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Inhibition of VEGF signalling by dietary polyphenols as a plausible mechanism for their health benefits

Reference	BBS/E/F/00042625
Principal Investigator / Supervisor	Dr Paul Kroon
Co-Investigators / Co-Supervisors
Institution	Quadram Institute Bioscience
Department	Quadram Institute Bioscience Department
Funding type	Research
Value (£)	204,700
Status	Completed
Type	Institute Project
Start date	01/05/2011
End date	30/04/2013
Duration	24 months

Abstract

Cardiovascular diseases (CVD) are the single biggest cause of death worldwide and are particularly prevalent in westernised populations including Europe. Epidemiological evidence indicates that consumption of flavonoid-rich diets is associated with reduced CVD risk. In addition, recent systematic reviews of data from high quality clinical trials have shown that consumption of certain flavonoids and flavonoid-rich foods significantly reduce CVD risk. There is huge potential for the development and marketing of flavonoid-rich foods that reduce CVD risk, and EFSA is reviewing hundreds of dossiers of evidence in support of such health claims. But, there is an almost complete lack of evidence of the mechanisms involved in vivo. This is largely because the majority of existing proposed mechanisms have not been shown to occur at the sub-micromolar concentrations observed in blood and tissues, and do not take account of extensive human metabolism of ingested flavonoids. The host research team have recently discovered that certain polyphenols that are present in red wine, strawberries and cocoa potently inhibit vascular endothelial growth factor (VEGF) signalling in vascular endothelial cells at sub-micromolar concentrations. Because VEGF is pro-atherosclerotic, inhibition of VEGF signalling is a plausible mechanism to explain flavonoid-induced reductions in CVD risk. The objectives of this project are to: (i) determine the molecular basis of the inhibition of VEGF signalling by dietary polyphenols, (ii) examine the effect of human metabolism of polyphenols on the efficacy of VEGF signalling inhibition, and (iii) develop and validate an in vitro cellular model, involving intestinal metabolism and absorption processes, suitable for assessing the potential impact of ingested polyphenols on VEGF signalling. The project will provide a molecular understanding of a plausible mechanism by which dietary flavonoids can reduce CVD risk.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Diet and Health
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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