Effect of aspirin and clopidogrel on platelet-dependent tissue factor expression in endothelial cells.
Tissue factor is an ubiquitous membrane-anchored glycoprotein that initiates blood coagulation by forming a complex with circulating factors VII and VIIa. Under normal circumstances, endothelial cells do not express tissue factor but, in some pathological situations, when the endothelium or the monocytes are exposed to inflammatory mediators, they can acquire procoagulant properties. When rat platelets were incubated with cultured bovine aortic endothelial cells, a significant increase in tissue factor expression was obtained. When added simultaneously, thrombin or 2-methylthio-ADP, a stable analogue of ADP, potentiated in a time and dose-dependent manner the effect obtained with platelets alone. In order to determine if antiplatelet agents can modulate these effects, the activity of two compounds was evaluated. When administered orally at the dose of 25 mg/kg, clopidogrel, a potent and selective analogue of ticlopidine, was able to inhibit platelet-induced tissue factor expression whereas aspirin (100 mg/kg, p.o.) was ineffective. These effects were closely correlated to their respective anti-aggregatory and antithrombotic activities showing that platelet activation which has already been shown to be mainly involved in arterial-type thrombosis could also play an important role in the initiation of venous thrombosis where tissue factor expression is thought to play a major role.
Savi
P
P
Sanofi Recherche, Toulouse, France.
Bernat
A
A
Dumas
A
A
Aït-Chek
L
L
Herbert
J M
JM
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D001792:Blood Platelets / Q000502:physiology*; D002417:Cattle; D000077144:Clopidogrel; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D008026:Ligation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D013873:Thionucleotides / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D013925:Thromboplastin / Q000096:biosynthesis*; D013927:Thrombosis / Q000517:prevention & control; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014682:Vena Cava, Inferior
D010975:Platelet Aggregation Inhibitors; D013873:Thionucleotides; C002480:methylthio-ADP; D000244:Adenosine Diphosphate; D013925:Thromboplastin; D000077144:Clopidogrel; D013917:Thrombin; D013988:Ticlopidine; D001241:Aspirin