Role of exercise on alleviating pressure overload-induced left ventricular dysfunction and remodeling via ampk-dependent autophagy activation

Zhichao Ma, Jie Qi, Li Gao, Jun Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1022-1033
Number of pages12
JournalInternational Heart Journal
Volume61
Issue number5
DOIs
StatePublished - 2020

Keywords

  • Apoptosis
  • Heart function
  • Hypertrophy
  • Myocardial fibrosis
  • Transverse aortic constriction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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