title: 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.
authors: Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Paprika Bioanalytics BT, Debrecen, Hungary.
authors: Monika
authors: M
authors: Szklenar
authors: Janine
authors: J
authors: Kalkowski
authors: Verena
authors: V
authors: Stangl
authors: Mario
authors: M
authors: Lorenz
authors: Ralph
authors: R
authors: Rühl
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004281:Docosahexaenoic Acids / Q000097:blood / Q000378:metabolism*; D015777:Eicosanoids / Q000097:blood / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000097:blood; D008297:Male; D053858:Metabolic Networks and Pathways; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011817:Rabbits; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D002791:Cholesterol, Dietary; D015777:Eicosanoids; D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001092:Arachidonate 12-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases