Han Yaling, Liang Ming, Kang Jian, Qi Yanmei, Deng Jie, Xu Kai, Yan Chenghui
Department of Cardiology, Cardiovascular Research Institute, Shenyang Northern Hospital, Shenyang, China.
Catheter Cardiovasc Interv. 2007 Nov 1;70(5):647-53. doi: 10.1002/ccd.21156.
The goal of this study was to evaluate the efficacy and the mechanism of 17beta-estradiol-eluting stents on inhibiting neointimal formation of abdominal aortas in rabbits fed with high fat diet.
Animal experiments have shown that local delivery of estrogen reduced neointimal formation after coronary angioplasty. Preliminary trial of estrogen-eluting stent implantation in patients with coronary disease also suggests a reduction in restenosis.
We implanted 17beta-estradiol-eluting stents, or control phosphorylcholine- coated stents, or bare metal stents of abdominal aortas in rabbits fed with high fat diet. Histology, immunohistochemistry, and Western blot analysis were used to assess the efficacy and mechanism of inhibiting neointimal formation of 17beta-estradiol-eluting stents.
Western blot analysis revealed marked increase in ERK phosphorylation in 30 min after deployment of phosphorylcholine-coated or bare metal stents, indicating activation of MAP kinase pathway. Immunohistochemistry showed intense staining of phospho-ERK in the medial smooth muscle cells in stent-implanted region. Extensive neointimal hyperplasia developed 12 weeks after stenting. In contrast, we observed significant inhibition of ERK phosphorylation and neointimal thickening in estrogen-eluting stent-implanted animals. Immunohistochemistry of factor VIII-related antigen demonstrated an accelerated reendothelialization as compared with the bare metal stent or phosphorylcholine-coated stent-implanted controls.
Current study suggests that estrogen-eluting stents reduce neointimal formation and hence prevent restenosis after angioplasty possibly by inhibiting ERK activation in smooth muscle cells and promoting reendothelialization.
本研究旨在评估17β-雌二醇洗脱支架对高脂饮食喂养的兔腹主动脉新生内膜形成的抑制作用及其机制。
动物实验表明，局部给予雌激素可减少冠状动脉成形术后的新生内膜形成。冠心病患者雌激素洗脱支架植入的初步试验也提示再狭窄率降低。
我们将17β-雌二醇洗脱支架、对照的磷酸胆碱涂层支架或裸金属支架植入高脂饮食喂养的兔腹主动脉。采用组织学、免疫组织化学和蛋白质印迹分析来评估17β-雌二醇洗脱支架抑制新生内膜形成的效果及其机制。
蛋白质印迹分析显示，磷酸胆碱涂层支架或裸金属支架植入后30分钟，ERK磷酸化显著增加，表明丝裂原活化蛋白激酶（MAP）激酶途径被激活。免疫组织化学显示，支架植入区域的中膜平滑肌细胞中有强烈的磷酸化ERK染色。支架植入12周后出现广泛的新生内膜增生。相比之下，我们观察到雌激素洗脱支架植入动物的ERK磷酸化和新生内膜增厚受到显著抑制。与裸金属支架或磷酸胆碱涂层支架植入对照组相比，因子VIII相关抗原的免疫组织化学显示再内皮化加速。
目前的研究表明，雌激素洗脱支架可能通过抑制平滑肌细胞中的ERK活化和促进再内皮化来减少新生内膜形成，从而预防血管成形术后的再狭窄。
