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Funk, C.D. et al.

Funk, Cao, Zhao, Habenicht,

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.[1]

References

Is there a role for the macrophage 5-lipoxygenase pathway in aortic aneurysm development in apolipoprotein e-deficient mice? Funk, C.D., Cao, R.Y., Zhao, L., Habenicht, A.J. Ann. N. Y. Acad. Sci. (2006) [Pubmed]

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