Functional Overlap and Cooperativity Among αv and β1 Integrin Subfamilies During Skin Angiogenesis

摘要: Angiogenesis requires endothelial cell survival and proliferation, which depend upon cytokine stimulation together with integrin-mediated adhesion to extracellular matrix; however, the question of specific integrins are best targets for suppressing neovascularization is controversial unresolved. Therefore, we designed experiments compare contributions individual from both α v β 1 integrin subfamilies. With immobilized antibodies, determined that through , 2 3 5 each individually supported dermal microvascular survival. Also, substratum coated collagen I (which binds ) vitronectin Importantly, combinations were most effective at promoting survival, on three-dimensional gels was strongly enhanced by vitronectin. Vascular growth factor activation p44/p42 mitogen-activated protein kinase pathway, required angiogenesis, either or pharmacologic inhibition this pathway blocked proliferation suppressed these studies establish support viability, collaborate vascular robust mediates Moreover, significantly matrices, engage all in combination. Consistent important complementary overlapping functions, combined antagonism provided superior angiogenesis skin, indicating multiplicity involvement should be considered designing strategies controlling neovascularization.