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Divergent effects of quercetin conjugates on angiogenesis

Published online by Cambridge University Press:  08 March 2007

Sandra Donnini ,
Federica Finetti ,
Lorenzo Lusini ,
Lucia Morbidelli ,
Veronique Cheynier ,
Denis Barron ,
Gary Williamson ,
Johannes Waltenberger  and
Marina Ziche
Sandra Donnini
Affiliation:
Section of Pharmacology, Department of Molecular Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy
Federica Finetti
Affiliation:
Section of Pharmacology, Department of Molecular Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy
Lorenzo Lusini
Affiliation:
Section of Pharmacology, Department of Molecular Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy
Lucia Morbidelli*
Affiliation:
Section of Pharmacology, Department of Molecular Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy
Veronique Cheynier
Affiliation:
UnitéMixte de Recherche Sciences pour l'oenologie, Equipe Polyphénols, INRA, 2, Place Viala, 34060 Montpellier Cedex, France
Denis Barron
Affiliation:
Nestle Research Center, Vers-Chez-Les-Blanc, PO Box 44, CH-1000 Lausanne 26, Switzerland
Gary Williamson
Affiliation:
Institute of Food ResearchNorwich Research Park, Colney, Norwich NR4 7UA, UK
Johannes Waltenberger
Affiliation:
Department of Cardiology, University Hospital and Cardiovascular Research Institute (CARIM), 6202 AZ Maastricht, The Netherlands
Marina Ziche
Affiliation:
Section of Pharmacology, Department of Molecular Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy
*
*Corresponding author: Dr Lucia Morbidelli, fax +39 0577 234343, emailmorbidelli@unisi.it
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Abstract

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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.

Keywords

AngiogenesisQuercetinQuercetin conjugatesMicrovascular endothelial cellsProliferationMitogen-activated protein kinase
Type
Research Article
Information
British Journal of Nutrition , Volume 95 , Issue 5 , May 2006 , pp. 1016 - 1023
Copyright
Copyright © The Nutrition Society 2006

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