HOW DOES AN APPLE A DAY KEEP THE DOCTOR AWAY?

SET for BRITAIN 2010 Event: Monday 8th March 2010 - The House of Commons UK

The overall aim of SET for BRITAIN is (and has always been) to encourage, support and promote Britain's early-stage and early-career research scientists, engineers and technologists who are the "engine-room" of continued progress in and development of UK research and R&D, and ultimately of UK plc. Many will be Britain's future scientific and technological leaders and others will clearly be leaders in other fields. Such researchers are a vital asset and investment for the UK. The SET for BRITAIN series of poster competitions and exhibitions in the House of Commons came to an abrupt halt with the untimely death in 2007 of its inspirational organiser, Dr Eric Wharton. In 2008, the Parliamentary and Scientific Committee joined together with the Royal Academy of Engineering, the Royal Society of Chemistry, the Institute of Physics and the Institute of Biology to revive SET for BRITAIN because we all believe that early-stage Researchers deserve particular encouragement to continue developing their work. Dr Douglas Naysmith MP, Chairman of the SET for BRITAIN organising group of the Parliamentary and Scientific Committee, will sponsor an exhibition and reception in the House of Commons Terrace Marquee on Monday, 8th March 2010 in the run up to National Science and Engineering Week. In order to encourage maximum participation by early-career researchers and Members of Parliament the competition will be divided into three distinct areas: Physical Sciences (Chemistry and Physics), Engineering and Biological and Biomedical Science

Each section will have a separate two-hour poster exhibition and judging session during the day, ending with a reception and prize-giving. We expect there will be about 60 posters on display in each session, representing the best in each field as part of a national competition for a prestigious Medal and substantial monetary prize. There will also be significant Runner-Up Prizes and/or Commendation Awards.

SET for BRITAIN Awards are made solely on the basis of the very best research work and results by an early-stage or early-career researcher.

Abstract

C.W.A Moyle¹, W. Hollands¹, M. Winterbone¹, P. Needs¹, J. Bacon¹, R. Wood² and P.A. Kroon¹ - ¹Institute of Food Research, NorwichResearchPark, Colney, Norwich, NR4 7UA, ²Coressence ltd, Herefordshire, HR2 8DA

Cardiovascular disease (CVD) is one of the most significant causes of global morbidity and mortality and has a major impact on social and economic costs. In 2006, CVD cost the UK more than £29 billion. Development of atherosclerosis and the rupture of atherosclerotic plaques play an important role in CVD and it is known that angiogenesis has a key role in the development and destabilization of atherosclerotic plaques. Angiogenesis is regulated via the vascular endothelial growth factor (VEGF) signalling pathway. A link has been established, through epidemiological studies, between fruit and vegetable intake and a reduced risk of CVD. Part of this protective effect is due to an intake of polyphenols, especially flavonoids. Major sources of polyphenols include tea, apples, cocoa and coffee. In-vitro studies have also shown that flavonoids possess numerous biological functions that cause a reduction in CVD risk, when applied at pharmacological doses. However, there is little evidence of mechanisms relevant to dietary doses that take into account bioavailability. In a previous study, an apple procyanidin fraction was shown to alter the expression of multiple genes associated with angiogenesis at physiologically relevant concentrations [1]. The objectives of this study were to understand how flavanoids are able to inhibit the vascular endothelial growth factor (VEGF) signalling pathway and to determine how flavonoid structures affect this inhibition.

In order to determine if flavanoids affect angiogenesis, the ability of nine polyphenols to inhibit the VEGF signalling pathway were examined. Human umbilical vein endothelial cells were stimulated with VEGF and treated with the polyphenols. VEGF signalling was assessed using an enzyme-linked immunosorbent assay (ELISA) that detects endogenous levels of phosphorylated VEGFR2 protein. The apple procyanidin fraction (average dp=3.9) completely inhibited VEGFR2 phosphorylation at 0.3 µM. However, epicatechin, catechin and procyanidin B2 were ineffective at 10 µM, indicating that only (epi)catechin oligomers of dp≥3 are effective. The green tea catechin EGCG, which is galloylated at the 3-position and contains a trihydroxy B-ring, also completely inhibited VEGFR2 phosphorylation at 0.3 µM. Since EGC was a poor inhibitor, and ECG was better than EGC but not as effective as EGCG, both 3-galloylation and the trihydroxy B-ring are important for inhibitory activity. Methyl gallate did not inhibit phosphorylation, showing that a gallate ester is not sufficient for inhibitory activity. Gallic acid was a weak inhibitor, while ellagic acid (a dimer of gallic acid) completely inhibited VEGF signalling. This study demonstrated that the structure of the flavonoids (the size of the flavonoid and number of hydroxyl groups) is important in having the ability to inhibit VEGF signalling and that a few flavanoids are effective at physiological concentrations, which is achievable through a normal diet.  

1. Garcia-Conesa, M.T., et al., Oligomeric procyanidins inhibit cell migration and modulate the expression of migration and proliferation associated genes in human umbilical vascular endothelial cells. Mol Nutr Food Res, 2009. 53(2): p. 266-76