Post-infarct treatment with microRNA145 reduces myocardial infarct size through acceleration of myocyte autophagy in rabbits

Abstract

Background: We previously reported that microRNA145 (miRNA145) attenuates the ischemia-reperfusion injury. However, it is not still unclear how miRNA145 attenuates the ischemia-reperfusion injury. 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 reperfusion, 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, and the infarct size was calculated as a percentage of the risk area of the left ventricle. In another series of experiments, rat myoblast H9C2 were treated with 20 nM of miRNA145 and investigated the morphological changes by electron microscopy and signals by western blot analysis such as LC3B. 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. In the myoblast experiment, treatment with miRNA145 caused autophagic changes such as autophagosome and autolysosome, and caused activation of 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.