Open AccessHigh‐density lipoprotein inhibits mechanical stress‐induced cardiomyocyte autophagy and cardiac hypertrophy through angiotensin II type 1 receptor‐mediated PI 3K/Akt pathway
Author(s) -
Lin Li,
Liu Xuebo,
Xu Jianfeng,
Weng Liqing,
Ren Jun,
Ge Junbo,
Zou Yunzeng
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12567
Subject(s) - autophagy , angiotensin ii , angiotensin ii receptor type 1 , medicine , endocrinology , protein kinase b , muscle hypertrophy , chemistry , downregulation and upregulation , receptor , phosphorylation , microbiology and biotechnology , biology , apoptosis , biochemistry , gene
Mechanical stress triggers cardiac hypertrophy and autophagy through an angiotensin II (Ang II) type 1 ( AT 1) 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 LC 3b‐II and beclin‐1. Our results indicated that HDL significantly reduced mechanical stretch‐induced rise in autophagy as demonstrated by LC 3b‐II and beclin‐1. In addition, mechanical stress up‐regulated AT 1 receptor expression in both cultured cardiomyocytes and in mouse hearts, whereas HDL significantly suppressed the AT 1 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 AT 1 receptor, and HDL ameliorated cardiac hypertrophy and autophagy via Akt‐dependent mechanism.