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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:833.)
© 2007 American Heart Association, Inc.

Vascular Biology

Increased In-Stent Stenosis in ApoE Knockout Mice

Insights from a Novel Mouse Model of Balloon Angioplasty and Stenting

Ziad A. Ali; Nicholas J. Alp; Henry Lupton; Nadine Arnold; Thomas Bannister; Yanhua Hu; Shafi Mussa; Mark Wheatcroft; David R. Greaves; Julian Gunn; Keith M. Channon

From the Department of Cardiovascular Medicine (Z.A.A., N.J.A., T.B., S.M., K.M.C.), University of Oxford, John Radcliffe Hospital, UK; Brivant Ltd (H.L., J.G.), Oranmore, Galway, Ireland; the Cardiovascular Research Group (N.A., M.W.), University of Sheffield, Northern General Hospital, UK; Sir William Dunn School of Pathology (D.R.G.), University of Oxford, UK; and the Cardiovascular Division (Y.H.), King’s College, London, UK.

Correspondence to Professor Keith Channon, Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK. E-mail keith.channon{at}cardiov.ox.ac.uk

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.

Methods and 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.

In this study we describe the first mouse model of balloon angioplasty and stenting. This new model reproduces features of human percutaneous coronary intervention and provides the potential to investigate molecular pathways and evaluate novel therapeutic targets for stent injury and restenosis.

Key Words: vascular biology • genetically modified mice • angioplasty • stents • restenosis

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