Objective :—This study is to explore the effect of valsartan-eluting stents on neointima formation after stenting and to elucidate possible mechanisms how locally used valsartan prevents in-stent restenosis (ISR). METHOD: valsartan- and carriereluting stents were manufactured by using multi-layer-coated technology. Bare stents, carrier-eluting stents and valsartan– eluting stents were implanted into the abdominal aortas of the rabbits respectively. Quantitative angiography (QA) before, immediately after and 3 months after stent implantation were compared between the groups of bare (n=8), carrier-eluting (n=8) and valsartan-eluting stent (n=10), which allows the comparison of vascular diameters of aortas as well as indices of vascular neointimal formation, i.e. luminal area (LA), neointimal area (NIA), inner elastic membrane luminal area (IELA) and the maximal inner-membrane thickness (MIT) in 15 rabbits. α-Actin protein expression were detected by Envision two-step immunohistochemistry. Mean positive indices (MPI) of the above protein were analyzed semi-quantatively by IMS(Information Management System) cell image analysis system. MPI=positive area×OD (optical density). Collagen deposition in neointima was observed through MASSON stain among the three groups. Result:—the mean aortic diameters were similar in the three groups:bare stents group(n=8), carrier-eluting stents group(n=8) and valsartan eluting stents group(n=10) measured by QA at different time. A larger luminal area and a less neointimal hyperplasia in valsartan eluting-stents group was found compared with the other two groups. The mean luminal areas were 4345548±125822um2; 4302061±167952 um2; 5016269±207934um2 respectively. The mean neointimal areas were 1119635±163503um2; 1135636±136555um2; 441577±74099um2 and the mean maximal inner-membrane thickness were 210±30um;192±21um; 116±12um respectively. α-Actin protein expression was significantly lower in neointima of valsartan eluting-stents group than the other two groups. Through MASSON stain we found that Collagen was much richer in neointima of bare stents group and carrier-eluting stents group than valsartan eluting-stents group. Conclusion:—Valsartan eluting-stents inhibited neointimal hyperplasia after stenting by decreasing collagen deposition and smooth muscle cell proliferation. Therefore it would be potentially effective in preventing in-stent restenosis. Abbreviations:—Quantitative angiography (QA), luminal area (LA), neointimal area (NIA), inner elastic membrane luminal area (IELA), the maximal inner-membrane thickness (MIT), Mean positive indices (MPI), optical density (OD), Drugeluting stents (DES), in-stent restenosis(ISR), percutaneous transluminal coronary angioplasty (PTCA), angiotensin α type 2 receptor (AT2).
Key words: eluting stent, valsartan, restenosis, collagen, AT2 receptor.