INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
artículos
Título:
Nitro-fatty acids reduce atherosclerosis in apolipoprotein e-deficient mice.
Autor/es:
RUDOLPH TK, RUDOLPH V, EDREIRA MM, COLE MP, BONACCI G, SCHOPFER FJ, WOODCOCK SR, FRANEK A, PEKAROVA M, KHOO NK, HASTY AH, BALDUS S, FREEMAN BA.
Revista:
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Editorial:
LIPPINCOTT WILLIAMS & WILKINS
Referencias:
Año: 2010 vol. 30 p. 938 - 945
ISSN:
1079-5642
Resumen:
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.