Effect Of CaN-NFAT On The Restenosis Following Balloon Injury In Rats

Investigate the pathogenesis of restenosis after percutaneous coronary intervention and find effective treatment which are the hot topics nowadays.Compared with balloon angioplasty,where the chance of restenosis is 30%-50%,stents have reduced the rate of restenosis to 10%-20%.In the recent years,a break through for the prevention of in-stent restenosis occurred in the form of drug-eluting-stents(DES).Recent data demonstrated that patients treated with DES have a decrease in RS formation compared with those who received non-DES.With the use of drug-eluting-stents,the restenosis rates have decreased to 0%-8%.However,stenting is bound to lead to endometrial inflammation. A variety of inflammatory cytokines mediated smooth muscle cell migration, proliferation after balloon injury, eventually leading to the occurrence of restenosis. Many inflammatory factors associated with restenosis are Ca²⁺/CaM-CaN-NFAT signaling pathway mediated by role.Based on the above speculation, Ca²⁺/CaM-CaN-NFAT signaling system play a role in the formation of restenosis.Objective:To investegate the effect of CaN-NFAT on the restenosis following balloon injury in rats,and Cyclosporine-A,Puerarin in preventing restenosis after rat abdominal aorta balloon injury,provide new theory for preventing restenosis post balloon injury.Methods:fourty-eight healthy adult male SD rats were randomly divided into four groups: sham group (n=12), balloon group (n=12) , cyclosporin-A group(n=12),and puerarin group(n=12). Three days before balloon injury , the cyclosporin-A group and puerarin group were treated with cyclosporin-A(12.5mg/Kg.d) and puerarin(50mg/Kg.d) everyday respectively. Sham group and balloon group of rats were fed with the same volume of tap water.Thirty days afer injury, Specimens were obtained from rats. HE staining and immunohistochemistry to measure the expression level of calcineurin in arterial wall.Pathological changes of the arterial wall were observed by light microscope.The expression of CaN mRNA,NFATc3 mRNA in the abdominal aortas were detected by Rea1 time PCR technique.The serum concentrations of MCP-1 was determined by Elisa.Results:Intimal hyperplasia were observed in balloon injured rats,the neointima was not uniform in thickness.The thickness of the intimal layers , the ratio of the intimal and the medial layers in the Cyclosporin-A group was obviously lower than balloon group (P<0.05). The expression of CaN mRNA,NFATc3 mRNA increased significantly in the arterial wall of balloon group,significantly different from that of the sham and Cyclosporin-A group (P<0.05). Immunohistochemistry studies revealed that CaN expression increased significantly in balloon group,and it was significantly different from that of the sham and Cyclosporin-A group (P<0.05).The serum concentrations of MCP-1 of balloon group is higher than that of sham and Cyclosporin-A group(P<0.05).compared with balloon group,the neointima,CaN protein,CaN mRNA,NFATc3 mRNA and concentrations of MCP-1 have no statistically significant.Conclusions:1. CaN-NFAT signal transduction pathway plays a role in the proliferation of VSMC following balloon injury.2. CaN-NFAT signaling transduction pathway in restenosis plays a role in the inflammatory process.3.Cyclosporin-A can attenuate restenosis by supressing CaN-NFAT signal transduction pathway,and decreasing the serum concentrations of MCP-1 in aorta-injured rats.