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Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology without Changes in Their DNA Methylation State

BACKGROUND: In a recent intervention study, the daily supplementation with 200 mg monomeric and oligomeric flavanols (MOF) from grape seeds for 8 weeks revealed a vascular health benefit in male smokers. The objective of the present study was to determine the impact of MOF consumption on the gene ex...

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Autores principales: Milenkovic, Dragan, Vanden Berghe, Wim, Boby, Céline, Leroux, Christine, Declerck, Ken, Szarc vel Szic, Katarzyna, Heyninck, Karen, Laukens, Kris, Bizet, Martin, Defrance, Matthieu, Dedeurwaerder, Sarah, Calonne, Emilie, Fuks, Francois, Haegeman, Guy, Haenen, Guido R. M. M., Bast, Aalt, Weseler, Antje R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998980/
https://www.ncbi.nlm.nih.gov/pubmed/24763279
http://dx.doi.org/10.1371/journal.pone.0095527
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author Milenkovic, Dragan
Vanden Berghe, Wim
Boby, Céline
Leroux, Christine
Declerck, Ken
Szarc vel Szic, Katarzyna
Heyninck, Karen
Laukens, Kris
Bizet, Martin
Defrance, Matthieu
Dedeurwaerder, Sarah
Calonne, Emilie
Fuks, Francois
Haegeman, Guy
Haenen, Guido R. M. M.
Bast, Aalt
Weseler, Antje R.
author_facet Milenkovic, Dragan
Vanden Berghe, Wim
Boby, Céline
Leroux, Christine
Declerck, Ken
Szarc vel Szic, Katarzyna
Heyninck, Karen
Laukens, Kris
Bizet, Martin
Defrance, Matthieu
Dedeurwaerder, Sarah
Calonne, Emilie
Fuks, Francois
Haegeman, Guy
Haenen, Guido R. M. M.
Bast, Aalt
Weseler, Antje R.
author_sort Milenkovic, Dragan
collection PubMed
description BACKGROUND: In a recent intervention study, the daily supplementation with 200 mg monomeric and oligomeric flavanols (MOF) from grape seeds for 8 weeks revealed a vascular health benefit in male smokers. The objective of the present study was to determine the impact of MOF consumption on the gene expression profile of leukocytes and to assess changes in DNA methylation. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiles were determined using whole genome microarrays (Agilent) and DNA methylation was assessed using HumanMethylation450 BeadChips (Illumina). MOF significantly modulated the expression of 864 genes. The majority of the affected genes are involved in chemotaxis, cell adhesion, cell infiltration or cytoskeleton organisation, suggesting lower immune cell adhesion to endothelial cells. This was corroborated by in vitro experiments showing that MOF exposure of monocytes attenuates their adhesion to TNF-α-stimulated endothelial cells. Nuclear factor kappa B (NF-κB) reporter gene assays confirmed that MOF decrease the activity of NF-κB. Strong inter-individual variability in the leukocytes' DNA methylation was observed. As a consequence, on group level, changes due to MOF supplementation could not be found. CONCLUSION: Our study revealed that an 8 week daily supplementation with 200 mg MOF modulates the expression of genes associated with cardiovascular disease pathways without major changes of their DNA methylation state. However, strong inter-individual variation in leukocyte DNA methylation may obscure the subtle epigenetic response to dietary flavanols. Despite the lack of significant changes in DNA methylation, the modulation of gene expression appears to contribute to the observed vascular health effect of MOF in humans.
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spelling pubmed-39989802014-04-29 Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology without Changes in Their DNA Methylation State Milenkovic, Dragan Vanden Berghe, Wim Boby, Céline Leroux, Christine Declerck, Ken Szarc vel Szic, Katarzyna Heyninck, Karen Laukens, Kris Bizet, Martin Defrance, Matthieu Dedeurwaerder, Sarah Calonne, Emilie Fuks, Francois Haegeman, Guy Haenen, Guido R. M. M. Bast, Aalt Weseler, Antje R. PLoS One Research Article BACKGROUND: In a recent intervention study, the daily supplementation with 200 mg monomeric and oligomeric flavanols (MOF) from grape seeds for 8 weeks revealed a vascular health benefit in male smokers. The objective of the present study was to determine the impact of MOF consumption on the gene expression profile of leukocytes and to assess changes in DNA methylation. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiles were determined using whole genome microarrays (Agilent) and DNA methylation was assessed using HumanMethylation450 BeadChips (Illumina). MOF significantly modulated the expression of 864 genes. The majority of the affected genes are involved in chemotaxis, cell adhesion, cell infiltration or cytoskeleton organisation, suggesting lower immune cell adhesion to endothelial cells. This was corroborated by in vitro experiments showing that MOF exposure of monocytes attenuates their adhesion to TNF-α-stimulated endothelial cells. Nuclear factor kappa B (NF-κB) reporter gene assays confirmed that MOF decrease the activity of NF-κB. Strong inter-individual variability in the leukocytes' DNA methylation was observed. As a consequence, on group level, changes due to MOF supplementation could not be found. CONCLUSION: Our study revealed that an 8 week daily supplementation with 200 mg MOF modulates the expression of genes associated with cardiovascular disease pathways without major changes of their DNA methylation state. However, strong inter-individual variation in leukocyte DNA methylation may obscure the subtle epigenetic response to dietary flavanols. Despite the lack of significant changes in DNA methylation, the modulation of gene expression appears to contribute to the observed vascular health effect of MOF in humans. Public Library of Science 2014-04-24 /pmc/articles/PMC3998980/ /pubmed/24763279 http://dx.doi.org/10.1371/journal.pone.0095527 Text en © 2014 Milenkovic et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Milenkovic, Dragan
Vanden Berghe, Wim
Boby, Céline
Leroux, Christine
Declerck, Ken
Szarc vel Szic, Katarzyna
Heyninck, Karen
Laukens, Kris
Bizet, Martin
Defrance, Matthieu
Dedeurwaerder, Sarah
Calonne, Emilie
Fuks, Francois
Haegeman, Guy
Haenen, Guido R. M. M.
Bast, Aalt
Weseler, Antje R.
Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology without Changes in Their DNA Methylation State
title Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology without Changes in Their DNA Methylation State
title_full Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology without Changes in Their DNA Methylation State
title_fullStr Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology without Changes in Their DNA Methylation State
title_full_unstemmed Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology without Changes in Their DNA Methylation State
title_short Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology without Changes in Their DNA Methylation State
title_sort dietary flavanols modulate the transcription of genes associated with cardiovascular pathology without changes in their dna methylation state
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998980/
https://www.ncbi.nlm.nih.gov/pubmed/24763279
http://dx.doi.org/10.1371/journal.pone.0095527
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