Concomitant effect of vildagliptin and ischemic post-conditioning on myocardial infarction and expression of microRNA-140 and microRNA-125b following ischemic injury-reperfusion injury in rats with type-II diabetes

This study investigated the effect of combination therapy with vildagliptin and ischemic post-conditioning (IPostC) on myocardial infarction and expression of micro ribonucleic acid miR-140 and miR-125b as the regulators of mitochondrial dynamics in myocardial ischemic-reperfusion (IR) injury of rats with type 2 diabetes mellitus.

Chronic diabetes was induced in rats using a high-fat diet protocol and a low dose of streptozotocin over a period of 3 months. In the last month of the diabetic period, vildagliptin was administered orally for 4 weeks once a day, and IR injury was induced by closing the anterior left coronary artery bypass graft for 35 min followed by reopening of it for 60 min. The IPostC protocol was performed at the onset of reperfusion in 6 alternative cycles of 10-second ischemia and reperfusion. At the end of the experiment, the ischemic region of left ventricles was sampled. The size of the risk area and myocardial infarction were studied by planimetry. The levels of miR-140 and miR-125b expression in the left ventricle were evaluated using real-time PCR.

The combination of vildagliptin and IPostC was able to reduce myocardial infarction compared to untreated diabetic group (p < 0.05),  inhibit the elevated expression of miR-140 caused by IR damage, and increase the expression of miR-125b in diabetic hearts (p < 0.05).

The combination of vildagliptin and IPostC has cardioprotective effect against IR injury in rats with type II diabetes by change in the expression of micro-RNAs involved in cardioprotection.