The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysm - PubMed (original) (raw)

Comparative Study

doi: 10.1038/nm1099. Epub 2004 Aug 22.

Michael P W Moos, Rolf Gräbner, Frédérique Pédrono, Jinjin Fan, Brigitte Kaiser, Nicole John, Sandra Schmidt, Rainer Spanbroek, Katharina Lötzer, Li Huang, Jisong Cui, Daniel J Rader, Jilly F Evans, Andreas J R Habenicht, Colin D Funk

Affiliations

• PMID: 15322539
• DOI: 10.1038/nm1099

Free article

Comparative Study

The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysm

Lei Zhao et al. Nat Med. 2004 Sep.

Free article

Abstract

Activation of the 5-lipoxygenase (5-LO) pathway leads to the biosynthesis of proinflammatory leukotriene lipid mediators. Genetic studies have associated 5-LO and its accessory protein, 5-LO-activating protein, with cardiovascular disease, myocardial infarction and stroke. Here we show that 5-LO-positive macrophages localize to the adventitia of diseased mouse and human arteries in areas of neoangiogenesis and that these cells constitute a main component of aortic aneurysms induced by an atherogenic diet containing cholate in mice deficient in apolipoprotein E. 5-LO deficiency markedly attenuates the formation of these aneurysms and is associated with reduced matrix metalloproteinase-2 activity and diminished plasma macrophage inflammatory protein-1alpha (MIP-1alpha; also called CCL3), but only minimally affects the formation of lipid-rich lesions. The leukotriene LTD(4) strongly stimulates expression of MIP-1alpha in macrophages and MIP-2 (also called CXCL2) in endothelial cells. These data link the 5-LO pathway to hyperlipidemia-dependent inflammation of the arterial wall and to pathogenesis of aortic aneurysms through a potential chemokine intermediary route.

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Comment in

• Aneurysms: leukotrienes weaken aorta from the outside.
  Palinski W. Palinski W. Nat Med. 2004 Sep;10(9):896-8. doi: 10.1038/nm0904-896. Nat Med. 2004. PMID: 15340408 No abstract available.

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