Failure of heparin to inhibit the expression of the thrombin receptor following endothelial injury of the rabbit carotid artery

Abstract

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 endothelial injury was measured by in situ hybridisation and immunohistochemistry. In healthy arteries, thrombin receptor mRNA and protein were detected in the endothelial cells only. In contrast, 14 days after endothelial injury, thrombin receptor mRNA expression increased in the smooth muscle cells present in the neointima, predominantly in areas of active cell proliferation. A 2-week subcutaneous treatment with heparin (10 mg/kg per day, s.c.) inhibited smooth muscle cell hyperplasia occurring in the intima following deendothelialization (80±7.8% inhibition, P<0.001). The 14-day heparin treatment strongly reduced thrombin receptor gene and protein expression observed in the endothelial cells in healthy arteries but did not affect thrombin receptor expression which occurred in smooth muscle cells which have proliferated in the neointima as a consequence of endothelial injury. These results therefore establish that thrombin receptor expression during intimal hyperplasia is an heparin-insensitive event.