The double bond in unsaturated fatty acids is the necessary and sufficient requirement for the inhibition of expression of endothelial leukocyte adhesion molecules through interference with nuclear factor‐κB activation

Abstract

Conclusions These results indicate that the single double bond present in oleic acid is a necessary and sufficient requirement for FA inhibition of endothelial activation. Since this occurred independent of the stimuli used and was present also with PMA, bypassing membrane receptors, these results point to an interference with a common signal transduction pathway for cytokine signaling. These results are accounted for by an inhibition of NF‐χB activation, here demonstrated at the same concentrations required for the inhibition of surface protein. Relevance of these observations to explaining the alleged beneficial antiatherogenic effects of the Mediterranean diet, in which oleic acid in olive oil is a major nutritional component, could lie in the relatively selective displacement of saturated FA by oleate addition to endothelial cells which was also shown to occur in our system. Thus, an increase in the unsaturation index in cell membranes by oleic acid‐rich diets is theoretically additive to the effects of polyunsaturated FA. By these mechanisms, monocyte recruitment in response to atherogenic stimuli might be decreased (3).

Inflammation associated with the postprandial lipolysis of triglyceriderich lipoproteins by lipoprotein lipase

“…In one such study, LA in combination with IL-1α was found to decrease the expression of adhesion molecules ICAM-1, VCAM-1, and E-selectin from endothelial cells when compared with IL-1α treatment alone, with decreased monocyte adherence as a fi nal end point [38]. In support of the anti-infl ammatory effects reported for LA, other investigators have found that endothelial cell activation decreases as the level of unsaturation increases [39,40]. However, most of these studies compare the cellular activation of LA in combination with a proinfl ammatory stimulus to the effects of the stimulus alone, whereas the effects of LA are still greater than no treatment.…”

The role of virgin olive oil components in the modulation of endothelial function

“…This condition might occur by two mechanisms: reduced enzymatic production of ROS or increased scavenging after their production. It has been suggested that the inhibitory potency of UFAs is directly proportional to their number of double bonds [153,156]. According to this, DHA, with six double bonds, would be six times more potent than oleic acid.…”

“…Supplementation of endothelial cells with oleic acid in vitro reduces endothelial cell sensitivity to oxidants, creating a reduced pro-oxidant environment as a consequence of reduced intracellular ROS [151,152]. In this environment, oleate reduces the activation and mRNA expression of NFnB and AP-1, thereby interfering with the endothelial expression of adhesion molecules for circulating monocytes and contributing to a direct vascular atheroprotective effect [153][154][155][156]. In addition, cellular treatment with this fatty acid protects endothelial cells against cytokine-induced VCAM-1, ICAM-1 or E-selectin overexpression [147].…”

Mechanisms of Action of Dietary Fatty Acids in Regulating the Activation of Vascular Endothelial Cells during Atherogenesis

“…PUFA. Both teams agreed on the pro-activating effect of saturated fatty acids and the inhibition of endothelial activation by oleic acid, but their opinions diverged with respect to linoleic acid: according to De Caterina and Libby, linoleic acid inhibits endothelial activation solely because of its unsaturation and independently of its nature, 37,38 but this observation opposed that of the pro-activating effect previously demonstrated with this fatty acid. 33,35,39 The latter study suggested a certain speci city regarding the respective roles of n-6 and n-3 PUFA in endothelial dysfunction.…”