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      Increased serum myeloid-related protein 8/14 level is associated with atherosclerosis in type 2 diabetic patients

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          Abstract

          Background

          Myeloid-related protein 8/14 (MRP8/14) is a stable heterodimer formed by two different calcium-binding proteins (MRP8 and MRP14). Studies have identified that MRP8/14 regulates vascular inflammation and serves as a novel marker of acute coronary syndrome. In this study, we evaluated the correlation between serum levels of MRP8/14, hsCRP, endogenous secretory receptor for advanced glycation end-products (esRAGE) and the occurrence of coronary artery disease (CAD), or carotid intima-media thickness (IMT) when CAD was not yet developed in diabetic patients.

          Methods

          Serum levels of MRP8/14, esRAGE and hsCRP were measured in 375 diabetic patients. Then the results of those who had CAD were compared against who had not. Also, we investigated the associations between above-mentioned indicators and IMT of subjects without CAD in both diabetic group and non-diabetic one.

          Results

          Serum MRP8/14 was significantly higher in CAD than in non-CAD group (9.7 ± 3.6 ug/ml vs. 8.2 ± 3.0 ug/ml, P < 0.001). It was associated with severity of CAD ( r = 0.16, P = 0.026). In non-CAD group, MRP8/14 was associated with IMT in patients with ( r = 0.30, P < 0.001) or without diabetes ( r = 0.26, P = 0.015). The areas under the curves of receiver operating characteristic for CAD were 0.63 (95% CI 0.57-0.68) for MRP8/14, 0.76 (95% CI 0.71-0.81) for hsCRP and 0.62 (95% CI 0.56 -0.67) for esRAGE.

          Conclusion

          In summary, we report that diabetic patients with CAD had elevated plasma MRP8/14 levels which were also positively correlated with the severity of CAD and carotid IMT in patients without clinically overt CAD.

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          Most cited references24

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          Prediction of Creatinine Clearance from Serum Creatinine

          A formula has been developed to predict creatinine clearance (C cr ) from serum creatinine (S cr ) in adult males: Ccr = (140 – age) (wt kg)/72 × S cr (mg/100ml) (15% less in females). Derivation included the relationship found between age and 24-hour creatinine excretion/kg in 249 patients aged 18–92. Values for C cr were predicted by this formula and four other methods and the results compared with the means of two 24-hour C cr’s measured in 236 patients. The above formula gave a correlation coefficient between predicted and mean measured Ccr·s of 0.83; on average, the difference between predicted and mean measured values was no greater than that between paired clearances. Factors for age and body weight must be included for reasonable prediction.
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            Proinflammatory S100 proteins in arthritis and autoimmune disease.

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              S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and MAP kinase-dependent pathway.

              The complex formed by two members of the S100 calcium-binding protein family, S100A8/A9, exerts apoptosis-inducing activity against various cells, especially tumor cells. Here, we present evidence that S100A8/A9 also has cell growth-promoting activity at low concentrations. Receptor of advanced glycation end product (RAGE) gene silencing and cotreatment with a RAGE-specific blocking antibody revealed that this activity was mediated via RAGE ligation. To investigate the signaling pathways, MAPK phosphorylation and NF-kappaB activation were characterized in S100A8/A9-treated cells. S100A8/A9 caused a significant increase in p38 MAPK and p44/42 kinase phosphorylation, and the status of stress-activated protein kinase/JNK phosphorylation remained unchanged. Treatment of cells with S100A8/A9 also enhanced NF-kappaB activation. RAGE small interfering RNA pretreatment abrogated the S100A8/A9-induced NF-kappaB activation. Our data indicate that S100A8/A9-promoted cell growth occurs through RAGE signaling and activation of NF-kappaB.
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                Author and article information

                Journal
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central
                1475-2840
                2011
                18 May 2011
                : 10
                : 41
                Affiliations
                [1 ]Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
                [2 ]Department of Endocrinology, Xinhua hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
                Article
                1475-2840-10-41
                10.1186/1475-2840-10-41
                3120649
                21592353
                06adaef6-43d4-4687-9617-467fac5f3631
                Copyright ©2011 Peng et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 January 2011
                : 18 May 2011
                Categories
                Original Investigation

                Endocrinology & Diabetes
                mrp8/14,diabetes mellitus,coronary artery disease,intima media thickness

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