THE RELATIONSHIP BETWEEN THE EXPRESSION LEVELS OF TISSUE INHIBITOR OF METALLOPROTEINASES-3 (TIMP3) AND SEVERITY OF ATHEROSCLEROSIS

Abstract

Objective: Tissue Inhibitor of Metalloproteinase-3 human (TIMP3) is one of tissue inhibitors of metalloproteinases (TIMPs), which binds to the components of the extracellular matrix, and has crucial roles in atherosclerogenesis and adipose tissue differentiation. In this study, it was aimed to determine the effects of TIMP3 gene expression levels on severity of atherosclerosis in different tissues. Material and Methods: The first group of the study (evaluated for coronary artery disease) were cases classified as high and low plaque scores according to the degree and location of atherosclerotic lesions. In the second group (post-mortem cases) were male cadavers who died due to coronary heart disease (CHD, n=26) and non-cardiac trauma (T-nonP, n=4). The TIMP3 expression levels were examined in leukocyte and peri-coronary epicardial adipose tissues (EAT) samples (n=69 and n=34, respectively) of the first group and EAT and coronary artery samples (n=12 and n=30, respectively) of the second group using quantitative RT-PCR. In addition, the protein expressions of TIMP3 were analysed on artery sections by immunofluorestaining. Results: In the post-mortem study group, the TIMP3 expression levels were found to increase in no plaque segments of arteries of cases with CHD (CHD-nonP) compared to advanced atherosclerotic arteries (CHD-P) and normal arteries of T-nonP cases (p=0.01 and p=0.05, respectively). The TIMP3 expressions in EATs and leukocytes were not statistically significant between the study groups. In addition, TIMP3 protein was detected in normal arteries, peri-coronary EATs and mostly in macrophages- rich areas in advanced atherosclerotic arteries. Conclusion: Tissue Inhibitor of Metalloproteinase-3 human (TIMP3) expression levels increase in normal coronary arterial segments of cases with CHD, which depict a protective role of TIMP3 in development of atherosclerosis.