Ischaemic preconditioning-regulated miR-21 protects heart against ischaemia/reperfusion injury via anti-apoptosis through its target PDCD4.
OBJECTIVE
The aims of the present study are to determine the miRNA expression signature in rat hearts after ischaemic preconditioning (IP) and to identify an IP-regulated miRNA, miR-21, in IP-mediated cardiac protection, and the potential cellular and molecular mechanisms involved.


RESULTS
The miRNA expression signature was investigated in rat hearts. Among the 341 arrayed miRNAs, 40 miRNAs were differentially expressed (21 up and 19 down) in rat hearts with IP, compared with their controls. Some of these differentially expressed miRNAs were further verified by quantitative reverse transcriptase-polymerase chain reaction. Remarkably, miR-21 was one of most upregulated miRNAs in hearts after IP. In vivo, IP-mediated cardiac protection against ischaemia/reperfusion injury was inhibited by knockdown of cardiac miR-21. In cultured cardiac myocytes, we identified that miR-21 also had a protective effect on hypoxia/reoxygenation-induced cell apoptosis that was associated with its target gene, programmed cell death 4. The protective effect of miR-21 on cardiac cell apoptosis was further confirmed in rat hearts after ischaemia/reperfusion injury in vivo.


CONCLUSIONS
The results suggest that miRNAs are involved in IP-mediated cardiac protection. Identifying the roles of IP-regulated miRNAs in cardiac protection may provide novel therapeutic and preventive targets for ischaemic heart disease.
Cheng
Yunhui
Y
RNA and Cardiovascular Research Laboratory, Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, MSB-E548, Newark, NJ 07101, USA.
Zhu
Ping
P
Yang
Jian
J
Liu
Xiaojun
X
Dong
Shimin
S
Wang
Xiaobin
X
Chun
Bao
B
Zhuang
Jian
J
Zhang
Chunxiang
C
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D019610:Cytoprotection / Q000235:genetics; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; C467042:Pdcd4 protein, rat; C546082:mirn21 microRNA, rat