L-4F differentially alters plasma levels of oxidized fatty acids resulting in more anti-inflammatory HDL in mice

Drug Metab Lett. 2010 Aug;4(3):139-48. doi: 10.2174/187231210791698438.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8,11,14-Eicosatrienoic Acid / analogs & derivatives
  • 8,11,14-Eicosatrienoic Acid / blood
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Atherosclerosis / blood
  • Atherosclerosis / genetics
  • Atherosclerosis / prevention & control
  • Chromatography, Liquid
  • Enzyme-Linked Immunosorbent Assay
  • Fatty Acids / blood*
  • Female
  • Hydroxyeicosatetraenoic Acids / blood
  • Injections, Subcutaneous
  • Linoleic Acids / administration & dosage
  • Linoleic Acids / blood
  • Linoleic Acids, Conjugated / blood
  • Lipid Peroxides / administration & dosage
  • Lipoproteins, HDL / blood*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oxidation-Reduction
  • Peptides / administration & dosage*
  • Species Specificity
  • Tandem Mass Spectrometry
  • Time Factors
  • Up-Regulation


  • Anti-Inflammatory Agents
  • Apolipoproteins E
  • Fatty Acids
  • Hydroxyeicosatetraenoic Acids
  • L-4F peptide
  • Linoleic Acids
  • Linoleic Acids, Conjugated
  • Lipid Peroxides
  • Lipoproteins, HDL
  • Peptides
  • 9-hydroxy-10,12-octadecadienoic acid
  • 13-hydroperoxy-9,11-octadecadienoic acid
  • 5-hydroxy-6,8,11,14-eicosatetraenoic acid
  • 13-hydroxy-9,11-octadecadienoic acid
  • 15-hydroxy-5,8,11,13-eicosatetraenoic acid
  • 14,15-epoxy-5,8,11-eicosatrienoic acid
  • 8,11,14-Eicosatrienoic Acid