Linoleic acid-stimulated vascular adhesion molecule-1 expression in endothelial cells depends on nuclear factor-kappaB activation.
Författare
Summary, in English
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.
Publiceringsår
2002
Språk
Engelska
Sidor
327-333
Publikation/Tidskrift/Serie
Metabolism, Clinical and Experimental
Volym
51
Issue
3
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Elsevier
Ämne
- Cell and Molecular Biology
Nyckelord
- 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
Status
Published
Forskningsgrupp
- Cardiovascular Research - Immunity and Atherosclerosis
ISBN/ISSN/Övrigt
- ISSN: 1532-8600