13-hydroperoxy-9-11-octadecadienoic-acid and Atherosclerosis

Increasing evidence for phosphatidylcholine hydroperoxide (PCOOH) as a marker of oxidative food deterioration and oxidative diseases has revealed the need for a pure PCOOH standard and a reliable quantification method. Recently, we synthesized the PCOOH isomers 1-palmitoyl-2-(9-hydroperoxyoctadecadienoyl)-sn-glycero-3-phosphocholine, (16:0/9-HpODE PC) and 1-palmitoyl-2-(13-hydroperoxyoctadecadienoyl)-sn-glycero-3-phosphocholine (16:0/13-HpODE PC). Using these standards along with liquid chromatography-tandem mass spectrometry, a reliable quantification method was developed. This mini-review describes these analytical techniques, with a particular emphasis on clinical sample analysis.

Topics: Atherosclerosis; Biomarkers; Chromatography, High Pressure Liquid; Humans; Isomerism; Linoleic Acids; Lipid Peroxidation; Lipid Peroxides; Oxidative Stress; Phosphatidylcholines; Tandem Mass Spectrometry

To determine in vivo if L-4F differentially alters plasma levels of oxidized fatty acids resulting in more anti-inflammatory HDL. Injecting L-4F into apoE null mice resulted in a significant reduction in plasma levels of 15-HETE, 5-HETE, 13-HODE and 9-HODE. In contrast, plasma levels of 20-HETE were not reduced and plasma levels of 14,15-EET, which are derived from the cytochrome P450 pathway, were elevated after injection of L-4F. Injection of 13(S)-HPODE into wild-type C57BL/6J mice caused an increase in plasma levels of 13-HODE and 9-HODE and was accompanied by a significant loss in the anti-inflammatory properties of HDL. The response of atherosclerosis resistant C3H/HeJ mice to injection of 13(S)-HPODE was similar but much more blunted. Injection of L-4F at a site different from that at which the 13(S)-HPODE was injected resulted in significantly lower plasma levels of 13-HODE and 9-HODE and significantly less loss of HDL anti-inflammatory properties in both strains. i) L-4F differentially alters plasma levels of oxidized fatty acids in vivo. ii) The resistance of the C3H/HeJ strain to atherosclerosis may in part be mediated by a reduced reaction of this strain to these potent lipid oxidants.

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Anti-Inflammatory Agents; Apolipoproteins E; Atherosclerosis; Chromatography, Liquid; Enzyme-Linked Immunosorbent Assay; Fatty Acids; Female; Hydroxyeicosatetraenoic Acids; Injections, Subcutaneous; Linoleic Acids; Linoleic Acids, Conjugated; Lipid Peroxides; Lipoproteins, HDL; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Oxidation-Reduction; Peptides; Species Specificity; Tandem Mass Spectrometry; Time Factors; Up-Regulation

The decomposition of peroxidized lipids of low-density lipoprotein (LDL) has been suggested to be involved in atherosclerosis. In this study, an in vitro system with 13-hydroperoxylinoleic acid (13-HPODE) was used to determine the effects of antioxidants on its decomposition. Decomposition of 13-HPODE was not affected by alpha-tocopherol, several other antioxidants, or antioxidant enzymes. Moreover, the inclusion of alpha-tocopherol during the decomposition of 13-HPODE resulted in an accumulation of aldehydes. Further oxidation of aldehydes to carboxylic acids by a number of oxidases was prevented by alpha-tocopherol. Conversely, the formation of carboxylic acids may be conducive to plaque stabilization via immunomodulation, rapid degradation, and by calcium sequestration. Thus, the inhibition of formation of carboxylic acids could be a serious deleterious effect of antioxidant treatment. In contrast, alpha-keto acids, like pyruvic acid, promoted the conversion of 13-HPODE to 13-hydroxylinoleic acid (13-HODE) by readily undergoing decarboxylation into acetate. These observations suggest that agents that promote the reduction of lipid peroxides into lipid hydroxides could be far more effective in treating cardiovascular diseases as opposed alpha-tocopherol-like antioxidants that could affect additional steps in the oxidation cascade.

Topics: Aldehydes; alpha-Tocopherol; Antioxidants; Atherosclerosis; Carboxylic Acids; Chromatography, Liquid; Chromatography, Thin Layer; Humans; Linoleic Acids; Lipid Peroxides; Mass Spectrometry; Models, Biological; Oxidation-Reduction; Pyruvic Acid; Spectrophotometry, Infrared