Is there a role for the macrophage 5-lipoxygenase pathway in aortic aneurysm development in apolipoprotein E-deficient mice?

Ann N Y Acad Sci. 2006 Nov:1085:151-60. doi: 10.1196/annals.1383.012.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aortic Aneurysm / genetics
  • Aortic Aneurysm / metabolism*
  • Aortic Aneurysm / pathology*
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism*
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Atherosclerosis / metabolism
  • Disease Progression
  • Humans
  • Inflammation Mediators / metabolism
  • Macrophages / enzymology*
  • Mice
  • Signal Transduction*

Substances

  • Apolipoproteins E
  • Inflammation Mediators
  • Arachidonate 5-Lipoxygenase