Nitro-fatty acids reduce atherosclerosis in apolipoprotein E-deficient mice
Standard
Nitro-fatty acids reduce atherosclerosis in apolipoprotein E-deficient mice. / Rudolph, Tanja K; Rudolph, Volker; Edreira, Martin M; Cole, Marsha P; Bonacci, Gustavo; Schopfer, Francisco J; Woodcock, Steven R; Franek, Andreas; Pekarova, Michaela; Khoo, Nicholas K H; Hasty, Alyssa H; Baldus, Stephan; Freeman, Bruce A.
in: ARTERIOSCL THROM VAS, Jahrgang 30, Nr. 5, 05.2010, S. 938-945.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Nitro-fatty acids reduce atherosclerosis in apolipoprotein E-deficient mice
AU - Rudolph, Tanja K
AU - Rudolph, Volker
AU - Edreira, Martin M
AU - Cole, Marsha P
AU - Bonacci, Gustavo
AU - Schopfer, Francisco J
AU - Woodcock, Steven R
AU - Franek, Andreas
AU - Pekarova, Michaela
AU - Khoo, Nicholas K H
AU - Hasty, Alyssa H
AU - Baldus, Stephan
AU - Freeman, Bruce A
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
KW - Actins/metabolism
KW - Animals
KW - Anti-Inflammatory Agents/administration & dosage
KW - Antioxidants/administration & dosage
KW - Aortic Diseases/genetics
KW - Apolipoproteins E/deficiency
KW - Atherosclerosis/genetics
KW - Cell Adhesion Molecules/metabolism
KW - Cells, Cultured
KW - Chemokine CCL2/metabolism
KW - Collagen/metabolism
KW - Disease Models, Animal
KW - Dose-Response Relationship, Drug
KW - Foam Cells/drug effects
KW - Injections, Subcutaneous
KW - Lipoproteins, LDL/metabolism
KW - Male
KW - Mice
KW - Mice, Knockout
KW - Oleic Acids/administration & dosage
KW - Oxidants/metabolism
KW - Oxidative Stress/drug effects
KW - Phosphorylation
KW - STAT1 Transcription Factor/metabolism
KW - Signal Transduction/drug effects
U2 - 10.1161/ATVBAHA.109.201582
DO - 10.1161/ATVBAHA.109.201582
M3 - SCORING: Journal article
C2 - 20167658
VL - 30
SP - 938
EP - 945
JO - ARTERIOSCL THROM VAS
JF - ARTERIOSCL THROM VAS
SN - 1079-5642
IS - 5
ER -