EFFECT OF ASPIRIN AND CLOPIDOGREL ON PLATELET-DEPENDENT TISSUE FACTOREXPRESSION IN ENDOTHELIAL-CELLS

Tissue factor is an ubiquitous membrane-anchored glycoprotein that ini tiates blood coagulation by forming a complex with circulating factors VII and VIIa. Under normal circumstances, endothelial cells do not ex press tissue factor but, in some pathological situations, when the end othelium 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 a lone. In order to determine if antiplatelet agents can modulate these effects, the activity of two compounds was evaluated. When administere d orally at the dose of 25 mg/kg, clopidogrel, a potent and selective analogue of ticlopidine, was able to inhibit platelet-induced tissue f actor expression whereas aspirin (100 mg/kg, p.o.) was ineffective. Th ese effects were closely correlated to their respective anti-aggregato ry and antithrombotic activities showing that platelet activation whic h has already been shown to be mainly involved in arterial-type thromb osis could also play an important role in the initiation of venous thr ombosis where tissue factor expression is thought to play a major role .