title: Acetaldehyde dehydrogenase 2 (ALDH2) deficiency exacerbates pressure overload-induced cardiac dysfunction by inhibiting Beclin-1 dependent autophagy pathway.
abstract: Mitochondrial aldehyde dehydrogenase 2 (ALDH2) was demonstrated to play cardioprotective roles in cardiovascular diseases. Nonetheless, little is known about the roles and mechanisms of ALDH2 in pressure overload-induced cardiac damages. In this study, we revealed that ALDH2 deficiency overtly exacerbated transverse aortic constriction (TAC)-induced cardiac dysfunction. Cardiomyocyte enlargement was observed in both WT and ALDH2-/- mice in HE-stained myocardial tissue samples at 8 weeks post TAC surgery. Mitochondrial morphology and structure were also significantly damaged post TAC surgery and the changes were aggravated in ALDH2-/- TAC hearts. ALDH2 deficiency also depressed myocardial autophagy in hearts at 8 weeks post TAC surgery with a potential mechanism of repressing the expression of Beclin-1 and promoting the interaction between Bcl-2 and Beclin-1. These data indicate that ALDH2 deficiency exacerbates the pressure overload induced cardiac dysfunction partly by inhibiting Beclin-1 dependent autophagy pathway. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Shen
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Fan
authors.affiliation: Institute of Behavioral Medicine, Jining Medical College, Jining 272067, China.
authors.forename: Zhiyin
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Sun
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China; Institute of Biomedical Science, Fudan University, Shanghai 200032, China.
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China; Institute of Biomedical Science, Fudan University, Shanghai 200032, China. Electronic address: sun.aijun@zs-hospital.sh.cn.
authors.forename: Aijun
authors.initials: A
authors.lastname: Sun
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China; Institute of Biomedical Science, Fudan University, Shanghai 200032, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000172:deficiency* / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D015153:Blotting, Western; D006332:Cardiomegaly / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology*; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D010766:Phosphorylation; D011312:Pressure; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; C515029:ALDH2 protein, mouse; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase
keywords: ALDH2; Autophagy; Beclin-1; Heart failure; Pressure overload