title: Inhibition of autophagy recovers cardiac dysfunction and atrophy in response to tail-suspension.
abstract: OBJECTIVE
  Physical inactivity during space flight or prolonged bed rest may cause cardiac dysfunction and atrophy, but the exact mechanism that governs the regulation of myocardial dysfunction and cardiac atrophy remains poorly understood. Autophagy, a protein degradation pathway, has recently been shown to be involved in the regulation of cardiac dysfunction and atrophy. In this study, we investigated the relationships between dysfunction and inactivity-induced atrophy and autophagy in rat cardiac tissue.
  
  
  METHODS
  Physical inactivity was simulated by a tail suspension model, and cardiac function was examined by echocardiography. Cardiac atrophy was measured by wheat germ agglutinin staining and autophagic activity was detected by Western blot analysis and immunofluorescence staining.
  
  
  RESULTS
  We demonstrated that cardiac function, especially contractility, declined and the area of cardiac atrophy increased in the tail-suspended cardiac tissue. Additionally, the cross-sectional area of myocardial cells decreased; however, apoptosis did not increase with tail suspension. Similarly, the expression of autophagy-related proteins and the number of autophagosomes were elevated in the tail-suspended cardiac tissue. Moreover, the administration of chloroquine, an autophagy inhibitor, reversed cardiac dysfunction and atrophy via the suppression of autophagic activity during suspension. Our results indicate that autophagy facilitates the development and progression of cardiac dysfunction and atrophy induced by tail suspension.
  
  
  CONCLUSIONS
  Our studies hint that the components of the autophagy-related signaling pathway are potential therapeutic targets for the treatment of cardiac diseases induced by physical inactivity.
authors.affiliation: Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, 1# Tiantan Xili, Beijing 100050, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Centre, 26# Beiqing Road, Beijing 100094, PR China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Centre, 26# Beiqing Road, Beijing 100094, PR China.
authors.forename: Bing-Mu
authors.initials: BM
authors.lastname: Xin
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Centre, 26# Beiqing Road, Beijing 100094, PR China.
authors.forename: Jun-Lian
authors.initials: JL
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Centre, 26# Beiqing Road, Beijing 100094, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Centre, 26# Beiqing Road, Beijing 100094, PR China.
authors.forename: Yong-Zhi
authors.initials: YZ
authors.lastname: Li
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Centre, 26# Beiqing Road, Beijing 100094, PR China. Electronic address: wangjiaping_1113@163.com.
authors.forename: Jia-Ping
authors.initials: JP
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001284:Atrophy / Q000473:pathology; D001343:Autophagy / Q000187:drug effects*; D006331:Heart Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D019417:Hindlimb Suspension / Q000009:adverse effects*; D008297:Male; D009043:Motor Activity; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Cardiac atrophy; Cardiac dysfunction; Inhibiting autophagy; Myocardial contractility; Physical inactivity