Silencing of angiotensin-converting enzyme by RNA interference prevents H9c2 cardiomyocytes from apoptosis induced by anoxia/reoxygenation through regulation of the intracellular renin-angiotensin system

Abstract

Inhibition of the angiotensin-converting enzyme (ACE) attenuated apoptotic cardiomyocytes induced by ischemic reperfusion (I/R). However, it is difficult to evaluate the effects of inhibition of the intracellular ACE in vivo. The objective of this study was to determine whether the apoptosis in H9c2 cardiomyocytes following anoxia/reoxygenation (A/R) would be improved by the silencing of intracellular ACE by RNA interference (RNAi). H9c2 cardiomyocytes were subjected to A/R 48 h following transfection with ACE-shRNA plasmid. The results showed that the gene silencing of intracellular ACE significantly inhibited the decrease of cell viability and the increase of apoptotic H9c2 cardiomyocytes undergoing A/R. Additionally, the gene silencing of intracellular ACE significantly promoted the expression of ACE2, decreased caspase-3 activity and Bax levels, and enhanced the expression of Bcl-2 in H9c2 cardiomyocytes subjected to A/R. The results suggest that the gene silencing of intracellular ACE holds great potential in the treatment of cardiomyocyte apoptosis following I/R injury through the regulation of the intracellular renin-angiotensin system, thereby regulating the intrinsic pathway of apoptosis.