Cramer Thomas J, Griffin John H, Gale Andrew J
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, Calif., USA.
Pathophysiol Haemost Thromb. 2010;37(1):17-23. doi: 10.1159/000315141. Epub 2010 May 22.
Coagulation factor V (FV) promotes inactivation of activated factor VIII (FVIIIa) by activated protein C (APC) and protein S. Loss of this APC cofactor activity is proposed to be partially responsible for the APC resistance phenotype of FV(Leiden). However, FVIIIa loses activity rapidly due to dissociation of the A2 domain, and this may be the primary mechanism of FVIIIa inactivation. APC/protein S also readily inactivates activated FV (FVa). We therefore hypothesized that FV can function as an anticoagulant cofactor for APC/protein S in the inactivation of FVa. FV was titrated into FV-deficient plasma, and the APC sensitivity ratio (APCsr; a measure of APC activity) was measured in a clotting assay that was not sensitive to FVIII. Our results showed an increase in APCsr as the FV concentration increased, suggesting an anticoagulant function for FV in this assay. FV(Leiden) showed APC resistance with an APCsr of 1.0. Therefore, under our experimental conditions, FV acted as an anticoagulant cofactor for APC in the inactivation of FVa.
凝血因子V(FV)促进活化蛋白C(APC)和蛋白S对活化因子VIII(FVIIIa)的失活作用。据推测,这种APC辅因子活性的丧失部分导致了FV(莱顿)的APC抵抗表型。然而,FVIIIa由于A2结构域的解离而迅速失去活性,这可能是FVIIIa失活的主要机制。APC/蛋白S也能迅速使活化的FV(FVa)失活。因此,我们推测FV在FVa失活过程中可作为APC/蛋白S的抗凝辅因子发挥作用。将FV滴定加入FV缺乏的血浆中,并在对FVIII不敏感的凝血试验中测量APC敏感率(APCsr;一种衡量APC活性的指标)。我们的结果显示,随着FV浓度的增加,APCsr升高,表明在此试验中FV具有抗凝功能。FV(莱顿)表现出APC抵抗,APCsr为1.0。因此,在我们的实验条件下,FV在FVa失活过程中作为APC的抗凝辅因子发挥作用。