Flavanol metabolites reduce monocyte adhesion to endothelial cells through modulation of expression of genes via p38-MAPK and p65-Nf-kB pathways

Authors

  • Sylvain Claude,

    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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  • Celine Boby,

    1. INRA, UMR1213 Herbivores, Plate-Forme d'Exploration du Métabolisme, Saint-Genès-Champanelle, France
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  • Ana Rodriguez-Mateos,

    1. Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading, UK
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  • Jeremy P. E. Spencer,

    1. Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading, UK
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  • Nicolas Gérard,

    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. INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France
    2. Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France
    • Correspondence: Dr. Christine Morand, INRA centre de recherche de Clermont-Ferrand/Theix, Unité de Nutrition Humaine (UNH), Micronutrients and Cardiovascular Health Team, 63 122 Saint-Genès-Champanelle, France

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

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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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Abstract

Scope

Consumption of flavanol-rich foods is associated with an improvement in endothelial function. However, the specific biologically active flavanol metabolites involved in this benefit, as well as their molecular mechanisms of action have not been identified. The aim of this work was to examine the effect of plasma flavanol metabolites on adhesion of monocytes to TNF-α-activated endothelial cells and identify potential underlying mechanisms.

Methods and results

4′-O-methyl(−)-epicatechin, 4′-O-methyl(−)-epicatechin-7-β-d-glucuronide, and (−)­epicatechin-4′-sulfate decreased the adhesion of monocytes to endothelial cells at physiologically relevant concentrations, from 0.2 to 1 μM. Transcriptomic studies showed that each of the flavanol metabolites affected the expression of different genes in endothelial cells. However, these genes are involved in the cellular processes that control adhesion and migration of monocytes to vascular endothelium, most notably those regulating cell adhesion, cell–cell junctions, focal adhesion, and cytoskeleton remodeling. Gene expression profiles obtained suggest lower monocyte recruitment, in agreement with results from cell adhesion assays. The nutrigenomic effect of metabolites seems to be mediated through their capacity to modulate phosphorylation of p65 and p38 cell-signaling proteins.

Conclusion

Our study provides findings into the molecular mechanisms by which plasma flavanol metabolites could be efficient to preserve vascular endothelium integrity in nutritionally relevant conditions.

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