High‐density lipoprotein inhibits mechanical stress‐induced cardiomyocyte autophagy and cardiac hypertrophy through angiotensin II type 1 receptor‐mediated PI3K/Akt pathway

Journal of Cellular and Molecular Medicine

Li Lin¹  Xuebo Liu¹  Jianfeng Xu²  Liqing Weng¹  Jun Ren²  Junbo Ge² 

[1] Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China;Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Science, Fudan University, Shanghai, China

关键词: autophagy;    cardiac hypertrophy;    heart failure;    AT1 receptor;    HDL;   

DOI  :  10.1111/jcmm.12567

来源: Wiley

【 摘 要 】

Abstract

Mechanical stress triggers cardiac hypertrophy and autophagy through an angiotensin II (Ang II) type 1 (AT1) receptor-dependent mechanism. Low level of high density lipoprotein (HDL) is an independent risk factor for cardiac hypertrophy. This study was designed to evaluate the effect of HDL on mechanical stress-induced cardiac hypertrophy and autophagy. A 48-hr mechanical stretch and a 4-week transverse aortic constriction were employed to induce cardiomyocyte hypertrophy in vitro and in vivo, respectively, prior to the assessment of myocardial autophagy using LC3b-II and beclin-1. Our results indicated that HDL significantly reduced mechanical stretch-induced rise in autophagy as demonstrated by LC3b-II and beclin-1. In addition, mechanical stress up-regulated AT1 receptor expression in both cultured cardiomyocytes and in mouse hearts, whereas HDL significantly suppressed the AT1 receptor. Furthermore, the role of Akt phosphorylation in HDL-mediated action was assessed using MK-2206, a selective inhibitor for Akt phosphorylation. Our data further revealed that MK-2206 mitigated HDL-induced beneficial responses on cardiac remodelling and autophagy. Taken together, our data revealed that HDL inhibited mechanical stress-induced cardiac hypertrophy and autophagy through downregulation of AT1 receptor, and HDL ameliorated cardiac hypertrophy and autophagy via Akt-dependent mechanism.

【 授权许可】

CC BY   
© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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