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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.
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页码:4865 / 4873
页数:9
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