On the mechanism of thrombin-induced angiogenesis: involvement of αvβ3-integrin

Thrombin has been 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 α v β 3 -integrin. This thrombin-mediated effect is specific, dose dependent, and requires the catalytic site of thrombin. In addition, thrombin interacts with α v β 3 as demonstrated by direct binding of α v β 3 protein to immobilized thrombin. This interaction of thrombin with α v β 3 -integrin, which is an angiogenic marker in vascular tissue, is of functional significance. Immobilized thrombin promotes endothelial cells attachment, migration, and survival. Antibody to α v β 3 or a specific peptide antagonist to α v β 3 can abolish all these α v β 3 -mediated effects. Furthermore, in the chick chorioallantoic membrane system, the antagonist peptide to α v β 3 diminishes both basal and the thrombin-induced 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.