Eicosanoids and docosanoids in plasma and aorta of healthy and atherosclerotic rabbits.

ABSTRACT

Eicosanoids and docosanoids have been shown to be involved in atherosclerosis. Polyunsaturated fatty acids (PUFAs) are important nutrients that are metabolized by lipoxygenases and cyclooxygenases to various mono-hydroxy metabolites which can be further metabolized by specific enzymes to more complex eicosanoids and docosanoids. In this study a high-performance liquid chromatography methodology was established and rabbits were fed with a control or a high-cholesterol diet to induce atherosclerotic lesions to determine pro- or anti-inflammatory lipid mediators in atherosclerotic vessels. In aortic samples from atherosclerotic rabbits we determined for the first time various eicosanoids/docosanoids and observed an increased concentration of 12-lipoxygenase metabolites. Increased levels of 12-hydroxyeicosatetraenoic acid (12-HETE) in high-cholesterol versus control animals as well as increased ratios of 12-HETE/arachidonic acid ratios indicate that 12-lipoxygenase metabolites may have importance in atherosclerosis. In addition, decreased concentrations of the 5-lipoxygenase metabolite leukotriene B4 levels were detected in high-cholesterol animals. A positive correlation of total plaque area with plasma levels of 12-HETE and a negative correlation with aortic levels of endogenous PPARγ-ligand 13-oxo-octadecadienoic acid were found. This study let us conclude that the cholesterol content in the diet might influence atherosclerosis via increased 12-lipoxygenase- and cyclooxygenase-mediated pathways and reduced 5-lipoxygenase pathways.