TY - JOUR
T1 - Role of exercise on alleviating pressure overload-induced left ventricular dysfunction and remodeling via ampk-dependent autophagy activation
AU - Ma, Zhichao
AU - Qi, Jie
AU - Gao, Li
AU - Zhang, Jun
N1 - Funding Information:
From the 1School of Physical Education, Wuhan Business University, Wuhan, China, 2Physical Education College, Shanghai Normal University, Shanghai, China and 3Division of Allergy & Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, USA. This study was funded by Scientific Research Projects of Wuhan Business University (grant number 2014A010) and National Natural Science Foundation of China (grant number 31571223). Address for correspondence: Jun Zhang, PhD, Physical Education College, Shanghai Normal University, Shanghai 200234, China. E-mail: zhangjyzh@sina. com or Li Gao, MD, Division of Allergy & Clinical Immunology, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Room 3B.65 B, Baltimore, MD 21224, USA. E-mail: lgao2@jhmi.edu Received for publication August 28, 2019. Revised and accepted April 16, 2020. doi: 10.1536/ihj.19-443 All rights reserved by the International Heart Journal Association.
Publisher Copyright:
© 2020, International Heart Journal Association. All rights reserved.
PY - 2020
Y1 - 2020
N2 - Cardiac hypertrophy is one of the significant risk factors that result in maladaptive cardiac remodeling and heart failure, and exercise is known to exert cardioprotection. In this research, the cardioprotective function and exercise mechanisms were explored. The rats underwent transverse aortic constriction (TAC) or a sham operation. The rats that received TAC were randomly assigned to five groups: (1) rats subjected to a sham operation as control group (SC), (2) rats that underwent TAC group (TC), (3) TAC and moderate-intensity exercise group (TE), (4) TE plus 3-MA group (TEM), and (5) TE plus Compound C group (TEC). The heart function was measured via echocardiography. Histological analysis and relative protein testing were conducted to analyze collagen deposition and apoptosis. Furthermore, western blot was employed to measure the protein expression of relevant signaling pathways. Impaired cardiac function, interstitial fibrosis, enhanced apoptosis, and ER stress were observed in the TAC-induced left ventricular hypertrophy. Exercise attenuated TAC-induced cardiac dysfunction, interstitial fibrosis, and ER stress-related apoptosis. In addition, exercise significantly improved autophagy and upregulated AMPK phosphorylation. Furthermore, AMPK inhibitor Compound C repressed the activation of AMPK, and autophagy inhibitor 3-methyladenine reversed exercise-induced autophagy. All of these abolished the protection of exercise against cardiac dysfunction and fibrosis induced by TAC. Our results indicated that 4 weeks of treadmill exercise could alleviate pressure overload-induced LV dysfunction and remodeling via an autophagy-dependent mechanism, which was induced by enhancing autophagy through the activation of AMPK.
AB - Cardiac hypertrophy is one of the significant risk factors that result in maladaptive cardiac remodeling and heart failure, and exercise is known to exert cardioprotection. In this research, the cardioprotective function and exercise mechanisms were explored. The rats underwent transverse aortic constriction (TAC) or a sham operation. The rats that received TAC were randomly assigned to five groups: (1) rats subjected to a sham operation as control group (SC), (2) rats that underwent TAC group (TC), (3) TAC and moderate-intensity exercise group (TE), (4) TE plus 3-MA group (TEM), and (5) TE plus Compound C group (TEC). The heart function was measured via echocardiography. Histological analysis and relative protein testing were conducted to analyze collagen deposition and apoptosis. Furthermore, western blot was employed to measure the protein expression of relevant signaling pathways. Impaired cardiac function, interstitial fibrosis, enhanced apoptosis, and ER stress were observed in the TAC-induced left ventricular hypertrophy. Exercise attenuated TAC-induced cardiac dysfunction, interstitial fibrosis, and ER stress-related apoptosis. In addition, exercise significantly improved autophagy and upregulated AMPK phosphorylation. Furthermore, AMPK inhibitor Compound C repressed the activation of AMPK, and autophagy inhibitor 3-methyladenine reversed exercise-induced autophagy. All of these abolished the protection of exercise against cardiac dysfunction and fibrosis induced by TAC. Our results indicated that 4 weeks of treadmill exercise could alleviate pressure overload-induced LV dysfunction and remodeling via an autophagy-dependent mechanism, which was induced by enhancing autophagy through the activation of AMPK.
KW - Apoptosis
KW - Heart function
KW - Hypertrophy
KW - Myocardial fibrosis
KW - Transverse aortic constriction
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U2 - 10.1536/ihj.19-443
DO - 10.1536/ihj.19-443
M3 - Article
C2 - 32999189
AN - SCOPUS:85091720759
SN - 1349-2365
VL - 61
SP - 1022
EP - 1033
JO - International Heart Journal
JF - International Heart Journal
IS - 5
ER -