Definition of two angiogenic pathways by distinct alpha v integrins.
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-alpha depended on alpha v beta 3, whereas angiogenesis initiated by vascular endothelial growth factor, transforming growth factor-alpha, or phorbol ester depended on alpha v beta 5. 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 alpha v beta 5 but not by alpha v beta 3.
D000818:Animals; D000911:Antibodies, Monoclonal; D002642:Chick Embryo; D003315:Cornea / Q000098:blood supply*; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D008222:Lymphokines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D019030:Receptors, Vitronectin / Q000276:immunology / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000911:Antibodies, Monoclonal; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D016023:Integrins; D008222:Lymphokines; D009281:Naphthalenes; D010456:Peptides, Cyclic; D019030:Receptors, Vitronectin; D016211:Transforming Growth Factor alpha; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C092111:cyclic(arginyl-alanyl-aspartyl-phenylalanyl-valyl); C064660:integrin alphaVbeta5; D016222:Fibroblast Growth Factor 2; D011493:Protein Kinase C; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate