Integrin α4β1-VCAM-1-mediated adhesion between endothelial and mural cells is required for blood vessel maturation

Neovascularization depends on vascular cell proliferation and on the stabilization of vessels by association of vascular smooth muscle-like pericytes with ECs. Here we show that integrin alpha(4)beta(1) (VLA-4) and VCAM-1 promote close intercellular adhesion between ECs and pericytes and that this interaction is required for blood vessel formation. integrin alpha(4)beta(1) is expressed by proliferating but not quiescent ECs, while its ligand VCAM-1 is expressed by proliferating but not quiescent mural cells. Antagonists of this integrin-figand pair block the adhesion of mural cells to proliferating endothelia in vitro and in vivo, thereby inducing apoptosis of ECs and pericytes and inhibiting neovascularization. These studies indicate that integrin alpha(4)beta(1) and VCAM-1 facilitate a critical cell-cell adhesion event required for survival of endothelial and mural cells during vascularization.