Document Detail


Nitro-fatty acids reduce atherosclerosis in apolipoprotein E-deficient mice.
MedLine Citation:
PMID:  20167658     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
8978478 - Metabolic fate of oleic acid derived from lysosomal degradation of cholesteryl oleate i...
9576808 - Preparation of conjugates of oligodeoxynucleotides and lipid structures and their inter...
18690758 - Therapeutic effects of fibrates in postprandial lipemia.
2958078 - Isotretinoin and serum lipids: studies on fatty acid, apolipoprotein and intermediary m...
2499338 - Independent regulation of thromboxane and prostaglandin synthesis in liver macrophages.
16013388 - Microbicidal activity of tripotassium phosphate and fatty acids toward spoilage and pat...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-02-18
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  30     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-15     Completed Date:  2010-05-03     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  938-45     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA. t.rudolph@uke.de
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Actins / metabolism
Animals
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
Cells, Cultured
Chemokine CCL2 / metabolism
Collagen / metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
Foam Cells / drug effects,  metabolism
Injections, Subcutaneous
Lipoproteins, LDL / metabolism
Male
Mice
Mice, Knockout
Oleic Acids / administration & dosage,  pharmacology*
Oxidants / metabolism
Oxidative Stress / drug effects
Phosphorylation
STAT1 Transcription Factor / metabolism
Signal Transduction / drug effects
Grant Support
ID/Acronym/Agency:
HL089466/HL/NHLBI NIH HHS; HL58115/HL/NHLBI NIH HHS; HL64937/HL/NHLBI NIH HHS; K99 HL095769-02/HL/NHLBI NIH HHS; R01 HL058115-11/HL/NHLBI NIH HHS; R01 HL064937-09/HL/NHLBI NIH HHS; R37 HL058115-15/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
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
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Inhibition of Glycosphingolipid Synthesis Induces a Profound Reduction of Plasma Cholesterol and Inh...
Next Document:  DGAT1 Participates in the Effect of HNF4A on Hepatic Secretion of Triglyceride-Rich Lipoproteins.