Flavanol Consumption in Healthy Men Preserves Integrity of Immunological‐Endothelial Barrier Cell Functions: Nutri(epi)genomic Analysis

• Published in: Molecular nutrition & food research 2022-11, Vol.66 (21), p.e2100991-n/a
• Main Authors: Milenkovic, Dragan, Rodriguez‐Mateos, Ana, Lucosz, Margarete, Istas, Geoffrey, Declerck, Ken, Sansone, Roberto, Deenen, René, Köhrer, Karl, Corral‐Jara, Karla Fabiola, Altschmied, Joachim, Haendeler, Judith, Kelm, Malte, Berghe, Wim Vanden, Heiss, Christian
• Format: Article
• Language: English
• Subjects: Actin; Adhesion; Angiogenesis; Biomarkers; Blood Pressure; Cacao - chemistry; Cardiovascular diseases; Cell adhesion; Cell adhesion & migration; Cell signaling; Chemotaxis; clinical trial; Cocoa; cocoa flavanol; Consumption; Cytoskeleton; Deoxyribonucleic acid; DNA; DNA methylation; DNA microarrays; Double-Blind Method; epicatechin; Flavanols; Flavonols - pharmacology; Food and Nutrition; Gene expression; Genes; Genomic analysis; Genomics; Health risks; Humans; Immune response; Immune system; Immunology; Integrity; Life Sciences; Male; Metabolites; Middle Aged; Molecular modelling; Monocytes; Nitric oxide; Polyphenols - pharmacology; Signaling; Stiffness; Transcription factors
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.202100991

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 consume CF (bi‐daily 450 mg) or control drinks for 1 month. Microarray analysis identifies 2235 differentially expressed genes (DEG) involved in processes regulating immune response, cell adhesion, or cytoskeleton organization. Distinct patterns of DEG correlate with CF‐related changes in endothelial function, arterial stiffness, and blood pressure. DEG profile negatively correlates with expression profiles of cardiovascular disease patients. CF modulated DNA methylation profile of genes implicates in cell adhesion, actin cytoskeleton organization, or cell signaling. In silico docking analyses indicate that CF metabolites have the potential of binding to cell signaling proteins and transcription factors. Incubation of plasma obtained after CF consumption decrease monocyte to endothelial adhesion and dose‐dependently increase 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 expression and DNA methylation towards a cardiovascular protective effect, in agreement with clinical results, by preserving integrity of immunological‐endothelial barrier functions. Consumption of cocoa flavanol (CF) by healthy middle‐aged men modulate global gene expression and DNA methylation profile in circulating immune cells. Identified genes are involved in regulation of immune response, cell adhesion, or cytoskeleton organization. These results reveal molecular mechanisms of CF which may mediate vascular protective effects, in agreement with clinical results, by preserving integrity of endothelial barrier functions.