJECTIVES Currently the predictive evidence of heart rate (HR) in heart failure (HF) with atrial fibrillation (AF) is limited. We attempted to investigate the role of HR in prognosis of HF patients with AF by Holter recording.
METHODS A prospective cohort study was conducted with hospitalized HF subjects with AF from January 2015 to September 2017. Patients were stratified into paroxysmal AF and persistent AF. We followed the patients until December 2017. The all-cause mortality was investigated. Univariate and multivariate logistic regression analysis was performed to explore the relationship of HR with prognosis in HF with paroxysmal and persistent AF. Areas under the curve (AUCs) were calculated to compare the prognostic value of different HR indexes.
RESULTS 267 HF patients with AF were screened for final analysis. It was illustrated that total beats (adjusted odds ratio: 1.37, 95% CI: 1.08–1.73, P=0.009), average HR (adjusted odds ratio: 1.47, 95% CI: 1.04–2.08, P=0.031) and maximum HR (adjusted odds ratio: 1.22, 95% CI: 1.02–1.46, P=0.028) were independently associated with all-cause mortality in HF with paroxysmal AF but not with persistent AF patients. The AUC of maximum HR-based Cox model was superior to that of resting HR for mortality in HF with paroxysmal AF (0.83 vs. 0.65, P=0.029). The best cutoff value of maximum HR was 148 bpm (sensitivity: 82.4%; specificity: 85.5%).
CONCLUSIONS Compared to resting HR, total beats, average HR and maximum HR can be better predictors for all-cause mortality in HF with paroxysmal AF patients. Moreover, the prognostic value for all-cause mortality on the basis of maximum HR in those paroxysmal AF group was significantly better than that of resting HR. Holter recording would be useful for prognosis in HF with paroxysmal AF, which still need to be identified in large randomized studies.
[GW30-e0247]
Tao Wang, Wei Zhou, Xiaoshu Cheng
Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang of Jiangxi, China
OBJECTIVES Evidence regarding the relationship between serum gamma-glutamyltranspeptidase (GGT) and risk of dabigatran-related bleeding in patients with non-valvular atrial fibrillation was limited. Therefore, we aimed to assess the association between GGT and bleeding in non-valvular atrial fibrillation patients treated with dabigatran.
METHODS A prospective cohort study was conducted at multicenter in China from February 2015 to December 2017. Participants completed the follow-up at outpatient reviews 3 months. The exposure and outcome variable were the GGT at the baseline and minor bleeding, respectively. Univariate and multivariate Cox proportional hazards models were used to assess the association between GGT and risk of bleeding.
RESULTS Overall 80 subjects occurred minor bleeding. Multivariate Cox proportional hazards models analysis showed that per 1 U/L increase in GGT was associated with a 2% reduced risk of bleeding (P=0.027). A non-linear relationship was detected between GGT and bleeding by using smooth curve fitting. Further, threshold and saturation effect analysis showed that the inflection point of GGT was 32 U/L. The effect sizes and the confidence intervals of the left and right sides of inflection point were 0.95 (0.91–0.98) and 1.00 (0.98–1.02), respectively. The association between GGT and bleeding was consistent in the different subgroups.
CONCLUSIONS The relationship between GGT and bleeding was non-linear. GGT levels less than 32 U/L was related to reduce dabigatran-related bleeding.
[GW30-e0249]
Minghui Li, Xiaoshu Cheng
The Second Affiliated Hospital of Nanchang University
OBJECTIVES Uncertainty remains regarding the relationship between body mass index (BMI) and the risk of bleeding in nonvalvular atrial fibrillation (NVAF), especially in elderly patients. We aimed to investigate the relationship between BMI and the risk of bleeding in elderly patients with NVAF treated with dabigatran.
METHODS A prospective cohort study was conducted at multicenter in China from February 2015 to December 2017. Participants completed the follow-up at outpatient reviews 3 months. The exposure and outcome variable were the BMI at the baseline and 3 months bleeding, respectively.
RESULTS Finally a total of 499 elderly NVAF patients were recruited, 47 participants occurred minor bleeding, the incidence rate was 9.42% (47/499). On multivariate Cox proportional hazards models analysis, for every 1 kg/m2 increase in BMI, the risk of bleeding increased by 16% (95% confidence interval [CI]: 1.05, 1.27). When BMI was used as a categorical variable (<24 kg/m2; 24–28 kg/m2; ≥28 kg/m2), BMI ≥28 kg/m2 was associated with increased risk of bleeding (hazard ratio [HR] 2.96, 95% CI: 1.15, 7.65 vs. BMI <24 kg/m2). Moreover, the Cox proportional hazards regression with cubic spline functions and smooth curve fitting showed that the relationship between BMI and bleeding was linear. The subgroup analyses was consistent in the different subgroups.
CONCLUSIONS Elevated BMI at baseline was association with the incidence of bleeding in elderly NVAF patient treated with dabigatran.
[GW30-e0251]
Wei Zhou, Xiaoshu Cheng
The Second Affiliated Hospital of Nanchang University, Nanchang of Jiangxi, China
OBJECTIVES The association between peripheral leukocyte count and bleeding events in nonvalvular atrial fibrillation (NVAF) patients treated with -dabigatran remains unclear. We aimed to explore the association between leukocyte count and bleeding events after excluding other confounders.
METHODS A total of 851 NVAF patients treated with dabigatran (110 mg bid) were recruited from 12 centers in China from February 2015 to December 2017. Follow-up was completed by May 2018. The exposure and outcome variables were leukocyte count and bleeding. Multivariate Cox proportional hazards models were constructed to analyze independent associations, and a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (penalized spline method) was used to address nonlinearity between leukocyte count and bleeding. The inflection point was calculated using a recursive algorithm, and then a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed.
RESULTS Bleeding events occurred in 87 participants. For every 1*109/L increase in leukocyte count, the risk of bleeding increased by 11% (hazard ratio [HR] was 1.11, 95% confidence interval [CI]: 0.99–1.25). The inflection point of the leukocyte count was 6.75*109/L. For leukocyte counts <6.75*109/L, the HR and 95% CI were 0.88 and 0.69–1.13, respectively. For leukocyte counts ≥6.75*109/L, the HR and 95% CI were 1.28 and 1.09–1.51, respectively.
CONCLUSIONS A high leukocyte count at baseline was associated with an increased risk of bleeding in a nonlinear pattern. Leukocyte counts greater than 6.75*109/L in NVAF patients treated with dabigatran are associated with an increased risk of bleeding.
[GW30-e0254]
Yurong Xiong 1 , Lihua Hu 1 , Wei Zhou 2 , Minghui Li 1 , Tao Wang 1 , Juanling Zhu 1 , Huihui Bao 1,2 , Xiaoshu Cheng 1,2
1Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang of Jiangxi, China
2Center for Prevention and Treatment of Cardiovascular Diseases, the Second Affiliated Hospital of Nanchang University, Nanchang of Jiangxi, China
OBJECTIVES There is still a lack of effective biomarkers for predicting the risk of dabigatran-related bleeding events. Therefore, we aimed to investigate the relationship between changes of total bilirubin (TBIL) equals the difference of serum total bilirubin at 3-month follow-up from baseline serum total bilirubin and the risk of dabigatran-related bleeding events in patients with non-valvular atrial fibrillation (NVAF).
METHODS A total of 486 NVAF patients treated with dabigatran (110 mg bid) were recruited from 12 centers in China from February 2015 to December 2017. Everyone was followed 3 months. Cox proportional hazard regression analysis was used to evaluate the association between TBIL and risk of bleeding.
RESULTS The mean (SD) follow-up duration was 81.2 (20.2) days. 67 patients occurred bleeding events. Smooth curve fitting showed a U-shaped curve between TBIL and bleeding. We further calculated the inflection point of the TBIL was 6.63 μmol/L. The effect values and 95% confidence intervals (CI) on the left side and the right side of the inflection point were 0.90 (0.84, 0.96) and 1.35 (1.14, 1.60), respectively.
CONCLUSIONS Our findings showed a U-shaped relationship between TBIL and dabigatran-related bleeding. The inflection point of TBIL was 6.63 μmol/L.
[GW30-e0263]
Jing Yang, Ping Zhang
Beijing Tsinghua Changgung Hospital
OBJECTIVES Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal autosomal dominant heritable arrhythmia syndrome and it is characterised by a normal baseline electrocardiogram (ECG), the occurrence of bidirectional ventricular tachycardia (bVT) or polymorphic ventricular tachyarrhythmias (pVT) induced by adrenergic stress. However atrial arrhythmia is rarely described in previous studies.
METHODS A retrospective analysis of all 24-hour ambulatory ECG and exercise treadmill test data for 20 patients with CPVT diagonosed in the Department of Cardiology of Beijing Tsinghua Changgung Hospital and Peking University People’s Hospital between September 2006 and March 2019.
RESULTS During 24-hour ambulatory ECG test, atrial arrhythmia is common in CPVT patients. Thirteen cases (13/20, 65%) were present with frequent atrial premature contractions, in addtion two patients (2/20, 10%) had paroxysmal atrial tachycardia. Besides ventricular arrhythmias triggered during the treadmill exercise test, the presence of atrial Arrhythmias also may be associated with CPVT patients. Atrial arrhythmia existed in 15 patients (15/20, 75%), in which isolated premature atrial contractions (PACs) only were common (11/15, 73%), one case (1/15, 7%) showed only atrial tachycardia and thiree remaining child (3/15, 20%) was recorded exercise-induced PACs and atrial tachycardia. Referring to twelve cases with PACs, the atrial threshold heart rate was 88.5±25.1 beats/minute, while ventricular premature contractions (PVCs) threshold heart rate of twelve cases was 119.4±19.1 beats/minute, there was a statistically significant difference between them (P<0.05), namely atrial arrhythmias threshold heart rate was significantly lower than ventricular arrhythmias. Meanwhile, atrial arrhythmia was not always benign as ventricular fibrillation could be induced by atrial arrhythmia, and he had an operation of atrial tachycardia ablation.
CONCLUSIONS Atrial arrhythmia is common in CPVT patients and was not always benign.
[GW30-e0274]
Zidun Wang, Minglong Chen
The First Affiliated Hospital with Nanjing Medical University
OBJECTIVES Atrial fibrillation (AF) patients with a previous stroke are often at a high risk of recurrent stroke and bleeding. Anticoagulation therapy in such patients is a challenging dilemma. Currently, thoracoscopic left atrial appendage excision (LAAE) plus AF ablation is an interventional approach offered to some AF patients. We hypothesized that this approach may be suitable as a secondary stroke prevention strategy for these high-risk patients.
