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Arterioscler Thromb Vasc Biol. 2010 May;30(5):938-45. doi: 10.1161/ATVBAHA.109.201582. Epub 2010 Feb 18.

Nitro-fatty acids reduce atherosclerosis in apolipoprotein E-deficient mice.

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  • 1Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA. t.rudolph@uke.de

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.

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.

PMID:
20167658
[PubMed - indexed for MEDLINE]
PMCID:
PMC2857965
Free PMC Article

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