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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1204.)
© 2006 American Heart Association, Inc.

Editorials

Lipoxygenase Pathways as Mediators of Early Inflammatory Events in Atherosclerosis

Colin D. Funk

From the Departments of Physiology and Biochemistry, Queen’s University, Kingston, Canada.

Correspondence to Colin Funk, Department of Physiology, Stuart Street, Queen’s University, Kingston, ON K7L 3N6 Canada. E-mail funkc@post.queensu.ca

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Oxidative modification of low density lipoproteins has been a leading hypothesis in atherogenesis, and throughout the 1990’s there was intense interest in the discovery of pathways leading to this modification.^1,2 In a commentary to an article dealing with 12/15-lipoxygenase gene disruption in the atherosclerotic apolipoprotein E (apoE)-deficient mouse model in 1999, Daniel Steinberg declared "at last direct evidence that lipoxygenases play a role in atherosclerosis."^3,4 Since this article seven years ago, the lipoxygenase pathway involvement in atherogenesis has become rather more complicated.

See page 1260

Lipoxygenases are non-heme iron–containing enzymes that catalyze the stereospecific incorporation of molecular oxygen into polyunsaturated fatty acids with a 1,4-cis, cis-pentadiene motif.⁵ With respect to atherosclerosis 2 of the 6 (human)/7 (mice) lipoxygenase family members have received the most attention because of their expression patterns in inflammatory cells and in some settings within endothelial cells; these are the 12/15-lipoxygenase (12/15-LO; also known as the leukocyte-type 12-lipoxygenase and 15-lipoxygenase-1) and 5-lipoxygenase.^6,7 12/15-LO catalyzes the transformation of free arachidonic acid to 12-hydroperoxy-eicosatetraenoic acid (12-HPETE) and 15-HPETE. These products are reduced to the corresponding hydroxy derivatives 12-HETE and 15-HETE by cellular peroxidases. Mice make predominantly 12-HETE whereas humans produce mainly 15-HETE. Both human and mouse 12/15-LO enzymes metabolize linoleic acid to 13-hydroperoxy-octadecadienoic acid (13-HPODE; the reduced product is 13-HODE) as well as metabolizing more complex lipids including cholesteryl linoleate and sn2 polyunsaturated fatty acids within phospholipids. Thus, 12/15-LO has been shown to oxidatively modify the key lipid components of LDL. 5-Lipoxygenase, on the other hand, only . . . [Full Text of this Article]

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12/15 Lipoxygenase Mediates Monocyte Adhesion to Aortic Endothelium in Apolipoprotein E–Deficient Mice Through Activation of RhoA and NF-B

David T. Bolick, Suseela Srinivasan, Angela Whetzel, Lauren C. Fuller, and Catherine C. Hedrick
Arterioscler Thromb Vasc Biol 2006 26: 1260-1266. [Abstract] [Full Text] [PDF]

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