METHODS Between January 2013 and December 2016, a total of 44 patients (26 male; mean age 65.0±9.1 years) with nonvalvular AF and a previous stroke or systemic thromboembolic event were enrolled in our study. The patients underwentthoracoscopic LAAE plus AF ablationby experienced operators and were followed up for 2 years (at 1, 3, 6, 9, and 12 months postoperatively and every 6 months thereafter). Thromboembolic and major bleeding events were recorded. Cerebral computed tomography or magnetic resonance imaging and 7-day Holter monitoring were performed annually.
RESULTS Mean CHA2DS2-VASc and HAS-BLED scores were 4.2±1.2 and 3.3±0.7, respectively. All patients discontinued oral anticoagulation (OAC) therapy after the surgical intervention. One patient suffered a periprocedural transient ischemic attack, and another was diagnosed with a new ischemic stroke at 491 days after surgery. The annual rate of total thromboembolism was 2.05%. No deaths or major bleeding events were observed postoperatively. The rate of successful AF ablation with no AF recurrence is 76.3%.
CONCLUSIONS Trans-thoracoscopic LAAE plus AF ablation may be a promising approach for this high-risk population. Thromboembolism prevention in this secondary prevention cohort was low, even without OAC treatment.
[GW30-e0276]
Sheng Rong Deng, Zhiyuan Song
Department of Cardiovascular diseases, the First Affiliated Hospital of the Army Military Medical University
OBJECTIVES To compare the efficacy and safety of radiofrequency catheter ablation (RFCA) guided by the 3-dimensional electro-anatomic mapping system (Carto3 electro-anatomic mapping) with fluoroscopy or nonfluoroscopy on ventricular outflow tract idiopathic ventricular arrythmias (VOT-IVAs).
METHODS From January 2016 to April 2017, 103 cases of premature ventricular contractions (PVCs) and ventricular tachycardias (VTs) from ventricular outflow tract were treated with radiofrequency catheter ablation under the guidance of Carto3 in the Department of Cardiology, First Affiliated Hospital of the Army Military Medical University: 53 cases underwent radiofrequency ablation under conventional Carto3 mapping (with fluoroscopy group), and 50 cases underwent radiofrequency ablation without radiography under Carto3 mapping (with nonfluoroscopy group). The anatomical construction of the target area, mapping time, ablation time, X-ray exposure time, total procedure time, and complication rate were compared between the two groups; observation and follow-up efficacy.
RESULTS The fluoroscopy group was shorter than the nonfluoroscopy group in the time of anatomical construction of the target area and mapping, ablation time, fluoroscopic time and the total procedure time (P<0.05). The difference was statistically significant. The immediate success rates were both 100% in two groups, the success rates of 3 days after RFCA were similar in both groups, 98.0% (49/50) in the fluoroscopy group and 96.2% (51/53) in the nonfluoroscopy group (P=0.618), the difference between two groups was not statistically significant; At the follow-up of 1 month and 3 months after RFCA, there were no recurrence cases in both groups, and the success rates were both 100%. There were no serious complications in the two groups during and after operation.
CONCLUSIONS The radiofrequency catheter ablation on ventricular outflow tract idiopathic ventricular arrythmias guided by the 3-dimensional electro-anatomic mapping system achieved significant success rates in both the nonfluoroscopy group and the fluoroscopy group. Both methods are safe and effective. The radiofrequency catheter ablation under the guidance of Carto3 without X-ray is safe and effective in the treatment of outflow tract idiopathic ventricular arrhythmia, and it can be clinically applied in cardiac centers with extensive experience in the operation of radiofrequency ablation catheters.
[GW30-e0383]
Suhua Li 1 , Xixiang Tang 2 , Xing Liu 1 , Junlin Zhong 3 , Zhenda Zheng 1 , Jieming Zhu 1 , Jinlai Liu 1
1Department of Cardiology, the Third Affiliated Hospital, Sun Yat-sen University
2Advanced Medical Center, the Third Affiliated Hospital, Sun Yat-sen University
3Department of Ultrasonography, the Third Affiliated Hospital, Sun Yat-sen University
OBJECTIVES To investigate the relationship between serum Chemerin levels and left atrial electrical and anatomical remodeling in patients with atrial fibrillation (AF).
METHODS A total of 322 AF patients (109 paroxysmal and 213 persistent) admitted to the Department of Cardiology from January 2016 to May 2019 were enrolled, including 208 males and 114 females. The average age was 66.8±10.2 years. Another 100 gender- and age-matched patients with sinus rhythm were selected as the control group. Serum levels of Chemerin were measured by ELISA and compared between two groups. In addition, AF patients would further receive 12-lead ECG (Patients with persistent AF received ECG after -cardioversion or ablation) and echocardiography to determine the P wave dispersion, left atrial diameter, and left atrial volume. Multivariate linear regression was used to analyze the correlation between serum Chemerin levels and the above indicators in AF patients.
RESULTS Serum Chemerin levels were significantly elevated in AF patients when compared to patients with sinus rhythm (20.68±4.22 pg/mL vs. 11.24±3.75 pg/mL, P<0.001). Furthermore, serum Chemerin levels were higher in patients with persistent AF when compared to patients with paroxysmal AF (22.47±5.02 pg/mL vs. 16.48±3.97 ng/nL, P<0.001). For AF patients, after adjusting for age, gender, AF duration, and medication, multivariate linear regression analysis showed that serum Chemerin levels were positively associated with the P wave dispersion [β(SE)=3.808 (0.564), P<0.001], maximum P-wave duration [β(SE)=4.305 (0.615), P<0.001], left atrial diameter [β(SE)=1.764 (0.305), P<0.001], left atrial maximum volume [β(SE)=1.424 (0.244), P<0.001], and left atrial minimum volume[β(SE)=1.158 (0.172), P<0.001].
CONCLUSIONS Serum Chemerin levels are significantly elevated in AF patients, and positively correlated with the left atrial electrical and anatomical remodeling.
[GW30-e0450]
Xiaocheng Cheng, Dongying Zhang
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
OBJECTIVES The sex-related differences in the clinical outcomes of rhythm and safety after catheter ablation remain unclear. The purpose of this study was to compare the clinical outcomes of catheter ablation for atrial fibrillation (AF) in women and men.
METHODS The Medline and EMBASE databases were searched for published articles up to December 2018. Studies that met our predefined inclusion criteria were included. The primary endpoints were freedom from AF/atrial tachycardia (AT) recurrence, stroke/transient ischemic attack (TIA) and all-cause mortality. Random-effects modeling was used to calculate odds ratio (OR) and 95% confidence interval (CI) for each endpoint.
RESULTS After literature search and detailed assessment, 19 observational studies (151,370 patients; 34% women) were identified. Our analyses showed that the rate of freedom from AF/AT recurrence was lower in women than men at the 2.4-year follow-up (OR: 0.75; 95% CI 0.69–0.81; P<0.0001). Moreover, women had an increased risk of stroke/TIA (OR: 1.42; 95% CI 1.21–1.67; P<0.0001) and all-cause mortality (OR: 1.53; 95% CI 1.02–2.28; P=0.04). Nevertheless, for the endpoint of all-cause mortality, there was no significant difference between the two genders in the subgroup of prospective studies (OR: 1.19; 95% CI 0.69–2.05; P=0.53). Additionally, women were more likely to experience major complications compared with men (pericardial effusion/tamponade, major bleeding requiring transfusion and pacemaker implantation).
CONCLUSIONS Women who underwent catheter ablation of AF might experience lower efficacy and a higher risk of stroke/TIA and major complications than men. The reasons for these sex-related differences need to be further studied.
[GW30-e0466]
Hongjun You, Fuqiang Liu
People’s Hospital of Shaanxi Province
OBJECTIVES To perform bioinformatics analysis on the genetic chip data of patients with atrial fibrillation (AF), in order to investigate the expression profiles of circular RNAs (circRNAs) and proposed circRNA–microRNA (miRNA) regulatory network in atrial fibrillation (AF).
METHODS Gene chip data in GEO database was used to screen out AF information chip and differentially expressed circRNAs in AF were selected. Several differentially expressed circRNAs were chosed for MREs. Co-expression networks of circRNA–miRNA were constructed based on the correlation analyses between the differentially expressed RNAs. We used arraystar’s home-made target prediction software based on TargetScan, miRDB and miRTarBase to predict mRNA, to further demonstrate microRNA/mRNA interaction. The Gene Ontology (GO) enrichment analysis of mRNAs was performed to predict the potential functions of the differentially expressed genes and for functional annotation of mRNAs. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to explore the signal pathways invovled significantly.
RESULTS Compared with healthy controls, there were 1317 circRNAs differentially expressed in AF through a combination of statistical significance. Among them, 823 were up-regulated, and 494 were down-regulated. We constructed correlated expression networks between circRNAs and miRNAs. Furthermore, hsa_circ_0058792, hsa_circ_0045114, and hsa_circ_0058794 interacted with 3 miRNAs, miR-6077, miRNA-7-5p and miRNA-6079 simultaneously. The GO and KEGG pathway enrichment analysis of target genes in hsa_circ_0006867-miRNA-mRNA axis were executed to determine the principal functions and to investigate the potential signal pathway involved in AF. We found that the most significantly enriched GO terms were ubiquitin-protein transferase activity (GO:0004842) and ubiquitin-like protein transferase activity (GO:0019787). And the significantly enriched KEGG pathways were TGF-beta signaling pathway (hsa04350), MAPK signaling pathway (hsa04010), ubiquitin mediated proteolysis signaling pathway (hsa04120), signaling pathways regulating pluripotency of stem cells (hsa04550), and longevity regulating pathway (hsa04211) and so on.
CONCLUSIONS Our findings provided a novel perspective on circRNAs involved in AF and establish the foundation for future research of the potential roles of circRNAs in AF. Otherwise, we deliveried a novel strategy for research the potential ralationship between different RNAs in circRNA-miRNA-mRNA axis.
[GW30-e0478]
Nixiao Zhang 1 , Wei Hua 1 , Xiaoping Li 2 , Yiran Hu 1 , Hongxia Niu 1 , Chi Cai 1 , Min Gu 1 , Xuhua Chen 1 , Shu Zhang 1 , Wei Hua 1
1Cardiac Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College
2Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital
OBJECTIVES To examine the association between left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD), and long-term risk of all-cause mortality in adults with hypertrophic cardiomyopathy (HCM) following pacemaker implantation over 5-year follow-up.
METHODS A total of 103 adult patients with HCM admitted to our Arrhythmia Center for symptomatic bradycardia and received pacemaker implantation from November 2002 to June 2013 were enrolled. During follow-up, 9 were excluded for generator upgrading of an implantable cardiac defibrillator (ICD). We retrospectively evaluated the clinical characteristics in 94 patients (57.0±15.9 years, mean follow-up 7.3±3.4 years).
