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Linoleic acid-stimulated vascular adhesion molecule-1 expression in endothelial cells depends on nuclear factor-kappaB activation.

Dichtl, Wolfgang; Ares, Mikko LU ; Niemann-Jönson, Audrey; Jovinge, Stefan LU ; Pachinger, Otmar; Giachelli, Cecilia M; Hamsten, Anders; Eriksson, Per and Nilsson, Jan LU (2002) In Metabolism, Clinical and Experimental 51(3). p.327-333
Abstract
Endothelial activation is an important step in atherogenesis. In addition to established cardiovascular risk factors, such as hypercholesterolemia, hypertension, diabetes mellitus, and homocysteinemia, high plasma levels of triglyceride-rich lipoproteins may be an important cause of endothelial activation as well. Free fatty acids hydrolyzed from core triglycerides of these particles can exert both pro- and anti-inflammatory effects on the vascular wall. omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to inhibit cytokine-induced endothelial activation. In contrast, we and others have previously shown that the omega-6 fatty acid linoleate activates transcription factor nuclear... (More)
Endothelial activation is an important step in atherogenesis. In addition to established cardiovascular risk factors, such as hypercholesterolemia, hypertension, diabetes mellitus, and homocysteinemia, high plasma levels of triglyceride-rich lipoproteins may be an important cause of endothelial activation as well. Free fatty acids hydrolyzed from core triglycerides of these particles can exert both pro- and anti-inflammatory effects on the vascular wall. omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to inhibit cytokine-induced endothelial activation. In contrast, we and others have previously shown that the omega-6 fatty acid linoleate activates transcription factor nuclear factor-kappaB (NF-kappaB) in endothelial cells. In this study, we show that linoleic acid stimulates vascular adhesion molecule-1 (VCAM-1) protein and mRNA expression in cultured human endothelial cells, as assessed by immunofluorescence and Northern blotting. Release of shedded soluble VCAM-1 from cultured human endothelial cells was also increased by the addition of linoleic acid, as determined by enzyme-linked immunosorbent assay (ELISA). By use of cultured rat aortic endothelial cells transfected with an IkappaB super-repressor (DeltaN2 cells), we provide evidence that NF-kappaB signalling is required in the linoleic acid-induced VCAM-1 expression in endothelial cells, whereas other transcription factors appear to be involved in the increased endothelial plasminogen activator inhibitor-1 (PAI-1) production in response to linoleic acid. These findings suggest that diets rich in linoleic acid may be proinflammatory and thus atherogenic by activating vascular endothelial cells. (Less)
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keywords
Reverse Transcriptase Polymerase Chain Reaction, Support, Non-U.S. Gov't, U.S. Gov't, P.H.S., Vascular Cell Adhesion Molecule-1/genetics/*metabolism, Linoleic Acid/*pharmacology, NF-kappa B/*physiology, Plasminogen Activator Inhibitor 1/metabolism, Human, Fluorescent Antibody Technique, Vascular/cytology/*metabolism, Enzyme-Linked Immunosorbent Assay, RNA, Messenger/metabolism, Endothelium, Cultured, Cells, Northern, Blotting, Aorta/cytology/metabolism, Animal, Rats
in
Metabolism, Clinical and Experimental
volume
51
issue
3
pages
327 - 333
publisher
Elsevier
external identifiers
  • wos:000174266200011
  • pmid:11887169
  • scopus:0036121744
ISSN
1532-8600
DOI
10.1053/meta.2002.29963
language
English
LU publication?
yes
id
0b934a34-c2b6-4d92-92c7-0abac902df45 (old id 106104)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11887169&dopt=Abstract
date added to LUP
2007-07-17 14:45:20
date last changed
2017-01-01 07:01:05
@article{0b934a34-c2b6-4d92-92c7-0abac902df45,
  abstract     = {Endothelial activation is an important step in atherogenesis. In addition to established cardiovascular risk factors, such as hypercholesterolemia, hypertension, diabetes mellitus, and homocysteinemia, high plasma levels of triglyceride-rich lipoproteins may be an important cause of endothelial activation as well. Free fatty acids hydrolyzed from core triglycerides of these particles can exert both pro- and anti-inflammatory effects on the vascular wall. omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to inhibit cytokine-induced endothelial activation. In contrast, we and others have previously shown that the omega-6 fatty acid linoleate activates transcription factor nuclear factor-kappaB (NF-kappaB) in endothelial cells. In this study, we show that linoleic acid stimulates vascular adhesion molecule-1 (VCAM-1) protein and mRNA expression in cultured human endothelial cells, as assessed by immunofluorescence and Northern blotting. Release of shedded soluble VCAM-1 from cultured human endothelial cells was also increased by the addition of linoleic acid, as determined by enzyme-linked immunosorbent assay (ELISA). By use of cultured rat aortic endothelial cells transfected with an IkappaB super-repressor (DeltaN2 cells), we provide evidence that NF-kappaB signalling is required in the linoleic acid-induced VCAM-1 expression in endothelial cells, whereas other transcription factors appear to be involved in the increased endothelial plasminogen activator inhibitor-1 (PAI-1) production in response to linoleic acid. These findings suggest that diets rich in linoleic acid may be proinflammatory and thus atherogenic by activating vascular endothelial cells.},
  author       = {Dichtl, Wolfgang and Ares, Mikko and Niemann-Jönson, Audrey and Jovinge, Stefan and Pachinger, Otmar and Giachelli, Cecilia M and Hamsten, Anders and Eriksson, Per and Nilsson, Jan},
  issn         = {1532-8600},
  keyword      = {Reverse Transcriptase Polymerase Chain Reaction,Support,Non-U.S. Gov't,U.S. Gov't,P.H.S.,Vascular Cell Adhesion Molecule-1/genetics/*metabolism,Linoleic Acid/*pharmacology,NF-kappa B/*physiology,Plasminogen Activator Inhibitor 1/metabolism,Human,Fluorescent Antibody Technique,Vascular/cytology/*metabolism,Enzyme-Linked Immunosorbent Assay,RNA,Messenger/metabolism,Endothelium,Cultured,Cells,Northern,Blotting,Aorta/cytology/metabolism,Animal,Rats},
  language     = {eng},
  number       = {3},
  pages        = {327--333},
  publisher    = {Elsevier},
  series       = {Metabolism, Clinical and Experimental},
  title        = {Linoleic acid-stimulated vascular adhesion molecule-1 expression in endothelial cells depends on nuclear factor-kappaB activation.},
  url          = {http://dx.doi.org/10.1053/meta.2002.29963},
  volume       = {51},
  year         = {2002},
}