Guihua Li, Wang Lei, Sanqing Jia, Ren Wenlin, Lin Zhao, Daokuo Yao, Rongjing Ding
Cardiovascular center of Chuiyangliu Hospital, Beijing, PRC, 100022 China.
J Cardiovasc Dis Res. 2010 Jan;1(1):19-22. doi: 10.4103/0975-3583.59980.
#ENTITYSTARTX02014; 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).
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.
#ENTITYSTARTX02014; 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±125822um(2); 4302061±167952 um(2); 5016269±207934um(2) respectively. The mean neointimal areas were 1119635±163503um(2); 1135636±136555um(2); 441577±74099um(2) 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.
#ENTITYSTARTX02014; 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.
#ENTITYSTARTX02014; 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).
本研究旨在探讨缬沙坦洗脱支架对支架置入后新生内膜形成的影响,并阐明局部应用缬沙坦预防支架内再狭窄(ISR)的可能机制。
采用多层涂层技术制造缬沙坦洗脱支架和载体洗脱支架。将裸支架、载体洗脱支架和缬沙坦洗脱支架分别植入兔腹主动脉。比较裸支架组(n = 8)、载体洗脱支架组(n = 8)和缬沙坦洗脱支架组(n = 10)在支架植入前、植入后即刻及植入后3个月的定量血管造影(QA),以比较主动脉血管直径以及血管新生内膜形成指标,即管腔面积(LA)、新生内膜面积(NIA)、内弹性膜管腔面积(IELA)和15只兔的最大内膜厚度(MIT)。采用Envision两步免疫组织化学法检测α -肌动蛋白蛋白表达。通过IMS(信息管理系统)细胞图像分析系统对上述蛋白的平均阳性指数(MPI)进行半定量分析。MPI = 阳性面积×光密度(OD)。通过MASSON染色观察三组新生内膜中的胶原沉积情况。
通过QA在不同时间测量发现,三组(裸支架组,n = 8;载体洗脱支架组,n = 8;缬沙坦洗脱支架组,n = 10)的平均主动脉直径相似。与其他两组相比,缬沙坦洗脱支架组的管腔面积更大,新生内膜增生更少。平均管腔面积分别为4345548±125822μm²、4302061±167952μm²、5016269±207934μm²。平均新生内膜面积分别为1119635±163503μm²、1135636±136555μm²、441577±74099μm²,平均最大内膜厚度分别为210±30μm、192±21μm、116±12μm。缬沙坦洗脱支架组新生内膜中α -肌动蛋白蛋白表达明显低于其他两组。通过MASSON染色发现,裸支架组和载体洗脱支架组新生内膜中的胶原比缬沙坦洗脱支架组丰富得多。
缬沙坦洗脱支架通过减少胶原沉积和平滑肌细胞增殖来抑制支架置入后的新生内膜增生。因此,其在预防支架内再狭窄方面可能具有潜在疗效。
定量血管造影(QA)、管腔面积(LA)、新生内膜面积(NIA)、内弹性膜管腔面积(IELA)、最大内膜厚度(MIT)、平均阳性指数(MPI)、光密度(OD)、药物洗脱支架(DES)、支架内再狭窄(ISR)、经皮腔内冠状动脉成形术(PTCA)、血管紧张素2型α受体(AT2)