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Integrin α4β1–VCAM-1–mediated adhesion between endothelial and mural cells is required for blood vessel maturation
Barbara Garmy-Susini, … , Rosa Hwang, Judy Varner
Barbara Garmy-Susini, … , Rosa Hwang, Judy Varner
Published June 1, 2005
Citation Information: J Clin Invest. 2005;115(6):1542-1551. https://doi.org/10.1172/JCI23445.
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Research Article Angiogenesis Article has an altmetric score of 7

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

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Abstract

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 α4β1 (VLA-4) and VCAM-1 promote close intercellular adhesion between ECs and pericytes and that this interaction is required for blood vessel formation. Integrin α4β1 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 α4β1 and VCAM-1 facilitate a critical cell-cell adhesion event required for survival of endothelial and mural cells during vascularization.

Authors

Barbara Garmy-Susini, Hui Jin, Yuhong Zhu, Rou-Jia Sung, Rosa Hwang, Judy Varner

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Figure 4

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VCAM-1 is expressed on pericytes and integrin α4β1 on the endothelia of ...
VCAM-1 is expressed on pericytes and integrin α4β1 on the endothelia of the same tumor vessels. Cryosections of murine MMTV-PyV-mT spontaneous breast carcinoma (left) and human breast carcinoma (middle and right) were immunostained with anti–integrin α4β1 (arrows) and anti–VCAM-1 (arrowheads) antibodies. Magnification, ×200 (left and middle panels); ×600 (right panels). Scale bar: 50 μm. Integrin α4β1 expression is generally restricted to the inner EC layer, and VCAM-1 expression is restricted to the outer cell layer of both small and large vessels.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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