Is there a role for the macrophage 5-lipoxygenase pathway in aortic aneurysm development in apolipoprotein E-deficient mice?
Is there a role for the macrophage 5-lipoxygenase pathway in aortic aneurysm development in apolipoprotein E-deficient mice?
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DOI：
10.1196/annals.1383.012
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Habenicht, Andreas J. R.
中科院分区：
文献类型：
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作者：
Funk, Colin D.;Cao, Richard Yang;Habenicht, Andreas J. R.
5-脂氧合酶(5-LO)途径的激活导致巨噬细胞、肥大细胞和其他类型的炎性细胞生物合成前炎性白三烯(LT)脂质介质。最近，人们对心血管系统内这一途径的兴趣激增，因为在人类和小鼠身上使用了遗传学、病理学标本和生化方法的各种令人兴奋的发现。我们发现，CD68阳性的巨噬细胞亚群定位于载脂蛋白E(ApoE)缺陷小鼠的外膜，表达5-LO，这些细胞代表了含有胆酸盐的致动脉粥样硬化饮食诱导的主动脉瘤的重要细胞成分。令人惊讶的是，在同一组小鼠的动脉粥样硬化病变中几乎没有观察到5-LO表达细胞。相应地，脂肪喂养的小鼠的病变大小并不取决于5-LO基因的表达，但在缺乏5-LO途径的情况下，动脉瘤的发生率降低了。我们目前正在探索5-LO/LT参与动脉瘤发病的潜在机制，以及这一途径是否可能在其他模型中发挥作用，如血管紧张素II诱导。
Activation of the 5-lipoxygenase (5-LO) pathway leads to the biosynthesis of proinflammatory leukotriene (LT) lipid mediators in macrophages, mast cells, and other inflammatory cell types. A recent surge in interest in this pathway within the cardiovascular system has arisen from a variety of exciting findings using genetic, pathological specimen, and biochemical approaches in humans and mice. We found that a subset of CD68-positive macrophages, localized within the adventitial layer of apolipoprotein E (apo E)-deficient mice, expressed 5-LO and that these cells represented a significant cellular component of aortic aneurysms induced by an atherogenic diet containing cholate. Surprisingly, almost no 5-LO-expressing cells were observed in atherosclerotic lesions in the same mice. Correspondingly, lesion size in the fat-fed mice did not depend on 5-LO gene expression but aneurysm incidence was reduced in the absence of the 5-LO pathway. We are currently exploring the potential mechanisms for 5-LO/LT involvement in aneurysm pathogenesis and if this pathway might come into play in other models such as induction by angiotensin II.