Epicatechin metabolites exert epigenetic regulation in endothelial cells by modulating DNA methylation profile

Diets rich in flavanols are known to exert beneficial cardiovascular health effects. We previously showed that epicatechin metabolites reduce monocyte-endothelial cell adhesion by modulating expression of genes in HUVECs involved in cell adhesion signaling pathways. The aim of the present study is to examine potential epigenetic remodeling of HUVEC cells upon inflammation in presence or absence of cocoa derived epicatechin metabolites through genomewide DNA methylation profiling. Epicatechin metabolites were found to trigger DNA hypermethylation in gene bodies and intergenic genomic regions, while hypomethylation in promoter regions. In addition, pathway enrichment of differentially methylated genes demonstrates epigenetic remodeling cell adhesion and cytoskeleton signaling pathways. Finally, in silico docking supports evidence for direct regulation of DNMTs through epicatechin binding. In conclusion, our study provides evidence that epicatechin metabolites elicit vascular health effects in part through epigenetic regulation of endothelial cell adhesion functions. HUVEC cells were treated with single epicatechin metabolites or a mixture of epicatechin metabolites for 3h. After 18h incubation in flavanol-free medium, cells were treated with TNFalpha for 4h. DNA methylation was measured using the 450k methylation array.