MicroRNA-34a promotes cardiomyocyte apoptosis post myocardial infarction through down-regulating aldehyde dehydrogenase 2

• Published in: Current pharmaceutical design Vol. 19; no. 27; p. 4865
• Main Authors: Fan, Fan, Sun, Aijun, Zhao, Hangtian, Liu, Xiangwei, Zhang, Wenbin, Jin, Xueting, Wang, Cong, Ma, Xin, Shen, Cheng, Zou, Yunzeng, Hu, Kai, Ge, Junbo
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 2013
• Subjects: 3' Untranslated Regions; Aged; Aged, 80 and over; Aldehyde Dehydrogenase - antagonists & inhibitors; Aldehyde Dehydrogenase - genetics; Aldehyde Dehydrogenase - metabolism; Aldehyde Dehydrogenase, Mitochondrial; Animals; Animals, Newborn; Apoptosis; Cell Hypoxia; Cells, Cultured; Down-Regulation; Female; Genes, Reporter; HEK293 Cells; Humans; Male; MicroRNAs - blood; MicroRNAs - metabolism; Middle Aged; Mitochondrial Proteins - antagonists & inhibitors; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Myocardial Infarction - blood; Myocardial Infarction - enzymology; Myocardial Infarction - metabolism; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Rats; Rats, Sprague-Dawley
• ISSN: 1873-4286
• DOI: 10.2174/13816128113199990325

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.