Is There a Role for the Macrophage 5-Lipoxygenase Pathway in Aortic Aneurysm Development in Apolipoprotein E-Deficient Mice?

: 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.