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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Editorial Board Member: Gillery, Philippe / Kazmierczak, Steven / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Schlattmann, Peter / Whitfield, John B.

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Potential role of the lipoxygenase derived lipid mediators in atherosclerosis: leukotrienes, lipoxins and resolvins

Martin Hersberger1

1Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich and Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland

Corresponding author: Martin Hersberger, Division of Clinical Chemistry and Biochemistry, University Children's Hospital, Steinwiesstr. 75, 8032 Zurich, Switzerland Phone: +41 44 266 7541, Fax: +41 44 266 7169,

Citation Information: Clinical Chemistry and Laboratory Medicine. Volume 48, Issue 8, Pages 1063–1073, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2010.212, May 2010

Publication History

Received:
2010-01-15
Accepted:
2010-02-01
Published Online:
2010-05-04

Abstract

Atherogenesis is an inflammatory process with leukocytes infiltrating the arterial intima. The lipoxygenase pathways play a role in leukocyte recruitment through the generation of two classes of arachidonic acid lipid mediators, the leukotrienes and the lipoxins, and one class of omega-3 fatty acid metabolites, the resolvins. There is evidence from animal studies and human genetic studies that the leukotrienes and the enzymes necessary for their generation play a role in atherosclerosis, and possibly even in the development of the vulnerable plaque. Less is known about the effect of the anti-inflammatory lipid mediators in atherosclerosis, the lipoxins and the resolvins. Studies modulating the activity of an enzyme necessary for the production of these lipid mediators, 12/15-lipoxygenase, showed discrepant results in several animal models. Also, human genetic studies have not clearly dissected the effect of the enzyme on atherosclerosis. However, stable forms of the lipoxins and the resolvins protect animals from inflammatory diseases. Whether blocking the leukotrienes or applying anti-inflammatory lipoxins and resolvins will be effective in attenuating human atherosclerosis needs to be demonstrated in future studies. In this review, the biosynthesis of these lipid mediators, their biological effects and the evidence for their possible role in atherosclerosis are discussed with an emphasis on human disease.

Clin Chem Lab Med 2010;48:1063–73.

Keywords: atherosclerosis; inflammation; leukotrienes; lipoxins; lipoxygenase; resolvins

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