Habib Anwer, Karmali Vinit, John Michael C, Polavarapu Rohini, Nakazawa Gaku, Pachura Kim, Davis Talina, Kolodgie Frank D, Virmani Renu, Finn Aloke V
From the Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (A.H., V.K., M.C.J., R.P., K.P., T.D., A.V.F.); and CVPath Institute, Inc, Gaithersburg, MD (G.N., F.D.K., R.V.).
Circ Cardiovasc Interv. 2014 Aug;7(4):526-32. doi: 10.1161/CIRCINTERVENTIONS.113.001023. Epub 2014 Jun 10.
Preclinical evaluation of the vascular response of drug-eluting stents is limited especially in the setting of diabetes mellitus preventing the evaluation of changes in drug-eluting stent design and eluted drugs after clinical use.
Cultured human aortic endothelial cells were used to assess the differences between sirolimus and its analog, everolimus, in the setting of hyperglycemia on various cellular functions necessary for endothelial recovery. A diabetic rabbit model of iliac artery stenting was used to compare histological and morphometric characteristics of the vascular response to everolimus-eluting, sirolimus-eluting, and bare metal stent placement. Under hyperglycemic conditions, sirolimus impaired human aortic endothelial cell barrier function, migration, and proliferation to a greater degree compared with everolimus. In our in vivo model of diabetes mellitus, endothelialization at 28 days was significantly lower and endothelial integrity was impaired in sirolimus-eluting stent compared with both everolimus-eluting and bare metal stents. Neointimal area, uncovered struts, and fibrin deposition were significantly higher in sirolimus-eluting compared with everolimus-eluting and bare metal stents.
Use of everolimus-eluting stent results in improved vascular response in our preclinical models of diabetes mellitus.
药物洗脱支架血管反应的临床前评估有限，尤其是在糖尿病背景下，这阻碍了对临床使用后药物洗脱支架设计和洗脱药物变化的评估。
使用培养的人主动脉内皮细胞评估西罗莫司及其类似物依维莫司在高血糖环境下对内皮恢复所需各种细胞功能的差异。使用糖尿病兔髂动脉支架置入模型比较依维莫司洗脱支架、西罗莫司洗脱支架和裸金属支架置入后血管反应的组织学和形态学特征。在高血糖条件下，与依维莫司相比，西罗莫司对人主动脉内皮细胞屏障功能、迁移和增殖的损害更大。在我们的糖尿病体内模型中，与依维莫司洗脱支架和裸金属支架相比，西罗莫司洗脱支架在28天时的内皮化明显更低，内皮完整性受损。与依维莫司洗脱支架和裸金属支架相比，西罗莫司洗脱支架的新生内膜面积、未覆盖的支架和纤维蛋白沉积明显更高。
在我们的糖尿病临床前模型中，使用依维莫司洗脱支架可改善血管反应。
