Flavanol metabolites reduce monocyte adhesion to endothelial cells through modulation of expression of genes via p38-MAPK and p65-Nf-kB pathways
Article first published online: 15 JAN 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 5, pages 1016–1027, May 2014
How to Cite
Claude, S., Boby, C., Rodriguez-Mateos, A., Spencer, J. P. E., Gérard, N., Morand, C. and Milenkovic, D. (2014), Flavanol metabolites reduce monocyte adhesion to endothelial cells through modulation of expression of genes via p38-MAPK and p65-Nf-kB pathways. Mol. Nutr. Food Res., 58: 1016–1027. doi: 10.1002/mnfr.201300658
- Issue published online: 22 APR 2014
- Article first published online: 15 JAN 2014
- Manuscript Accepted: 21 NOV 2013
- Manuscript Revised: 19 NOV 2013
- Manuscript Received: 9 SEP 2013
- European Union project “Flaviola”. Grant Number: 226588
- Endothelial cells;
- Flavanol metabolites;
- Gene expression;
- Monocyte adhesion
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.
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.