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

Sylvain Claude; Celine Boby; Ana Rodriguez-Mateos; Jeremy P E Spencer; Nicolas Gérard; Christine Morand; Dragan Milenkovic

doi:10.1002/mnfr.201300658

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

Sylvain Claude, Celine Boby, Ana Rodriguez-Mateos, Jeremy P E Spencer, Nicolas Gérard, Christine Morand, Dragan Milenkovic

Research output: Contribution to journal › Article › peer-review

55 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1016-27
Number of pages	12
Journal	Molecular Nutrition & Food Research
Volume	58
Issue number	5
DOIs	https://doi.org/10.1002/mnfr.201300658
Publication status	Published - May 2014

Keywords

Catechin
Cell Adhesion
Endothelial Cells
Endothelium, Vascular
Flavonols
Human Umbilical Vein Endothelial Cells
Humans
Monocytes
Nutrigenomics
Phosphorylation
Signal Transduction
Sulfuric Acid Esters
Transcription Factor RelA
Transcription Factors
Tumor Necrosis Factor-alpha
p38 Mitogen-Activated Protein Kinases

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10.1002/mnfr.201300658

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@article{891d35156db54b0dbd92de6a5737a92d,

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

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.",

keywords = "Catechin, Cell Adhesion, Endothelial Cells, Endothelium, Vascular, Flavonols, Human Umbilical Vein Endothelial Cells, Humans, Monocytes, Nutrigenomics, Phosphorylation, Signal Transduction, Sulfuric Acid Esters, Transcription Factor RelA, Transcription Factors, Tumor Necrosis Factor-alpha, p38 Mitogen-Activated Protein Kinases",

author = "Sylvain Claude and Celine Boby and Ana Rodriguez-Mateos and Spencer, {Jeremy P E} and Nicolas G{\'e}rard and Christine Morand and Dragan Milenkovic",

note = "{\textcopyright} 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",

year = "2014",

month = may,

doi = "10.1002/mnfr.201300658",

language = "English",

volume = "58",

pages = "1016--27",

journal = "Molecular Nutrition & Food Research",

issn = "1613-4125",

publisher = "Wiley-VCH Verlag",

number = "5",

}

TY - JOUR

T1 - Flavanol metabolites reduce monocyte adhesion to endothelial cells through modulation of expression of genes via p38-MAPK and p65-Nf-kB pathways

AU - Claude, Sylvain

AU - Boby, Celine

AU - Rodriguez-Mateos, Ana

AU - Spencer, Jeremy P E

AU - Gérard, Nicolas

AU - Morand, Christine

AU - Milenkovic, Dragan

PY - 2014/5

Y1 - 2014/5

N2 - 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.

AB - 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.

KW - Catechin

KW - Cell Adhesion

KW - Endothelial Cells

KW - Endothelium, Vascular

KW - Flavonols

KW - Human Umbilical Vein Endothelial Cells

KW - Humans

KW - Monocytes

KW - Nutrigenomics

KW - Phosphorylation

KW - Signal Transduction

KW - Sulfuric Acid Esters

KW - Transcription Factor RelA

KW - Transcription Factors

KW - Tumor Necrosis Factor-alpha

KW - p38 Mitogen-Activated Protein Kinases

U2 - 10.1002/mnfr.201300658

DO - 10.1002/mnfr.201300658

M3 - Article

C2 - 24425450

SN - 1613-4125

VL - 58

SP - 1016

EP - 1027

JO - Molecular Nutrition & Food Research

JF - Molecular Nutrition & Food Research

IS - 5

ER -

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

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Keywords

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