Objective-To characterize the role of a vascular-expressed class 3 semaphorin (semaphorin 3G [Sema3G] Key Words: endothelial cell Ⅲ smooth muscle cell Ⅲ angiogenesis Ⅲ semaphorin Ⅲ neuropilin T he growth of new blood vessels (angiogenesis) is associated with a distinct transition of endothelial cells (ECs) from the quiescent growth-arrested state to an invasive, migratory, and proliferating phenotype. The early steps of the angiogenic cascade are initiated by an intricate interplay between the vascular endothelial growth factor (VEGF) and the VEGF receptor and the Notch and Delta systems to control capillary sprout formation. 1 Invading capillary sprouts eventually anastomose to form a new capillary network that matures by recruiting mural cells to establish directional blood flow. Neuronal guidance molecules (ephrin-Eph, semaphorin-neuropilin (NP)-plexin, netrin-unc, and slit-robo) 2-4 and vessel maturation molecules (angiopoietin/Tie and platelet-derived growth factorplatelet-derived growth factor receptor) 5,6 have been identified as key regulators of these successive steps. The cross talk between ECs and periendothelial mural cells (pericytes and smooth muscle cells [SMCs]) is particularly important for controlling the activation status of the vascular endothelium. Mural cells are in intimate contact with the maturing EC monolayer to control their quiescent phenotype and their ability to respond to exogenous cytokines, including angiogenic growth factors. 7 Conversely, the loosening of EC/mural cell contacts is an important early step of the angiogenic cascade involving molecules of the transforming growth factor ␤, platelet-derived growth factor-BB, and angiopoietin families of vasculotropic growth factors. 8

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