Transient functional expression of αvβ3 on vascular cells during wound repair

During early granulation tissue formation of wound repair, new capillaries invade the fibrin clot, a process that undoubtedly requires an interaction of vascular cells with the wound provisional matrix composed mainly of fibrin, fibronectin, and vitronectin. Integrin αvβ3 is the vascular cell receptor for these wound-associated adhesive proteins. Therefore, we investigated the expression of this receptor on new capillaries of healing full-thickness cutaneous porcine wounds. During granulation tissue formation, αvβ3 was expressed specifically on capillary sprouts invading the central fibrin clot whereas the closely related integrin αvβ5 failed to localize to these cells. Cyclic peptides or antibody antagonists of αvβ3 specifically inhibited granulation tissue formation in a transient manner during the period of invasive angiogenesis. Immunolocalization studies revealed that αvβ3 became aggregated and lost from sprouting vessels after treatment with a peptide antagonist. In contrast, β1 integrins were not modulated by this treatment. Once granulation tissue filled the wound and invasive angiogenesis terminated, the αvβ3 showed little or no expression in the granulation tissue microvasculature. These data demonstrate that integrin αvβ3 plays a fundamental, but transient, role during invasive angiogenesis and granulation tissue formation in a healing wound.