(-)-Epicatechins promote vascular health through epigenetic reprogramming of endothelial-immune cell signaling and reversing systemic low-grade inflammation

Abstract : Ingestion of (-)-epicatechin flavanols reverses endothelial dysfunction by increasing flow mediated dilation and by reducing vascular inflammation and oxidative stress, monocyte-endothelial cell adhesion and transendothelial monocyte migration in vitro and in vivo. This involves multiple changes in gene expression and epigenetic DNA methylation by poorly understood mechanisms. By in silico docking and molecular modeling we demonstrate favorable binding of different glucuronidated, sulfated or methylated (-)-epicatechin metabolites to different DNA methyltransferases (DNMT1/DNMT3A). In favour of this model, genomewide DNA methylation profiling of endothelial cells treated with TNF and different (-)-epicatechin metabolites revealed specific DNA methylation changes in gene networks controlling cell adhesion-extravasation endothelial hyperpermeability as well as gamma-aminobutyric acid, renin-angiotensin and nitric oxide hypertension pathways. Remarkably, blood epigenetic profiles of an 8 week (-)-epicatechin diet intervention in male smokers revealed individual epigenetic gene changes targeting similar pathways as the in vitro exposure experiments in endothelial cells. Furthermore, epigenetic changes following (-)-epicatechin diet intervention oppose atherosclerosis associated epigenetic changes. In line with biological data, the individual epigenetic response to an (-)-epicatechin diet is associated with different vascular health parameters (glutathione peroxidase 1 and endothelin-1 expression, acetylcholine response), in part involving systemic shifts in blood immune cell types which reduce the neutrophil-lymphocyte ratio (NLR). Altogether, our study suggests that different (-)-epicatechin metabolites promote vascular health in part via epigenetic reprogramming of endothelial-immune cell signaling and reversing systemic low-grade inflammation.
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https://hal.archives-ouvertes.fr/hal-02383601
Contributor : Archive Ouverte Prodinra <>
Submitted on : Wednesday, November 27, 2019 - 8:09:10 PM
Last modification on : Thursday, November 28, 2019 - 1:41:11 AM

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Dragan Milenkovic, K. Declerck, Y. Guttman, Z. Kerem, S Claude, et al.. (-)-Epicatechins promote vascular health through epigenetic reprogramming of endothelial-immune cell signaling and reversing systemic low-grade inflammation. Biochemical Pharmacology, Elsevier, 2019, ⟨10.1016/j.bcp.2019.113699⟩. ⟨hal-02383601⟩

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