Ischaemia reperfusion injury (IR) is characterised by abnormal increases in intracellular calcium during myocardial reperfusion that lead to cardiomyocyte death. In addition, IR is accompanied by an increase in the expression of microRNAs (miRNAs) such as miR-214, which has previously been identified as a sensitive marker of cardiac stress.
In this study, Aurora et al. found that genetic deletion of miR-214 in mice was associated with an increase in cardiomyocyte apoptosis, loss of cardiac contractility, and excessive fibrosis following IR injury. Subsequent work demonstrated that the cardioprotective role of miR-214 was due to its repression the mRNA encoding a key regulator of calcium influx, the Ncx1 sodium/calcium exchanger, and also to repression of several downstreatm effectors of calcium signalling that mediate cell death.
Conclusions:
This paper reveals a key role for the microRNA miR-214 in the response to ischaemia-reperfusion injury through its influence on calcium homeostasis. Therefore, increasing levels of miR-214 to attentuate calcium overload – and therefore cell death – could be a new therapeutic strategy for limiting ischaemia-reperfusion injury.
- Aurora AB, Mahmoud AI, Luo X et al. MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca2+ overload and cell death. J Clin Invest 2012;122:1222-1232.