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A systems biology network analysis of nutri(epi)genomic changes in endothelial cells exposed to epicatechin metabolites
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Edité par CCSD ; Nature Publishing Group -
Presented at 2. COST POSITIVe Scientific Workshop on « Omics breakthroughs in the Health effects of plant food bioactives ; Thessalonique (Grèce) - (2017-09-20 - 2017-09-21) / Workshop (Prodinra 408917). International audience. Although vasculo-protective effects of flavan-3-ols are widely accepted today, their impact on endothelial cell function and underlying molecular mechanisms of action remain unexplored. The aim of this study was to characterize the potential endothelium-protective effects of epicatechin metabolites and to define underlying mechanisms of action by an integrated systems biology approach. Upon dietary epicatechin supplementation in a mouse model of inflammation, reduced leukocyte rolling over vascular endothelium was observed. Pathway enrichment analysis of transcriptome, epigenome and miRNome profiles of endothelial cells exposed to plasma concentrations of epicatechin metabolites suggested significant changes in interactions with immune cell as well as permeability regarding immune cell transmigration. In line with our in-silico network analysis, in-vitro experiments confirmed that epicatechin metabolites reduce monocyte adhesion to endothelial cells and their transendothelial migration. Altogether, our in-vivo and in-vitro results support the outcome of a systems biology based network analysis of epigenome, transcriptome and miRNome profiles, which suggests that epicatechin metabolites mediate their vasculoprotective effects through dynamic regulation of endothelial cell monocyte adhesion and permeability. This study illustrates complex and multimodal mechanisms of action by which epicatechin modulate endothelial cell integrity.
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