Increased Expression of MiR-13oa Improves Cardiac Function and Reduces Ventricular Remodeling Following Myocardial Infarction

MicroRNA130a has been reported to promote angiogenesis which is an important factor in cardiac repair following myocardial infarction (MI). This study examined the role of miR-130a in cardiac function and cardiac remodeling following MI. Lentivirus expressing miR-130 (LmiR-130a) was delivered into mouse hearts (n=11) through the right carotid artery. Lentivirus expressing control miR (LmiR-con) served as transfection control (n=9). Seven days after transfection, the mice were subjected to MI by permanent ligation of LAD. Untransfected MI mice (n=24) served as MI control. Cardiac function was assessed by echocardiography before and after MI (1, 3, 7, 14, and 21 days). In LmiR-130a transfected MI group, EF% and %FS were significantly greater (~50%) than in LmiR-con and MI groups. LVESD and LVEDD values in LmiR-130a MI mice were markedly lower than in LmiR-con and MI groups. LmiR-130 transfection markedly increased the number of capillaries and decreased fibrotic deposition in the myocardium compared with LmiR-con and MI controls. To examine the effect of miR-130a on myocardial infarction, we induced myocardial ischemia (45 min) followed by reperfusion (24 h). Infarct size was analyzed by TTC staining. Transfection of LmiR-130a (n=8) significantly reduced myocardial infarct size by 53% compared with untransfected I/R group (n=7). LmiR-con transfection did not alter I/R induced infarct size (n=7). In a separate experiment, mice transfected with LmiR-130a (n=6) or LmiR-con (n=6) and untransfected (n=6) were subjected to MI for 3 days. Sham surgical operation served as sham controls (n=4/groups). Hearts were harvested and cellular proteins were prepared for Western blot analysis. LmiR-130a transfection suppressed PTEN expression, increased the levels of phospho-Akt and phospho-GSK-3β, enhanced VEGF and decreased HoxA5 levels, when compared with LmiR-con and MI groups. In addition, LmiR-130a transfection significantly reduced myocardial apoptosis, increased Bcl2 and prevented MI-increased Bax levels. We concluded that miR-130a improves cardiac function and reduces cardiac remodeling following MI. The mechanisms involve activation PI3K/Akt signaling, stimulation of angiogenesis, and attenuation of MI-induced apoptosis.