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

D. Milenkovic, W. Vanden Berghe, C. Boby, C. Leroux, K. Declerck, K. Szarc Vel Szic, K. Heyninck, K. Laukens, M. Bizet, M. Defrance, S. Dedeurwaerder, E. Calonne, F. Fuks, G. Haegeman, G.R. Haenen, A. Bast, A.R. Weseler

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Scopus)

Abstract

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-alpha-stimulated endothelial cells. Nuclear factor kappa B (NF-kappaB) reporter gene assays confirmed that MOF decrease the activity of NF-kappaB. 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.
Original languageEnglish
Article numbere95527
Number of pages13
JournalPLOS ONE
Volume9
Issue number4
DOIs
Publication statusPublished - 24 Apr 2014

Keywords

  • BLOOD MONONUCLEAR-CELLS
  • FACTOR-KAPPA-B
  • LEUKOCYTE ADHESION
  • EPIGENETIC MECHANISMS
  • EXPRESSION PROFILES
  • ENDOTHELIAL-CELLS
  • SMOKING
  • DISEASE
  • POLYPHENOLS
  • PATTERNS

Cite this

Milenkovic, D. ; Vanden Berghe, W. ; Boby, C. ; Leroux, C. ; Declerck, K. ; Szarc Vel Szic, K. ; Heyninck, K. ; Laukens, K. ; Bizet, M. ; Defrance, M. ; Dedeurwaerder, S. ; Calonne, E. ; Fuks, F. ; Haegeman, G. ; Haenen, G.R. ; Bast, A. ; Weseler, A.R. / Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology without Changes in Their DNA Methylation State. In: PLOS ONE. 2014 ; Vol. 9, No. 4.
@article{610810a24e884da689264709ce3298c2,
title = "Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology without Changes in Their DNA Methylation State",
abstract = "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-alpha-stimulated endothelial cells. Nuclear factor kappa B (NF-kappaB) reporter gene assays confirmed that MOF decrease the activity of NF-kappaB. 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.",
keywords = "BLOOD MONONUCLEAR-CELLS, FACTOR-KAPPA-B, LEUKOCYTE ADHESION, EPIGENETIC MECHANISMS, EXPRESSION PROFILES, ENDOTHELIAL-CELLS, SMOKING, DISEASE, POLYPHENOLS, PATTERNS",
author = "D. Milenkovic and {Vanden Berghe}, W. and C. Boby and C. Leroux and K. Declerck and {Szarc Vel Szic}, K. and K. Heyninck and K. Laukens and M. Bizet and M. Defrance and S. Dedeurwaerder and E. Calonne and F. Fuks and G. Haegeman and G.R. Haenen and A. Bast and A.R. Weseler",
year = "2014",
month = "4",
day = "24",
doi = "10.1371/journal.pone.0095527",
language = "English",
volume = "9",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

Milenkovic, D, Vanden Berghe, W, Boby, C, Leroux, C, Declerck, K, Szarc Vel Szic, K, Heyninck, K, Laukens, K, Bizet, M, Defrance, M, Dedeurwaerder, S, Calonne, E, Fuks, F, Haegeman, G, Haenen, GR, Bast, A & Weseler, AR 2014, 'Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology without Changes in Their DNA Methylation State', PLOS ONE, vol. 9, no. 4, e95527. https://doi.org/10.1371/journal.pone.0095527

Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology without Changes in Their DNA Methylation State. / Milenkovic, D.; Vanden Berghe, W.; Boby, C.; Leroux, C.; Declerck, K.; Szarc Vel Szic, K.; Heyninck, K.; Laukens, K.; Bizet, M.; Defrance, M.; Dedeurwaerder, S.; Calonne, E.; Fuks, F.; Haegeman, G.; Haenen, G.R.; Bast, A.; Weseler, A.R.

In: PLOS ONE, Vol. 9, No. 4, e95527, 24.04.2014.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology without Changes in Their DNA Methylation State

AU - Milenkovic, D.

AU - Vanden Berghe, W.

AU - Boby, C.

AU - Leroux, C.

AU - Declerck, K.

AU - Szarc Vel Szic, K.

AU - Heyninck, K.

AU - Laukens, K.

AU - Bizet, M.

AU - Defrance, M.

AU - Dedeurwaerder, S.

AU - Calonne, E.

AU - Fuks, F.

AU - Haegeman, G.

AU - Haenen, G.R.

AU - Bast, A.

AU - Weseler, A.R.

PY - 2014/4/24

Y1 - 2014/4/24

N2 - 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-alpha-stimulated endothelial cells. Nuclear factor kappa B (NF-kappaB) reporter gene assays confirmed that MOF decrease the activity of NF-kappaB. 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.

AB - 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-alpha-stimulated endothelial cells. Nuclear factor kappa B (NF-kappaB) reporter gene assays confirmed that MOF decrease the activity of NF-kappaB. 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.

KW - BLOOD MONONUCLEAR-CELLS

KW - FACTOR-KAPPA-B

KW - LEUKOCYTE ADHESION

KW - EPIGENETIC MECHANISMS

KW - EXPRESSION PROFILES

KW - ENDOTHELIAL-CELLS

KW - SMOKING

KW - DISEASE

KW - POLYPHENOLS

KW - PATTERNS

U2 - 10.1371/journal.pone.0095527

DO - 10.1371/journal.pone.0095527

M3 - Article

VL - 9

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 4

M1 - e95527

ER -