RESULTS The mean LAD was 41.7±7.8 mm and the mean LVEDD was 45.7±6.6 mm. Overall, 25 died during follow-up, of which 68% were cardiovascular death. Based on the receiver operating characteristic curve, the cut-off value of LAD=43.5 mm was identified to predict all-cause mortality, with sensitivity and specificity of 0.722 and 0.732, respectively. The cut-off value of LVEDD=42.5 mm was identified to predict all-cause mortality, with sensitivity and specificity of 0.944 and 0.482, respectively. In the Kaplan-Meier survival, LAD≥43.5 mm and LVEDD≥42.5 mm were both associated with all-cause mortality (log-rank test P<0.05). Cox regression analysis indicated that LAD≥43.5 mm (HR 3.254; 95%CI=1.043–10.158, P=0.042) and LAD as a continuous variable (HR 1.072; 95%CI=1.009–1.139, P=0.025) were significantly independent predictors of all-cause mortality, while LVEDD≥42.5 mm was not significantly associated with all-cause mortality in the multivariate model but in the univariate model.
CONCLUSIONS In HCM patients with pacemaker implantation, LAD was an independent predictor for all-cause mortality, especially with a cut-off value of 43.5 mm.
[GW30-e0501]
Gang Yang 1 , Cheng Cai 1 , Benqi Wang 2 , Fengxiang Zhang 1 , Weizhu Ju 1 , Hongwu Chen 1 , Mingfang Li 1 , Kai Gu 1 , Minglong Chen 1
1Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
2Boston Scientific Ltd.
OBJECTIVES Linear ablation of the cavotricuspid isthmus (CTI) has been recognized as a highly successful and safe technique in the treatment of typical atrial flutter. However, it could be extremely difficult in some patients. The possible explanation would be complex and individual anatomy of the CTI. And the anatomic property could be translated into different activation patterns through the CTI. The purpose of this study was to test the hypothesis that CTI conduction is not in step and preferential conduction could be revealed by ultra high-resolution mapping.
METHODS A total of 28 patients with typical flutter were included between September 2016 to August 2018 (average age: 52 ±16 years, right atrium: 39±5 mm, left ventricular ejection fraction: 60±9%). High-resolution 3D mapping (Rhythmia mapping system, Boston Scientific, Natick, Massachusetts) was performed. Maps were analyzed retrospectively to characterize wave front propagation patterns in CTI region. The length of CTI, the width of preferential conduction area and their ratio were measured. The relationships between the ratio and termination or cycle length prolongation were also evaluated.
RESULTS 16 (57%) patients underwent previous cardiac surgery. 1 (3%) patient has received previous ablation in CTI. There are five different activation patterns through CTI (Figure 1). Type I in 4 patients (14%) was homogenous conduction without preferential wave front though CTI. Type II in 15 patients (53%) was with preferential wave font close to tricuspid annulus. Type III in 1 patients (3%) was with preferential wave front in the middle of CTI. Type IV in 7 patients (25%) was with preferential wave front close to inferior vena cava (IVC). Type V in 1 patients (3%) was with double preferential wave fronts. We found that the termination sites were exactly located at preferential wavefront in 18 of 28 patients (64%). The width of preferential wave front in termination group was shorter than those in non-termination group (16.6±1.0 mm vs. 23.3±3.4 mm, P=0.025). The cycle length (CL) prolongation (20 ms longer than baseline) before termination was noted in 16 of 28 patients (57%). However the width of preferential wave front in CL prolongation group was similar with those in non-prolongation group (18.4±1.5 mm vs. 19.8±3.0 mm, P=0.655). the relationship between the ablation reaction and the ratio (the width of preferential wave front and CTI) were showed in table 1.
CONCLUSIONS Activation conduction through CTI is heterogeneous. The preferential conduction was common and the majority was close to tricuspid annulus. If the preferential conduction is more apparent, it is more likely to terminate atrial flutter during ablation exactly at the preferential wave front site.
[GW30-e0539]
Hongyuan Bai 1 , Haiquan Li 1 , Limin Chai 2 , Songlin Zhang 3 , Yajuan Ni 1 , Hongtao Wang 1 , Qiangsun Zheng 1
1Cardiovascular Department, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China
2Respiratory Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China
3Cardiovascular Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China
OBJECTIVES Arrhythmia, is a common complication in patients with ischemic/non-ischemic heart disease and has been identified as an independent risk factor for increased cardiovascular events. Previous studies have suggested that coenzyme Q10 can reduce the incidence of arrhythmia in heart disease patients. In this study, we collected the existing evidence to conduct a comprehensive analysis on whether coenzyme Q10 can reduce arrhythmia of heart disease patients.
METHODS We performed a meta-analysis, searching EMBASE, PubMed, Web of Science and Cochrane Library from 1990 to 2018, for randomized controlled trials (RCTs) on coenzyme Q10 in patients with heart disease. Primary outcome was arrhythmia.
RESULTS We identified 6 RCTs enrolling 750 patients who fulfilled our inclusion criteria. When compared with conventional treatment alone, conventional treatment plus coenzyme Q10 was associated with significant decrease in arrhythmia for all enrolled patients (risk ratio [RR], 0.32; 95% confidence intervals [CI], 0.22–0.48). Furthermore, compared with conventional treatment alone, conventional treatment plus coenzyme Q10 could also reduce the incidence of arrhythmia in ischemic heart disease subgroup (RR, 0.31; 95% CI, 0.20–0.49), heart failure subgroup (RR, 0.36; 95% CI, 0.15–0.88), and coronary artery bypass grafting (CABG) subgroup (RR, 0.29; 95% CI, 0.17–0.50). Adverse events observed in 6 RCTs were not severe and resolved without special treatment.
CONCLUSIONS This meta-analysis indicated that coenzyme Q10 can reduce arrhythmia in patients with heart disease. However, further studies with more subjects, long-term follow-up, and evaluation of systemic adverse events are still required to verify the efficacy and safety of coenzyme Q10 on arrhythmia in heart disease patients.
[GW30-e0554]
Rongjie Lin, Ziliang Song, Xu Liu
Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
OBJECTIVES We have reported female sex was a risk factor of AF recurrence after ablation in aged patients. It was unknown whether this result was applicable to young patients.
METHODS From November 2012 to November 2017, 185 young AF patients (mean age: 39.4±5.1; 31 females, 16.8%; 87 paroxysmal AF, 47%) were included at our center and underwent catheter ablation.
RESULTS After a median follow-up of 41 months (IQL: 25–56 months) and a mean of 1.2±0.5 (median 1, range 1–4) ablation procedures, 142 (76.8%) patients were in stable SR. A second procedure was performed for 36 patients, a third for 8 patients and a forth for 1 patients. Progression towards persistent AF was observed in 4 patients (4.6%). Survival analysis revealed that the ATa-free survival rate in women was significantly lower than that in men after initial and last ablation (P=0.006 and P=0.002). In multivariate analysis, LAD [HR 1.058 (95% CI 1.008–1.110) P=0.022], RA enlargement [HR 1.911 (95% CI 1.066–3.428) P=0.030], structural heart disease (SHD) [HR 2.022 (95% CI 1.147–3.565) P=0.015] and female sex [HR 2.303 (95% CI 1.299–4.084) P=0.004] independently predicted AF recurrence.
CONCLUSIONS Young AF patients can achieve a satisfactory long-term outcome after catheter ablation. Female sex, LAD, RA enlargement and SHD are predictors of atrial fibrillation recurrence after catheter ablation.
[GW30-e0566]
Nan Wu, Gang Yang, Fengming Wu, Minglong Chen
The First Affiliated Hospital of Nanjing Medical University
OBJECTIVES Cardiac tamponade (CT) is the most common potential life threatening complication associated with radio-frequency catheter ablation (RFCA) for atrial fibrillation (AF). Based on current clinical practice, the decision of conservative therapy or surgical intervention remains unclear. The aim of this study is to retrospectively analyze the occurrence and management of CT during RFCA for AF in our experienced medical center.
METHODS All patients with a cardiac tamponade perforation who have undergone radio-frequency catheter ablation for atrial fibrillation in our center were included.
RESULTS Of 2890 procedures performed from 2013 to 2018, 28 (0.97%) patients occurred cardiac tamponade. Among them, the left atrium dimension was 35.5±3.7 mm on average. 22 (78.6%) patients were noted during ablation procedure, 6 (21.4%) patients were noted within 1 hour after the procedure. 25 (89.3%) patients were required to perform pericardiocentesis immediately. Ten patients underwent emergency surgical repairs due to the hemodynamic unstable state among whom the average of drainage was 2250 mL (627.5–3050). The perforation sites could be identified during the surgical repairs: 5 at right superior pulmonary vein, 2 at coronary sinus, 1 at left atrium appendage, 1 at left superior pulmonary vein and 1 at tricuspid isthmus, respectively. During the surgical procedure, Cox maze procedure (4/10) and left atrial appendage excision (2/10) were performed accordingly. The drainage volume was strongly associated with decision of surgical repair (OR: 1.003, P=0.033), the cutoff value was 400 mL (AUC: 0.919, sensitivity: 100%, specificity: 72.22%, P<0.001). No patient died of CT in our cohort.
CONCLUSIONS The incidence of CT (0.97%) was lower than 1% in our center. The annual incidence rate was 0.19%. Latent CT occured in 6 (21.4%) patients. The dimension of left atrium was small (35 mm) in patients with CT. The most common perforation site was RSPV. If the drainage was more than 400 mL during the procedure, emergency surgical repair should be recommended.
[GW30-e0755]
Mu Qin, Weifeng Jiang, Rongjie Lin, Shaohui wu, Kai Xu, Xu Liu
Shanghai Chest Hospital, Shanghai Jiaotong University
OBJECTIVES To investigate the role of driver mechanism at different stages of atrial fibrillation (AF) progression and to evaluate the effect of electrogram dispersion guided driver mapping and ablation in AF.
METHODS Two hundred and fifty-six consecutive AF patients who had undergone PVI plus driver ablation or conventional ablation were divided into 3 groups: paroxysmal AF (PAF, Group A, n=51), persistent AF (PsAF) (Group B, n=38); and long-standing persistent AF (LS-PsAF) (Group C, n=39). PVI was performed with guidance of ablation index. The electrogram dispersion was analyzed for driver mapping (Figure 1).
