Role des anthocyanes et des métabolites sur la fonction des cellules endothéliales et plaquettes humaine in vitro.

Abstract : Increasing number of scientific evidence suggests the beneficial role of dietary anthocyanins, phytochemicals mainly present in berries and derived products, in cardiovascular health. These anthocyanin health benefits may be attributed to their effect on endothelial cells or platelets that represent the key players in the development of cardiovascular diseases (CVD). However, the exact molecular mechanisms underlying anthocyanin cardioprotective effects are not fully understood. The aim of this thesis was to investigate the effect of anthocyanins and their metabolites in vitro on endothelial and platelet function and identify the underlying mechanisms of their action using physiologically relevant conditions.Results from this thesis showed that the pretreatment of endothelial cells with physiologically relevant concentrations of circulating anthocyanins and their metabolites attenuated monocyte adhesion to activated endothelial cells as well as their transendothelial migration, which are the initial steps in the development of atherosclerosis that precede CVD. In agreement with these results, gene expression analysis revealed that the treatment of endothelial cells with these compounds modulated the expression of genes involved in regulation of cell-cell adhesion, actin cytoskeleton reorganisation, focal adhesion and leukocyte transmigration. Bioinformatics analyses of gene expression data allowed the identification of potential transcription factors involved in the observed nutrigenomic effects and cell signalling proteins regulating their activity.Molecular docking analyses further revealed cell signalling proteins to which these bioactives may bind to and potentially affect their activity and the activation of downstream signalling proteins and transcription factors, effects that were in agreement with the results of Western blot analyses. Anthocyanins and their metabolites also modulated the expression of microRNAs, especially those involved in regulation of endothelial cell permeability, contributing to the observed changes in endothelial cell function.In addition to their effects on endothelial cells, anthocyanins and their metabolites displayed the capacity to modulate platelet function by decreasing platelet activation and their aggregation with leukocytes, the processes that are important contributors to CVD development.In conclusion, results from this thesis revealed the positive effects of anthocyanins and their metabolites, at physiologically relevant concentrations, on endothelial and platelet function and provided new insights into the mechanisms underlying their cardioprotective effects.
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Irena Krga. Role des anthocyanes et des métabolites sur la fonction des cellules endothéliales et plaquettes humaine in vitro.. Sciences agricoles. Université Clermont Auvergne, 2018. Français. ⟨NNT : 2018CLFAS004⟩. ⟨tel-02280890⟩

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