Impact of vildagliptin on vascular and fibrotic remodeling of myocardium in experimental diabetic cardiomyopathy

Abstract

The effect of dipeptidyl peptidase-4 inhibitors (DPP-4is) on myocardium in diabetic cardiomyopathy (DCM) remains a matter of debate. In the current study we investigated the effect of vildagliptin (VILDA, 3 mg/kg/d) on myocardium of DCM focusing on coronary microcirculation as well as on endothelial stress markers (ICAM and VCAM). We divided animals equally into 4 groups; nondiabetic (ND), VILDA per se, DCM and DCM + VILDA and their myocardium was evaluated for the fibro-vascular remodeling immunohistochemically as well as for molecular changes. VILDA had reversed the histological changes occurred in DCM including the disintegration, degeneration, and steatosis of cardiomyocytes with disappearance of the edema fluid. In addition VILDA significantly increased (p < 0.05) density of the coronary microcirculation and relieved endothelial stress. However, it did not prevent the development of fibrotic remodeling including the increased collagen deposition and the significantly upregulated (p < 0.05) corresponding genes. Therefore VILDA may have a positive impact on the microvascular remodeling, but not on fibrotic changes, in DCM.