Vitamin D attenuates proangiogenic properties of pericytes through increased production of VEGF (679.1)

Abstract

Retinal neovascularization is associated with pathogenesis of several major eye diseases including retinopathy of prematurity. Vitamin D compounds inhibit the growth of a variety of tumors perhaps through inhibition of angiogenesis. We showed that the active form of vitamin D, calcitriol (1, 25‐dihydroxyvitamin D3), is a potent inhibitor of retinal neovascularization during oxygen‐induced ischemic retinopathy. However, the identity of the molecular mechanisms and cellular targets remain unknown. We showed that calcitriol did not affect pro‐angiogenic properties of endothelial cells (EC). Pericytes (PC), play important roles during angiogenesis, vascular maturation and stabilization of newly forming blood vessels. Here we investigated the impact of calcitriol on retinal PC function. We show that PC express significantly higher level of vitamin D receptor compared with EC, and that calcitriol decreased proliferation and migration of PC, and caused G0/G1 arrest without affecting apoptosis. We also observed alterations in PC adhesion and expression of various matrix proteins. In addition, PC in the presence of calcitriol expressed increased level of VEGF, and antagonism of VEGF signaling by soluble VEGF‐R1 (sFlt‐1) restored proangiogenic properties of PC incubated with calcitriol. Together, our results suggest an important role for PC as target of vitamin D action and attenuation of angiogenesis.Grant Funding Source: Supported by: RC4 EY021357, P30 EY016665, P30 CA014520, RPB, ADA 1‐10‐BS‐160, and RRF