Mechanisms for reduction of endothelial activation by oleate: inhibition of nuclear factor-kappaB through antioxidant effects.
In a model of early atherogenesis based on cultured endothelial cells, we observed that the incorporation of oleic acid in cellular lipids decreases the stimulated expression of several endothelial adhesion molecules and soluble products typically expressed during endothelial activation and involved in monocyte recruitment. We investigated possible mechanisms for this effect assessing the stimulated induction of nuclear factor-kappaB. In parallel, we also measured glutathione (GSH) content and the activity of antioxidant enzymes after oleate treatment and cytokine stimulation. Oleate prevented the stimulated depletion of GSH without any change in the activity of antioxidant enzymes. These results suggest an antioxidant mechanism by which oleate may exert direct vascular atheroprotective effects.
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D000975:Antioxidants; D007375:Interleukin-1; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D019301:Oleic Acid; D005978:Glutathione