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

Autor:	Milenkovic D; INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand; Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000, Clermont-Ferrand, France. dragan.milenkovic@inra.fr.; Department of Internal Medicine, Division of Cardiovascular Medicine, School of Medicine, University of California Davis, Davis, California, 95616, United States of America. dragan.milenkovic@inra.fr., Berghe WV; PPES, Department of Biomedical Sciences, University of Antwerp (UA), Wilrijk, Belgium.; L-GEST, Department of Biochemistry and Microbiology, University of Gent, Ghent, Belgium., Morand C; INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand; Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000, Clermont-Ferrand, France., Claude S; INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand; Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000, Clermont-Ferrand, France., van de Sandt A; Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany., Gorressen S; Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany., Monfoulet LE; INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand; Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000, Clermont-Ferrand, France., Chirumamilla CS; PPES, Department of Biomedical Sciences, University of Antwerp (UA), Wilrijk, Belgium., Declerck K; PPES, Department of Biomedical Sciences, University of Antwerp (UA), Wilrijk, Belgium., Szic KSV; PPES, Department of Biomedical Sciences, University of Antwerp (UA), Wilrijk, Belgium., Lahtela-Kakkonen M; School of Pharmacy, University of Eastern Finland, Kuopio, Finland., Gerhauser C; Division of Epigenomics and Cancer Risk Factors, DKFZ, Heidelberg, Germany., Merx MW; Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.; KRH Klinikum Robert Koch Gehrden, Department of Cardiovascular Diseases and Internal Intensive Medicine, Von-Reden-Straße 1, 30989, Gehrden, Germany., Kelm M; Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2018 Oct 19; Vol. 8 (1), pp. 15487. Date of Electronic Publication: 2018 Oct 19.
DOI:	10.1038/s41598-018-33959-x
Abstrakt:	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.
Databáze:	MEDLINE
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