ADAM-mediated shedding, a new flavor in angiogenesis regulation.

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis (ie, blood vessel formation). VEGF acts by binding to the VEGF receptor 2 (VEGFR2) tyrosine kinase, expressed on endothelial cells. In healthy individuals, the vasculature is quiescent; invasion of vascular sprouts into the surrounding tissue during angiogenesis is tightly regulated by the Notch family of ligands and receptors. VEGF is also a critical regulator of vascular permeability, which involves disruption of endothelial adherens junctions through disengagement of vascular endothelial (VE) cadherin.1