The emerging role of dipeptidyl peptidase-4 inhibitors in cardiovascular protection: current position and perspectives.

Dipeptidyl peptidase-4 (DPP-4 or CD26) inhibitors, a new class of oral anti-hyperglycemic agents that prolong the bioavailability of the endogenously secreted incretin hormone glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic polypeptide (GIP), are effective in the treatment of diabetes. Accumulating data have indicated that DPP-4 inhibitors play important protective roles in the cardiovascular system. DPP-4 inhibitors act to decrease myocardial infarct size, stabilize the cardiac electrophysiological state during myocardial ischemia, reduce ischemia/reperfusion injury, and prevent left ventricular remodeling after myocardial infarction. Moreover, DPP-4 inhibitors can mobilize stem/progenitor cells to move to sites of cardiovascular injury, thus further promoting tissue repair. In addition, DPP-4 inhibitors not only improve myocardial metabolism but also regulate cardioactive peptides. DPP-4 inhibitors can also protect the vasculature through their anti-inflammatory and anti-atherosclerotic effects and through the ability of the inhibitors to promote vascular relaxation. Finally, the potential effects of DPP-4 inhibitors on blood pressure and lipid metabolism have also been investigated. However, some reports on the cardioprotective activities of DPP-4 inhibitors are controversial. Herein, we summarize the available data on cardiovascular protection by DPP-4 inhibitors that have emerged in recent years and discuss current position and future perspectives concerning the use of DPP-4 inhibitors in cardiovascular medicine.