Angiotensin II-induced abdominal aortic aneurysm occurs independently of the 5-lipoxygenase pathway in apolipoprotein E-deficient mice
Angiotensin II-induced abdominal aortic aneurysm occurs independently of the 5-lipoxygenase pathway in apolipoprotein E-deficient mice
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DOI：
10.1016/j.prostaglandins.2007.03.005
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发表时间：
2007-08-01
影响因子：
2.9
通讯作者：
Funk, Colin D.
中科院分区：
文献类型：
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作者：
Cao, Richard Yang;Adams, Michael A.;Funk, Colin D.
心血管疾病标本的遗传关联研究和病理分析暗示了5-脂氧合酶（5-LO）/白三烯（LT）通路在人类心血管疾病中的作用。以前，我们已经检测到这一途径在高脂血症、含胆酸盐、饮食诱导的小鼠主动脉瘤的发生率和严重程度中的作用。本研究的目的是评估5-LO/LT途径在血管紧张素II（Ang II）诱导的小鼠腹主动脉瘤（AAA）形成中的重要性。在载脂蛋白E缺陷（apoE（-/-））背景下，对5-LO通路进行遗传（5-LO-/-）或药理学（MK-0591）抑制的小鼠接受正常饲料，并输注Ang 11（500 ng/kg/min）28天，以评估AAA发生率和严重程度。在用FLAP抑制剂MK-0591处理的5-LO-/- apoE-/-、5-LO（+/+）apoE（-/-）和5-LO（+/+）apoE（-/-）小鼠中，Ang II诱导了显著的主动脉壁重构，AAA形成的发生率分别为32%、29%和40%，各组之间的发生率或严重程度没有统计学显著差异。小鼠中5-LO途径的消除表明白三烯在Ang II诱导的AAA发病机制中缺乏作用，强调需要测试额外的非啮齿动物AAA临床前模型。0 2007 Elsevier Inc. All rights reserved.
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.