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.
Funk
Colin D
CD
Department of Physiology, Queen's University, Kingston, ON K7L 3N6 Canada. funkc@post.queensu.ca
Cao
Richard Yang
RY
Zhao
Lei
L
Habenicht
Andreas J R
AJ
D000818:Animals; D001014:Aortic Aneurysm / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D015398:Signal Transduction
D001057:Apolipoproteins E; D018836:Inflammation Mediators; D001094:Arachidonate 5-Lipoxygenase