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.