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

被引:92
|
作者
Fan, Fan [1 ]
Sun, Aijun [1 ,2 ]
Zhao, Hangtian [1 ]
Liu, Xiangwei [1 ]
Zhang, Wenbin [1 ]
Jin, Xueting [1 ]
Wang, Cong [1 ]
Ma, Xin [1 ]
Shen, Cheng [1 ]
Zou, Yunzeng [1 ,2 ]
Hu, Kai [1 ]
Ge, Junbo [1 ,2 ]
机构
[1] Fudan Univ, Zhongshan Hosp, Shanghai Inst Cardiovasc Dis, 180 Feng Lin Rd, Shanghai 200032, Peoples R China
[2] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China
基金
中国国家自然科学基金;
关键词
Myocardial infarction; apoptosis; cardiomyocyte; MiRNA-34a; ALDH2; hypoxia; CIRCULATING MICRORNAS; ACTIVATION; BIOMARKERS; PROTEIN; POLYMORPHISM; ASSOCIATION; DIAGNOSIS; TOXICITY; DISEASE; MIR-34A;
D O I
10.2174/13816128113199990325
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:4865 / 4873
页数:9
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