A novel association between TGF$b$1 and ADAMTS4 in coronary artery disease: A new potential mechanism in the progression of atherosclerosis and diabetes
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Date
2015
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Abstract
Objective: Coronary artery disease is characterized by atherosclerosis in the vessel wall. Recently, it has been thought that increasing LDL-bindingcapacity of subendothelial proteoglycan fragments that are formed by protease activity can be responsible for the initiation of atherosclerosis.ADAMTS4 is a member of the versican-degrading proteinases. In vitro studies demonstrated that TGFb inhibits the expression of ADAMTS4 inmacrophages. In this study, we aimed to investigate the role and association between TGFb1 and ADAMTS4 in coronary artery disease.Methods: A total of 84 cases with atheroma plaque and 72 controls without plaque were analyzed. The severity of disease was determined byGensini score. TGFb1 gene polymorphisms were genotyped by the PCR-RFLP method. TGFb1 and ADAMTS4 serum levels were measured by ELISAmethod. Statistical analyses of genotypes and their relationship with serum levels were performed by chi-square, student t test and ANOVA.Results: ADAMTS4 levels were higher in cases compared with controls (p<0.05). In the patient group, ADAMTS4 levels were higher than incontrols and correlated with TGFb1 serum levels (r=0.29; p<0.05) and severity of disease (r=0.20; p<0.05). The TGFb1 gene CCA haplotype wasassociated with 3.3-fold increase in coronary artery disease (OR=3.26 95% CI 1.22-8.68; p<0.05). Unexpectedly, ADAMTS4 serum levels werealso higher in diabetic cases (p=0.05).Conclusion: This study has demonstrated that ADAMTS4 may be responsible for the pathogenesis of atherosclerosis. This is the first reportabout the association between ADAMTS4 and TGFb1 serum levels in the progression of atherosclerosis in CAD. Furthermore, it is seen thatTGFb1 haplotype can cause a genetic susceptibility to CAD in the Turkish population. To our knowledge, this is also the first report suggestinghigher serum ADAMTS4 levels in diabetic patients. (Anatol J Cardiol 2015; 15: 823-9)