| 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: 2011-07-28 |
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.