Sulfatide can markedly enhance thrombogenesis in rat deep vein thrombosis model.
Although sulfatide (galactosylceramide I3-sulfate) has been reported to activate blood coagulation factor XII (Hageman factor), it has been administered to animals without subsequent thrombus formation. We recently found that sulfatide binds to fibrinogen and thus disturbs fibrin formation in vitro, suggesting its possible role as an anticoagulant rather than as a coagulant. We therefore examined the in vivo effects of sulfatide on thrombogenesis by using a rat deep vein thrombosis model in which thrombus is induced by ligating the inferior vena cava. Sulfatide and gangliosides were each separately administered to rats 1 min before the vein ligation, and after 3 h, sulfatide but not gangliosides markedly (P < .001) enhanced the thrombogenesis. A kinetic turbidmetric assay of plasma coagulation initiated by CaCl2 in the wells of a microtiter plate revealed that coagulation was also markedly accelerated in the presence of sulfatide but not gangliosides, the results of which seemed to be very consistent with those of the in vivo experiments. Because sulfatide could not induce thrombosis without vein ligation in rats, the enhancement of thrombogenesis by sulfatide in the in vivo model might require endothelial damage and/or venous congestion, both of which could be induced by vein ligation.
Seikagaku Corporation, Tokyo Research Institute, Japan. Kyogashimamo@ma4.justnet.ne.jp
M
M
Kyogashima
J
J
Onaya
A
A
Hara
T
T
Taketomi
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D002122:Calcium Chloride / Q000494:pharmacology; D004195:Disease Models, Animal; D005174:Factor XII / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D005732:Gangliosides / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D011517:Prothrombin Time; D051381:Rats; D017207:Rats, Sprague-Dawley; D013433:Sulfoglycosphingolipids / Q000494:pharmacology*; D020246:Venous Thrombosis / Q000209:etiology / Q000503:physiopathology*
D005732:Gangliosides; D013433:Sulfoglycosphingolipids; D005174:Factor XII; D005340:Fibrinogen; D002122:Calcium Chloride