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Very low-density lipoprotein activates nuclear factor-kappaB in endothelial cells

Author:
  • W Dichtl
  • L Nilsson
  • Isabel Goncalves
  • Mikko Ares
  • C Banfi
  • F Calara
  • A Hamsten
  • P Eriksson
  • Jan Nilsson
Publishing year: 1999
Language: English
Pages: 1085-1094
Publication/Series: Circulation Research
Volume: 84
Issue: 9
Document type: Journal article
Publisher: American Heart Association

Abstract english

High plasma levels of VLDL are associated with increased risk for atherosclerosis. Here we show that VLDL (75 to 150 microg/mL) activates nuclear factor-kappaB (NF-kappaB), a transcription factor known to play a key role in regulation of inflammation. Oxidation of VLDL reduced its capacity to activate NF-kappaB in vitro, whereas free fatty acids such as linoleic and oleic acid activated NF-kappaB 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-kappaB as assessed by electrophoretic mobility shift assay. Aortic endothelial cells showed positive nuclear staining for the activated RelA (p65) subunit of NF-kappaB 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-alpha. Pretreatment of the rats with diet containing 1% of the antioxidant probucol for 8 weeks did not inhibit arterial activation of NF-kappaB in response to injection of VLDL. Moreover, injection of triglycerides (10% Intralipid, 5 mL/kg) activated arterial expression of NF-kappaB 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-kappaB. The effect appears to be mediated by a release of VLDL fatty acids but not to involve VLDL oxidation.

Keywords

  • Cardiac and Cardiovascular Systems

Other

Published
  • Cardiovascular Research - Immunity and Athersosclerosis
  • ISSN: 0009-7330
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

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