(Circulation. 1995;91:1914-1917.)
© 1995 American Heart Association, Inc.
Articles |
Aspirin Inhibits Nuclear Factor–
B Mobilization and Monocyte Adhesion in Stimulated Human Endothelial Cells
From the Institut für Prophylaxe der Kreislaufkrankheiten, Ludwig-Maximilians-Universität, München, Germany.
Correspondence to C. Weber, MD, Institut für Prophylaxe der Kreislaufkrankheiten, Pettenkoferstrasse 9, D-80336 München, FRG.
Background The induction of vascular cell adhesion
molecule–1 (VCAM-1) and E-selectin by tumor necrosis factor–
(TNF)
is mediated by mobilization of the transcription factor nuclear
factor–
B (NF-B). Since salicylates have been reported to
inhibit
NF-B activation by preventing the degradation of its inhibitor
IB, we studied a potential inhibition of this pathway by
acetylsalicylate (aspirin) in human umbilical vein endothelial cells
(HUVECs).
Methods and Results Gel-shift analyses demonstrated
dose-dependent inhibition of TNF-induced NF-B mobilization by
aspirin at concentrations ranging from 1 to 10 mmol/L. Induction of
VCAM-1 and E-selectin surface expression by TNF was dose-dependently
reduced by aspirin over the same range, while induction of
intercellular adhesion molecule–1 (ICAM-1) was hardly affected.
Aspirin appeared to prevent VCAM-1 transcription, since it
dose-dependently inhibited induction of VCAM-1 mRNA by TNF. As a
functional consequence, adhesion of U937 monocytes to TNF-stimulated
HUVECs was markedly reduced by aspirin due to suppression of VCAM-1 and
E-selectin upregulation. These effects of aspirin were not related to
the inhibition of cyclooxygenase activity, since indomethacin was
ineffective.
Conclusions Our data suggest that aspirin inhibits NF-B
mobilization, induction of VCAM-1 and E-selectin, and subsequent
monocyte adhesion in endothelial cells stimulated by TNF, thereby
providing an additional mechanism for therapeutic effects of
aspirin.
Key Words: aspirin • nuclear factor--B • endothelium
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