Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2019924 | Prostaglandins & Other Lipid Mediators | 2007 | 9 Pages |
Abstract
Genetic association studies and pathological analysis of cardiovascular disease specimens implicate a role for the 5-lipoxygenase (5-LO)/leukotriene (LT) pathway in human cardiovascular disease. Previously, we had detected a role for this pathway in the incidence and severity of hyperlipidemic, cholate-containing, diet-induced aortic aneurysm in mice. The goal of the present study was to assess the importance of the 5-LO/LT pathway in angiotensin II (Ang II)-induced murine abdominal aortic aneurysm (AAA) formation. Mice with either genetic (5-LOâ/â) or pharmacological (MK-0591) inhibition of the 5-LO pathway on an apolipoprotein E-deficient (apoEâ/â) background were subjected to a normal chow diet with infusion of Ang II (500Â ng/kg/min) for 28 days for assessment of AAA incidence and severity. Ang II-induced marked aortic wall remodeling with an incidence of 32, 29 and 40% AAA formation in 5-LOâ/â apoEâ/â, 5-LO+/+apoEâ/â and 5-LO+/+apoEâ/â mice treated with FLAP inhibitor MK-0591, respectively, with no statistically significant differences in incidence or severity between groups. Abrogation of the 5-LO pathway in mice indicates a lack of role of leukotrienes in Ang II-induced AAA pathogenesis stressing the need for additional non-rodent AAA pre-clinical models to be tested.
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Authors
Richard Yang Cao, Michael A. Adams, Andreas J. Habenicht, Colin D. Funk,