Corosolic acid ameliorates cardiac hypertrophy via regulating autophagy.

Zhao-Peng Wang,Sha-Sha Wang,Ya-Ge Jin,Heng Zhou,Qing-Qing Wu,Yan Che,Difei Shen,Yuan Yuan,Yan-Yan Meng

doi:10.1042/bsr20191860

Abstract

Aim: In this work, we explored the role of corosolic acid (CRA) during pressure overload-induced cardiac hypertrophy. Methods and results: Cardiac hypertrophy was induced in mice by aortic banding. Four weeks post-surgery, CRA-treated mice developed blunted cardiac hypertrophy, fibrosis, and dysfunction, and showed increased LC3 II and p-AMPK expression. In line with the in vivo studies, CRA also inhibited the hypertrophic response induced by PE stimulation accompanying with increased LC3 II and p-AMPK expression. It was also found that CRA blunted cardiomyocyte hypertrophy and promoted autophagy in Angiotensin II (Ang II)-treated H9c2 cells. Moreover, to further verify whether CRA inhibits cardiac hypertrophy by the activation of autophagy, blockade of autophagy was achieved by CQ (an inhibitor of the fusion between autophagosomes and lysosomes) or 3-MA (an inhibitor of autophagosome formation). It was found that autophagy inhibition counteracts the protective effect of CRA on cardiac hypertrophy. Interestingly, AMPK knockdown with AMPKα2 siRNA-counteracted LC3 II expression increase and the hypertrophic response inhibition caused by CRA in PE-treated H9c2 cells. Conclusion: These results suggest that CRA may protect against cardiac hypertrophy through regulating AMPK-dependent autophagy.

Highlights

Cardiac hypertrophy is an initially adaptive response after pressure or volume overload, but prolonged cardiac hypertrophy contributes to the development of heart failure
It was found that corosolic acid (CRA) blunted cardiomyocyte hypertrophy and promoted autophagy in Angiotensin II (Ang II)-treated H9c2 cells
It was found that autophagy inhibition achieved by Chloroquine diphosphate (CQ) or 3-MA counteracts the protective effect of CRA on cardiomyocyte hypertrophy

Summary

Introduction

Cardiac hypertrophy is an initially adaptive response after pressure or volume overload, but prolonged cardiac hypertrophy contributes to the development of heart failure. In the moderate transverse aortic constriction model, both up-regulation of autophagy and down-regulation of protein synthesis are involved in regression of cardiac hypertrophy [3]. It is generally considered that cardiac autophagosome–lysosome pathway (ALP) insufficiency occurs in sustained cardiac hypertrophy as seen in chronic pressure overload-induced left ventricular hypertrophy, especially during the progression from adaptive cardiac hypertrophy to heart failure. The ALP insufficiency caused by either inadequate autophagosome formation or impaired autophagosome clearance during the pressure overload progression that may contribute to the maladaptation of pressure overload-induced cardiac hypertrophy and the development of heart failure [4]

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