Construction of antisense rat thrombin receptor gene and its effect on proliferation of rat aortic smooth muscle cells

Thrombin-induced receptor activation which leads to a number of intracellular signaling events as well asstimulation of endogenous PDGF-A and bFGF production may be important to the induction of proliferation of arterialsmooth muscle cells in the development of vascular disease. To obtain a better understanding of the mechanismsunderlying ASMC prolifeation after arterial injury and explore an effective therapy approach, a plasmid (pLXSN/ATR),which expresses antisense thrombin receptor (ATR) mRNA directed against the sequences of translation initiationregion, thrombin cleavage and binding sites of the thrombin receptor, was constructed and transfected into thecultured RASM. The results showed that 3H-TdR incorporation in the transfected RASM was inhibited with recombi-nant pLXSN/ATR. This indicated that specific inhibition of thrombin receptor-mediated ASMC proliferation waspossible using a receptor specific antisense DNA.