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      Evaluation of serum platelet-derived growth factor receptor-ß and brain-derived neurotrophic factor levels in microvascular angina

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          Abstract

          Objective:

          Microvascular angina (MVA) is a coronary microcirculation disease. Research on microcirculatory dysfunction has revealed several biomarkers involved in the etiopathogenesis of MVA. Platelet-derived growth factor receptor β (PDGFR-β) and brain-derived neurotrophic factor (BDNF) are 2 biomarkers associated with microcirculation, particularly pericytes function. The aim of this study was to investigate the role of PDGFR-β and BDNF in MVA.

          Methods:

          Ninety-one patients (median age, 56 y; age range, 40–79 y; 36 men) with MVA and 61 control group subjects (median age, 52 y; age range, 38–76 y; 29 men) were included in the study. Serum concentrations of PDGFR-β and BDNF were measured with commercially available enzyme-linked immunosorbent assay kits.

          Results:

          PDGFR-β [2.82 ng/ml; interquartile range (IQR), 0.57–7.79 ng/ml vs. 2.27 ng/ml; IQR, 0.41–7.16 ng/ml; p<0.0005] and BDNF (2.41 ng/ml; IQR, 0.97–7.97 ng/ml vs. 1.92 ng/ml; IQR, 1.07–6.67 ng/ml; p=0.023) concentrations were significantly higher in patients with MVA compared with the controls. PDGFR-β correlated positively with age (r=0.26, p=0.001), low-density lipoprotein (r=0.18; p=0.02), and BDNF (r=0.47; p<0.001), and BDNF showed a significant positive correlation with age (r=0.20; p=0.01). In binary logistic regression analysis, high-sensitivity C-reactive protein, uric acid, and PDGFR-β values were found to be independent predictors of MVA.

          Conclusion:

          MVA is associated with higher PDGFR-β and BDNF levels. This association may indicate an abnormality in microvascular function. Future studies are required to determine the role of these biomarkers in the pathogenesis of MVA. (Anatol J Cardiol 2020; 24: 397-404)

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          Most cited references42

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          International standardization of diagnostic criteria for microvascular angina.

          Standardization of diagnostic criteria for ischemic symptoms due to coronary microvascular dysfunction (CMD) is needed for further investigation of patients presenting with anginal chest pain consistent with "microvascular angina" (MVA). At the annual Coronary Vasomotion Disorders International Study Group (COVADIS) Summits held in August 2014 and 2015, the following criteria were agreed upon for the investigative diagnosis of microvascular angina: (1) presence of symptoms suggestive of myocardial ischemia; (2) objective documentation of myocardial ischemia, as assessed by currently available techniques; (3) absence of obstructive CAD ( 0.80) (4) confirmation of a reduced coronary blood flow reserve and/or inducible microvascular spasm. These standardized criteria provide an investigative structure for mechanistic, diagnostic, prognostic and clinical trial studies aimed at developing an evidence base needed for guidelines in this growing patient population. Standardized criteria will facilitate microvascular angina registries and recruitment of suitable patients into clinical trials. Mechanistic research will also benefit from the implementation of standardized diagnostic criteria for MVA.
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            Endothelial-mural cell signaling in vascular development and angiogenesis.

            Mural cells are essential components of blood vessels and are necessary for normal development, homeostasis, and organ function. Alterations in mural cell density or the stable attachment of mural cells to the endothelium is associated with several human diseases such as diabetic retinopathy, venous malformation, and hereditary stroke. In addition mural cells are implicated in regulating tumor growth and have thus been suggested as potential antiangiogenic targets in tumor therapy. In recent years our knowledge of mural cell function and endothelial-mural cell signaling has increased dramatically, and we now begin to understand the mechanistic basis of the key signaling pathways involved. This is mainly thanks to sophisticated in vivo experiments using a broad repertoire of genetic technologies. In this review, we summarize the five currently best understood signaling pathways implicated in mural cell biology. We discuss PDGFB/PDGFRbeta- dependent pericyte recruitment, as well as the role of angiopoietins and Tie receptors in vascular maturation. In addition, we highlight the effects of sphingosine-1-phosphate signaling on adherens junction assembly and vascular stability, as well as the role of TGF-beta-signaling in mural cell differentiation. We further reflect recent data suggesting an important function for Notch3 signaling in mural cell maturation.
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              Endothelial/pericyte interactions.

              Interactions between endothelial cells and mural cells (pericytes and vascular smooth muscle cells) in the blood vessel wall have recently come into focus as central processes in the regulation of vascular formation, stabilization, remodeling, and function. Failure of the interactions between the 2 cell types, as seen in numerous genetic mouse models, results in severe and often lethal cardiovascular defects. Abnormal interactions between the 2 cell types are also implicated in a number of human pathological conditions, including tumor angiogenesis, diabetic microangiopathy, ectopic tissue calcification, and stroke and dementia syndrome CADASIL. In the present review, we summarize current knowledge concerning the identity, characteristics, diversity, ontogeny, and plasticity of pericytes. We focus on the advancement in recent years of the understanding of intercellular communication between endothelial and mural cells with a focus on transforming growth factor beta, angiopoietins, platelet-derived growth factor, spingosine-1-phosphate, and Notch ligands and their respective receptors. We finally highlight recent important data contributing to the understanding of the role of pericytes in tumor angiogenesis, diabetic retinopathy, and hereditary lymphedema.
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                Author and article information

                Journal
                Anatol J Cardiol
                Anatol J Cardiol
                Anatolian Journal of Cardiology
                Kare Publishing (Turkey )
                2149-2263
                2149-2271
                2020
                22 November 2020
                : 24
                : 6
                : 397-404
                Affiliations
                [1]Department of Cardiology, Faculty of Medicine, Koç University Hospital; İstanbul- Turkey
                [1 ]Department of Cardiology, Bakırköy Dr. Sadi Konuk Training and Research Hospital; İstanbul- Turkey
                [2 ]Düzen Laboratory; İstanbul- Turkey
                Author notes
                Address for correspondence: Dr. Gamze Aslan, Koç Üniversitesi Tıp Fakültesi Hastanesi, Kardiyoloji Anabilim Dalı, 34010, Zeytinburnu, İstanbul- Türkiye Phone: +90 212 467 87 00 E-mail: gaslan@ 123456kuh.ku.edu.tr - gamzeaslan@ 123456e-mail.com.tr
                Article
                AJC-24-397
                10.14744/AnatolJCardiol.2020.44388
                7791298
                33253128
                b20c0bdc-c835-46a2-aa1a-886fcc47526b
                Copyright: © 2020 Turkish Society of Cardiology

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

                History
                : 14 September 2020
                Categories
                Original Investigation

                brain-derived neurotrophic factor,microvascular angina,pericytes,platelet-derived growth factor receptor beta

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