A role for miR‐471 in cardiac ischemia‐reperfusion injury

Abstract

MicroRNAs (miRNAs) are involved in translational and transcriptional regulation of gene and protein expression. Specific miRNA patterns and targets have been identified for cardiac pathologies such as cardiac hypertrophy, angiogenesis, and heart failure. However, a role for miRNA in ischemia‐reperfusion injury is not clear. Preliminary miRNA array studies revealed a subset of miRNAs induced by ischemic preconditioning, with miR‐471 showing the largest fold‐change. We hypothesized that infusion of miR‐471 will induce cardiac protection. Pure, synthesized miR‐471 was conjugated to a peptide transduction domain‐dsRNA binding domain fusion protein (vehicle). The conjugated miR‐471 or vehicle alone was injected into a Langendorff‐perfused mouse heart model before the onset of global ischemia‐reperfusion. Left ventricular developed pressure (LVDP) was continuously measured. Our results show that miR‐471 significantly increased LVDP and rate of recovery of LVDP normalized to pre‐ischemia as compared to vehicle‐injected controls. Our data suggest that miR‐471 plays an important role in protection of the myocardium against ischemia‐reperfusion injury and may represent a novel therapeutic target.