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

Abstract

BackgroundIn 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 FindingsGene 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.ConclusionOur 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.

Coumarins — An Important Class of Phytochemicals

“…Therefore, the role of food-based "epi-bioactive" compounds has become an emerging field. Nutri-epigenomics is part of this new era too, since this approach on research has been carried out on chronic or degenerative diseases [129][130][131][132][133].…”

An Epigenome-Wide Association Study of Inflammatory Response to Fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network

“…An 8-week daily supplementation with 200 mg oligomeric flavonoids from grape seeds did not cause major changes of DNA methylation state but influenced the expression of genes associated with cardiovascular disease pathways [54]. SAM is a methyl donor in DNA methylation, and has been shown to lower lipopolysaccharide-induced expression of the proinflammatory cytokine TNF-α and increase the expression of the anti-inflammatory cytokine IL-10 in macrophages.…”

Nutriepigenomics Advances into Personalized Nutrition

“…The prenatal exposure to the Dutch famine has been repeatedly shown to be related to the impaired metabolic phenotypes such as elevated levels of plasma lipids and body mass index (BMI), as well as enhanced risks of obesity and cardiovascular disease (CVD) later in life. Severe malnourishment during late gestation was also related to impaired glucose tolerance of the offspring into adult life [6,[11][12][13][14].…”

“…Subsequently, this observation has been extended by examination of a set of 15 additional candidate loci responsible for development of metabolic and cardiovascular phenotypes. Levels of methylation of six of these loci (GNASAS, IL10, LEP, ABCA1, INSIGF and MEG3) have been found to be associated with prenatal exposure to famine [6,11,13,14].…”

“…These eight PPL-associatedmethylation sites, also correlated with fasting TG, account for a substantially greater amount of phenotypic variance (14.9%) in PPL and fasting TG (16.3%) when compared with the genetic contribution of loci identified by a previous GWAS (4.5%). In summary, the epigenomeis a large contributor to the variation in PPL, and this has the potential to be used to modulate PPL and reduce CVD [3,6,[13][14][15].…”