AIMS: 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.
METHODS AND 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.
CONCLUSION: 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.