Aliskiren‐attenuated myocardium apoptosis via regulation of autophagy and connexin‐43 in aged spontaneously hypertensive rats

Journal of Cellular and Molecular Medicine

Wenbin Zhang³  Gang Zhao¹  Xiaona Hu²  Min Wang³  Hua Li¹  Yong Ye¹  Qijun Du¹  Jin Yao⁴  Zhijun Bao²  Wei Hong⁵  Guosheng Fu³  Junbo Ge¹ 

[1] Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China;Gastroenterology Department, Huadong Hospital, Fudan University, Shanghai, China;Department of Cardiology, Biomedical Research (Therapy) Center, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China;Cardiovascular Department, Huadong Hospital, Fudan University, Shanghai, China;Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China

关键词: connexin‐43;    aged spontaneously hypertensive rats;    apoptosis;    autophagy;    Aliskiren;    Survivin;    AKT;    Caspase3;   

DOI  :  10.1111/jcmm.12273

来源: Wiley

【 摘 要 】

Abstract

There are controversies about the mechanism of myocardium apoptosis in hypertensive heart disease. The aim of this study was to investigate the relationship among autophagy, Cx43 and apoptosis in aged spontaneously hypertensive rats (SHRs) and establish whether Aliskiren is effective or not for the treatment of myocardium apoptosis. Twenty-one SHRs aged 52 weeks were randomly divided into three groups, the first two receiving Aliskiren at a dose of 10 and 25 mg/kg/day respectively; the third, placebo for comparison with seven Wistar-Kyoto (WKY) as controls. After a 2-month treatment, systolic blood pressure (SBP), heart to bw ratios (HW/BW%) and angiotensin II (AngII) concentration were significantly enhanced in SHRs respectively. Apoptotic cardiomyocytes detected with TUNEL and immunofluorescent labelling for active caspase-3 increased nearly fourfolds in SHRs, with a decline in the expression of survivin and AKT activation, and an increase in caspase-3 activation and the ratio of Bax/Bcl-2. Myocardium autophagy, detected with immunofluorescent labelling for LC3-II, increased nearly threefolds in SHRs, with the up-regulation of Atg5, Atg16L1, Beclin-1 and LC3-II. The expression of Cx43 plaque was found to be down-regulated in SHRs. Aliskiren significantly reduced SBP, HW/BW%, AngII concentration and the expression of AT₁R. Thus, Aliskiren protects myocardium against apoptosis by decreasing autophagy, up-regulating Cx43. These effects showed a dose-dependent tendency, but no significance. In conclusion, the myocardium apoptosis developed during the hypertensive end-stage of SHRs could be ameliorated by Aliskiren via the regulation of myocardium autophagy and maladaptive remodelling of Cx43.

【 授权许可】

CC BY   
© 2014 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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