Integrin alpha4beta1-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 alpha4beta1 (VLA-4) and VCAM-1 promote close intercellular adhesion between ECs and pericytes and that this interaction is required for blood vessel formation. Integrin alpha4beta1 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-ligand 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 alpha4beta1 and VCAM-1 facilitate a critical cell-cell adhesion event required for survival of endothelial and mural cells during vascularization.
Garmy-Susini
Barbara
B
John and Rebecca Moores Comprehensive Cancer Center, University of California, San Diego, La Jolla, California 92093-0912, USA.
Jin
Hui
H
Zhu
Yuhong
Y
Sung
Rou-Jia
RJ
Hwang
Rosa
R
Varner
Judy
J
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D049109:Cell Proliferation; D002470:Cell Survival; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000098:blood supply* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D020286:Pericytes / Q000378:metabolism / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1