A Systems Biology Network Analysis of Nutri(epi)genomic Changes in Endothelial Cells Exposed to Epicatechin Metabolites

Overview

Journal Sci Rep

Specialty Science

Date 2018 Oct 21

PMID 30341379

Citations 16

Authors

Dragan Milenkovic

Wim Vanden Berghe

Christine Morand

Sylvain Claude

Annette van de Sandt

Simone Gorressen

Laurent-Emmanuel Monfoulet

Chandra S Chirumamilla

Ken Declerck

Katarzyna Szarc Vel Szic

Maija Lahtela-Kakkonen

Clarissa Gerhauser

Marc W Merx

Malte Kelm

Affiliations

Soon will be listed here.

Abstract

Although vasculo-protective effects of flavan-3-ols are widely accepted today, their impact on endothelial cell functions and molecular mechanisms of action involved is not completely understood. The aim of this study was to characterize the potential endothelium-protective effects of circulating epicatechin metabolites and to define underlying mechanisms of action by an integrated systems biology approach. Reduced leukocyte rolling over vascular endothelium was observed following epicatechin supplementation in a mouse model of inflammation. Integrative pathway analysis of transcriptome, miRNome and epigenome profiles of endothelial cells exposed to epicatechin metabolites revealed that by acting at these different levels of regulation, metabolites affect cellular pathways involved in endothelial permeability and interaction with immune cells. In-vitro experiments on endothelial cells confirmed that epicatechin metabolites reduce monocyte adhesion and their transendothelial migration. Altogether, our in-vivo and in-vitro results support the outcome of a systems biology based network analysis 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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