RESULTS The most prominent driver regions were at roof (28.0%), posterior wall (17.6%) and bottom (21.3%). With AF progression (groups A to C), the complexity of extra-PV drivers including distribution, mean number and area of dispersion region increased significantly (P<0.001) (Figure 2). Procedural AF termination rate showed significant differences between driver and conventional ablation (76.6% vs. 28.1%, P<0.001). With AF progression, the termination rate gradually decreased from group A to C, and the role of PVI in AF -termination was also gradually weakened from group A to C (39.6%, 7.4% and 4.3%, P<0.001) in patients with driver ablation. At the end of the follow-up, the rate of SR maintenance was significantly higher in patients with driver ablation than those with conventional ablation (89.1% vs. 70.3%, P<0.001) (Figure 3).
CONCLUSIONS The formation of extra-PV drivers provides an important mechanism for AF maintenance and their complexity of drivers increase with AF progression. Electrogram dispersion guided driver ablation appears to be an efficient adjunctive approach to PVI for AF treatment.
[GW30-e0766]
Weijian Huang 1,2 , Songjie Wang 1,2 , Weijian Huang 1,2
1Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
2The Key Lab of Cardiovascular Disease of Wenzhou, Wenzhou, China
OBJECTIVES Persistent atrial fibrillation (AF) may lead to higher probability of inappropriate shocks in heart failure (HF) patients with implantable cardioverter defibrillator (ICD) implantation. The aim of the study was to evaluate the impact of His-Purkinje conduction system pacing (HPSP) combined with atrioventricular node (AVN) ablation in preventing inappropriate shock therapy and improving heart function in these patients.
METHODS Ninety-six consecutive patients with persistent AF and HF who had indications for ICD implantation were enrolled from Jan, 2010 to Mar, 2018. With patients consent, HPSP with dual chamber ICD and AVN ablation was attempted in 62 patients, while the remaining patients underwent single chamber ICD implantation only. Left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), New York Heart Association (NYHA) heart failure classification, shock therapies and use of drugs were assessed during follow-up.
RESULTS Thirty-six patients received only ICD therapy, 1 of them failed AVN ablation (Group 1). AVN ablation combined with HPSP was successfully achieved in 62 patients (Group 2), 4 of who had prior single chamber ICD implantation (Figure 1). During follow-up, patients in group 2 had lower incidence of inappropriate shock (P<0.01) and adverse event (P=0.011). Meanwhile, improvements in LVEF (37.89±14.41% to 43.61±14.36% vs. 35.15±11.66% to 48.79±14.39%, P=0.01) and LVESV (138.27±68.37 mL to 127.37±82.86 mL vs. 126.03±67.35 mL to 82.11±58.01 mL, P<0.01) were significant in group 2 (Figure 2). NYHA class improved from a baseline 2.57±0.68 to 1.73±0.74 in group 1, from a baseline 2.73±0.59 to 1.42±0.53 in group 2.
CONCLUSIONS HPSP combined with AVN ablation is feasible and safe with high success rate in persistent AF patients with HF and ICD implantation. It can significantly reduce the incidence of inappropriate shocks and improve left ventricular function.
[GW30-e0767]
Weijian Huang, Fangyi Xiao, Weijian Huang
Department of Cardiology, The Key Lab of Cardiovascular Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
OBJECTIVES Left atrial appendage (LAA) closure is an attractive alternative for stroke prevention in patients with atrial fibrillation (AF). The risk of stroke in patients with AF after LAA closure is still lacking of thorough studies. Our objective was to evaluate the potential risk factors of stroke in patients with AF after LAA closure.
METHODS Non-valvular AF patients at high risk of stroke were enrolled in the study and underwent LAA closure. Follow-up was performed at 45 days, 6 months, and 12 months. Univariate Cox regression analysis was computed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for exploring the potential risks for incidence of stoke after LAA closure. Multivariable Cox proportional hazards regression analysis was performed for exploring independent clinical predictors for stroke.
RESULTS The multivariate Cox proportional hazards regression analyses showed that the peri-device flow (HR=4.584, 95% CI: 1.65–12.739, P=0.004) and continue coagulation (HR=0.272, 95% CI: 0.089–0.829, P=0.022) was association with stroke in patients with AF after LAA closure. The stroke rate for patients in the leak group was significantly higher, compared with the no-leak group (12.3 events/100 patient-years versus 1.9 events/100 patient-years, P<0.001). Furthermore, patients with persistent peri-device flow may have an increased rate of strokes (HR=5.041 (95%CI: 1.668–15.230)).
CONCLUSIONS Peri-device flow was associated with the rate of strokes at short-term follow-up.
[GW30-e0768]
Weijian Huang, FangYi Xiao, Weijian Huang
Department of Cardiology, The Key Lab of Cardiovascular Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
OBJECTIVES Catheter ablation is an effective therapy for symptomatic, drug-refractory atrial fibrillation (AF) patients. Left atrial appendage occlusion (LAAO) was an attractive alternative for stroke prevention. The concomitant catheter ablation and LAAO may be a feasible way to relieve symptom, reduce stroke and abolish anticoagulation simultaneously. The aim was to evaluate the feasibility and efficacy of the novel one-stop procedure.
METHODS Patients with AF at high risk of thromboembolic events and bleeding who underwent one-stop combined ablation and LAAO for drug-refractory and high risk of thromboembolic events were included. Follow-up was performed at 45-day, 6- and 12-month. Adverse events were recorded in the hospital’s on-line information systems. Transoesophageal echocardiography was utilized to detect device-related thrombus and evaluate the device position and width of residual flow. Holter monitoring was performed to screening the recurrence of AF. Baseline and 1-year brain computed tomography were used to detect symptomatic and silent stroke.
RESULTS Two hundred and thirty-eight patients underwent concomitant catheter ablation and LAAO and were included (mean age 69.4±7.5 years; 145 men). The mean CHA 2 DS 2 -VASc score was 3.9±1.6. Cryoballoon ablation (CBCA) was used in 99 patients and radiofrequency ablation (RFCA) was used in 139 patients. A mean follow-up of 26.2±10.1 months showed 54 documented atrial arrhythmias recurrence of AF. Two patients died at 10-day and 6-month follow-up respectively. Three patients have major bleeding and 5 patients has stroke (Table). Device thrombus occurred in 3 patients.
CONCLUSIONS The one-stop combined LAAO and catheter ablation may be a feasible and efficacious therapeutic option to relieve symptom and reduce stroke simultaneously in patients with AF at high risk of thromboembolic events and bleeding.
[GW30-e0943]
Yuchen Liu, Jiayu Shi, Chu Chen, Qi Lu
Affiliated Hospital of Nantong University
OBJECTIVES Radiofrequency catheter ablation is the most common treatment for atrial fibrillation (AF), but it has been controversial due to its high recurrence rate. Left atrial volume (LAV), as a commonly used indicator for predicting postoperative recurrence of AF, presents poor specificity and sensitivity, and is vulnerable to the subjective judgment of the operator and the error of the machine. Therefore, at present, exploring biomarkers that can assist in predicting postoperative recurrence of AF is urgent, so as to help clinicians to preoperatively evaluate patients with paroxysmal AF effectively, and then choose appropriate treatment for the patients.
METHODS The blood samples of untreated patients with paroxysmal AF were collected and the general data (age, gender, electrocardiogram, color Doppler echocardiography, therapeutic drugs, etc.) were analyzed. The blood samples were centrifuged. After serum was separated, isolation of IgG, glycan release and purification, glycan fluorescence labeling and HILIC-UPLC analysis of labeled glycan were carried out. The data were automatically processed by traditional integration algorithm and manually corrected. The degree of galactosylation of IgG was calculated using the formula G4/((GP8b+GP9)+2·GP14). Moreover, it was planed to record the patients’ electrocardiogram at 3, 6, 12 and 18 months after surgery and at the occurrence of symptoms.
RESULTS In the study of 218 patients with elevated left atrial volume index levels (>93 mL/m2), we found that the quantitative analysis of galactosylation in the relapsed group was significantly lower than in the non-recurrent group (0.72 vs. 1.68; P<0.05). ROC analysis showed that galactosylation increased the specificity of atrial fibrillations’ postoperative recurrence from 69.1% (predicted only by left atrial volume index) to 82.7%. However, in the current test, the left atrial volume index combined with quantitative analysis of IgG galactosylation can maintain the sensitivity at 90%.
CONCLUSIONS Left atrial volume combined with quantitatively altered IgG galactosylation may provide a more comprehensive and reliable method for predicting recurrence after paroxysmal atrial fibrillation.
[GW30-e0944]
Jinzhu Hu 1 , Jianhua Yu 1 , Qi Chen 1 , Jianxin Hu 1 , Qianghui Huang 1 , Zirong Xia 1 , Zhen Xia 1 , Qinmei Xiong 1 , Bo Zhu 1 , Yanqing Wu 1 , Xiaoshu Cheng 1 , Ali J Marian 2 , Juxiang Li 1 , Kui Hong 1
1Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University
2Center for Cardiovascular Genetics, The University of Texas Health Science Center
OBJECTIVES Patients with Wolff-Parkinson-White (WPW) syndrome and atrial fibrillation (pre-excited AF), are at an increased risk of spontaneous ventricular fibrillation. The objective was to assess efficacy of nifekalant in pre-excited AF.
METHODS The study populations were comprised of patients with sustained pre-excited AF (n=51), paroxysmal supraventricular tachycardia (PSVT, n=201), and persistent AF without accessory pathway (AP) (n=87). Effects of intravenous infusion of nifekalant was assessed on electrophysiologic and clinical parameters.
RESULTS Nifekalant prolonged the shortest pre-excited R-R, average pre-excited R-R, and the average R-R intervals from 290±35 to 333±44 ms, 353±49 to 443±64 ms, and 356±53 to 467±75 ms, respectively, in patients with pre-excited AF (all P-values<0.001). Nifekalant also decreased the percent of -pre-excited QRS complexes from 100 (100–100%) to 79% (70–91%) [median (percentiles 25–75)], heart rate from 172±25 to 132±24 beat/min, and increased systolic blood pressure from 84±9 to 99±12 mmHg (all P-values<0.001). Nifekalant infusion terminated AF in 33 of 51 patients (65%), in an average of 11±5 min from the start of infusion. Similar effects were also observed in a subgroup of 12 patients with pre-excited AF and impaired left ventricular function.
In patients with PSVT, nifekalant prolonged effective refractory period (ERP) and the block cycle length (BCL) of antegrade accessory pathway (AP) from 272±52 to 309±59 ms, and from 323±51 to 381±63 ms, respectively (n=78, P<0.001 for both). It also prolonged atrial ERP from 202±25 to 235±33 ms (n=168, P<0.001). Nifekalant had no effect on ERP of antegrade atrioventricular node (AVN) (315±69–321±77 ms, n=102, P=0.06). Finally, in patients with persistent AF without AP, nifekalant did not significantly decrease the ventricular rate of AF. One patient with low serum potassium and sinus bradycardia developed Torsades de pointes (TdP). No other adverse effects were observed.
