Resveratrol Attenuates Cardiomyocyte Apoptosis in Rats Induced by Coronary Microembolization Through SIRT1-Mediated Deacetylation of p53.

Abstract

Coronary microembolization (CME)-induced cardiomyocyte apoptosis is the primary factor in causing cardiac dysfunction. Resveratrol (RES) is known to play a protective role in a variety of cardiovascular diseases, yet it is not known whether RES has a protective role in CME. Therefore, the effect of RES on cardiomyocyte apoptosis and cardiac function damage which are induced by CME in rats was investigated in this study. Fifty Sprague-Dawley rats were separated into 5 groups randomly (10 rats were included in each): sham group, CME group, RES+CME group, RES+CME+Sirtuin-1 (SIRT-1) inhibitor EX527 (RES+CME+EX) group, and CME+EX group. Cardiac function, serum c-troponin I (cTnI) level, apoptotic index, and microinfarct were measured by cardiac ultrasound, myocardial enzyme assessment, TdT-mediated dUTP Nick-end labeling and hematoxylin-basic fuchsin-picric acid staining. The levels of p53, p53 acetylation, SIRT-1, Bax, Bcl-2, and cleaved caspase-3 were detected by Western blot. Myocardial dysfunction, enhanced apoptotic index as well as cTnI were caused after the operation of CME. Coronary microembolization induced increased expression of p53 acetylation and cleaved caspase-3, while the SIRT-1 and Bcl-2/Bax ratio was reduced. The CME effect was reversed by RES while EX527 attenuated this protective effect. Resveratrol can improve cardiac function, in the sense that it attenuates CME-induced cardiomyocyte apoptosis, which is perhaps associated with its inhibition pro-apoptotic pathway of p53 which is transcription-independent.