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

Dichtl, W; Nilsson, L; Goncalves, Isabel LU ; Ares, Mikko LU ; Banfi, C; Calara, F; Hamsten, A; Eriksson, P and Nilsson, Jan LU (1999) In Circulation Research 84(9). p.1085-1094
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Circulation Research
volume
84
issue
9
pages
1085 - 1094
publisher
American Heart Association
external identifiers
  • scopus:0033553429
ISSN
0009-7330
language
English
LU publication?
yes
id
3a1e5a79-fb29-4271-a164-b19548b5d305 (old id 1296683)
alternative location
http://circres.ahajournals.org/cgi/content/full/84/9/1085
date added to LUP
2009-07-30 14:42:37
date last changed
2017-07-23 04:40:50
@article{3a1e5a79-fb29-4271-a164-b19548b5d305,
  abstract     = {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.},
  author       = {Dichtl, W and Nilsson, L and Goncalves, Isabel and Ares, Mikko and Banfi, C and Calara, F and Hamsten, A and Eriksson, P and Nilsson, Jan},
  issn         = {0009-7330},
  language     = {eng},
  number       = {9},
  pages        = {1085--1094},
  publisher    = {American Heart Association},
  series       = {Circulation Research},
  title        = {Very low-density lipoprotein activates nuclear factor-kappaB in endothelial cells},
  volume       = {84},
  year         = {1999},
}