Regulation of Postangiogenic Neovessel Survival by β₁ and β₃Integrins in Collagen and Fibrin Matrices

Abstract

We used the aortic ring model of angiogenesis to investigate the role of β₁ and β₃ integrins in postangiogenic vascular survival in collagen and fibrin matrices. Confocal microscopy studies showed that both β₁ and β₃ integrins were expressed in endothelial cells and pericytes of sprouting neovessels. Antibody blocking experiments demonstrated that β₁ integrins but not β₃ integrins were required for angiogenic sprouting in collagen. Conversely, in fibrin, blockade of both integrins was needed to inhibit angiogenesis whereas treatment with either antibody alone was ineffective. Antibody-mediated blockade of β₁ but not β₃ integrins accelerated vascular regression in collagen. In contrast, both anti-β₁ and -β₃ integrin antibodies were required to promote neovessel breakdown in fibrin. These results demonstrate that angiogenic sprouting and postangiogenic neovessel survival in collagen are critically dependent on β₁ integrins. They also indicate that these processes involve a redundant repertoire of β₁ and β₃ integrins when angiogenesis occurs in fibrin. Thus, pharmacologic targeting of integrin receptors aimed at blocking neovessel formation and survival must be tailored to the specific extracellular matrix environment in which angiogenesis takes place.

Angiopoietin 2 Induces Pericyte Apoptosis via α3β1 Integrin Signaling in Diabetic Retinopathy

“…However, a role for integrin a3b1 in the pericyte is yet to be determined (22). Inhibition of b1 integrin induced a rounded morphology of the pericytes, suggesting pericyte adhesive properties were affected or that these cells were undergoing apoptosis (27). In this study, we suggested that integrin a3b1 was important for Ang2-induced apoptosis.…”

Molecular Mechanisms Controlling Vascular Lumen Formation in Three-Dimensional Extracellular Matrices

“…Two types of ECM appear to be particularly conducive to EC tube morphogenesis and sprouting and they include collagen type I and fibrin matrices [Davis and Senger, 2005;Senger and Davis, 2011]. Interestingly, the ␣ 2 ␤ 1 integrin controls EC tube formation and sprouting in collagen matrices [Davis and Camarillo, 1996;Senger et al, 1997;Bayless and Davis, 2003] while ␣ 5 ␤ 1 and ␣ v ␤ 3 control these events in fibrin matrices [Bayless et al, 2000;Bayless and Davis, 2003;Carnevale et al, 2007]; thus, the integrins involved in vascular morphogenesis are directly linked to the ECM environment in which the process is occurring. These integrins have also been shown to be involved in regulating EC tube morphogenesis during developmental and adult neovascularization events [Drake et al, 1992;Senger et al, 1997;Stupack and Cheresh, 2004;San Antonio et al, 2009;van der Flier et al, 2010;Zovein et al, 2010].…”

Integrins

“…60 ␤1 integrin expression on pericytes is thought to help stabilize the blood vessels. 55 In ex vivo aortic ring assays, inhibition of this integrin induced a rounded morphology of the pericytes, suggesting pericyte adhesive properties were affected or that these cells were undergoing apoptosis. In vivo, ␤1 integrin deficiency results in pericytes being unable to spread properly.…”