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|Public on Jul 30, 2014
|Dietary flavanols modulate the transcription of genes involved in cardiovascular pathology with complex changes of their DNA methylation state
|Methylation profiling by genome tiling array
|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. However, in individuals, significant changes in DNA methylation of genes involved in leukocyte rolling, adhesion and cytoskeleton remodelling were seen. Conclusion: Our study revealed that regular consumption of MOF modulates the expression of genes in immune cells which, however, cannot be correlated to alterations in the DNA methylome. Remarkably, at the individual level, genes related to leukocyte adhesion pathways present complex variation in DNA methylation. As such, the individual transcriptional and epigenetic modulation of genes involved in early manifestation of cardiovascular diseases constitutes important subcellular mechanisms by which MOF promote vascular health in humans.
|DNA methylation levels of blood samples from 10 subjects were assessed using HumanMethylation450 BeadChips (Illumina), both before and after a diet intervention with MOF.
|Milenkovic D, Vanden Berghe W, Boby C, Leroux C, Declerck K, Szarc vel Szic K, Heyninck K, Laukens K, Fuks F, Haegeman G, Haenen GR, Bast A, Weseler AR
|Feb 03, 2014
|Last update date
|Mar 22, 2019
|Centre INRA Auvergne-Rhône-Alpes
|Saint Genes Champanelle
|Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
|This SubSeries is part of SuperSeries:
|Transcriptome-Methylome study of blood samples from flavanol diet intervention Paper title: Dietary flavanols modulate the transcription of genes associated with cardiovascular pathology and induces complex changes of their DNA methylation state.