Anthocyanins and their gut metabolites reduce monocyte adhesion and migration across TNFa-activated endothelial cells trough nutrigenomic mechanisms regulating endothelial permeability - Archive ouverte HAL Accéder directement au contenu
Poster De Conférence Année : 2017

Anthocyanins and their gut metabolites reduce monocyte adhesion and migration across TNFa-activated endothelial cells trough nutrigenomic mechanisms regulating endothelial permeability

Résumé

Cardioprotective effects of dietary anthocyanins are partly attributed to their ability to maintain endothelial function. However, the underlying mechanisms of action are not fully understood. This study aimed to test the effect of anthocyanins and their gut metabolites, at physiologically-relevant conditions, on endothelial cell function and decipher the underlying molecular mechanisms of action using integrated omics approaches. Primary endothelial cells were treated with a mix of 0.1μM cyanidin-3-arabinoside, 0.1μM cyanidin-3- galactoside, 0.1μM cyanidin-3-glucoside, 0.1μM delphinidin-3-glucoside, 0.1μM peonidin-3-glucoside and 0.5μM 4-hydroxybenzaldehyde for 3h or with a mix of gut metabolites: 0.2μM protocatechuic, 2μM vanillic, 1μM ferulic and 2μM hippuric acids for 18h. Additionally, successive treatment with both mixes mimicked the anthocyanin pharmacokinetics following their dietary intake. Endothelial cell dysfunction was induced using TNFa and monocytes added to asses adhesion and transmigration. Gene and miRNA expression, signaling protein phosphorylation and molecular docking were investigated. All mixes significantly reduced monocyte adhesion and transendothelial migration by 24.5% and 46.2% in average. Gene expression analysis using TLDA arrays showed that mixtures modulated the expression of genes involved in cell-cell adhesion, cytoskeleton organization or focal adhesion. Bioinformatic analyses were done to identify potential transcription factors involved in the observed nutrigenomic effects and signalling proteins regulating their activity. Western blot analysis showed the ability of tested compounds to modulate phosphorylation of NfkB-p65 or p38 signalling proteins. Docking identified 25 out of 63 potential cell signaling proteins to which these compounds can bind to and initiate the observed nutrigenomic effect. The mixes also affected miRNA expression. Bioinformatic analysis showed that more than half of modulated miRNAs are involved in regulation of endothelial cell permeability, contributing to the observed changes in endothelial cell function. Integration of these results revealed endothelial-protective properties of anthocyanins and their gut metabolites and deciphered new underlying multi-target and multi-layered mode of action.

Dates et versions

hal-01736379 , version 1 (16-03-2018)

Identifiants

Citer

Irèna Krga, Radu Tamaian, Sylvie Mercier, Céline Boby, Laurent-Emmanuel Monfoulet, et al.. Anthocyanins and their gut metabolites reduce monocyte adhesion and migration across TNFa-activated endothelial cells trough nutrigenomic mechanisms regulating endothelial permeability. Bordeaux VIVA Winter School - XXXIII LIAC MEETING, Nov 2017, Bordeaux, France. Biomedical and Biopharmaceutical Research, 14 (2), 22 p., 2017, Biomedical and Biopharmaceutical Research. ⟨10.19277/bbr.14.2.169⟩. ⟨hal-01736379⟩
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