Involvement of integrin áíâ3 in thrombin-induced angiogenesis

Thrombin was reported to be a potent angiogenic factor both in vitro and in vivo and many of the cellular effects of thrombin may contribute to activation of angiogenesis. In this report we show that thrombin-treatment of human endothelial cells increases mRNA and protein levels of ανβ3 integrin. This thrombin-mediated effect is specific, dose-dependent and requires the catalytic site of thrombin. In addition thrombin interacts with ανβ3 as demonstrated by direct binding of ανβ3 protein to immobilized thrombin. This interaction of thrombin with ανβ3 integrin, which is an angiogenic marker in vascular tissue, is of functional significance. Immobilized thrombin promotes endothelial cells attachment, migration and survival. Antibody to ανβ3 or a specific peptide antagonist to ανβ3 can abolish all these ανβ3-mediated effects. Furthermore, in chick chorioallantoic membrane system the antagonist peptide to ανβ3 diminishes both basal and the thrombininduced angiogenesis. These results support the pivotal role of thrombin in activation of endothelial cells and angiogenesis and may be related to the clinical observation of neovascularization within thrombi.