Antisense Thrombin Receptor Gene Inhibits Intimal Hyperplasia After Rat Carotid Artery Injury Molecular Pathology

Percutaneous transluminal coronary angioplasty (PTCA) is a breakthrough in cardiovascular therapeutics. After twenty years' development, its procedural success rates can reach 95%. But its long-dated curative effect is greatly affected by restenosis, which takes place in 30% patients. So prevention of restenosis becomes very important in current cardiovascular research.Alpha-thrombin is a multifunctional serine proteinase that is concentrated at sites of vascular injury. A great deal of research about the role of thrombin and thrombin receptor on vascular healing responses following balloon injury show that thrombin is a very important mitogen and thrombin as well as thrombin receptor plays an very important role in neointima formation and restenosis after PTCA.Thrombin-induced receptor activation, which leads to a number of intracellular signaling events as well as stimulation of endogenous PDGF-A and bFGF production, may be important to the induction of proliferation of arterial smooth muscle cells in the development of vascular disease. To obtain a better understanding of the mechanisms underlying RASM cells proliferation after arterial injury and explore an effective therapy approach to restenosis, a plasmid (pLXSN/ATR), which expresses antisense thrombin receptor (ATR) RNA directed against the sequences of translation initiation region, thrombin cleavage and binding sites of the thrombin receptor, was constructed and transfected into the cultured RASM and then balloon injured artery. The main results were showed as following:1 An antisense rat thrombin receptor gene was constructed. DNA sequence analysis confirmed that the fragment of rat thrombin receptor gene was inserted into the multiple cloning site of pLXSN correctly and accurately.2 pLXSN/ATR was transfected into cultured RASM cells with Fugene 6 reagent. The...