Activated platelets stimulate tissue factor expression in smooth muscle cells

Tissue factor (TF)-induced activation of the coagulation plays a key role in the pathophysiology of acute coronary syndromes. Because TF represents the initial trigger of the coagulation cascade, its expression in the arterial wall is tightly regulated. Objective: To determine whether and which soluble mediators released during platelet activation may upregulate TF expression in smooth muscle cells (SMCs). Methods and results: Rabbit SMCs were challenged with collagen-activated platelets and. their effects on TF mRNA transcription and protein expression were evaluated at different time points (30 min, 1, 2, 4, 8, 12 and 24 h) by RT-PCR, immunofluorescence and a two-stage colorimetric assay. A progressive increase in TF mRNA, peaking at 2 It, was evident in SMCs stimulated with activated platelets with respect to baseline. The increase in TF mRNA expression was associated with a parallel increase in TF protein, as demonstrated by immunofluorescence and by colorimetric assay. In a different set of experiments, selected platelet-derived soluble mediators were shown to induce TF mRNA expression. Conclusions: Activated platelets upregulate TF, via release of several soluble mediators, in a cell population widely expressed in the vessel wall and in atherosclerotic plaques, such as SMCs. This phenomenon might play an important role in sustaining thrombus formation in vivo. (C) 2004 Elsevier Ltd. All rights reserved