© 1995 American Heart Association, Inc.
Articles |
Docosahexaenoic Acid Selectively Attenuates Induction of Vascular Cell Adhesion Molecule–1 and Subsequent Monocytic Cell Adhesion to Human Endothelial Cells Stimulated by Tumor Necrosis Factor–
From the Institut für Prophylaxe der Kreislaufkrankheiten, Ludwig-Maximilians-Universität, München, Germany.
Correspondence to C. Weber, MD, Institut für Prophylaxe der Kreislaufkrankheiten, Pettenkoferstr 9, D-80336 München, Germany.
Abstract Incorporation of the n-3 polyunsaturated fatty
acid docosahexaenoic acid (DHA) but not eicosapentaenoic acid or n-6
arachidonic acid into human umbilical vein endothelial cell (HUVEC)
phospholipids dose-dependently reduced tumor necrosis factor–
(TNF-)–induced surface expression of vascular cell adhesion
molecule–1 (VCAM-1). In parallel, DHA inhibited TNF-–stimulated
monocytic U937 cell adhesion to HUVECs but did not affect TNF-– or
interferon gamma–induced expression of intercellular adhesion
molecule–1 and endothelial leukocyte adhesion molecule–1 or VCAM-1
induction by interleukin-1ß. DHA appeared to attenuate VCAM-1
transcription, as it reduced induction of VCAM-1 mRNA by TNF-.
VCAM-1 induction is regulated by activation of nuclear
factor–kB, which can be mediated by a TNF-–responsive
phosphatidylcholine-specific phospholipase C (PC-PLC). Gel-shift
analysis showed inhibition of TNF-–induced nuclear
factor–kB mobilization by DHA. While the PC-PLC inhibitor
D609 dose-dependently prevented VCAM-1 induction by TNF-,
1,2-diacyl-glycerol (DAG) stimulated VCAM-1 expression, suggesting that
VCAM-1 induction by TNF- may be mediated by activation of PC-PLC.
Treatment with DHA resulted in a fourfold enrichment in PC. In
addition, DHA or D609 but not eicosapentaenoic acid or arachidonic acid
suppressed activation of PC-PLC by TNF-, estimated as
[14C]DAG synthesis in prelabeled HUVECs. Incorporation of
DHA into phospholipids selectively attenuates VCAM-1 induction by
TNF- and subsequent monocytic cell adhesion by inhibition of
TNF-–stimulated PC-PLC activation in HUVECs.
Key Words: endothelial cell • polyunsaturated fatty acid • adhesion molecules • monocytic cell adhesion • tumor necrosis factor–
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