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

Författare:
  • Wolfgang Dichtl
  • Mikko Ares
  • Audrey Niemann-Jönson
  • Stefan Jovinge
  • Otmar Pachinger
  • Cecilia M Giachelli
  • Anders Hamsten
  • Per Eriksson
  • Jan Nilsson
Publiceringsår: 2002
Språk: Engelska
Sidor: 327-333
Publikation/Tidskrift/Serie: Metabolism
Volym: 51
Nummer: 3
Dokumenttyp: Artikel
Förlag: Elsevier

Sammanfattning

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.

Disputation

Nyckelord

  • Medicine and Health Sciences
  • 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

Övrigt

Published
Yes
  • ISSN: 0026-0495

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