On the control of the plasma contact activation system on human endothelium: Comparisons with heparin surface

The endothelial lining in segments of the human saphenous vein harvested be fore and shortly after systemic heparinization of patients was investigated with regard to the ability to inhibit activated FXII. Comparisons were mad e with a surface modified by endpoint attached heparin, which, like the end othelium, is negatively charged and exposes the specific antithrombin bindi ng sequence and also binds FXII and antithrombin. The heparin surface prein cubated with plasma or blood and endothelium in vivo having been exposed to non-heparinzed blood and expressed similar amounts of FXII but no FXIIa. O n both surfaces activation of bound FXII with ellagic acid resulted in cons umption of the proenzyme and in inhibition of formed FXIIa. On both heparin surface and the endothelium consumption of antithrombin occurred concomita ntly, demonstrating the importance of this inhibitor in the control of cont act activation system. On the endothelium, in vivo or ex vivo, exposed to h eparinized blood, most FXII was present in the active form and only incubat ion with purified antithrombin could restore the FXIIa inhibitory capacity. It is suggested that antithrombin bound by the specific antithrombin bindi ng sequence of endothelial heparan sulphate, like antithrombin bound to the specific antithrombin binding sequence on heparin surface, inhibits alpha- FXIIa. This makes the endothelium consonant with the plasma contact activat ion system. It is suggested that systemic heparinzation of patients may bot h activate endothelial bound FXII and interfere in the inhibition of formed FXIIa by depriving the endothelium of required amounts of antithrombin. (C ) 1998 Elsevier Science Ltd.