PMID: 9169607May 1, 1997Paper

Dissimilar interaction of factor VIII with endothelial cells and lipid vesicles during factor X activation

The Biochemical Journal
H J BrinkmanJ A van Mourik

Abstract

A localized and regulated cascade of proteolytic events is a prerequisite for normal haemostasis. The activation of factor X by activated factor IX (factor IXa) in the presence of activated factor VIII (factor VIIIa) is essential for the formation of a fibrin clot at sites of vascular injury. We observed sustained activation of factor X on the surface of vascular endothelial cells, whereas, in agreement with others, on synthetic negatively charged phospholipid vesicles and activated blood platelets factor X activation is transient and starts to decline a few minutes after the onset of the reaction. We examined the mechanism responsible for these differences in factor X activation. Procoagulant membrane and solution were analysed separately for the occurrence of factor VIII and its activation fragments. On negatively charged phospholipid vesicles, on dissociation of factor VIIIa, the 67 kDa light-chain fragment remains associated with the lipid membrane. As a result, factor VIII-binding sites remain occupied, and dampening of factor X activation occurs. In contrast, on monolayers of endothelial cells, no residual factor VIIIa fragments associated with the cell membrane were observed. During endothelial-cell-mediated activation o...Continue Reading

Citations

Mar 9, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Herm-Jan M BrinkmanJan A van Mourik
Apr 5, 2008·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Herm Jan M BrinkmanKoen Mertens
Aug 14, 1999·The Journal of Biological Chemistry·P J LentingA J van Zonneveld

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