Everolimus-eluting stents improve vascular response in a diabetic animal model

Circ Cardiovasc Interv. 2014 Aug;7(4):526-32. doi: 10.1161/CIRCINTERVENTIONS.113.001023. Epub 2014 Jun 10.

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.

Keywords: diabetes mellitus; drug-eluting stents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / pathology*
  • Cell Movement / drug effects
  • Cells, Cultured
  • Diabetes Mellitus / therapy*
  • Disease Models, Animal
  • Drug-Eluting Stents / statistics & numerical data*
  • Endothelial Cells / drug effects*
  • Everolimus
  • Fibrin / metabolism
  • Humans
  • Hyperglycemia / therapy*
  • Iliac Artery / metabolism
  • Iliac Artery / pathology
  • Male
  • Neointima
  • Rabbits
  • Sirolimus / administration & dosage
  • Sirolimus / adverse effects
  • Sirolimus / analogs & derivatives

Substances

  • Fibrin
  • Everolimus
  • Sirolimus