FAILURE OF HEPARIN TO INHIBIT THE EXPRESSION OF THE THROMBIN RECEPTORFOLLOWING ENDOTHELIAL INJURY OF THE RABBIT CAROTID-ARTERY

The effect of heparin on thrombin receptor expression was evaluated in an experimental model of myointimal smooth muscle cell proliferation in rabbits. Myointimal hyperplasia was induced by an air-drying injury of the carotid artery and thrombin receptor expression following endo thelial injury was measured by in situ hybridisation and immunohistoch emistry. In healthy arteries, thrombin receptor mRNA and protein were detected in the endothelial cells only. In contrast, 14 days after end othelial injury, thrombin receptor mRNA expression increased in the sm ooth muscle cells present in the neointima, predominantly in areas of active cell proliferation. A 2-week subcutaneous treatment with hepari n (10 mg/kg per day, s.c.) inhibited smooth muscle cell hyperplasia oc curring in the intima following deendothelialization (80 +/- 7.8% inhi bition, P < 0.001). The 14-day heparin treatment strongly reduced thro mbin receptor gene and protein expression observed in the endothelial cells in healthy arteries but did not affect thrombin receptor express ion which occurred in smooth muscle cells which have proliferated in t he neointima as a consequence of endothelial injury. These results the refore establish that thrombin receptor expression during intimal hype rplasia is an heparin-insensitive event.