Effects of Sirt3-autophagy and resveratrol activation on myocardial hypertrophy and energy metabolism

Abstract

The aim of the present study was to examine the role of sirtuin 3 (Sirt3)-autophagy in regulating myocardial energy metabolism and inhibiting myocardial hypertrophy in angiotensin (Ang) II-induced myocardial cell hypertrophy. The primary cultured myocardial cells of neonatal Sprague Dawley rats were used to construct a myocardial hypertrophy model induced with Ang II. Following the activation of Sirt3 by resveratrol (Res), Sirt3 was silenced using small interfering (si)RNA-Sirt3, and the morphology of the myocardial cells was observed under an optical microscope. Reverse transcription-polymerase chain reaction was used to detect the mRNA expression of the following myocardial hypertrophy markers; atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), Sirt3, medium-chain acyl-CoA dehydrogenase (MCAD) and pyruvate kinase (PK). Western blot analysis was used to detect the protein expression of Sirt3, light chain 3 (LC3) and Beclin1. Ang II may inhibit the protein expression of Sirt3, LC3 and Beclin1. Res, an agonist of Sirt3, may promote the protein expression of Sirt3, LC3 and Beclin1. Res inhibited the mRNA expression of ANP and BNP, and reversed the Ang II-induced myocardial cell hypertrophy. The addition of siRNA-Sirt3 decreased the protein expression of Sirt3, LC3 and Beclin1, increased the mRNA expression of ANP and BNP, and weakened the inhibitory effect of Res on myocardial cell hypertrophy. Res promoted the mRNA expression of MCAD, inhibited the mRNA expression of PK, and reversed the influence of Ang II on myocardial energy metabolism. siRNA-Sirt3 intervention significantly decreased the effect of Res in eliminating abnormal myocardial energy metabolism. In conclusion, Sirt3 may inhibit Ang II-induced myocardial hypertrophy and reverse the Ang II-caused abnormal myocardial energy metabolism through activation of autophagy.