A role for IFITM proteins in angiogenesis

Abstract

The Interferon Inducible Transmembrane (IFITM) proteins were originally identified as part of a multi‐protein complex on the surface of lymphocytes that mediates homotypic adhesion and the transmission of antiproliferative signals. Recently, we have identified the IFITMs as regulators of endothelial cell (EC) sprouting in vitro, and angiogenesis in vivo. Angiogenesis is a multistep process whereby new blood vessels are formed from the preexisting vasculature in response to various angiogenic stimuli. During angiogenesis, EC shift from a quiescent phenotype, to migrating and proliferating cells as they sprout from parent vessels, and back to quiescent cells as the new vessels mature and stabilize. Both IFITM1 and IFITM2 are rapidly induced as EC sprout in vitro and form lumenized vessels, and knockdown of either disrupts both sprouting and lumen formation. Using a vascular bed xeno‐transplant model, we have also identified a role for the human IFITMs during in vivo angiogenesis. Immunohistochemical staining of multiple human tissues identified widespread IFITM expression on vessels. Our data suggest that IFITMs may regulate the transition of EC from a quiescent to an angiogenic state.