Vasohibin is up‐regulated by VEGF in the retina and suppresses VEGF receptor 2 and retinal neovascularization

Abstract

SPECIFIC AIMSVasohibin is a recently identified protein that is up-regulated in cultured vascular endothelial cells by vascular endothelial growth factor (VEGF) and fibroblast growth factor 2. It inhibits endothelial cell migration, proliferation, and tube formation, and suppresses angiogenesis in chick chorioallantoic membrane, after subcutaneous implantation of matrigel, and in a tumor xenograft model. In this study, we tested the hypothesis that vasohibin functions as a negative feedback inhibitor of VEGF in a well-characterized model of retinal neovascularization.PRINCIPAL FINDINGS1. VEGF stimulates the expression of vasohibin in the retinaOxygen-induced ischemic retinopathy is a useful model for study of hypoxia-induced regulation of VEGF expression. Placement of postnatal day (P) 7 mice into a high oxygen environment results in decreased expression of VEGF and regression of newly developed retinal blood vessels. When mice are returned to room air at P12, the poorly vascularized retina becomes hypoxi...