Knockout of Eva1a leads to rapid development of heart failure by impairing autophagy.
EVA1A (Eva-1 homologue A) is a novel lysosome and endoplasmic reticulum-associated protein that can regulate cell autophagy and apoptosis. Eva1a is expressed in the myocardium, but its function in myocytes has not yet been investigated. Therefore, we generated inducible, cardiomyocyte-specific Eva1a knockout mice with an aim to determine the role of Eva1a in cardiac remodelling in the adult heart. Data from experiments showed that loss of Eva1a in the adult heart increased cardiac fibrosis, promoted cardiac hypertrophy, and led to cardiomyopathy and death. Further investigation suggested that this effect was associated with impaired autophagy and increased apoptosis in Eva1a knockout hearts. Moreover, knockout of Eva1a activated Mtor signalling and the subsequent inhibition of autophagy. In addition, Eva1a knockout hearts showed disorganized sarcomere structure and mitochondrial misalignment and aggregation, leading to the lack of ATP generation. Collectively, these data demonstrated that Eva1a improves cardiac function and inhibits cardiac hypertrophy and fibrosis by increasing autophagy. In conclusion, our results demonstrated that Eva1a may have an important role in maintaining cardiac homeostasis.
Department of Cardiology, Peking University Third Hospital, Beijing 100191, China.
Shu
S
Zhang
Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.|Peking University Center for Human Disease Genomics, Beijing 100191, China.
Xin
X
Lin
Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.|Peking University Center for Human Disease Genomics, Beijing 100191, China.
Ge
G
Li
Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Xue
X
Shen
Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Di
D
Niu
Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.|Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
Guang
G
Lu
Department of Cardiology, Peking University Third Hospital, Beijing 100191, China.
Xin
X
Fu
Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.|Peking University Center for Human Disease Genomics, Beijing 100191, China.
Yingyu
Y
Chen
Department of Cardiology, Peking University Third Hospital, Beijing 100191, China.
Ming
M
Cui
Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Yun
Y
Bai
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; C000623320:Eva1a protein, mouse; D008565:Membrane Proteins; D000255:Adenosine Triphosphate