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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1996-10-21
pubmed:abstractText
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, docosa-hexaenoic 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, tumor-necrosis 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0024-4201
pubmed:author
pubmed:issnType
Print
pubmed:volume
31 Suppl
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S57-63
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Control of endothelial leukocyte adhesion molecules by fatty acids.
pubmed:affiliation
Vascular Medicine and Atherosclerosis Unit, Brigham and Woman's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't