Abstract 481: Disturbed Flow Arterial Intimal Hyperplasia Model in the Mouse Carotid Artery Induced by a Focal Stenosis
Objective: Murine models offer a power tool for the molecular dissection of remodeling and intimal hyperplasia mechanisms, though technical challenges limit their utility. While simple, complete carotid ligation lacks direct clinical relevance, and branch outflow ligations require advanced microsurgical skills. We thus developed a simple and clinically relevant mouse model based on the hypothesis that locally disturbed flow caused by a focal high grade stenosis would yield arterial intimal hyperplasia thickening, and that the standardized diet induced obesity (DIO) model would accentuate this response.
Methods: A focal stenosis in 8 week old C57BL/6J mice (normal chow (NC, 10 kcal% fat) or DIO chow (60 kcal% fat) throughout study) was created by placing 9-0 nylon suture around the distal common carotid artery and an external 35-gauge needle (outer diameter=0.14mm), and then removing the needle to restore blood flow (∼78% reduction of lumen diameter; n=20). Tissues were perfusion fixed for morphology 4 weeks later.
Results: Both NC and DIO groups developed intimal hyperplasia proximal to the stenosis, with approximately three-times more in the DIO animals (Figure 1).Conclusions: In the mouse, a surgically created focal stenosis yields an intimal hyperplastic wall response. DIO accentuates this response. This model offers a tool for investigating mechanisms of hemodynamically driven mechanisms governing intimal hyperplasia formation.
- © 2012 by American Heart Association, Inc.