Abstract
Scope:
While cocoa flavanol (CF) consumption improves cardiovascular risk biomarkers, molecular mechanisms underlying their protective effects are not understood.
Objective:
To investigate nutri(epi)genomic effects of CF and identify regulatory networks potential mediating vascular health benefits.
Methods and results:
Twenty healthy middle-aged men consumed CF (bi-daily 450mg) or control drinks for 1 month. Microarray analysis identified 2235 differentially expressed genes (DEG) involved in processes regulating immune response, cell adhesion or cytoskeleton organization. Distinct patterns of DEG correlated with CF-related changes in endothelial function, arterial stiffness and blood pressure. DEG profile negatively correlated with expression profiles of cardiovascular disease patients. CF modulated DNA methylation profile of genes implicated in cell adhesion, actin cytoskeleton organization or cell signaling. In silico docking analyses indicated that CF metabolites have the potential of binding to cell signaling proteins and transcription factors. Incubation of plasma obtained after CF consumption decreased monocyte to endothelial adhesion and dose-dependently increased nitric oxide-dependent chemotaxis of circulating angiogenic cells further validating the biological functions of CF metabolites.
Conclusion:
In healthy humans, CF consumption may mediate vascular protective effects by modulating gene expresion and DNA methylation towards a cardiovascular protective effect, in agreement with clinical results, by preserving integrity of immunological-endothelial barrier functions. This article is protected by copyright. All rights reserved.
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