Vascular Endothelial Growth Inhibitor (VEGI), an Endogenous Negative Regulator of Angiogenesis

Abstract

Vascular endothelial growth inhibitor (VEGI; TNFSF-15) is a new member of the tumor necrosis factor family. VEGI is predominantly an endothelial cell-specific gene, and recombinant VEGI is a potent inhibitor of endothelial cell proliferation, angiogenesis and tumor growth. VEGI exerts two activities on endothelial cells: early G1 arrest of G0/G1-cells responding to growth stimuli, and programmed death of proliferating cells. These activities are highly specific to endothelial cells. There are three VEGI isoforms identified thus far. One of the isoforms, VEGI-251, is a secreted protein. The gene products apparently play a role in normal vasculature, as the transcripts are found in normal adult tissues and some fetal tissues. VEGI gene expression is subject to regulation by inflammatory cytokines. VEGI is also able to regulate the expression of several important genes involved in angiogenesis. These findings are consistent with the view that VEGI functions as an autocrine cytokine to inhibit angiogenesis and stabilize the vasculature.