title: MicroRNA-34a promotes cardiomyocyte apoptosis post myocardial infarction through down-regulating aldehyde dehydrogenase 2.
abstract: MicroRNA-34a (miR-34a) promotes apoptosis via down-regulating many anti-apoptotic proteins. Aldehyde dehydrogenase 2 (ALDH2) is an anti-apoptotic enzyme whose activity decline associates with myocardial injury. We tested hypothesis that miR-34a might play a pro-apoptotic role in myocardial infarction (MI) by down-regulating ALDH2. MiR-34a was highly increased while ALDH2 expression was decreased after experimental MI. Overexpression of miR-34a in neonatal rat cardiomyocyte could significantly enhance apoptosis and down-regulate ALDH2 expression. In 293 cells, luciferase reporter assay results demonstrated that ALDH2 was a direct target of miR-34a. Serum miR-34a levels in acute myocardial infarction (AMI) patients and rats were significantly higher than healthy subjects and sham rats. Our results proved that miR-34a could promote cardiomyocyte apoptosis via negatively regulating ALDH2 and circulating miR-34a was increased in the condition of MI. Thus, miR-34a may constitute a new therapeutic target and diagnostic marker for patients with MI.
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, PR China.
authors: Fan
authors: F
authors: Fan
authors: Aijun
authors: A
authors: Sun
authors: Hangtian
authors: H
authors: Zhao
authors: Xiangwei
authors: X
authors: Liu
authors: Wenbin
authors: W
authors: Zhang
authors: Xueting
authors: X
authors: Jin
authors: Cong
authors: C
authors: Wang
authors: Xin
authors: X
authors: Ma
authors: Cheng
authors: C
authors: Shen
authors: Yunzeng
authors: Y
authors: Zou
authors: Kai
authors: K
authors: Hu
authors: Junbo
authors: J
authors: Ge
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D000369:Aged, 80 and over; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D015687:Cell Hypoxia; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020413:3' Untranslated Regions; C522425:MIRN34 microRNA, human; C560944:MIRN34 microRNA, rat; D035683:MicroRNAs; D024101:Mitochondrial Proteins; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat