|Nitro-fatty acids reduce atherosclerosis in apolipoprotein E-deficient mice.|
|PMID: 20167658 Owner: NLM Status: MEDLINE|
|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.
METHODS AND 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.
CONCLUSION: These results reveal the antiatherogenic actions of electrophilic nitro-fatty acids in a murine model of atherosclerosis.
|Tanja K Rudolph; Volker Rudolph; Martin M Edreira; Marsha P Cole; Gustavo Bonacci; Francisco J Schopfer; Steven R Woodcock; Andreas Franek; Michaela Pekarova; Nicholas K H Khoo; Alyssa H Hasty; Stephan Baldus; Bruce A Freeman|
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|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-02-18|
|Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 30 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2010 May|
|Created Date: 2010-04-15 Completed Date: 2010-05-03 Revised Date: 2014-09-22|
Medline Journal Info:
|Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States|
|Languages: eng Pagination: 938-45 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
Anti-Inflammatory Agents / administration & dosage, pharmacology*
Antioxidants / administration & dosage, pharmacology*
Aortic Diseases / genetics, metabolism, pathology, prevention & control*
Apolipoproteins E / deficiency*, genetics
Atherosclerosis / genetics, metabolism, pathology, prevention & control*
Cell Adhesion Molecules / metabolism
Chemokine CCL2 / metabolism
Collagen / metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
Foam Cells / drug effects, metabolism
Lipoproteins, LDL / metabolism
Oleic Acids / administration & dosage, pharmacology*
Oxidants / metabolism
Oxidative Stress / drug effects
STAT1 Transcription Factor / metabolism
Signal Transduction / drug effects
|HL089466/HL/NHLBI NIH HHS; HL58115/HL/NHLBI NIH HHS; HL64937/HL/NHLBI NIH HHS; K99 HL095769/HL/NHLBI NIH HHS; R01 HL058115/HL/NHLBI NIH HHS; R01 HL058115-11/HL/NHLBI NIH HHS; R01 HL064937/HL/NHLBI NIH HHS; R01 HL064937-09/HL/NHLBI NIH HHS; R37 HL058115/HL/NHLBI NIH HHS|
|0/10-nitro-oleic acid; 0/Actins; 0/Anti-Inflammatory Agents; 0/Antioxidants; 0/Apolipoproteins E; 0/Ccl2 protein, mouse; 0/Cell Adhesion Molecules; 0/Chemokine CCL2; 0/Lipoproteins, LDL; 0/Oleic Acids; 0/Oxidants; 0/STAT1 Transcription Factor; 0/Stat1 protein, mouse; 0/oxidized low density lipoprotein; 9007-34-5/Collagen|
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