CONCLUSIONS Nifekalant prolongs the ERP of antegrade AP and atrium, without blocking the antegrade conduction through the AVN, leading to slowing and/or termination of pre-excited AF. Thus, nifekalant might be an effective and a relatively safe drug in patients with pre-excited AF.
[GW30-e0963]
Liangjie Xu, Yan jinchuan
Affiliated Hospital of Jiangsu University
OBJECTIVES Increasing evidence indicates that inflammation and atrial fibrosis greatly contribute to atrial fibrillation recurrence (AFR) after catheter ablation (CA). Interleukin-17A (IL-17A) is a newly discovered pro--inflammatory cytokine. In the present study, we assessed the prognostic value of IL-17A in patients with AFR after CA.
METHODS A total of 126 patients who underwent first-time CA for paroxysmal AF were enrolled in the present study over a period of 12 months. Levels of IL-17A, N-terminal pro-type natriuretic peptide (NT-proBNP), matrix metallopeptidase 9 (MMP-9), procollagen type I, procollagen type III and the left atrial emptying fraction (LAEF) were determined at baseline. AFR used as the study endpoint.
RESULTS The level of serum IL-17A was increased in all 126 patients before CA, while it was markedly decreased in 71 patients with no recurrence (NR) at 3-month follow-up. The increased IL-17A level was significantly correlated with the levels of NT-proBNP, MMP-9, procollagen type III and LAEF. Receiver operating characteristic (ROC) revealed that the area under the curve of IL-17A for predicting of AFR was 0.959, (95% CI, 0.911–0.982; P<0.0001).
CONCLUSIONS IL-17A might be a novel predictor of AFR after CA. The pro-fibrotic effect of IL-17A might promote adverse cardiac remodeling and progression to AF.
[GW30-e0967]
Jinrui Guo, Jinqiu Huang, Ke Liu, Yulong Guo, Tao Guo, Guo Jinrui
Fuwai Yunnan Cardiovascular Disease Hospital, Kunming, Yunnan China
OBJECTIVES Impact of CF technology on ablation of atrial fibrillation (AF) is controversial. We sought to perform a meta-analysis of data from eligible studies to evaluate the true clinical impact of CF.
METHODS We systematically searched the literature to identify randomized controlled trials (RCTs) examining the efficacy and safety of CF technology for ablation of AF. The relative risk (RR) of AF recurrence/atrial tachycardia at follow-up was assessed as the primary outcome using a fix-effects meta-analysis.
RESULTS There were 861 subjects in the identified 8 studies. At a median follow-up of 12 months, the RR of recurrent AF/atrial tachycardia was not significantly different with CF guided ablation vs. Non -CF guided ablation (1.02, 95% confidence interval [CI] 0.94–1.12, P=0.61). Procedure time (weighted mean differences [WMD] –20.20, 95% CI –39.80 to –0.60, P=0.04) were significantly reduced in CF-guided catheter ablation. CF was significantly greater in the CF group than in the Non-CF group (WMD 3.23, 95% CI 0.84–5.63, P=0.008). Procedure-related complications (RR 1.01, 95% CI 0.53–1.94, P=0.98), cardiac tamponade/pericardial effusion (RR 1.34, 95% CI 0.43–4.21, P=0.61) and incidence of acute reconnection of pulmonary vein (RR 1.69, 95% CI 0.60–4.76, P=0.32) did not differ significantly.
CONCLUSIONS This meta-analysis of RCTs demonstrates similar long-term outcome, acute procedural efficacy and complications when comparing CF guided ablation to Non -CF guided ablation for AF. Procedure length is shorted when using CF technology.
[GW30-e0993]
Long Peng, Jiarui Wang, Jieming Zhu
The Third Affiliated Hospital of Sun Yat Sen University
OBJECTIVES To analyze whether conventional electrocardiogram (ECG), Ambulatory electrocardiogram (Holter) and multi lead electrocardiogram (MLE) have different diagnostic value for differentiatingventricular outflow tract tachycardia origin.
METHODS Seventy one patients with ventricular outflow tract tachycardiawho underwent intracardiac electrophysiologicalexamination and radiofrequency ablation in our department of Cardiology from January 2017 to December 2018 were enrolled. ECG, Holter and MLE were collected before operation, and the characteristics of QRS waves in each lead were analyzed. Four different methods, including V2 R wave amplitude index and time index, V2 transition ratio, chest lead transition zone indexand SV2/RV3, were used to analyze and compare the differences in the accuracy of three ECG mapping for location of left and right ventricular outflow tract.
RESULTS The main wave directions of the early QRS waves in the lead chambers of I, V2, V3 and V4 were statistically different among the three electrocardiograms. There were no statistical difference in the diagnostic accuracy of ECG, Holter and MLE in the right ventricular outflow tract, according to V2 R wave amplitude index and time limit index, and the V2 transition index. When the chest lead transitional zone index and SV2/RV3 were used to distinguishing left from right ventricular outflow tract tachycardia origin, the diagnostic accuracy of ECG and MLE are better than Holter.
CONCLUSIONS ECG and MLE are superior to Holter in judging left or right ventricular outflow tract tachycardia origin.
[GW30-e1001]
Weijian Huang 1,2 , Xueying Chen 3 , Weijian Huang 1,2
1Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University
2The Key Lab of Cardiovascular Disease of Wenzhou, Wenzhou, China
3Department of Cardiology, Zhongshan Hospital of Fudan University, Shanghai Institute of Cardiovascular Diseases
OBJECTIVES Recent studies demonstrated that left bundle branch pacing (LBBP) to capture proximal left conduction system (LCS) can optimize physiological LV synchronous activation with a low and stable threshold. However, how to confirm LCS capture and its characteristics are not well established. We aimed to identify LCS capture using anterograde and/or retrograde potentials.
METHODS The intraventricular septal pacing lead was fixed in the left ventricular sub-endocardium around the region of the proximal left conduction system. An additional His lead or multipolar electrodes catheter located at left ventricular septum were used to record anterograde and/or retrograde potentials. The relationship between recorded potential and LCS capture confirmed by our previous criteria was assessed. The characteristics of anterograde and/or retrograde potentials were established in LCS capture during selective and non-selective pacing. And the features of the EKG and Sti-LVAT in intraseptal pacing with and without LCS capture were studied and compared.
RESULTS Five intact His-ventricle (non-LBBB) patients with recorded retrograde His potential from His lead (group 1) and three LBBB patients with anterograde distal left conduction system (LCS) potential from LV multipolar electrodes catheter (group 2) during intraseptal lead pacing were included. In group 1, LBB potential were recorded in all patients with the His to LBB potential interval of 28±5.4 ms. Retrograde His potential was not observed in His lead during only septal myocardium pacing and it occurred when stimulus to peak LVAT shortened abruptly with increasing output at the same site (90.2±7.5 vs. 71.2±4.7 ms), with stimulus to retrograde His potential (Sti-RH) interval of 28.2±5.1 ms. Output dependent selective and non-selective LBBP were achieved at finial site in 3 patients, with the same Sti-RH interval of 28.5±5.7 ms. In group 2, stimulus to LBB potential interval was 19.7±2.4 ms during His corrective pacing (Figure 1B). Anterograde distal LCS potential was not observed in multipolar electrodes catheter during only septal myocardium pacing and it occurred when stimulus to peak LVAT shortened abruptly with increasing output at the same site (105±14.2 vs. 85.7±6.6 ms), with stimulus to anterograde distal LCS potential (Sti-ALCS) interval of 20.3±3.7 ms (Figure 1C). Output dependent selective and non-selective LBBP were achieved at finial site in all these patients, with the Sti-ALCS interval of 20.3±3.4 ms and 21±2.9 ms, respectively (Figure 1D).
CONCLUSIONS In intact His-ventricle patients, when LCS directly captured, LBB potential was recorded in all cases, with Sti-RH interval identical to the intrinsic His to LBB potential interval, and the distal LCS potential recorded in front of the ventricle, which could also be observed in LBBB corrected by HBP. The characteristics of LCS capture could be summarized as: (1) paced QRS as a RBBB pattern; (2) Sti-LVAT abruptly shortening from LVSP to LBB pacing and achieving shortest and constant.
[GW30-e1038]
Yifang Yuan 1 , Tingting Lv 1 , Huijuan Li 3 , Jing Yang 1 , Jiayu Wang 1 , Lingyun Kong 1 , Zhaoguo Zhang 1,2 , Yanfang Wang 3 , Hua Li 1 , Xingjie Li 4 , Yingxian Sun 5 , Xuewen Li 6 , Zheng Zhang 7 , Xiaoshu Cheng 8 , Lirong Wu 9 , Xuerui Tan 10 , Bing Han 11 , Yangfeng Wu 2 , Jihong Guo 3 , Ping Zhang 1
1Beijing Tsinghua Changgung Hospital
2Peking University Clinical Research Institute
3Department of Cardiology, Peking University People’s Hospital
4Jining NO. 1 People’s Hospital
5The First Hospital of China Medical University
6Shanxi Academy of medical sciences, Shanxi Dayi Hospital
7The First hospital of Lanzhou University
8The Second Affiliated Hospital of Nanchang University
9The Affiliated Hospital of Guiyang Medical College
10Department of Cardiology, the First Affiliated Hospital of Shantou University Medical College
11Xuzhou Central Hospital
12Beijing Sijiqing Hospital
OBJECTIVES Tpeak-to-Tend interval (Tpe) is defined as the interval between the top of T wave to the end of T-wave. It was considered to reflect the dispersion of ventricular repolarization and as a novel risk marker of cardiovascular death. Recently, Bachmann et al. reported U-shaped associations between TpTe and cardiovascular risk. However, research on the association between TpTe and LV diastolic function remains limited. Accordingly, we examined their association in general Chinese population enrolled in a China National Survey of ECG Parameters.
METHODS A multi-stage, stratified cluster sampling across China was performed to select the representative Chinese adults aged 18–85 years old. TpTe were measured using Marquette 12SL algorithm in MUSE Cardiology Information System (GE Healthcare, USA). Only data from lead II, V2, V5 were investigated to limit the amount of statistical tests but cover most of the heart over different axes and planes. LV end-diastolic volume (LVEDV) and E/A as measures for LV diastolic function were collected by echocardiography. The study population was categorized into seven groups according to Tpe, Tpe/◻, or Tpe/QT ratio, with cut-offs at 5th, 20th, 40th, 60th, 80th, 95th percentiles and reference group as 0–5th. GLM was used to assess the association between Tpe measures and LVEDD, LVEDV as well as E/A in overall population and each group. All models were adjusted for age, gender, center, history of hypertension and body mass index (BMI).
