L-4F differentially alters plasma levels of oxidized fatty acids resulting in more anti-inflammatory HDL in mice.
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.
Imaizumi
Satoshi
S
Department of Medicine, and David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USA.
Grijalva
Victor
V
Navab
Mohamad
M
Van Lenten
Brian J
BJ
Wagner
Alan C
AC
Anantharamiah
G M
GM
Fogelman
Alan M
AM
Reddy
Srinivasa T
ST
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics / Q000517:prevention & control; D002853:Chromatography, Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood; D007279:Injections, Subcutaneous; D008041:Linoleic Acids / Q000008:administration & dosage / Q000097:blood; D044243:Linoleic Acids, Conjugated / Q000097:blood; D008054:Lipid Peroxides / Q000008:administration & dosage; D008075:Lipoproteins, HDL / Q000097:blood*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D010455:Peptides / Q000008:administration & dosage*; D013045:Species Specificity; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D001057:Apolipoproteins E; D005227:Fatty Acids; D006893:Hydroxyeicosatetraenoic Acids; C472885:L-4F peptide; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; D008054:Lipid Peroxides; D008075:Lipoproteins, HDL; D010455:Peptides; C024347:9-hydroxy-10,12-octadecadienoic acid; C038649:13-hydroperoxy-9,11-octadecadienoic acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C024348:13-hydroxy-9,11-octadecadienoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D015126:8,11,14-Eicosatrienoic Acid