title: Nitro-fatty acids reduce atherosclerosis in apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  Inflammatory processes and foam cell formation are key determinants in the initiation and progression of atherosclerosis. Electrophilic nitro-fatty acids, byproducts of nitric oxide- and nitrite-dependent redox reactions of unsaturated fatty acids, exhibit antiinflammatory signaling actions in inflammatory and vascular cell model systems. The in vivo action of nitro-fatty acids in chronic inflammatory processes such as atherosclerosis remains to be elucidated.
  
  
  RESULTS
  Herein, we demonstrate that subcutaneously administered 9- and 10-nitro-octadecenoic acid (nitro-oleic acid) potently reduced atherosclerotic lesion formation in apolipoprotein E-deficient mice. Nitro-fatty acids did not modulate serum lipoprotein profiles. Immunostaining and gene expression analyses revealed that nitro-oleic acid attenuated lesion formation by suppressing tissue oxidant generation, inhibiting adhesion molecule expression, and decreasing vessel wall infiltration of inflammatory cells. In addition, nitro-oleic acid reduced foam cell formation by attenuating oxidized low-density lipoprotein-induced phosphorylation of signal transducer and activator of transcription-1, a transcription factor linked to foam cell formation in atherosclerotic plaques. Atherosclerotic lesions of nitro-oleic acid-treated animals also showed an increased content of collagen and alpha-smooth muscle actin, suggesting conferral of higher plaque stability.
  
  
  CONCLUSIONS
  These results reveal the antiatherogenic actions of electrophilic nitro-fatty acids in a murine model of atherosclerosis.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA. t.rudolph@uke.de
authors.forename: Tanja K
authors.initials: TK
authors.lastname: Rudolph
authors.forename: Volker
authors.initials: V
authors.lastname: Rudolph
authors.forename: Martin M
authors.initials: MM
authors.lastname: Edreira
authors.forename: Marsha P
authors.initials: MP
authors.lastname: Cole
authors.forename: Gustavo
authors.initials: G
authors.lastname: Bonacci
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Schopfer
authors.forename: Steven R
authors.initials: SR
authors.lastname: Woodcock
authors.forename: Andreas
authors.initials: A
authors.lastname: Franek
authors.forename: Michaela
authors.initials: M
authors.lastname: Pekarova
authors.forename: Nicholas K H
authors.initials: NK
authors.lastname: Khoo
authors.forename: Alyssa H
authors.initials: AH
authors.lastname: Hasty
authors.forename: Stephan
authors.initials: S
authors.lastname: Baldus
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Freeman
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism; D007279:Injections, Subcutaneous; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009829:Oleic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C521487:10-nitro-oleic acid; D000199:Actins; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D008077:Lipoproteins, LDL; D009829:Oleic Acids; D016877:Oxidants; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; C099252:oxidized low density lipoprotein; D003094:Collagen