Increased in-stent stenosis in ApoE knockout mice: insights from a novel mouse model of balloon angioplasty and stenting.
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.
Ali
Ziad A
ZA
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Alp
Nicholas J
NJ
Lupton
Henry
H
Arnold
Nadine
N
Bannister
Thomas
T
Hu
Yanhua
Y
Mussa
Shafi
S
Wheatcroft
Mark
M
Greaves
David R
DR
Gunn
Julian
J
Channon
Keith M
KM
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
D001057:Apolipoproteins E