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Flavanol Consumption in Healthy Men Preserves Integrity of Immunological‐Endothelial Barrier Cell Functions: Nutri(epi)genomic Analysis
Author(s) -
Milenkovic Dragan,
RodriguezMateos Ana,
Lucosz Margarete,
Istas Geoffrey,
Declerck Ken,
Sansone Roberto,
Deenen René,
Köhrer Karl,
CorralJara Karla Fabiola,
Altschmied Joachim,
Haendeler Judith,
Kelm Malte,
Berghe Wim Vanden,
Heiss Christian
Publication year - 2022
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202100991
Subject(s) - microbiology and biotechnology , biology , in silico , dna methylation , endothelial stem cell , cell adhesion , actin cytoskeleton , endothelium , immunology , immune system , nitric oxide , cytoskeleton , cell , gene expression , gene , genetics , endocrinology , in vitro
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.