Oleic Acid Inhibits Endothelial Activation

TLDR

Oleic acid, a major component of the Mediterranean diet, is believed to exert anti‑atherogenic effects. The study aimed to determine whether oleic acid can modulate endothelial activation, specifically the expression of adhesion molecules involved in leukocyte recruitment and early atherogenesis. Human umbilical vein endothelial cells were treated with sodium oleate for up to 72 h, then exposed to inflammatory stimuli (TNF, IL‑1α/β, IL‑4, LPS, or PMA) for 6–24 h, and adhesion molecule expression and VCAM‑1 mRNA were quantified by enzyme immunoassays, flow cytometry, and Northern blotting. Oleate (10–100 µM) markedly suppressed VCAM‑1, E‑selectin, and ICAM‑1 expression (>40 % reduction after 72 h plus LPS), decreased monocyte adhesion, lowered VCAM‑1 mRNA, inhibited NF‑κB activation, and shifted endothelial lipid composition toward higher oleate at the expense of saturated fatty acids, suggesting a potential anti‑atherogenic mechanism despite being less potent than polyunsaturated fatty acids.

Abstract

Abstract —Because oleic acid is implicated in the antiatherogenic effects attributed to the Mediterranean diet, we investigated whether this fatty acid can modulate endothelial activation, ie, the concerted expression of gene products involved in leukocyte recruitment and early atherogenesis. We incubated sodium oleate with human umbilical vein endothelial cells for 0 to 72 hours, followed by coincubation of oleate with human recombinant tumor necrosis factor, interleukin (IL)-1α, IL-1β, IL-4, Escherichia coli lipopolysaccharide (LPS), or phorbol 12-myristate 13-acetate for a further 6 to 24 hours. The endothelial expression of vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and intercellular adhesion molecule-1 was monitored by cell surface enzyme immunoassays or flow cytometry, and steady-state levels of VCAM-1 mRNA were assessed by Northern blot analysis. At 10 to 100 μmol/L for >24 hours, oleate inhibited the expression of all adhesion molecules tested. After a 72-hour incubation with oleate and a further 16-hour incubation with oleate plus 1 μg/mL LPS, VCAM-1 expression was reduced by >40% compared with control. Adhesion of monocytoid U937 cells to LPS-treated endothelial cells was reduced concomitantly. Oleate also produced a quantitatively similar reduction of VCAM-1 mRNA levels on Northern blot analysis and inhibited nuclear factor-κB activation on electrophoretic mobility shift assays. Incubation of endothelial cells with oleate for 72 hours decreased the relative proportions of saturated (palmitic and stearic) acids in total cell lipids and increased the proportions of oleate in total cell lipids without significantly changing the relative proportions of polyunsaturated fatty acids. Although less potent than polyunsaturated fatty acids in inhibiting endothelial activation, oleic acid may contribute to the prevention of atherogenesis through selective displacement of saturated fatty acids in cell membrane phospholipids and a consequent modulation of gene expression for molecules involved in monocyte recruitment.