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.

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.

• Authors: 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
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 27 Issue 4 Pg. 833-40 (Apr 2007) ISSN: 1524-4636 [Electronic] United States
• PMID: 17204666 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E

Topics

• Angioplasty, Balloon (adverse effects)
• Animals
• Aorta, Thoracic (injuries, pathology, transplantation)
• Apolipoproteins E (deficiency)
• Atherosclerosis (etiology, metabolism)
• Carotid Arteries (surgery)
• Constriction, Pathologic (etiology)
• Female
• Hyperplasia
• Immunochemistry
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Stents (adverse effects)
• Time Factors
• Tunica Intima (pathology)
• Vasculitis (etiology, pathology)