Dual Role of Dipeptidyl Peptidase IV (DPP IV) in Angiogenesis and Vascular Remodeling

Conclusion

Our studies, both in vivo and in vitro, strongly indicate a critical role of DPP IV in modifying NPY’s actions in the cardiovascular system. The protein can act as an NPY converting enzyme, cleaving the full length NPY_1–36 to its shorter form, NPY_3–36, and shifting the peptide’s activities from Y1-mediated vasoconstriction and vascular smooth muscle cell growth to Y2/Y5-mediated angiogenesis. On the other hand, the intriguing phenomenon of DPP IV being a necessary factor in Y1/Y5-mediated vascular smooth muscle cell proliferation implicates its possible role as a co-receptor facilitating signalling of and/or ligand binding to NPY receptors. Additional studies are required to determine mechanisms of DPP IV actions in certain cellular models, e.g. why does the enzyme not inactivate NPY_1–36 in the vascular smooth muscle cell-Y1/Y5 system by cleavage of the peptide, or whether or not other proteases, such as aminopeptidase P, can compensate for loss of DPP IV. If DPP IV proves to be indeed a critical step required for inhibiting NPY’s contractile and pro-atherosclerotic effect and potentiating its angiogenic activities, abnormally low DPP IV expression and activity could be a risk factor for hypertension and ischemic cardiovascular diseases, in which NPY has already been implicated²⁸. Research into this area seems particularly necessary as DPP IV inhibitors are being considered as a potential therapy for type II diabetes — a disease, which by itself increases the risk for cardiovascular consequences.