Definition of Two Angiogenic Pathways by Distinct α v Integrins

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Abstract
Angiogenesis depends on cytokines and vascular cell adhesion events. Two cytokine-dependent pathways of angiogenesis were shown to exist and were defined by their dependency on distinct vascular cell integrins. In vivo angiogenesis in corneal or chorioallantoic membrane models induced by basic fibroblast growth factor or by tumor necrosis factor-α depended on αvβ3, whereas angiogenesis initiated by vascular endothelial growth factor, transforming growth factor-α, or phorbol ester depended on αvβ5. Antibody to each integrin selectively blocked one of these pathways, and a cyclic peptide antagonist of both integrins blocked angiogenesis stimulated by each cytokine tested. These pathways are further distinguished by their sensitivity to calphostin C, an inhibitor of protein kinase C that blocked angiogenesis potentiated by αvβ5 but not by αvβ3.