Abstract |
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.
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Authors | Colin D Funk, Richard Yang Cao, Lei Zhao, Andreas J R Habenicht |
Journal | Annals of the New York Academy of Sciences
(Ann N Y Acad Sci)
Vol. 1085
Pg. 151-60
(Nov 2006)
ISSN: 0077-8923 [Print] United States |
PMID | 17182931
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Apolipoproteins E
- Inflammation Mediators
- Arachidonate 5-Lipoxygenase
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Topics |
- Animals
- Aortic Aneurysm
(genetics, metabolism, pathology)
- Apolipoproteins E
(deficiency, genetics, metabolism)
- Arachidonate 5-Lipoxygenase
(metabolism)
- Atherosclerosis
(metabolism)
- Disease Progression
- Humans
- Inflammation Mediators
(metabolism)
- Macrophages
(enzymology)
- Mice
- Signal Transduction
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