Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1584-1590
© 1995 American Heart Association, Inc.
Articles |
Oxidized LDL Induces Transcription Factor Activator Protein–1 but Inhibits Activation of Nuclear Factor–
B in Human Vascular Smooth Muscle Cells
From the Atherosclerosis Research Unit, King Gustaf Vth Research Institute, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Correspondence to Dr Mikko Ares, King Gustaf Vth Research Institute, Karolinska Hospital, S-171 76 Stockholm, Sweden.
Abstract Oxidized LDL (Ox-LDL) has been implicated in the
development of atherosclerotic lesions, mainly due to its enhanced
uptake by macrophages and its ability to alter gene expression
in arterial cells. In the present study we demonstrated
that Ox-LDL activates activator protein–1 (AP-1),
a transcription factor generally induced by mitogenic
substances. Lysophosphatidylcholine, which is generated during
oxidation of LDL, stimulated AP-1 in a dose-dependent manner. In
contrast, the radical-dependent transcription factor nuclear
factor–
B (NF-B) was not activated by Ox-LDL, and at a
concentration of 50 µg/mL, Ox-LDL inhibited
lipopolysaccharide-induced activation of NF-B.
Oxysterols but not lysophosphatidylcholine inhibited
lipopolysaccharide-induced NF-B activation,
suggesting that they may be responsible for the inhibitory
effect of Ox-LDL. In conclusion, Ox-LDL has opposing effects on the
activities of NF-B and AP-1, suggesting involvement of mechanisms
for transcriptional regulation that are strongly affected by lipid
oxidation products.
Key Words: oxidized LDL • transcription factor activator protein–1 • lysophosphatidylcholine • nuclear factor–B • oxysterol
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