RESULTS After an exclusion of potential ambiguous Tpe interval, 6251 participants with 47% female and a mean age of 47± 14 years old were finally included from the nationwide study. Tpe was normally distributed with a mean of 90±14, 112±16 and 96±11 ms in lead II, V2 and V5. The median of LVEDD, LVEDV and e/a ratio were of 4.6 (4.3, 4.9) cm, 99 (83, 113) mL and 1.2 (0.9, 1.5), respectively. When treated as continuous variable, Tpe in lead II and V2 showed significant association with LVEDV but not in lead V5 (lead II: β=0.05, 95% CI 0.01, 0.09, P=0.008; lead V2: β=0.04, 95% CI 0.01, 0.08 P=0.008). However, Tpe/◻, or Tpe/QT ratio in lead V5 demonstrated negative association with LVEDV (Tpe/◻; β=–0.05, 95% CI –0.09, –0.02, P=0.005; Tpe/QT ratio: β=–21, 95% CI –38, –5 P=0.01). Surprisingly, when treated as categorical variable, a U-shape association was illustrated for Tpe groups and LVEDV, where the 20th–40th Tpe group in lead V2 (100–107 ms) and the 5th–20th (68–81 ms) Tpe group in lead II showed the least mean of LVEDV. No clear pattern was observed for the association between E/A and Tpe measures.
CONCLUSIONS There might be association between Tpe and LVEDV, either U-shape or linear. However, results differed by different leads. Further study is warranted for clear definition of Tpe and a possibility of non-linear between Tpe and subclinical outcomes.
[GW30-e1051]
Yu Xia 1 , L. Xiaofeng 1 , Hao Zhang 1 , Li Liu 2 , Lijuan Fu 3 , Wei Yan 4 , Qingxia Li 5 , Yukun Zhang 6 , Miao Yu 1 , Jun Liu 1 , Pihua Fang 1
1State Key Laboratory of Cardiovascular Disease, Cardiac Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2Department of Cardiology, Qitaihe City People’s Hospital, Heilongjiang, China
3Department of Cardiology, Chuiyangliu Hospital affiliated to Tsinghua, Beijing, China
4Department of Cardiology, Youjiang Medical University for Nationalities, Guangxi, China
5Intensive Care Unit, Gansu Provincial Hospital of Traditional Chinese Medicine, Gansu, China
6Department of Cardiology, Guizhou Aerospace Hospital, Guizhou, China
OBJECTIVES Based on small sample of patients with hypertension, a few studies have reported that the newly proposed S D +SV 4 criterion for left ventricular hypertrophy (LVH) is better than traditional criteria. This study was to verify the diagnostic capability of S D +SV 4 criterion in Chinese population with or without hypertension and analyze the factors affecting diagnostic accuracy of LVH.
METHODS A total of 248 patients with LVH or paroxysmal supraventricular tachycardia (PSVT) discharged from Fuwai Hospital from January 2010 to July 2018 were enrolled. Patients with LVH were diagnosed according to left ventricular mass index (LVMI) calculated by the parameter of echocardiogram as the gold standard in this study. The S D +SV 4 criterion refers to the sum of the amplitude of the deepest S wave (S D ) in all leads and the amplitude of S wave in V 4 lead (SV 4 ). As an important comparison criterion, the Cornell standard refers to the amplitude of the R wave in the aVL lead plus the amplitude of the S wave in the V 3 lead, that is, RaVL+SV 3 . The Sokolow-Lyon criterion refers to the S-wave amplitude in the V 1 lead plus the R-wave amplitude of the higher one in the V 5 or V 6 leads, that is, SV 1 +RV 5 /RV6. The ROC curve was performed to assess the diagnostic capability of S D +SV 4 , RavL+SV 3 and SV 1 +RV 5 /RV 6 criteria for LVH. Then, the multivariate logistic regression analyses were performed to investigate the factors affecting the accuracy of the S D +SV 4 criterion.
RESULTS There were 170 (68.5%) patients with hypertension and 110 (44.4%) with PSVT. According to LVMI, 107 (43.1%) patients were diagnosed with LVH. The area under curve (AUC) of S D +SV 4 criterion was the largest compared with RavL+SV 3 and SV 1 +RV 5 /RV 6 criteria (AUC: 0.765 vs. 0.718 vs. 0.713, respectively). AUC of three criteria were similar (AUC: 0.746 vs. 0.758 vs. 0.730, respectively) in male, while the AUC of S D +SV 4 criterion were apparently higher than that of RavL+SV 3 and SV 1 +RV 5 /RV 6 criteria (AUC: 0.842 vs. 0.712 vs. 0.641, respectively) in female (Figure 1). The gender-specific S D +SV 4 criterion has the highest consistency with gold standard (r=0.532±0.054, P<0.01), accompanied by highest sensitivity (70.1%) and specificity (85.8%). According to the consistency of diagnostic results by the gender-specific S D +SV 4 criterion and gold standard, patients were divided into a consistent group and an inconsistent group. Univariate analysis showed significant differences in history of PSVT (50.0% vs. 25.0%, P<0.01), Posterior wall thickness (PWT) (10.5±2.3 vs. 11.7±3.5, P<0.05) and LVEF (Left ventricular ejection fraction) (61.6±9.6 vs. 54.1±7.9, P<0.001) between the two groups. Variables with P<0.10 in the univariate analysis were included in multivariate logistic regression analysis. The results showed that after adjusting for hypertension, PSVT history, body surface area, interventricular septum thickness, PWT and left ventricular internal diameter, only LVEF (OR=0.920, 95% CI 0.882~0.959, P<0.001) was significantly different between the two groups (Table 1).
CONCLUSIONS The newly proposed S D +SV 4 criterion provide improved sensitivity and accuracy for the diagnosis of LVH in Chinese population. The decrease of LVEF is an independent factor affecting diagnostic accuracy of the LVH.
[GW30-e1056]
Weijian Huang 1,2 , Shengjie Wu 1,2 , Weijian Huang 1,2
1Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University
2The Key Lab of Cardiovascular Disease of Wenzhou, Wenzhou, China
OBJECTIVES His bundle pacing can correct left bundle branch block (LBBB) but may be limited by suboptimal lead delivery and high thresholds. To assess the feasibility of left bundle branch pacing achieved by capture the left conduction system via a novel intraseptal technique (iLCS) to deliver cardiac resynchronization therapy (CRT).
METHODS Patients with LBBB from multicenters indicated for CRT or pacing therapy were included. iLCSP was performed by fixing 3830 lead into the left ventricular septal sub-endocardium targeting the region of the proximal left conduction system. Pacing characteristics, success rate, threshold and R-wave amplitude were assessed.
RESULTS A total of 94 patients with the native QRS duration of 167.2±17.2 ms were included. In 92 patients, iLCSP was achieved and demonstrated RBBB pattern with the paced QRS duration of 116.4±12.6 ms (Figure 1B, middle panel). Fusion of iLCSP and native conduction via the RBB eliminated RBBB and resulted in an average QRS duration of 103.2±10.1 ms (Figure 1C). In a subgroup that underwent a two-lead implantation technique (n=21), a Purkinje pre-potential was recorded during His corrective pacing from the intraseptal lead (Figure 1B, right panel). Output dependent selective and non-selective iLCSP were demonstrated in 52% patients, with the same stimulus to peak left ventricular activation time of 82 ms (Figure 1B, left and middle panel). Lead parameters remained stable at 1-year (threshold 0.61±0.17V/0.5 ms, R wave 13±5.8 mV, Figure 1D,E). During follow-up, only one patient had an increase in LBB capture threshold to 2.5 V/0.5 ms and there were no other complications such as dislodgment, infections, embolism or stroke associated with the implantation.
CONCLUSIONS Permanent iLCSP is feasible and safe in patients with LBBB.
[GW30-e1066]
Jamol Uzokov, Baxrom Alyavi, Akbar Abdullaev
Republican specialized scientific practical medical center of therapy and medical rehabilitation
OBJECTIVES Prevalence of atrial fibrillation (AF) and metabolic syndrome (MS) are rising and co-existence of these two conditions will increase related complications. Aim of the study was to assess the efficacy and safety of rivaroxaban in patients with AF and MS.
METHODS We compared the efficacy and safety of rivoraxaban and varfarin in patients with AF and metabolic syndrome. One hundred and twenty-four patients were enrolled in this study dividing into two group by 62 (Aged 42–67 years; mean age 51.2 years; 46% male). First group were treated with rivoraxaban and the second group with varfarin. Mean follow-up period was 1.8 years. Metabolic syndrome was diagnosed by the Harmonized definition of the MS. In both treatment groups for efficacy and safety, primary outcomes were stroke, embolism, major and non-major bleeding.
RESULTS During the follow-up period primary endpoints were similar in both groups (1 stroke event in rivoraxaban vs. 1 stroke event in varfarin). There was no embolism in both groups. However, major and non-major clinically relevant bleeding were observed more in varfarin group when compared rivoraxaban group (HR 1.2; CI 95% 1.06–1.29; P=0.03). Among components of MS hypertension and dyslipidemia were correlated with major and non-major bleeding (HR 1.23; CI 95% 1.08–1.32; P=0.04 and HR 1.09; CI 95% 1.05–1.14; P=0.05). There were no correlations between AO and IR with major and non-major bleeding.
CONCLUSIONS Rivaraxaban is superior than varfarin in AF patients with metabolic syndrome. Among components of MS, hypertension and dyslipidemia are risk factors for major and non-major bleeding. Further studies with large amount of patients are needed to clarify.
HEART FAILURE
[GW30-e0047]
Shaozhao Zhang 1,2 , Xiaodong Zhuang 1,2 , Zhimin Du 1,2 , Xinxue Liao 1,2
1Cardiology department, first affiliated hospital of Sun Yat-Sen University
2NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
OBJECTIVES We aimed to examine the association between temporal change in QT interval and cardiovascular diseases and all-cause mortality in the Atherosclerosis Risk in Communities (ARIC) study.
METHODS We included 10,808 participants (age, 60.1±5.7, 45.2% male and 80.0% white) who obtained the 12-lead Electrocardiography (ECG) in both Visit 1 (1987–1989) and Visit 3 (1993–1995) in the Atherosclerosis Risk in Communities (ARIC) study. QT interval duration was corrected by using Bazett’s formula (QTc). The change in corrected QT interval duration (ΔQTc) was calculated by subtracting QTc in Visit 3 from Visit 1. The main outcomes measures included all-cause mortality, incident heart failure (HF), coronary artery disease (CHD), stroke and atrial fibrillation (AF). We used multivariable Cox regression models to assess the association between ΔQTc and these outcomes.
