Phosphatidylethanolamine incorporation into vesicles selectively enhances factor Va inactivation by activated protein C.
Membrane surfaces accelerate the proteolytic inactivation of factor Va by activated protein C. In most coagulation complexes, the most active membrane phospholipid is believed to be phosphatidylserine. In this study, we demonstrate that with phosphatidylserine-containing vesicles, incorporation of phosphatidylethanolamine increased the rate of factor Va inactivation approximately 10-fold at all concentrations of factor Va studied and at all vesicle concentrations at or below the optimum for prothrombin activation. In contrast, phosphatidylethanolamine had very little influence on prothrombin activation. Phosphatidylethanolamine was a critical component of vesicles for the vesicles to support activated protein C anticoagulant activity optimally in plasma. These results demonstrate that the membrane requirements for the different coagulation/anticoagulation complexes differ much more than previously appreciated.
Smirnov
M D
MD
Howard Hughes Medical Institute, University of Oklahoma Health Sciences Center, Oklahoma City.
Esmon
C T
CT
D000818:Animals; D002417:Cattle; D004789:Enzyme Activation; D015943:Factor Va / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D008563:Membrane Lipids / Q000502:physiology*; D010714:Phosphatidylethanolamines / Q000502:physiology*; D011486:Protein C / Q000378:metabolism*; D011516:Prothrombin / Q000378:metabolism
D008081:Liposomes; D008563:Membrane Lipids; D010714:Phosphatidylethanolamines; D011486:Protein C; D015943:Factor Va; D011516:Prothrombin