title: Increased in-stent stenosis in ApoE knockout mice: insights from a novel mouse model of balloon angioplasty and stenting.
abstract: OBJECTIVE
  We aimed to develop and validate a model of angioplasty and stenting in mice that would allow investigation of the response to stent injury using genetically modified mouse strains.
  
  
  RESULTS
  Aortic segments from either C57BL/6 wild-type or atherosclerotic ApoE-KO mice underwent balloon angioplasty alone or balloon angioplasty and stenting with a 1.25x2.5 mm stainless steel stent. Vessels were carotid-interposition grafted into genetically identical littermate recipients and harvested at 1, 7, 14, or 28 days. In wild-type mice, stenting generated an inflammatory vascular injury response between days 1 to 7, leading to the development of neointimal hyperplasia by day 14, which further increased in area by day 28 leading to the development of in-stent stenosis. Uninjured vessels and vessels injured by balloon angioplasty alone developed minimal neointimal hyperplasia. In stented ApoE-KO mice, neointimal area at 28 days was 30% greater compared with wild-type mice.
  
  
  CONCLUSIONS
  By reproducing important features of human stenting in atherosclerotic mice, we provide the potential to investigate molecular pathways and evaluate novel therapeutic targets for stent injury and restenosis.
authors.affiliation: Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Ali
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Alp
authors.forename: Henry
authors.initials: H
authors.lastname: Lupton
authors.forename: Nadine
authors.initials: N
authors.lastname: Arnold
authors.forename: Thomas
authors.initials: T
authors.lastname: Bannister
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Hu
authors.forename: Shafi
authors.initials: S
authors.lastname: Mussa
authors.forename: Mark
authors.initials: M
authors.lastname: Wheatcroft
authors.forename: David R
authors.initials: DR
authors.lastname: Greaves
authors.forename: Julian
authors.initials: J
authors.lastname: Gunn
authors.forename: Keith M
authors.initials: KM
authors.lastname: Channon
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001013:Aorta, Thoracic / Q000293:injuries / Q000473:pathology / Q000637:transplantation; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism*; D002339:Carotid Arteries / Q000601:surgery; D003251:Constriction, Pathologic / Q000209:etiology; D005260:Female; D006965:Hyperplasia; D007120:Immunochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015607:Stents / Q000009:adverse effects*; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology; D014657:Vasculitis / Q000209:etiology / Q000473:pathology
chemical_list: D001057:Apolipoproteins E