Mechanisms of endothelial protection by dietary flavonoids

[Truncated abstract] Cardiovascular disease (CVD) is the major cause of morbidity and mortality in developed countries, therefore an understanding of the role of lifestyle factors in ameliorating this condition would be beneficial in order to prevent or reduce its impact. We are seeking to extend knowledge in this area by investigating the role of some common dietary flavonoid compounds in the biological pathways relevant to the pathogenesis of atherosclerosis. As indicated by epidemiological studies, regular dietary intake of plant-derived foods and beverages benefits cardiovascular health and reduces the risk of CVD and stroke. Flavonoids are water-soluble plant pigments which are produced as secondary metabolites, and belong to the larger group of plant polyphenols. A number of studies have highlighted the beneficial effects of flavonoid-rich foods on vascular function (flow-mediated dilation), blood pressure, lipid profile, the development of atherosclerosis. These observations led to the suggestion that flavonoids might contribute to such health benefits. We have concentrated on the effects of quercetin, since preliminary data suggest that this common flavonoid has biological activity relevant to cardiovascular health. Following ingestion, flavonoids are metabolized rapidly by methylation or glucuronidation, which can alter their biological activity. Certain dietary flavonoids have been shown to up-regulate the expression of adenosine monophosphate-activated protein kinase (AMPK). AMPK is a conserved key enzyme in cellular energy homeostasis that affects fatty acid oxidation. In the first study, we investigated the effects of physiological concentrations of quercetin and its methyl and glucuronide metabolites (3'-O-methyl-quercetin and quercetin-3-O-glucuronide) on expression of AMPK and activation of eNOS in human aortic endothelial cells (HAECs) and endothelial function in isolated aortic rings from C57BL mice.