P565Identification of microRNAs involved in ischemia/reperfusion injury and cardioprotection by pre- and postconditioning

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Abstract

Aims

The role of microRNAs in cardioprotection is unexplored. Therefore, here we characterized early changes in microRNA expression and identified microRNAs involved in ischemia/reperfusion injury, ischemic preconditioning, and ischemic postconditioning in rat hearts.

Methods and results

Hearts isolated from male Wistar rats were subjected to i) time-matched normoxic perfusion, ii) test ischemia/reperfusion induced by 30 min coronary occlusion followed by 120 min reperfusion, iii) preconditioning (3 cycles of 5 min coronary occlusion and 5 min reperfusion) followed by test ischemia/reperfusion, or iv) test ischemia/reperfusion with postconditioning induced by 6 consecutive cycles of 10s global ischemia and 10s reperfusion at the onset of the 120 min reperfusion. Infarct size measured by TTC staining at 120 min reperfusion was significantly reduced by both preconditioning and postconditioning, when compared to ischemia/reperfusion. Out of the 350 microRNAs assessed by microRNA microarray analysis, approximately 150 microRNAs showed expression. 17 microRNAs were identified to be involved in ischemia/reperfusion (e.g. let7 family members, microRNA-328, and 92a), 10 in preconditioning (e.g. microRNA-320, 139-5p and -3p) and 52 in postconditioning (e.g. microRNA-208, -21, -494, -499). Expression of selected microRNAs was also validated by QRT-PCR.

Conclusions

Ischemia/reperfusion-induced acute alterations in myocardial microRNA expression profile are significantly influenced by both pre- and postconditioning, which shows the involvement of microRNAs in cardioprotective signaling. By a systematic comparison of the microRNA expression patterns in ischemia/reperfusion, pre-, and postconditioning, we were able to identify specific microRNAs involved in ischemia/reperfusion injury and cardioprotection and to reveal several microRNAs as potential therapeutic targets for cardioprotection.

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