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-kappa B activation

We previously showed that n-3 polyunsaturated fatty acids (FA) inhibit endothelial activation, i.e., early events involved in early atherogenesis and inflammation. These include the expression of endothelial leukocyte adhesion molecules, such as VCAM-1, ICAM-l, E-selectin, and endothelial chemoattractants (1). We further analyzed endothelial effects of various FA differing in chain length, number, position, and cis/trans configuration of the double bonds, concluding that saturated FA are inactive, while potency of polyunsaturates increases with the number of unsaturation (2). We now analyze the extent and mechanisms of modulation of endothelial activation by the monounsaturated FA oleic acid (18:1n-9), as the basis for such effects of the single double bond, and a possible contribution to healthy effects of olive oil in the Mediterranean diet. Methods. Sodium oleate, in medium with 15% serum, was incubated with human umbilical vein endothelial cells for 24-72 h followed by coincubation of oleate with interleukin- 1, Escherichia coli lipopolysaccharide (LPS), or phorbol myristate acetate (PMA) for a further 1-16 h. U937 monocytoid cell adhesion was measured by adhesion assays, the endothelial. expression of VCAM-1, E-selectin, and ICAM-1 by cell surface enzyme immunoassays, steady-state levels of VCAM-1 mRNA by Northern analysis, and nuclear factor (NF)-KB activation by electrophoretic mobility shift assays (EMSA). Fatty acid composition of total cell lipid extracts was monitored with gas-liquid chromatography.