Inhibition of the tissue factor-factor VII complex: involvement of factor Xa and lipoproteins

Inhibition of the procoagulant activity of a tissue factor-Factor VII (TF-FVII) complex by Al(OH)3-adsorbed plasma (AP) was found to require the presence of Factor Xa (FXa). Inhibitory activity seems to be generated through the interaction of FXa with a component in AP rather than with the TF-FVII complex. Quantitation of inhibitor activity was carried out using an amidolytic assay for TF-FVII activity. Incubation of AP with various antisera demonstrated that the inhibition was mainly associated with the presence of apolipoprotein B (apo B) rather than alpha 2-macroglobulin or antithrombin III. Purified lipoprotein-rich fractions prepared from AP, using density gradient ultracentrifugation, all contained some inhibitory activity. Incubation with anti-apo B greatly reduced the inhibitor in the very low density lipoprotein (VLDL)- and low density lipoprotein (LDL)-rich fractions but had essentially no effect on inhibition by the high density lipoprotein (HDL) fraction, which was rich in apo A. The inhibitory activity of AP was 60% that of normal plasma and this correlated well with the relative apo A and apo B concentrations. It is proposed that inhibition requires the interaction of FXa with plasma lipoproteins or associated components and that the product of this interaction is then able to bind to and inhibit the TF-FVII complex.