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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1296683
- author
- Dichtl, W
; Nilsson, L
; Goncalves, Isabel
LU
; Ares, Mikko
LU
; Banfi, C
; Calara, F
; Hamsten, A
; Eriksson, P
and Nilsson, Jan
LU
- organization
- publishing date
- 1999
- 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
- 2016-04-01 16:24:22
- date last changed
- 2022-02-07 11:13:45
@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}},
url = {{http://circres.ahajournals.org/cgi/content/full/84/9/1085}},
volume = {{84}},
year = {{1999}},
}