Elsevier

Metabolism

Volume 51, Issue 3, March 2002, Pages 327-333
Metabolism

Linoleic acid-stimulated vascular adhesion molecule-1 expression in endothelial cells depends on nuclear factor-[kappa ]B activation

https://doi.org/10.1053/meta.2002.29963Get rights and content

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-[kappa ]B (NF-[kappa ]B) 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 immunoflourescence 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 I[kappa ]B super-repressor ([Delta ]N2 cells), we provide evidence that NF-[kappa ]B 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.

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Supported by grants from the Swedish Medical Research Council (8311 and 8691), the Swedish Heart-Lung Foundation, the Marianne and Marcus Wallenberg Foundation, the King Gustaf V 80th Birthday Foundation, the Petrus and Augusta Hedlund Foundation, the Foundation For Old Servants, the Professor Nanna Svartz Foundation, and the King Gustaf V and Queen Victoria Foundation. P.E. is supported by a postdoctoral research fellowship from the Swedish Medical Research Council and C.M.G. supported by Grant No. HL18645 from the National Institutes of Health.

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