Quenching of intracellular ROS generation as a mechanism for oleate-induced reduction of endothelial activation and early atherogenesis.
We previously showed that the exposure of vascular endothelium to oleate results in reduced endothelial activation. We now investigate possible mechanisms for this effect in relation to generation of reactive oxygen species (ROS). We stimulated several types of endothelial cells with cytokines or lipopolysaccharide, with or without preincubation with 10-100 mumol/L oleate. Oleate preincubation reduced VCAM-1 expression in all cell types, as well as macrophage-colony stimulating factor release. We simultaneously measured the concentration of intracellular glutathione (GSH), the activity of GSH-related antioxidant enzymes and the production of intracellular ROS. Stimulation of endothelial cells caused a decrease of GSH and an increase in intracellular ROS. The addition of oleate before stimulation, prevented the depletion of GSH and partially prevented stimuli-induced increase of intracellular ROS. This occurred without any change in the activity of GSH-related antioxidant enzymes, superoxide dismutase and catalase. Furthermore, in a cell-free superoxide anion-generating system, oleate quenched the generation of ROS. These results indicate that oleate may exert direct vascular atheroprotective effects by inhibiting endothelial activation through a quenching of stimuli-induced increase in ROS.
Laboratory for Thrombosis and Vascular Research, C.N.R. Institute of Clinical Physiology, Pisa, Italy.
Marika
M
Massaro
Giuseppina
G
Basta
Guido
G
Lazzerini
Maria Annunziata
MA
Carluccio
Francesca
F
Bosetti
Giancarlo
G
Solaini
Francesco
F
Visioli
Aldo
A
Paolicchi
Raffaele
R
De Caterina
D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control*; D002374:Catalase / Q000032:analysis; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000032:analysis; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D019301:Oleic Acid / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000187:drug effects
D016207:Cytokines; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D019301:Oleic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione