A systems biology network analysis of nutri(epi)genomic changes in endothelial cells exposed to epicatechin metabolites

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 ep...

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Bibliographic Details
Published in:Scientific reports 2018-10, Vol.8 (1), p.15487-17, Article 15487
Main Authors: Milenkovic, Dragan, Berghe, Wim Vanden, Morand, Christine, Claude, Sylvain, van de Sandt, Annette, Gorressen, Simone, Monfoulet, Laurent-Emmanuel, Chirumamilla, Chandra S., Declerck, Ken, Szic, Katarzyna Szarc vel, Lahtela-Kakkonen, Maija, Gerhauser, Clarissa, Merx, Marc W., Kelm, Malte
Format: Article
Language:English
Subjects:
13/106
38/61
631/337/2019
631/553/2694
Adhesion
Biology
Endothelial cells
Endothelium
Epicatechin
Gene expression
Humanities and Social Sciences
Leukocyte migration
Leukocyte rolling
Metabolites
Molecular modelling
Monocytes
multidisciplinary
Permeability
Rodents
Science
Science (multidisciplinary)
Supplements
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-33959-x