title: Aegyptin inhibits collagen-induced coagulation activation in vitro and thromboembolism in vivo.
abstract: 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's pro-coagulant activity. This is the first description of a collagen-binding protein that also inhibits collagen-mediated coagulant activity.
authors.affiliation: Institute of Medical Biochemistry, Federal University of Rio de Janeiro, RJ, Brazil.
authors.forename: Daniella M
authors.initials: DM
authors.lastname: Mizurini
authors.forename: Ivo M B
authors.initials: IM
authors.lastname: Francischetti
authors.forename: Robson Q
authors.initials: RQ
authors.lastname: Monteiro
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D003094:Collagen / Q000494:pharmacology*; D009033:Culicidae / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011655:Pulmonary Embolism / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012471:Salivary Proteins and Peptides / Q000235:genetics / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism
chemical_list: D019476:Insect Proteins; D011994:Recombinant Proteins; D012471:Salivary Proteins and Peptides; C583517:aegyptin protein, Aedes aegypti; D003094:Collagen; D013917:Thrombin; D004837:Epinephrine