Abstract
BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: Use of everolimus-eluting stent results in improved vascular response in our preclinical models of diabetes mellitus.