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 antithrombin (4.6 micromol/l) on the surface of cultured human EC, derived from different parts of the circulation, and on the surface of human vessel 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+/-0.72 nmol/l, 60 sec: 10.49+/-1.04 nmol/l. In the presence of exogenous heparin (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 such heparin effects. Incubation of EC with heparin resulted in an EC-surface 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 accelerating effects on TAT formation, 2) an EC localized heparin activity is only generated when EC are incubated with amounts clearly exceeding therapeutical doses, and 3) an acceleration of TAT formation at the EC surface by heparin causes a switching off of the TM-PC-system.
Ruzicka
K
K
Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Austria.
Wojta
J
J
Artemiou
O
O
Birsan
T
T
Quehenberger
P
P
Kapiotis
S
S
Hofbauer
R
R
Speiser
W
W
D000925:Anticoagulants / Q000378:metabolism* / Q000494:pharmacology; D000991:Antithrombins / Q000378:metabolism*; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001777:Blood Coagulation / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006490:Hemostatics / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D011485:Protein Binding; D011486:Protein C / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism*; D018180:Thrombomodulin / Q000378:metabolism; D014684:Venae Cavae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000925:Anticoagulants; D000991:Antithrombins; D006490:Hemostatics; D011486:Protein C; D018180:Thrombomodulin; D006493:Heparin; D013917:Thrombin