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Transcriptomic and Epigenomic Changes in Human Leukocytes Upon 8 Weeks Supplementation with Monomeric and Oligomeric Flavanols
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International audience. Consumption of flavanol-rich foods is associated with a reduced risk of cardiovascular diseases, which was linked to improvements in endothelial function. A recent randomized, double-blind, placebo controlled clinical trial unveiled pleiotropic health benefits in the vasculature of healthy male smokers upon 8 weeks supplementation with daily 200 mg flavanols. In order to unravel the flavanols’ underlying molecular mechanisms, we investigated the transcriptomic and epigenomic changes in leukocytes. Methods: Gene expression profiles were determined using whole genome microarrays (Agilent) and DNA methylation was assessed using HumanMethylation450 BeadChips (Illumina). Results: Flavanol consumption 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 flavanols exposure of monocytes attenuates their adhesion to TNF-α- timulated endothelial cells. Nuclear factor kappa B (NF-κB) reporter gene assays confirmed that flavanols 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 flavanols supplementation could not be found. Conclusion: Altogether, flavanols may elicit protective effects in the vasculature by decreasing inflammatory and cell adhesion pathways at the transcriptional level. Moreover, smoking history may be a confounding factor in epigenetic profiling studies of leukocytes from subjects involved in a flavanol-rich diet intervention.
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