P268	Differential activation of MAPK pathways in human coronary artery smooth muscle cells and endothelial cells in response to exogenous tissue factor.
1C.Wood, 2I.Chetter, 2P.McCollum, 1C.Ettelaie
1University of Hull, Hull, GB; 2Department of vascular surgery, Hull Royal Infirmary, Hull, GB.

Percutaneous transluminal coronary angioplasty (PTCA) is a widely accepted procedure to treat coronary stenosis. However, post-injury intimal hyperplasia and the resultant vascular restenosis remain the principle reasons of failure. Tissue factor (TF) activity has been shown to correlate with the rate of restenosis following PTCA. We compared the influence of exogenous TF (0.1-10 U/ml) in cultured human coronary artery smooth muscle cells (HCASMC) and human aortic cells (HCAoEC) in the absence of serum. The activation of the three principle mechanisms of the MAPK pathway, the extra-cellular regulated kinase (ERK), the p38 MAPK and c-Jun N-terminal kinase pathway (JNK) was compared using the Fast Activated Cell-based ELISA (FACE™) Kits. Our data demonstrate the activation of the ERK pathway in HCASMC but not the HCAoEC, on incubation with TF (1-10 U/ml). Moreover, the activation of p38 MAPK was induced only at high concentrations of TF (10 U/ml) in smooth muscle cells but not in the endothelial cells. Finally, the activation of the JNK/SAPK pathway occurred at the lower range of concentrations (0.1-1 U/ml) in HCAoEC, while HCASMC were only responsive on incubation with higher concentrations of TF (1-10 U/ml). We therefore suggest that arterial endothelial and smooth muscle cells react disparately to increasing concentrations of TF. This may in turn lead to the incongruent outcomes such as apoptosis and proliferation leading to simultaneous endothelial denudation and smooth muscle layer thickening. “The support of the British Heart Foundation is acknowledged”

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