Loss of p53 Compensates for v-Integrin Function in Retinal Neovascularization*

v-Integrin antagonists block neovascularization in various species, whereas 20% of v-integrin null mice are born with many normal looking blood vessels. Given that blockade of v-integrins during angiogenesis induces p53 activity, we utilized p53 null mice to elucidate whether loss of p53 can compensate for v-integrin function in neovascularization of the retina. Murine retinal vascularization was inhibited by systemic administration of an v-integrin antagonist. In contrast, mice lacking p53 were refractory to this treatment, indicating that neovascularization in normal mice depends on vintegrin-mediated suppression of p53. Blockade of vintegrins during neovascularization resulted in an induction of p21 in wild type and, surprisingly, in p53 null retinas, indicating that v-integrin ligation regulates p21 levels in a p53-independent manner. In conclusion, we demonstrate for the first time an in vivo intracellular mechanism for compensation of integrin function and that p53 and v-integrins act in concert during retinal neovascularization.