RESULTS During a median follow-up of 19.6 years, 3918 cases (36.3%) of death, 1833 cases (17.8%) of HF, 1110 cases (11.1%) of CHD, 765 cases (7.2%) of stroke and 1789 cases (16.9%) of AF occurred. The hazard ratios for all-cause mortality, HF, CHD, stroke and AF with 10 ms increased in ΔQTc were 1.03 (95% CI, 1.01, 1.05; P=0.002), 1.05 (95% CI, 1.03, 1.08; P<0.001), 1.01 (95% CI, 0.98, 1.05; P=0.636), 1.05 (95% CI, 1.01, 1.09; P=0.026) and 1.03 (95% CI, 1.00, 1.06; P=0.051) separately, after adjusted for traditional cardiovascular risk factor, QTc and QRS duration.
CONCLUSIONS Temporal increases in QTc are independently associated with increased risk of death, HF and stroke.
[GW30-e0083]
Le Hoang Nguyen Khoa 1 , Pham Cong Danh 1 , Thach Nguyen 1,2 , Gianluca Rigatelli 3
1Tan Tao University School of Medicine, Long An Vietnam
2Cardiovascular Research Department, Methodist Hospital. Merrillville IN, USA
3Endovascular interventions, Rovigo General Hospital, Rovigo, Italy
OBJECTIVES At the present time, there is no criterion to estimate the optimal treatment for heart failure (HF) with preserved ejection fraction (HFpEF). In the past, our group suggested the criteria for diagnosis of HFpEF with normal EF and fluid overload using the size of the femoral vein (FV), measured by ultrasound. Since then, when the patients with HF were treated, we used the size of the femoral vein as a criteria of fluid overload or euvolemic status. Is this criterion the best marker of optimal treatment of HFpEF? Which physical sign could guarantee a best treatment result?
METHODS Patients with HFpEF were enrolled. All patients had echocardiography to confirm EF>50% and also underwent the ultrasound test to assess the size and expansibility of the femoral vein (SEFV). The SEFV is the ultrasound study of femoral vein (FV) examining its size and expansibility with cough. The location of the femoral artery (FA) and FV to be checked is the coronal plane immediately proximal to the bifurcation of the superficial and deep femoral artery. The normal size of FV is a little larger than of the FA (Figure 1). If the size of the FV is twice larger than the FA, the patient has fluid overload in the venous compartment. (Figure 2) Then the patient was asked to cough in order to measure the size of the FV.
RESULTS During the 2 years of treatment, the patients were followed up with detailed physical examination in the office (including weight) and had the SEFV at regular 6 months intervals. Patients also underwent right heart catheterization to measure to the pulmonary capillary wedge pressure (PCWP).
CONCLUSIONS With the SEFV test, we could accurately confirm the presence of fluid overload in patients with HFpEF. However, in the follow-up by physical examination, the loss of cutaneous venous volume was an excellent marker of the euvolemic status of the patients with HFpEF. This marker was as sensitive as the SEFV test which measured the size of the femoral vein. Further randomized trials are needed to confirm the above preliminary results.
[GW30-e0102]
Xiaodong Zhuang 1,2 , Lizhen Liao 3 , Shaozhao Zhang 1,2 , Zhimin Du 1,2 , Xinxue Liao 1,2
1Cardiology Department, The First Affiliated Hospital of Sun Yat-Sen University
2NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
3Department of Health, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center
OBJECTIVES Identifying unrecognized potentially modifiable risk factors is essential to improve the outcome of HF. However, the relationship of serum albumin with incident HF is uncertain. We aim to characterize the nature and magnitude of prospective association between serum albumin and incident heart failure (HF), and to investigate any causal relevance to the associationusingMendelian randomization.
METHODS Serum albumin levels were measured at baseline in the Atherosclerosis Risk in Communities (ARIC) prospective study of 15,792 participantswithout HF. Hazard ratios (95% confidence intervals) of serum albumin with incident HF were assessed. Eight single-nucleotide polymorphisms associated with serum albumin at genome-wide significance were used as instrumental variables. Mendelian randomization based on summary-level data was used to estimate the causal influence of the exposure on the outcome.
RESULTS During a median follow-up of 25.1 years, 2446 (19.9%) HF were observed. After multiple adjustment, serum albumin was inversely associated with incidence of HF (HR: 0.54, 95% CI: 0.46–0.64, per 1 g/dL increase; HR: 0.71, 95% CI: 0.63–0.81, Q4 vs. Q1). In MR analysis, no causal relationship was detected between serum albumin level and HF (odds ratio [OR]: 1.00, 95% CI: 0.99–1.01, per 1 g/dL increase of albumin; P=0.38) without evidence of heterogeneity between estimates from individual SNPs (P heterogeneity =0.21) and pleiotropy effect (P pleiotropy =0.83).
CONCLUSIONS The serum albumin level is independently inverse associated with incident HF in a linear pattern. However, MR analyses did not support a causal role of serum albumin in the etiology of HF.
[GW30-e0116]
Yi Yu, Jian Li
Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
OBJECTIVES To investigate the relationship between the change of diastolic blood pressure (DBP) during hospitalization and the prognosis after discharge with a relatively low DBP (<55 mmHg).
METHODS Three hundred and sixty patients with heart failure from the First Affiliated Hospital of Sun Yat-sen University between January 01, 2012 to December 31, 2018 were selected as the subjects in our study. Patients with chronic heart failure and DBP less than 100 mmHg at admission. The change of DBP during hospitalization (ΔDBP) was calculated by subscribing the admission DBP values from the discharge values. All-cause mortality at 1 year and 5 years were recorded during the follow up period and compared among patients with different ΔDBP levels. Multivariable Cox regression hazard model was used to analyze the association between the ΔDBP level and clinical outcomes.
RESULTS The patients were included and divided into two groups according to the ΔDBP level, including ΔDBP<–10 mmHg group (n=160) (44.4%) and ΔDBP≥–10 mmHg group (n=200) (55.6%). All-cause mortality at 1 year was higher in the ΔDBP<–10 mmHg group than those in the ΔDBP≥–10 mmHg group (31.5 vs. 21%, P<0.01). There was no significant statistical difference in the all-cause mortality at 5 years (39.3 vs. 31.1%, P>0.05) between the two groups. After adjusted the age, gender at discharge, NYHA class in the multivariable Cox regression hazard model, we found the adjusted risk of 1 year all-cause mortality in the ΔDBP<–10 mmHg group was approximate twice higher than those in the ΔDBP≥–10 mmHg group (HR=2.011, 95% CI: 1.501–2.509, P<0.05).
CONCLUSIONS DBP value decrease more than 10 mmHg during -hospitalization is associated with adverse outcomes in the post-discharged prognosis.
[GW30-e0117]
Yi Yu, Jian Li
Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
OBJECTIVES To observe the correlation between hyperuricemia and prognosis in patients with heart failure of dilated cardiomyopathy.
METHODS Three hundred and fifty-two patients with heart failure of dilated cardiomyopathy from the First Affiliated Hospital of Sun Yat-sen University between January 01, 2012 to December 31, 2018 were selected as the subjects in our study. Retrospective analysis of 164 patients with heart failure of dilated cardiomyopathy was the A group. A total of 188 patients with non-heart failure of dilated cardiomyopathy admitted to our hospital during the same period were selected as the B group. The basic diseases, correlation between hyperuricemia and heart failure was analyzed, and the mortality rate was followed up for 3 years.
RESULTS The level of serum uric acid in the A group was significantly higher than that in the B group, and the cardiac function index was significantly lower than that in the B group. The rate of combined basic diseases was 57.43% in the A group, the rate of mortality rate was 7.1% in the follow-up 3 years, 27.13% in the B group and the rate of mortality rate was 1.3%. The difference was statistically significant (P<0.05). Multiple logistic regression analysis showed that log hyperuricemia, was independently and signifcantly associated in a positive manner with heart failure (odds ratio: 7.28, 95% confdence interval: 1.03–16.41, P=0.03).
CONCLUSIONS We found a positive and independent association of serum hyperuricemia with heart failure in dilated cardiomyopathy patients. Hyperuricemia is a common problem in patients with heart failure of dilated cardiomyopathy, and it is a risk factor to induce changes in cardiac function.
[GW30-e0119]
Lei Huang 1 , Ronghuan Shen 2 , Longfei Huang 3 , Jing Yu 3 , Hao Rong 1 , Lei Huang 1
1Ningbo Hangzhou Bay Hospital, Ningbo, China
2Ningbo Medical Center Lihuili Hospital, Ningbo, China
3Tianjin Medical University General Hospital, Tianjin, China
OBJECTIVES Copper dyshomeostasis can lead to many diseases, including cardiovascular disease. However, there are conflicting reports on the relationship between serum copper levels and heart failure (HF). To explore the relationship between serum copper levels and HF by performing a meta-analysis.
METHODS The PubMed and ScienceDirect databases until June 2017 were searched for reports on the association between serum copper levels and HF.
RESULTS Thirteen reports with 1504 subjects from 29 case-control studies were chosen for the meta-analysis. The pooled analysis indicated that patients with HF had higher copper levels than the control subjects [standardized mean difference (SMD), 0.982; 95% confidence interval (CI), (0.679, 1.285)]. Subgroup analysis stratified by different geographic locations found that HF patients had higher copper levels than the control subjects in Asia and Europe [Asia: SMD, 0.948 and 95% CI, (0.569, 1.327); Europe: SMD, 1.275 and 95% CI, (0.633, 1.917)], but not in America [America: SMD, 0.637 and 95% CI, (–0.109, 1.383)]. Additionally, subgroup analysis revealed that patients with ischemic cardiomyopathy (ICM) [SMD, 1.171; 95% CI, (0.717, 1.624)], idiopathic dilated cardiomyopathy (IDCM) [SMD, 0.569; 95% CI, (0.097, 1.042)] and other types of HF [SMD, 1.152; 95% CI, (0.594, 1.710)] all had higher copper levels than controls. Further subgroup analysis stratified by NOS scores also found higher serum copper levels in patients with HF than controls within each subgroup.
CONCLUSIONS Our meta-analysis identified a significant association between high copper levels and HF.
[GW30-e0120]
Yi Yu, Jian Li
Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
OBJECTIVES To investigate the changes of myocardial fibrosis indexes in patients with chronic heart failure between different NYHA patients.
METHODS One hundred and three patients with heart failure from the First Affiliated Hospital of Sun Yat-sen University between January 01, 2015 to December 31, 2018 were selected as the subjects in our study, while another 101 healthy subjects were selected as the control group. All the subjects received an electrocardiogram examination. The serum myocardial fibrosis indexes [Laminin (LN), pre-III collagen (PCIII), hyaluronic acid (HA)] in patients with chronic heart failure between different NYHA patients were calculated.
