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Control of endothelial leukocyte adhesion molecules by fatty acids
Author(s) -
De Caterina Raffaele,
Libby Peter
Publication year - 1996
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02637052
Subject(s) - cell adhesion molecule , cell adhesion , endothelial stem cell , endothelium , docosahexaenoic acid , microbiology and biotechnology , endothelial activation , biochemistry , biology , intercellular adhesion molecule 1 , chemistry , inflammation , polyunsaturated fatty acid , immunology , fatty acid , cell , endocrinology , in vitro
Abstract Dietary balance of long‐chain fatty acids (FA) may influence human susceptibility to pathological processes which involve the interaction of leukocytes with vascular endothelium, such as atherogenesis and inflammation. Such interaction is largely mediated by the de novo or increased expression of endothelial leukocyte adhesion molecules on vascular endothelial cells, able to tether and stably bind leukocytes onto the vessel wall, and by the production of leukocyte chemoattractants. Endothelial cells do not normally support high levels of leukocyte adhesion. They do so, however, when exposed to a number of stimuli, such as oxidized low density lipoprotein bacterial lipopolysaccharides, and inflammatory cytokines, which induce phenotypic changes generally referred to as “endothelial activation.” We compared various FA in their ability to modulate endothelial activation by cytokines. FA included linoleic, arachidonic, oleic, eicosapentaenoic and, docosahexaenoic acid (DHA) as representatives of the n‐6, n‐3 polyunsaturated FA and of the monounsaturated FA. The n‐3 FA DHA, and, to a lesser extent, oleate, at nutritionally compatible concentrations, were able to reduce endothelial expression of Vascular Cell and Adhesion Molecule‐1 (VCAM‐1). In further studies, DHA dose‐ and time‐dependently reduced also the expression of E‐selectin, Intercellular Adhesion Molecule‐1, interleukin (IL)‐6 and IL‐8, in response to IL‐1, IL‐4, tumornecrosis factor, or bacterial endotoxin. The magnitude of this effect paralleled its incorporation into cellular phospholipids. Also, coordinate with reduced surface adhesion molecule expression, DHA reduced the adhesion of human monocytes and of monocytic U937 cells to cytokine‐stimulated endothelial cells. These effects were accompanied by a quantitatively consistent reduction in VCAM‐1 mRNA, indicating a pretranslational control of adhesion molecule gene expression. These novel properties of FA as modulators of endothelial activation may help to explain the influence of dietary FA intake on atherogenesis and inflammation.