Endothelial Injury, Thrombin Receptor Expression In Vascular Smooth Muscle Cells And Antisense Thrombin Receptor Gene Inhibitory Effect

Restenosis after angioplasty severely limits the application of this therapeutic technique. Study on the fundamental mechanisms of restenosis and search for an effectively preventive approach to improve the long-term effect of angioplasty have attracted great attention in world-wide cardiovascular research area.As a vasoactive substance, thrombin was known previously for its action on blood coagulation and thrombogenesis. As the development of modern biological technique in recent years, more and more functions of thrombin were found. Lots of evidence indicated that thrombin played a central role in the formation of restenosis : â‘  To activate the thrombogenesis and blood coagulation cascade at the sites of vascular injury in vivo; â‘¡ to stimulate the proliferation and migration of cellular components of vascular wall;â‘¢ to stimulate the accumulation of extracellular matrix in vascular wall; â‘£ to stimulate the synthesis and release of chemotactic factors from intima and regulate inflammatory processes in blood leukocytes and cells of vascular wall. All these indicated the possibility of preventing restenosis by inhibiting the action of thrombin. Since most of the action of thrombin is mediated by its receptor(TR), the following studies were designed based on the inhibition of synthesis of TR.1. Mini pig aorta injury model was established using oversized balloon catheter (1.1-1.3 times of the vascular luminal size) combined with high cholesterol diet feeding. Four weeks after arterial injury, the serum level of total cholesterol and low density lipoprotein were increased, but that of high density lipoprotein remained almost unchanged. The intimal was thickened with an increased expression of TR indicated by immunohistochemistry. The proliferation of cultured aortic smooth muscle cells (ASMC) derived from injured artery was...