Flavanone metabolites decrease monocyte adhesion to TNF-a-activated endothelial cells by modulating expression of atherosclerosis-related genes.
2013
Chanet, Audrey | Milenkovic, Dragan | Claude, Sylvain | Maier, Jeannette | Khan, Muhammad Kamran | Rakotomanomana, Njara | Shinkaruk, Svitlana | Bérard, Annie M | Bennetau-Pelissero, Catherine | Mazur, André | Morand, Christine | Unité de Nutrition Humaine (UNH) ; Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université | Università degli Studi di Milano = University of Milan (UNIMI) | Sécurité et Qualité des Produits d'Origine Végétale (SQPOV) ; Avignon Université (AU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA) ; Université de Bordeaux (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS) | Physiopathologie de la plasticité neuronale ; Université Bordeaux Segalen - Bordeaux 2
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Show more [+] Less [-]English. Flavanones are found specifically and abundantly in citrus fruits. Their beneficial effect on vascular function is well documented. However, little is known about their cellular and molecular mechanisms of action in vascular cells. The goal of the present study was to identify the impact of flavanone metabolites on endothelial cells and decipher the underlying molecular mechanisms of action. We investigated the impact of naringenin and hesperetin metabolites at 0·5, 2 and 10 mM on monocyte adhesion to TNF-a-activated human umbilical vein endothelial cells (HUVEC) and on gene expression. Except hesperetin-7-glucuronide and naringenin-7-glucuronide (N7G), when present at 2 mM, flavanone metabolites (hesperetin-3 0-sulphate, hesperetin-3 0-glucuronide and naringenin-4 0-glucuronide (N4 0 G)) significantly attenuated monocyte adhesion to TNF-a-activated HUVEC. Exposure of both monocytes and HUVEC to N4 0 G and N7G at 2 mM resulted in a higher inhibitory effect on monocyte adhesion. Gene expression analysis, using TaqMan Low-Density Array, revealed that flavanone metabolites modulated the expression of genes involved in atherogenesis, such as those involved in inflammation, cell adhesion and cytoskeletal organisation. In conclusion, physiologically relevant concentrations of flavanone metabolites reduce monocyte adhesion to TNF-a-stimulated endothelial cells by affecting the expression of related genes. This provides a potential explanation for the vasculopro-tective effects of flavanones.
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