Effects of Dipeptidyl Peptidase 4 Inhibition on the Endothelial Control of the Vascular Tone.

Dipeptidyl peptidase 4 (DPP4) is a serine protease known to cleave incretin hormones, which stimulate insulin secretion after food intake, a fact that supported the development of its inhibitors (DPP4i, or gliptins) for the treatment of type 2 diabetes mellitus. In addition to their glucose lowering effects, DPP4i show benefits for the cardiovascular system that could be related, at least in part, to their protective action on the vascular endothelium. DPP4i has been associated with the reversal of endothelial dysfunction, an important predictor of cardiovascular events and a hallmark of diseases such as atherosclerosis, diabetes mellitus, hypertension, and heart failure. In animal models of these diseases, DPP4i increase nitric oxide bioavailability and limit oxidative stress, thereby improving the endothelium-dependent relaxation. Similar effects on flow-mediated dilation and attenuation of endothelial dysfunction have also been noted in human studies, suggesting a value for gliptins in the clinical scenario, despite the variability of the results regarding the DPP4i used, treatment duration and presence of comorbidities. In this mini review we discuss the advances in our comprehension of the DPP4i effects on endothelial regulation of vascular tone. Understanding the role of DPP4 and its involvement in the signaling mechanisms leading to endothelial dysfunction will pave the way for a broader use of DPP4i in conditions which endothelial dysfunction is an important pathophysiological player.