title: Activation of endogenous factor V by a homocysteine-induced vascular endothelial cell activator.
abstract: Vascular endothelium possesses multiple procoagulant properties, including synthesis and expression of Factor V. We studied the effects of homocysteine on the regulation of endothelial cell Factor V activity. Elevated levels of homocysteine are associated with the congenital thrombotic disorder homocystinuria. Treatment of cultured endothelial cells with 0.5-10 mM homocysteine had no effect on cell morphology, but did increase Factor V activity and prothrombin activation by Factor Xa. A radioimmunoassay for endothelial cell Factor V demonstrated that homocysteine treatment did not increase Factor V antigen levels. 125I-prothrombin was activated by treated endothelial cells and Factor Xa in the presence of thrombin inhibitors. Exogenous 125I-Factor V was cleaved by homocysteine-treated but not control endothelial cells. 125I-Factor V cleavage products distinct from those generated by thrombin and Factor Xa were identified. These data provide evidence for regulation of endothelial cell Factor V activity, and indicate that increased Factor V activity associated with homocysteine-treated vascular endothelium results primarily from induction of an activator of Factor V.
mesh_terms: D000818:Animals; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D016228:Endothelial Growth Factors; D005165:Factor V / Q000378:metabolism*; D005170:Factor X / Q000378:metabolism; D015951:Factor Xa; D006133:Growth Substances / Q000494:pharmacology*; D006710:Homocysteine / Q000494:pharmacology*; D006712:Homocystinuria / Q000150:complications; D006801:Humans; D008970:Molecular Weight; D011516:Prothrombin / Q000378:metabolism; D013927:Thrombosis / Q000150:complications; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D016228:Endothelial Growth Factors; D006133:Growth Substances; D006710:Homocysteine; D005165:Factor V; D011516:Prothrombin; D005170:Factor X; D015951:Factor Xa