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Dietary curcumin inhibits atherosclerosis by affecting the expression of genes involved in leukocyte adhesion and transendothelial migration

Authors

  • Dilek Coban,

    1. INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France
    2. Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France
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  • Dragan Milenkovic,

    1. INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France
    2. Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France
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  • Audrey Chanet,

    1. INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France
    2. Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France
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  • Jamila Khallou-Laschet,

    1. INSERM UMRS698, Cardiovascular Immunopathology, GH Bichat-Claude Bernard, France
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  • Linde Sabbe,

    1. Laboratory for Eukaryotic Gene Expression and Signal Transduction LEGEST, Department of Physiology, University Ghent, Ghent, Belgium
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  • Ajay Palagani,

    1. Laboratory for Eukaryotic Gene Expression and Signal Transduction LEGEST, Department of Physiology, University Ghent, Ghent, Belgium
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  • Wim Vanden Berghe,

    1. Laboratory for Eukaryotic Gene Expression and Signal Transduction LEGEST, Department of Physiology, University Ghent, Ghent, Belgium
    2. Laboratory of Protein Chemistry, Proteomics & Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium
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  • Andrzej Mazur,

    1. INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France
    2. Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France
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  • Christine Morand

    Corresponding author
    1. Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France
    • INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France
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Correspondence: Dr. Christine Morand, Human Nutrition Unit, UMR1019, National Institute of Agronomic Research (INRA), 63122 Saint-Genès Champanelle, France

E-mail: christine.morand@clermont.inra.fr

Fax: +33-473624638

Abstract

Scope

The aim of the study was to examine the atheroprotective effect of dietary curcumin in a mouse model of atherosclerosis and to identify its cellular and molecular targets at the vascular level.

Methods and results

ApoE–/– mice were fed with curcumin at 0.2% (wt/wt) in diet for 4 months. This supplementation reduced the extent of atherosclerotic lesion by 26% and induced changes in expression of genes implicated in cell adhesion and transendothelial migration or cytoskeleton organization, as revealed by a transcriptomic analysis in the aorta. Expression profile of these genes suggests reduction in both leukocyte adhesion and transendothelial migration. In agreement with this hypothesis, we observed a reduction (–37%) in macrophage infiltration in the plaque, as measured by immunohistochemistry, and, in vitro, a lower adhesion of monocytes to TNF-α-stimulated endothelial cells (–32%) after exposure to a nutritionally achievable concentration of curcumin. These changes in gene expression could be related to the observed increased expression of IκB protein and decrease of TNF-α-induced NF-κB/DNA binding and NF-κB-transcriptional activity upon exposure to curcumin.

Conclusion

Our findings pointed out that the antiatherogenic effect of curcumin could be linked to its effect on gene networks and cell functions related to leukocyte adhesion and transendothelial migration via NF-κB-dependent pathways.

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