MicroRNA expression signature and the role of microRNA-21 in the early phase of acute myocardial infarction.
Several recent reports have suggested that microRNAs (miRNAs) might play critical roles in acute myocardial infarction (AMI). However, the miRNA expression signature in the early phase of AMI has not been identified. In this study, the miRNA expression signature was investigated in rat hearts 6 h after AMI. Compared with the expression signature in the noninfarcted areas, 38 miRNAs were differentially expressed in infarcted areas and 33 miRNAs were aberrantly expressed in the border areas. Remarkably, miR-21 expression was significantly down-regulated in infarcted areas, but was up-regulated in border areas. The down-regulation of miR-21 in the infarcted areas was inhibited by ischemic preconditioning, a known cardiac protective method. Overexpression of miR-21 via adenovirus expressing miR-21 (Ad-miR-21) decreased myocardial infarct size by 29% at 24 h and decreased the dimension of left ventricles at 2 weeks after AMI. Using both gain-of-function and loss-of-function approaches in cultured cardiac myocytes, we identified that miR-21 had a protective effect on ischemia-induced cell apoptosis that was associated with its target gene programmed cell death 4 and activator protein 1 pathway. The protective effect of miR-21 against ischemia-induced cardiac myocyte damage was further confirmed in vivo by decreased cell apoptosis in the border and infarcted areas of the infarcted rat hearts after treatment with Ad-miR-21. The results suggest that miRNAs such as miR-21 may play critical roles in the early phase of AMI.
Dong
Shimin
S
Department of Anesthesiology, RNA and Cardiovascular Research Laboratory, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07101, USA.
Cheng
Yunhui
Y
Yang
Jian
J
Li
Jingyuan
J
Liu
Xiaojun
X
Wang
Xiaobin
X
Wang
Dong
D
Krall
Thomas J
TJ
Delphin
Ellise S
ES
Zhang
Chunxiang
C
D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014161:Transduction, Genetic
D035683:MicroRNAs
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