On the mechanism of thrombin-induced angiogenesis: involvement of v 3-integrin
نویسندگان
چکیده
Tsopanoglou, Nikos E., Paraskevi Andriopoulou, and Michael E. Maragoudakis. On the mechanism of thrombin-induced angiogenesis: involvement of v 3-integrin. Am J Physiol Cell Physiol 283: C1501–C1510, 2002. First published July 17, 2002; 10.1152/ajpcell.00162.2002.— 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 v 3integrin. This thrombin-mediated effect is specific, dose dependent, and requires the catalytic site of thrombin. In addition, thrombin interacts with v 3 as demonstrated by direct binding of v 3 protein to immobilized thrombin. This interaction of thrombin with v 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 v 3 or a specific peptide antagonist to v 3 can abolish all these v 3-mediated effects. Furthermore, in the chick chorioallantoic membrane system, the antagonist peptide to v 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.
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