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 α 4 β 1 (VLA-4) and VCAM-1 promote close intercellular adhesion between ECs and pericytes and that this interacti...

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Published inThe Journal of clinical investigation Vol. 115; no. 6; pp. 1542 - 1551
Main Authors Garmy-Susini, Barbara, Jin, Hui, Zhu, Yuhong, Sung, Rou-Jia, Hwang, Rosa, Varner, Judy
Format Journal Article
LanguageEnglish
Published American Society for Clinical Investigation 01.06.2005
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Summary: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 α 4 β 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 α 4 β 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-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 α 4 β 1 and VCAM-1 facilitate a critical cell-cell adhesion event required for survival of endothelial and mural cells during vascularization.
Bibliography:Address correspondence to: Judy Varner, John and Rebecca Moores Comprehensive Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0912, USA. Phone: (858) 822-0086; Fax: (858) 822-1325; E-mail: jvarner@ucsd.edu.
ISSN:0021-9738
DOI:10.1172/JCI23445