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 journalArticlepeer-review

55 Citations (Scopus)


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 languageEnglish
Pages (from-to)1016-27
Number of pages12
JournalMolecular Nutrition & Food Research
Issue number5
Publication statusPublished - May 2014


  • 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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