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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.

Explants of rat inferior vena cava embedded in collagen gel and cultured under serum-free conditions produced microvascular outgrowths composed of endothelial cells and pericytes. Exogenous vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) dose-dependently stimulated angiogenesis and induced the formation of complex networks of highly branched microvessels. VEGF and the VEGF/bFGF combination also promoted pericyte recruitment. Medium conditioned by untreated vena cava cultures contained endogenous VEGF, and a blocking antibody against VEGF significantly reduced the spontaneous angiogenic response of the explants. Vena cava explants exhibited a greater capacity to form neovessels than aortic rings when tested in parallel cultures from the same animal. When compared with aorta-derived microvessels, neovessels of vena cava origin were longer and had fewer pericytes. Vena cava-aorta cocultures produced extensive anastomosing networks of microvessels, which were primarily contributed by the venous explants. Because of its florid angiogenesis and exquisite sensitivity to angiogenic factor stimulation, the vena cava model may provide novel insights into the regulation of the angiogenic process, which typically initiates from the venous side of the vascular bed. Combined with the aortic ring model, this new assay may also enhance our understanding of the mechanisms of anastomosis formation between the arterial and the venous circulations.

We used the aortic ring model of angiogenesis to investigate the role of beta(1) and beta(3) integrins in postangiogenic vascular survival in collagen and fibrin matrices. Confocal microscopy studies showed that both beta(1) and beta(3) integrins were expressed in endothelial cells and pericytes of sprouting neovessels. Antibody blocking experiments demonstrated that beta(1) integrins but not beta(3) 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 beta(1) but not beta(3) integrins accelerated vascular regression in collagen. In contrast, both anti-beta(1) and -beta(3) 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 beta(1) integrins. They also indicate that these processes involve a redundant repertoire of beta(1) and beta(3) 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.