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The collected data have revealed the beneficial effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the vascular endothelium, including vildagliptin. However, the involved mechanisms are not yet clear. In this study, Sprague-Dawley rats were randomly divided into the following four groups: control, diabetic, diabetic + low-dose vildagliptin (10 mg/kg/d), and diabetic + high-dose vildagliptin (20 mg/kg/d). The diabetic model was created by feeding a high-fat diet for four weeks and injection of streptozotocin. Then, vildagliptin groups were given oral vildagliptin for twelve weeks, and the control and diabetic groups were given the same volume of saline. The metabolic parameters, endothelial function, and whole genome expression in the aorta were examined. After 12 weeks of treatment, vildagliptin groups showed significantly reduced blood glucose, blood total cholesterol, and attenuated endothelial dysfunction. Notably, vildagliptin may inhibit angiopoietin-like 3  (Angptl3)  and betaine-homocysteine S-methyltransferase  (Bhmt)  expression and activated paraoxonase-1  (Pon1)  in the aorta of diabetic rats. These findings may demonstrate the vasoprotective pathway of vildagliptin  in vivo .

A Possible Mechanism: Vildagliptin Prevents Aortic Dysfunction through Paraoxonase and Angiopoietin-Like 3