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MGI Accession ID: MGI:3769068
J Number: J:129321
Other Accession IDs: Title: Angiotensin II-induced abdominal aortic aneurysm occurs independently of the 5-lipoxygenase pathway in apolipoprotein E-deficient mice.
Authors: Cao RY; Adams MA; Habenicht AJ; Funk CD
Journal: Prostaglandins Other Lipid Mediat
Volume: 84
Issue: 1-2
Date: 2007 Aug
Year: 2007
Pages: 34-42
Review Status: Peer Reviewed

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-LO(-/-)) or pharmacological (MK-0591) inhibition of the 5-LO pathway on an apolipoprotein E-deficient (apoE(-/-)) background were subjected to a normal chow diet with infusion of Ang II (500 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-LO(-/-) apoE(-/-), 5-LO(+/+)apoE(-/-) and 5-LO(+/+)apoE(-/-) 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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