© 1999 American Heart Association, Inc.
Original Contributions |
Very Low-Density Lipoprotein Activates Nuclear Factor-
B in Endothelial Cells
From the Wallenberg Laboratory (W.D., I.G., M.P.S.A., F.C., J.N.), Department of Medicine, University of Lund, Malmö University Hospital, Malmö, Sweden; Atherosclerosis Research Unit (W.D., L.N., A.H., P.E.), King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden; and Institute of Pharmacological Science (C.B.), University of Milan, Italy.
Correspondence to Wolfgang Dichtl, Wallenberg Laboratory, Department of Medicine, University of Lund, Malmö University Hospital, S-205 02 Malmö, Sweden. E-mail wolfgang.dichtl{at}medforsk.mas.lu.se
Abstract—High plasma levels of
VLDL are associated with increased risk for
atherosclerosis. Here we show that VLDL (75 to 150
µg/mL) activates nuclear factor-
B (NF-B), a
transcription factor known to play a key role in regulation of
inflammation. Oxidation of VLDL reduced its capacity to
activate NF-B in vitro, whereas free fatty acids such as
linoleic and oleic acid activated NF-B to the same extent as
did VLDL. Intravenous injection of human VLDL (6 mg protein
per kg) into rats resulted in arterial activation of
NF-B as assessed by electrophoretic mobility shift assay. Aortic
endothelial cells showed positive nuclear staining for
the activated RelA (p65) subunit of NF-B at 6 to 24 hours
after injection. There was also a parallel expression of the adhesion
molecules intercellular adhesion molecule-1 and vascular cell adhesion
molecule-1, as well as the cytokine tumor necrosis factor-
.
Pretreatment of the rats with diet containing 1% of the antioxidant
probucol for 8 weeks did not inhibit arterial activation of
NF-B in response to injection of VLDL. Moreover, injection of
triglycerides (10% Intralipid, 5 mL/kg)
activated arterial expression of NF-B to the
same extent as VLDL. Our results suggest that VLDL may promote the
development of atherosclerotic lesions by activation of the
proinflammatory transcription factor NF-B. The effect appears to be
mediated by a release of VLDL fatty acids but not to involve VLDL
oxidation.
Key Words: VLDL • fatty acid • transcription factor • oxidation • atherosclerosis
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