title: High-density lipoprotein inhibits mechanical stress-induced cardiomyocyte autophagy and cardiac hypertrophy through angiotensin II type 1 receptor-mediated PI3K/Akt pathway.
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.
authors.affiliation: Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xuebo
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Science, Fudan University, Shanghai, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Weng
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Science, Fudan University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Science, Fudan University, Shanghai, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Science, Fudan University, Shanghai, China.
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D006332:Cardiomegaly / Q000473:pathology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013314:Stress, Mechanical
chemical_list: D002316:Cardiotonic Agents; D008075:Lipoproteins, HDL; D044140:Receptor, Angiotensin, Type 1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: AT1 receptor; HDL; autophagy; cardiac hypertrophy; heart failure