HUMAN ENDOTHELIAL-CELLS DO NOT EXERT HEPARIN-LIKE ACCELERATING EFFECTS ON THROMBIN-ANTITHROMBIN-COMPLEX FORMATION

In the present study the formation of thrombin-antithrombin-complexes (TAT) during incubation of thrombin (0.89, 4.5, 8.9 nmol/l) and antith rombin (4.6 mu mol/l) on the surface of cultured human EC, derived fro m different parts of the circulation, and on the surface of human vess el segments was studied. In the absence of EC TAT increased over time reaching a maximum at 60 sec; 10 sec (8.9 nmol/l thrombin): 6.35+/-0.7 2 nmol/l, 60 sec: 10.49+/-1.04 nmol/l. In the presence of exogenous he parin (0.1 IU/ml) maximum TAT levels were already reached after 10 sec (10.75+/-0.97); cultured EC and EC on vessel segments did not show su ch heparin effects. Incubation of EC with heparin resulted in an EC-su rface localized heparin activity only when very high doses (3.0 IU/ml) of the drug were used. When thrombin was incubated on the EC surface in the presence of AT the efficiency of the thrombomodulin(TM)-protein C(PC)-system was markedly reduced, while in the presence of exogenous heparin (0.5 IU/l) the activity of this pathway was nearly abolished. Our results demonstrate that 1) human EC do not exert heparin-like ac celerating effects on TAT formation, 2) an EC localized heparin activi ty is only generated when EC are incubated with amounts clearly exceed ing therapeutical doses, and 3) an acceleration of TAT formation at th e EC surface by heparin causes a switching off of the TM-PC-system.