Vildagliptin, a dipeptidyl peptidase-4 inhibitor, attenuated endothelial dysfunction through miRNAs in diabetic rats

Abstract

Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors have various cellular effects that are associated with vascular protection. Here, we examined whether vildagliptin protected endothelial function in diabetic rats and explored the involved mechanism. Material and methods: Experimental diabetic rats were obtained by feeding a high-fat diet and administering an intraperitoneal injection of streptozotocin. Rats were randomly divided into four groups: Controls (CON), diabetes (DM), diabetes + low dose of vildagliptin (Lvil, 10 mg/kg/day), and diabetes + high dose of vildagliptin (Hvil, 20 mg/kg/day). The metabolic parameters, endothelial function, and whole miRNA expression were measured. Results: After a 12-week treatment, vildagliptin-treated rats showed a significant reduction in blood glucose and blood lipid levels. Moreover, vildagliptin recovered aortic endothelial function in diabetic rats. We identified 31 miRNAs that were differentially expressed in the Hvil group compared with the diabetic group. Importantly, through miRNA target biological function and pathway analysis, we found that vildagliptin activated miR-190-5p to inhibit Ccl2 expression and inhibited miR-134-5p and miR-375-3p to increase Bdnf and Pdk1 expression in the aorta. Conclusions: Our present study indicates that vildagliptin can recover endothelial function in diabetic rats. Anti-inflammatory and anti-apoptosis mechanisms and endothelial moderation may be the intervention targets of vildagliptin to protect the cardiovascular system through miRNA regulation.