RESULTS Myocardial fibrosis indexes was signifcantly higher in study group [20.8 (15.0–25.1) μg/mL] than in control group [13.1 (10.9–26.8) μg/mL] (P=0.04). One-way ANOVA showed that there was significant difference in serum LN, PCIII, and HA levels between different NYHA patients (P<0.05). After multiple comparisons, serum LN, PCIII, and HA levels were higher in grade IV patients than those of grade II and III (P<0.05). Serum LN, PCIII, and HA levels were higher in grade IV and III patients than in grade II patients (P<0.05), after adjustment for age, smoking status, diabetes mellitus, and other risk factors.
CONCLUSIONS The level of myocardial fibrosis is significantly changed in patients with chronic heart failure and it can predict the severity of chronic heart failure.
[GW30-e0121]
Yi Yu, Jian Li
Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
OBJECTIVES To investigate the association between nutritional status (serum albumin and cholesterol levels) and prognosis in patients with chronic heart failure.
METHODS Three hundred and thirty-one hospitalized patients with heart failure from the First Affiliated Hospital of Sun Yat-sen University between January 01, 2015 to December 31, 2018 were selected as the subjects in our study. These 331 patients were divided into two groups according to their prognosis, the death group (n=141), and the relief discharge group (n=190). Multivariate analysis was used to analyze the association between nutritional status and prognosis in patients with chronic heart failure.
RESULTS The nutritional status scores in relief discharge group was significantly higher than in the death group (P=0.03). Multivariate analysis showed that nutritional status scores was an independent predictor of prognosis in patients with chronic heart failure (P=0.04), after adjustment for age, body mass index, smoking status, hypertension, hemoglobin, and other risk factors.
CONCLUSIONS We found a negative and independent association of nutritional status scores and prognosis in patients with chronic heart failure.
[GW30-e0122]
Yi Yu, Jian Li
Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
OBJECTIVES To investigate the clinical association between the level of total bilirubin (TBIL) and early renal damage in patients with acute heart failure (AHF).
METHODS Three hundred and fifty-two patients with AHF from the First Affiliated Hospital of Sun Yat-sen University between January 01, 2012 to December 31, 2018 were selected as the subjects in our study. They were divided into high TBIL group and low TBIL group according to TBIL at admission. Logistic regression was used to analyze the relation between TBIL and early renal damage.
RESULTS Left ventricular end diastolic diameter, N terminal brain natriuretic peptide (NT-proBNP), urinary α1-microglobulin and β2-microglobulin were signifcantly higher in high TBIL group than in low TBIL group (all P<0.05). Multiple logistic regression analysis showed that log TBIL, was independently and signifcantly associated in early renal damage in patients with AHF, after adjustment for age, body weight, percentage body fat, hemodialysis duration, smoking status, and other risk factors.
CONCLUSIONS We found a positive and independent association of serum TBIL with early renal damage in patients with AHF.
[GW30-e0123]
Yi Yu, Jian Li
Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
OBJECTIVES To investigate the clinical association between the serum concentration of growth differentiation factor 15 (GDF-15) and in patients with acute heart failure (AHF) caused by myocardial infarction (MI).
METHODS One hundred and three patients with heart failure from the First Affiliated Hospital of Sun Yat-sen University between January 01, 2012 to December 31, 2018 were selected as the subjects in our study (A group), and 80 healthy subjects who underwent physical examination were selected as B group. The levels of serum GDF-15, creatine kinase isoenzyme (CK-MB), and troponin I (cTN-I) between the two groups were analyzed.
RESULTS The serum levels of GDF-15, CK-MB and cTn-I in A group were significantly higher than those in B control group (P<0.05). Multiple logistic regression analysis showed that log GDF-15, but not log CK-MB and cTn-I, was independently and signifcantly associated with AHF (odds ratio: 15.28, 95% confdence interval: 1.01–29.41, P=0.02), after adjustment for age, body weight, percentage body fat, smoking status, and other risk factors.
CONCLUSIONS We found a positive and independent association of serum concentration of GDF-15 with AHF caused by MI, moreover, serum levels of GDF-15 are related to the degree of AHF and MI area in those patients.
[GW30-e0153]
Shuo Pan, Junkui Wang
People’s Hospital of Shaanxi Province
OBJECTIVES The study was designed to investigate lipid profile and SYNTAX score in patients with non-ST segment elevation myocardial infarction (NSTEMI).
METHODS Three hundred and eleven patients with NSTEMI were enrolled. The demographic, clinical data, blood samples and SYNTAX score were documented. The Pearson linear correlation was used to detect confounding factors linearly correlated with SYNTAX score. The significantly correlated confounding factors were put into the multiple linear regressions.
RESULTS The Pearson linear correlation showed that high-density lipoprotein- cholesterol (HDL-C) and apolipoprotein A1 (ApoA1) were significantly correlated with Syntax Score (r=–0.119, P=0.044 and r=–0.182, P=0.002, respectively). The multiple linear regressions for Syntax Score were built using HDL-C and ApoA1, respectively. After the adjustment of other significantly correlated confounding factors such as white blood cell count (WBC), myohemoglobin (MB), glutamic-oxalacetic transaminase (AST) and creatinine, the ApoA1 still showed significant association with Syntax Score (β=–0.151, P=0.028). The area under curve was (AUC) 0.624 and the optimal cutoff value is 1.07 g/L when using ApoA1 to predict moderate and severe coronary artery lesions. The patients with ApoA1 ≥1.07 g/L and <1.07 g/L have the Syntax Scores of 12.21±11.58 and 16.33±11.53, respectively (P=0.001).
CONCLUSIONS The ApoA1 is the only lipid factor significantly associated with complexity of coronary artery lesion in patients with NSTEMI, the patients with ApoA1 <1.07 g/L may have more complex coronary artery lesions.
[GW30-e0246]
Xiaoqun Wang, Jiawei Chen, Fenghua Ding, Ying Shen, Zhuhui Liu, Fang Wang, Ruiyan Zhang, Weifeng Shen, Lin Lu, Xiaoqun Wang
Department of Cardiology, Rui Jin Hospital, Shanghai Jiao-Tong University School of Medicine
OBJECTIVES High-density lipoprotein (HDL) confers protection against cardiovascular disease partly attributable to its robust anti-oxidant activities, which is largely impaired in diabetic conditions.
METHODS In this study, we analyzed the anti-oxidant activity of HDL, as represented by the arylesterase activity of paraoxonase 1 (PON1) in HDL particles, in 216 consecutive HF patients with (n=79) or without (n=137) type 2 diabetes, and age- and gender-matched 112 diabetic and 189 non-diabetic non-HF controls.
RESULTS We found arylesterase activity was significantly decreased in patients with than without HF, and was further decreased when comorbid with diabetes. After adjusting for conventional risk factors and apolipoprotein A-I levels, arylesterase activity remained correlated positively with left ventricular ejection fraction in diabetic (r=0.325, P=0.020) but not non-diabetic patients (r=0.089, P=0.415), and negatively with NT-proBNP and NYHA functional class in both subgroups. In regression analyses, a higher risk of HF was observed in diabetic than non-diabetic patients when having low arylesterase activities.
CONCLUSIONS In conclusion, our data demonstrate that impaired serum arylesterase activity in patients with HF is further reduced when comorbid with diabetes. The relationship of impaired arylesterase activity to HF is especially enhanced in diabetic patients.
[GW30-e0271]
Yi Yu, Li Jian
Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
OBJECTIVES To investigate the values of plasma iPTH, thyroid hormones, and cardiac function in elderly patients with chronic heart failure.
METHODS A total of 150 cases of elderly patients with chronic heart failure from the First Affiliated Hospital of Sun Yat-sen University between January 01, 2012 to December 31, 2018 were selected as the subjects in our study, to examine the relationship of plasma iPTH and thyroid hormones to cardiac function in elderly patients with chronic heart failure, whose plasma iPTH and thyroid hormones were detected. According to the NYHA cardiac function classification standard, these patients were divided into grade II, III, and IV groups, with 50 cases in each. Another 50 healthy elderly patients treated in the same period were selected as the control group.
RESULTS The levels of plasma iPTH in grade II, III and IV groups were significantly higher than those in the control group (P=0.03). The level of FT3 in grade II, III and IV groups was significantly lower than that in the control group (P=0.04). Multiple logistic regression analysis showed that log iPTH, but not log FT3, was independently and signifcantly associated with cardiac function (odds ratio: 4.81, 95% confdence interval: 1.10–8.41, P=0.04), after adjustment for age, body weight, and other risk factors.
CONCLUSIONS Plasma iPTH are strongly correlated with cardiac function grading in elderly patients with chronic heart failure, providing a novel method to evaluate the cardiac function of chronic heart failure patients.
[GW30-e0272]
Yi Yu, Li Jian
Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
OBJECTIVES To investigate the association between cystatin C and depression in patients with chronic heart failure.
METHODS A total of 180 cases of elderly patients with chronic heart failure from the First Affiliated Hospital of Sun Yat-sen University between January 01, 2013 to December 31, 2018 were selected as the subjects in our study. The patients were divided into Cys C abnormal group and Cys C normal group according to Cys C level. Hamilton depression scale (HAMD) was used to evaluate depression and the related clinical and biochemical indicators were measured.
RESULTS The proportion of depression in Cys C abnormal group was signifcantly higher than in Cys C normal group (P=0.03). Pearson correlation -analysis showed that depression scores were positively correlated with Cys C abnormalities (r=0.324, P=0.04). Logistic regression analysis showed that the Cys C abnormality was associated with depression (OR=6.03, P=0.01), after adjustment for age, body mass index, hypertension, hemoglobin, albumin, and other risk factors.
CONCLUSIONS Cys C are strongly correlated with cardiac function with chronic heart failure, providing a novel method to evaluate the cardiac function of chronic heart failure patients.
[GW30-e0273]
Yi Yu, Li Jian
Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
OBJECTIVES To explore the association between serum hyperhomocysteinemia and heart failure in uremia patient, and to provide clinical reference for better control of uremia heart failure.
METHODS A total of 205 cases of elderly patients with uremia from the First Affiliated Hospital of Sun Yat-sen University between January 01, 2013 to December 31, 2018 were selected as the subjects in our study. These 205 patients were divided into two groups according to their serum hyperhomocysteinemia concentration, the high- concentration group (n=101), and the low-concentration group (n=104). We analyzed the association between serum hyperhomocysteinemia and the incidence of heart failure.
RESULTS The proportion of the incidence of heart failure in the high serum hyperhomocysteinemia concentration group was signifcantly higher than in low-concentration group (P=0.01). Logistic regression analysis showed that the high ser