Enhancement by human umbilical vein endothelial cells of factor Xa-catalyzed activation of factor VII.
In blood coagulation on endothelium, an unperturbed vascular endothelial cell surface apparently provides activity equivalent to the phospholipid needed for generation of factor Xa and thrombin in soluble systems. Phospholipid in soluble systems also markedly enhances the ability of factor Xa to activate factor VII; therefore we investigated the influence of an unperturbed monolayer of human umbilical vein endothelial cells (HUVEC) upon factor VII activation. HUVEC were found to augment factor Xa-catalyzed activation of factor VII. This appeared to result from the binding of trace amounts of factor Xa to the cells. Adding active site-inhibited factor Xa to reaction mixtures, but not factor X, abolished the enhanced activation. Adding either anti-factor V antibodies or exogenous factor Va had no effect upon reaction rates. Thus factor Va does not function as a cofactor for the reaction. In further experiments the effect upon activation of factor VII and prothrombin was studied by varying the order of addition of factor Xa and factor Va to supernatants of HUVEC monolayers. Evidence was obtained that HUVEC, unlike platelets, possess a functional factor Xa binding site that is independent of factor Va. Since phospholipid is the only known cofactor for factor Xa/Ca2+-induced activation of factor VII, the demonstration of enhanced activation of factor VII in the presence of unperturbed cultured HUVEC supports a hypothesis that the functional equivalent of procoagulant phospholipid is available on the luminal surface of vascular endothelium in vivo.
Department of Medicine, University of California at San Diego, La Jolla.
L V
LV
Rao
S I
SI
Rapaport
M
M
Lorenzi
D000906:Antibodies / Q000502:physiology; D002384:Catalysis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005165:Factor V / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D005167:Factor VII / Q000502:physiology*; D015943:Factor Va; D015951:Factor Xa; D006801:Humans; D011516:Prothrombin / Q000502:physiology; D012697:Serine Endopeptidases / Q000378:metabolism / Q000502:physiology*; D015842:Serine Proteinase Inhibitors; D014471:Umbilical Veins
D000906:Antibodies; D015842:Serine Proteinase Inhibitors; D015943:Factor Va; D005165:Factor V; D005167:Factor VII; D011516:Prothrombin; D012697:Serine Endopeptidases; D015951:Factor Xa