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Divergent effects of quercetin conjugates on angiogenesis

Donnini, Sandra ; Finetti, Federica ; Lusini, Lorenzo ; Morbidelli, Lucia ; Cheynier, Veronique ; Barron, Denis ; Williamson, Gary ; Waltenberger, Johannes ; Ziche, Marina

In: British Journal of Nutrition, 2006, vol. 95, no. 5, p. 1016-1023

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    Titre
    • Divergent effects of quercetin conjugates on angiogenesis
    Auteur
    • Donnini, Sandra. Section of Pharmacology, Department of Molecular Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy
    • Finetti, Federica. Section of Pharmacology, Department of Molecular Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy
    • Lusini, Lorenzo. Section of Pharmacology, Department of Molecular Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy
    • Morbidelli, Lucia. Section of Pharmacology, Department of Molecular Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy
    • Cheynier, Veronique. UnitéMixte de Recherche Sciences pour l'oenologie, Equipe Polyphénols, INRA, 2, Place Viala, 34060 Montpellier Cedex, France
    • Barron, Denis. Nestle Research Center, Vers-Chez-Les-Blanc, PO Box 44, CH-1000 Lausanne 26, Switzerland
    • Williamson, Gary. Institute of Food ResearchNorwich Research Park, Colney, Norwich NR4 7UA, UK
    • Waltenberger, Johannes. Department of Cardiology, University Hospital and Cardiovascular Research Institute (CARIM), 6202 AZ Maastricht, The Netherlands
    • Ziche, Marina. Section of Pharmacology, Department of Molecular Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • British Journal of Nutrition, 2006, vol. 95, no. 5, p. 1016-1023. Cambridge University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:291597
    Summary
    The present study reports the activities of quercetin and its main circulating conjugates in man (quercetin-3′-sulphate (Q3′S) and quercetin-3-glucuronide (Q3G)) on in vivo angiogenesis induced by vascular endothelial growth factor (VEGF) and examines the effects of these molecules on cultured endothelial cells. We found opposing effects of quercetin and its metabolites on angiogenesis. While quercetin and Q3G inhibited VEGF-induced endothelial cell functions and angiogenesis, Q3′S per se promoted endothelial cell proliferation and angiogenesis. The inhibitory effect elicited by Q3G was linked to inhibition of extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation elicited by VEGF. The activation of endothelial cells by Q3′S was associated to stimulation of VEGF receptor-2 and to downstream signalling activation (phosphatidylinositol-3 kinase/Akt and nitric oxide synthase pathways), ultimately responsible for ERK1/2 phosphorylation. These data indicate that the effects of circulating quercetin conjugates on angiogenesis are different depending on the nature of the conjugate. Q3G andQ3′S are the two major conjugates in plasma, but their ratio is dependenton several factors, so thatinhibition or activation of angiogenesis could be subtly shifted as a result of metabolismin vivo