Enhanced thrombin receptor expression in human restenotic coronary arterial smooth muscle cells stimulated with fibroblast growth factor

Coronary restenosis following percutaneous revascularization is characterized by migration, growth and proliferation of arterial smooth muscle cells (SMC). Growth factors including thrombin and fibroblast growth factor (FGF) likely mitigate this process. The effect of thrombin is mediated by its receptor Expression of this thrombin receptor (TR) was examined in cultured SMC derived from tissue obtained during directional coronary atherectomy.TR expression in SMC from restenotic and primary atherosclerotic coronary lesions is compared both at baseline and after 6 hour stimulation with FGF (10ng/ml) using northern blot analysis. Relative TR gene expression is reported as the mean percent difference in TR levels between restenotic and primary atherosclerotic cells. Results: Native TR gene expression is observed to be 33% (p<0.005,n=3) lower in restenotic cells relative to SMC from primary atherosclerotic tissue.In contrast, although primary atherosclerotic cells responded to FGF with increased TR gene expression compared to untreated primary atherosclerotic SMC, the relative response of the TR gene in restenotic SMC stimulated with FGF was significantly enhanced by an average of 28.6% (p<0.5, n=3), compared to the response of FGF-treated primary atherosclerotic SMC. Conclusion: These results indicate that TR gene expression in coronary SMC may be down-regulated in the course of development of restenosis as demonstrated by the overall reduction in TR expression in restenotic cells compared with primary atherosclerotic tissue SMC. In contrast, these results indicate that SMC from restenotic tissue exhibit enhanced sensitivity to FGF stimulation relative to cells from PA tissue. This may enhance our understanding of the restenotic process and potential therapeutic strategies.