L-4F Differentially Alters Plasma Levels of Oxidized Fatty Acids Resulting in more Anti-Inflammatory HDL in Mice

Satoshi      Imaizumi; Victor      Grijalva; Mohamad      Navab; Brian      J. Van Lenten; Alan      C. Wagner; G.M.      Anantharamaiah; Alan      M. Fogelman; Srinivasa      T. Reddy

Abstract

To determine in vivo if L-4F differentially alters plasma levels of oxidized fatty acids resulting in more antiinflammatory 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. L-4F differentially alters plasma levels of oxidized fatty acids in mice and the resistance of C3H/HeJ mice to atherosclerosis may be mediated by a reduced reaction of this strain to these potent lipid oxidants.

Keywords: HETE, HODE, HPODE, EET, apoA-I mimetic peptides, L-4F, arachidonic acid metabolism

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