HypERlnc attenuates angiotensin II-induced cardiomyocyte hypertrophy via promoting SIRT1 SUMOylation-mediated activation of PGC-1α/PPARα pathway in AC16 cells.

Abstract

Cardiac hypertrophy is a well-established risk factor for cardiovascular mortality worldwide. According to a recent study, hypoxia-induced endoplasmic reticulum stress regulating long noncoding RNA (HypERlnc) is significantly reduced in the left ventricular myocardium of heart failure (HF) patients compared with healthy controls. However, the effect of HypERlnc on hypertrophy is unclear. In this study, the expression level of HypERlnc in serum of patients with chronic HF was analyzed. Moreover, the cardioprotective effect and mechanism of HypERlnc against cardiomyocyte hypertrophy were explored. Here, the level of HypERlnc expression was reduced in serum of patients with HF and in Angiotensin II (Ang II)-stimulated AC16 cells. HypERlnc overexpression could reduce cell size and inhibit expression of hypertrophy genes (ANP, BNP, and β-MHC) in the Ang II-induced cardiomyocyte hypertrophy. Meanwhile, HypERlnc could improve the Ang II-induced energy metabolism dysfunction and mitochondrial damage via upregulating PGC-1α/PPARα signaling pathway. Furthermore, it is found that SIRT1 SUMOylation mediated the HypERlnc-induced inhibition of cardiomyocyte hypertrophy and the improvement of energy metabolism. Taken together, this study suggests that HypERlnc suppresses cardiomyocyte hypertrophy and energy metabolism dysfunction via enhancing SUMOylation of SIRT1 protein. HypERlnc is a potential novel molecular target for preventing and treating pathological cardiac hypertrophy.