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    A novel association between TGF?1 and ADAMTS4 in coronary artery disease: A new potential mechanism in the progression of atherosclerosis and diabetes
    (Turkish Soc Cardiology, 2015) Ulucay, Safiye; Cam, Fethi Sirri; Batir, Muhammed Burak; Sutcu, Recep; Bayturan, Ozgur; Demircan, Kadir
    Objective: Coronary artery disease is characterized by atherosclerosis in the vessel wall. Recently, it has been thought that increasing LDL-binding capacity 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 TGF beta inhibits the expression of ADAMTS4 in macrophages. In this study, we aimed to investigate the role and association between TGF beta 1 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 by Gensini score. TGF beta 1 gene polymorphisms were genotyped by the PCR-RFLP method. TGF beta 1 and ADAMTS4 serum levels were measured by ELISA method. 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 in controls and correlated with TGF beta 1 serum levels (r = 0.29; p < 0.05) and severity of disease (r = 0.20; p < 0.05). The TGF beta 1 gene CCA haplotype was associated 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 were also 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 report about the association between ADAMTS4 and TGF beta 1 serum levels in the progression of atherosclerosis in CAD. Furthermore, it is seen that TGF beta 1 haplotype can cause a genetic susceptibility to CAD in the Turkish population. To our knowledge, this is also the first report suggesting higher serum ADAMTS4 levels in diabetic patients.