期刊
PROSTAGLANDINS & OTHER LIPID MEDIATORS
卷 84, 期 1-2, 页码 34-42出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.prostaglandins.2007.03.005
关键词
aneurysm; 5-lipoxygenase; leukotriene; mouse model; inflammation
资金
- NHLBI NIH HHS [HL53558] Funding Source: Medline
Genetic association studies and pathological analysis of cardiovascular disease specimens implicate a role for the 5-lipoxygenase (5-LO)/Ieukotriene (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 Il)-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 11 (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. 0 2007 Elsevier Inc. All rights reserved.
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