Linoleic acid-stimulated vascular adhesion molecule-1 expression in endothelial cells depends on nuclear factor-kappaB activation.
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.
Dichtl
Wolfgang
W
Wallenberg Laboratory, Department of Medicine, Malmö University Hospital, Lund University, Lund, Sweden.
Ares
Mikko P S
MP
Jönson
Audrey Niemann
AN
Jovinge
Stefan
S
Pachinger
Otmar
O
Giachelli
Cecilia M
CM
Hamsten
Anders
A
Eriksson
Per
P
Nilsson
Jan
J
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D015152:Blotting, Northern; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology*; D016328:NF-kappa B / Q000502:physiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D019787:Linoleic Acid