Divergent effects of quercetin conjugates on angiogenesis

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

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65 Citations (Scopus)

Abstract

The present study reports the activities of quercetin and its main circulating conjugates in man (quercetin-3′-sulphate (Q3′S) and quercetin-3-gluronide (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 and Q3′S are the two major conjugates in plasma, but their ratio is dependent on several factors, so that inhibition or activation of angiogenesis could be subtly shifted as a result of metabolism in vivo.

Original languageEnglish
Pages (from-to)1016-1023
Number of pages8
JournalBritish Journal of Nutrition
Volume95
Issue number5
DOIs
Publication statusPublished - 1 May 2006
Externally publishedYes

Keywords

  • Angiogenesis
  • Microvascular endothelial cells
  • Mitogen-activated protein kinase
  • Proliferation
  • Quercetin
  • Quercetin conjugates

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