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Control of endothelial leukocyte adhesion molecules by fatty acids

  • Cardiovascular System
  • Published:
Lipids

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 thede 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.

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Abbreviations

DHA:

docosahexaenoic acid

EIA:

enzyme immunoassay

EPA:

eicosapentaenoic acid

FA:

fatty acids

HSVEC:

human saphenous vein endothelial cells

ICAM-1:

Intercellular Adhesion Molecule-1

IL:

interleukin

LPS:

lipopolysaccharide

MHC-1:

Major Histocompatibility Complex-Class I

TNF:

tumor necrosis factor

VCAM-1:

Vascular Cell Adhesion Molecule-1

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  1. Vascular Medicine and Atherosclerosis Unit, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachussetts

    Raffaele De Caterina & Peter Libby

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  1. Raffaele De Caterina
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A substantial part of the data presented in this paper has been previously published [Arterioscler. Thromb. 14, 1829–1836 (1994)], and are here reported with permission of the American Heart Association.

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De Caterina, R., Libby, P. Control of endothelial leukocyte adhesion molecules by fatty acids. Lipids 31, S57–S63 (1996). https://doi.org/10.1007/BF02637052

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