Development of siRNA-eluting stent using PTD-peptide vector

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1. Coating method for siRNA on stent was examined. As one of the model cases, Glycosminoglycans were bound on the titanium oxide surface. A basic PTD peptide binding to GAGs was determined by QCM method. Further, the uptake of the peptide into the smooth muscle cells from the titanium surface was quantified. However; the uptake amount was not significantly different from the control. We suppose that the peptide could not stably bound on titanium after the cells were seeded.2. Various genes are induced by cytokines when the vascular smooth muscle cells proliferate in stent-restenosis. We predicted the ADAM-TS gene, a subfamily of matrix metaroproteinase, expression in this situation. These might be involved in the remodeling in the processes of restenosis. As a result, one of the ADAM-TS gene is upregurated 3-6 hrs after the IL-1 induction. Promoter of the gene contained putative NFAT-binding sites. NFAT inhibitors could suppress the ADAM-TS gene expression, indicating the induction through NFAT. These results might implicate the possible target of siRNA treatment.3. Small stent designed in this project was examined in rat Stent implantation was performed in aorta or femoral artery The implantation in aorta is rather successful compared to that in femoral artery. Narrowing the size and increasing the flexibility is required for stenting in the femoral artery