Aegyptin inhibits collagen-induced coagulation activation in vitro and thromboembolism in vivo

作者:Mizurini Daniella M; Francischetti Ivo M B; Monteiro Robson Q*
来源:Biochemical and Biophysical Research Communications, 2013, 436(2): 235-239.
DOI:10.1016/j.bbrc.2013.05.082

摘要

Aegyptin is a mosquito salivary gland protein and potent inhibitor of platelet aggregation. Aegyptin binds to the von Willebrand factor-binding site on collagen and prevents its interaction with platelets. Because collagen also induces plasma clotting by activation of factor XII, we evaluated the effects of aegyptin on collagen-induced coagulation activation and how it interferes with thrombosis in three different in vivo models. Our results demonstrate that aegyptin abolishes collagen-induced clot formation and thrombin generation in platelet-free plasma. Aegyptin has no antithrombotic activity in the arteriovenous shunt model (collagen-independent) but it prevents laser-induced collagen-mediated thrombus formation in rats. Furthermore, aegyptin protects mice from collagen and epinephrine-induced thromboembolism. Therefore, aegyptin has a dual antithrombotic mechanism: inhibition of platelet-collagen interaction and collagen%26apos;s pro-coagulant activity. This is the first description of a collagen-binding protein that also inhibits collagen-mediated coagulant activity.