title: Autophagy protects cardiomyocytes from the myocardial ischaemia-reperfusion injury through the clearance of CLP36.
abstract: Cardiovascular disease (CVD) is the leading cause of the death worldwide. An increasing number of studies have found that autophagy is involved in the progression or prevention of CVD. However, the precise mechanism of autophagy in CVD, especially the myocardial ischaemia-reperfusion injury (MI/R injury), is unclear and controversial. Here, we show that the cardiomyocyte-specific disruption of autophagy by conditional knockout of Atg7 leads to severe contractile dysfunction, myofibrillar disarray and vacuolar cardiomyocytes. A negative cytoskeleton organization regulator, CLP36, was found to be accumulated in Atg7-deficient cardiomyocytes. The cardiomyocyte-specific knockout of Atg7 aggravates the MI/R injury with cardiac hypertrophy, contractile dysfunction, myofibrillar disarray and severe cardiac fibrosis, most probably due to CLP36 accumulation in cardiomyocytes. Altogether, this work reveals autophagy may protect cardiomyocytes from the MI/R injury through the clearance of CLP36, and these findings define a novel relationship between autophagy and the regulation of stress fibre in heart.
authors: Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, People's Republic of China sgli2000@hotmail.com.
authors: Shiguo
authors: S
authors: Li
authors: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors: Chao
authors: C
authors: Liu
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors: Lei
authors: L
authors: Gu
authors: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors: Lina
authors: L
authors: Wang
authors: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors: Yongliang
authors: Y
authors: Shang
authors: Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, People's Republic of China.
authors: Qiong
authors: Q
authors: Liu
authors: Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, People's Republic of China.
authors: Junyi
authors: J
authors: Wan
authors: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors: Jian
authors: J
authors: Shi
authors: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors: Fang
authors: F
authors: Wang
authors: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors: Zhiliang
authors: Z
authors: Xu
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People's Republic of China gj28@ibp.ac.cn.
authors: Guangju
authors: G
authors: Ji
authors: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China leways@ioz.ac.cn.
authors: Wei
authors: 0000-0002-6235-0749
authors: W
authors: Li
mesh_terms: D000818:Animals; D001343:Autophagy; D000071193:Autophagy-Related Protein 7 / Q000235:genetics*; D002478:Cells, Cultured; D055786:Gene Knockout Techniques; D060588:LIM Domain Proteins / Q000378:metabolism*; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C502661:Atg7 protein, mouse; D060588:LIM Domain Proteins; C106649:Ldb2 protein, mouse; D014157:Transcription Factors; D000071193:Autophagy-Related Protein 7
keywords: Atg7; CLP36; autophagy; myocardial ischaemia-reperfusion injury; stress fibre