Related Experiment Videos
On the control of the plasma contact activation system on human endothelium: comparisons with heparin surface
1Department of Surgical Sciences, Thoracic Clinics, Karolinska Hospital, Stockholm, Sweden. jass@expkir.ks.se
The endothelial lining in segments of the human saphenous vein harvested before and shortly after systemic heparinization of patients was investigated with regard to the ability to inhibit activated FXII. Comparisons were made with a surface modified by endpoint attached heparin, which, like the endothelium, is negatively charged and exposes the specific antithrombin binding sequence and also binds FXII and antithrombin. The heparin surface preincubated with plasma or blood and endothelium in vivo having been exposed to non-heparinzed blood and expressed similar amounts of FXII but no FXIIa. On both surfaces activation of bound FXII with ellagic acid resulted in consumption of the proenzyme and in inhibition of formed FXIIa. On both heparin surface and the endothelium consumption of antithrombin occurred concomitantly, demonstrating the importance of this inhibitor in the control of contact activation system. On the endothelium, in vivo or ex vivo, exposed to heparinized blood, most FXII was present in the active form and only incubation with purified antithrombin could restore the FXIIa inhibitory capacity. It is suggested that antithrombin bound by the specific antithrombin binding 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 activation system. It is suggested that systemic heparinzation of patients may both activate endothelial bound FXII and interfere in the inhibition of formed FXIIa by depriving the endothelium of required amounts of antithrombin.
The endothelial lining in segments of the human saphenous vein harvested before and shortly after systemic heparinization of patients was investigated with regard to the ability to inhibit activated FXII. Comparisons were made with a surface modified by endpoint attached heparin, which, like the endothelium, is negatively charged and exposes the specific antithrombin binding sequence and also binds FXII and antithrombin. The heparin surface preincubated with plasma or blood and endothelium in vivo having been exposed to non-heparinzed blood and expressed similar amounts of FXII but no FXIIa. On both surfaces activation of bound FXII with ellagic acid resulted in consumption of the proenzyme and in inhibition of formed FXIIa. On both heparin surface and the endothelium consumption of antithrombin occurred concomitantly, demonstrating the importance of this inhibitor in the control of contact activation system. On the endothelium, in vivo or ex vivo, exposed to heparinized blood, most FXII was present in the active form and only incubation with purified antithrombin could restore the FXIIa inhibitory capacity. It is suggested that antithrombin bound by the specific antithrombin binding 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 activation system. It is suggested that systemic heparinzation of patients may both activate endothelial bound FXII and interfere in the inhibition of formed FXIIa by depriving the endothelium of required amounts of antithrombin.