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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

MicroRNA-34a Promotes Cardiomyocyte Apoptosis Post Myocardial Infarction Through Down-regulating Aldehyde Dehydrogenase 2

Author(s): Fan Fan, Aijun Sun, Hangtian Zhao, Xiangwei Liu, Wenbin Zhang, Xueting Jin, Cong Wang, Xin Ma, Cheng Shen, Yunzeng Zou, Kai Hu and Junbo Ge

Volume 19, Issue 27, 2013

Page: [4865 - 4873] Pages: 9

DOI: 10.2174/13816128113199990325

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.

Keywords: Myocardial infarction, apoptosis, cardiomyocyte, MiRNA-34a, ALDH2, hypoxia.


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