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. METHODS AND RESULTS: Aortic segments from either C57BL/6 wild-type or atherosclerotic ApoE-KO mice underwe...

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Λεπτομέρειες βιβλιογραφικής εγγραφής
Κύριοι συγγραφείς: Ali, Z, Alp, N, Lupton, H, Arnold, N, Bannister, T, Hu, Y, Mussa, S, Wheatcroft, M, Greaves, D, Gunn, J, Channon, K
Μορφή: Journal article
Γλώσσα:English
Έκδοση: 2007
Περιγραφή
Περίληψη: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.