Author: ["Lei Zhao","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"]
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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-1α (MIP-1α; also called CCL3), but only minimally affects the formation of lipid-rich lesions. The leukotriene LTD4 strongly stimulates expression of MIP-1α 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.Cite this article
Zhao, L., Moos, M., Gräbner, R. et al. The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysm. Nat Med 10, 966–973 (2004). https://doi.org/10.1038/nm1099 