IFITM1 regulates endothelial cell sprouting and lumen formation during angiogenesis

Interferon Inducible Transmembrane (IFITM) protein 1 was 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 IFITM1 as a regulator of endothelial cell (EC) sprouting and lumen formation 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. IFITM1 mRNA is rapidly induced as EC sprout in vitro and begin to form lumenized vessels, and knockdown of IFITM1 expression disrupts both sprouting and lumen formation. Although the early stages of lumenogenesis are normal, once an intercellular lumen has formed the nascent vessel then fails to expand. Using a vascular bed xeno‐transplant model, we also see a failure of proper lumen formation by human EC lacking IFITM1 expression. Immunohistochemical staining of multiple human tissues identified widespread IFITM1 expression on blood vessels. Our data suggest that IFITM1 may regulate the transition of EC from a quiescent to an angiogenic state. Research Support: NIH RO1 HL60067