Integrin α4β1–VCAM-1–mediated adhesion between endothelial and mural cells is required for blood vessel maturation
Barbara Garmy-Susini, Hui Jin, Yuhong Zhu, Rou-Jia Sung, Rosa Hwang, Judy Varner
Barbara Garmy-Susini, Hui Jin, Yuhong Zhu, Rou-Jia Sung, Rosa Hwang, Judy Varner
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Research Article Angiogenesis

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

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 1

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ECs in developing vessels express integrin α4β1. (A) Cryosections of sal...
ECs in developing vessels express integrin α4β1. (A) Cryosections of saline-, bFGF-, or VEGF-A–stimulated chick CAMs were immunostained to detect vWF (red) and integrin α4β1 (α4β1) (green). Yellow color indicates overlap of expression patterns. (B) Cryosections of normal mouse breast, growth factor–reduced Matrigel supplemented with 400 μg/ml recombinant human VEGF-A, and MMTV-PyV-mT spontaneous breast carcinoma were immunostained to detect vascular EC CD31 (red) and integrin α4β1 (green). Yellow color indicates overlap of expression patterns. (C) Cryosections of human ductal breast carcinoma in situ were immunostained to detect vWF (red) and integrin α4β1 (green). Yellow color indicates overlap of expression patterns. In A–C, Arrowheads indicate blood vessels. Nl, normal. Magnification, ×200. Scale bar: 100 μm.