Abstract 9434: Post-infarct Treatment With Microrna145 Protects the Heart Against Myocardial Ischemia-reperfusion Injury Through Acceleration of Myocyte Autophagy

Abstract

Background: We previously reported that microRNA145 (miRNA145) attenuates the ischemia-reperfusion injury. However, the mechanism how miRNA145 reduces the myocardial infarct size is still unclear. Objective: We aimed to investigate whether post-infarct treatment with miRNA145 reduces myocardial infarct size and its precise mechanism in a rabbit model of myocardial infarction. Methods: Male Japanese white rabbits underwent 30 min of coronary occlusion followed by 14 days of reperfusion. Rabbits received intravenous injection of saline (control group, n=7) or 0.035 mg/kg of miRNA145 encapsulated with liposome (miRNA145 group, n=7) immediately after reperfusion. At 14 days after reperefusion, rabbits were sacrificed and the hearts were removed. The area at risk and infarct areas were measured by evans blue dye and TTC staining, respectively. The infarct size was calculated as a percentage of the risk area of the left ventricle. Heart tissues were sampled and the morphological changes were investigated by electron microscopy, and the expression of LC3B, an indicator of autophagy, was assessed by western blot analysis. In another series of experiments, rat myoblast H9C2 were treated with 20 nM of miRNA145 and investigated the morphological changes by electron microscopy and the expression of LC3B by western blot analysis. Results: Post-infarct treatment with miRNA145 significantly reduced the myocardial infarct size (16.0±3.1 %) as compared to the control (28.7±6.1 %) group. Post-infarct treatment with miRNA145 significantly improved LV remodeling and improved ±dp/dt as compared to the control group. Both in vitro myoblast and in vivo experiments, treatment with miRNA145 induced autophagic changes such as autophagosome and autolysosome, and activated LC3B. Conclusions: It is suggested that post-infarct treatment with miRNA145 attenuated ischemia-reperfusion injury through acceleration of myocyte autophagy. The miRNA145 may be a promising strategy for treatment of acute myocardial infarction.