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Dietary flavanols modulate the transcription of genes associated with cardiovascular pathology without changes in their DNA methylation state

(2014) PLOS ONE. 9(4).
Author
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Project
FP7-Flaviola
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-kappa B) reporter gene assays confirmed that MOF decrease the activity of NF-kB. 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
FACTOR-KAPPA-B, BLOOD MONONUCLEAR-CELLS, LEUKOCYTE ADHESION, EPIGENETIC MECHANISMS, EXPRESSION PROFILES, ENDOTHELIAL-CELLS, SMOKING, DISEASE, POLYPHENOLS, PATTERNS

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Citation

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Chicago
Milenkovic, Dragan, Wim Vanden Berghe, Céline Boby, Christine Leroux, Ken Declerck, Katarzyna Szarc vel Szic, Karen Heyninck, et al. 2014. “Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology Without Changes in Their DNA Methylation State.” Plos One 9 (4).
APA
Milenkovic, D., Vanden Berghe, W., Boby, C., Leroux, C., Declerck, K., Szic, K. S. vel, Heyninck, K., et al. (2014). Dietary flavanols modulate the transcription of genes associated with cardiovascular pathology without changes in their DNA methylation state. PLOS ONE, 9(4).
Vancouver
1.
Milenkovic D, Vanden Berghe W, Boby C, Leroux C, Declerck K, Szic KS vel, et al. Dietary flavanols modulate the transcription of genes associated with cardiovascular pathology without changes in their DNA methylation state. PLOS ONE. 2014;9(4).
MLA
Milenkovic, Dragan, Wim Vanden Berghe, Céline Boby, et al. “Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology Without Changes in Their DNA Methylation State.” PLOS ONE 9.4 (2014): n. pag. Print.
@article{4423793,
  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-kappa B) reporter gene assays confirmed that MOF decrease the activity of NF-kB. 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.},
  articleno    = {e95527},
  author       = {Milenkovic, Dragan and Vanden Berghe, Wim and Boby, C{\'e}line and Leroux, Christine and Declerck, Ken and Szic, Katarzyna Szarc vel and Heyninck, Karen and Laukens, Kris and Bizet, Martin and Defrance, Matthieu and Dedeurwaerder, Sarah and Calonne, Emilie and Fuks, Fran\c{c}ois and Haegeman, Guy and Haenen, Guido RMM and Bast, Aalt and Weseler, Antje R},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {FACTOR-KAPPA-B,BLOOD MONONUCLEAR-CELLS,LEUKOCYTE ADHESION,EPIGENETIC MECHANISMS,EXPRESSION PROFILES,ENDOTHELIAL-CELLS,SMOKING,DISEASE,POLYPHENOLS,PATTERNS},
  language     = {eng},
  number       = {4},
  pages        = {13},
  title        = {Dietary flavanols modulate the transcription of genes associated with cardiovascular pathology without changes in their DNA methylation state},
  url          = {http://dx.doi.org/10.1371/journal.pone.0095527},
  volume       = {9},
  year         = {2014},
}

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