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Regular, moderate consumption of red wine is linked to a reduced risk of coronary heart disease and to lower overall mortality, but the relative contribution of wine's alcohol and polyphenol components to these effects is unclear. Here we identify procyanidins as the principal vasoactive polyphenols in red wine and show that they are present at higher(More)
Abnormal elevation of hepatic gluconeogenesis is central to the onset of hyperglycaemia in patients with type 2 diabetes mellitus (T2DM). Metformin corrects hyperglycaemia through inhibition of gluconeogenesis, but its mechanism of action is yet to be fully described. SIRT1 and GCN5 (listed as KAT2A in the MGI Database) have recently been identified as(More)
Statistical evidence of reduced coronary heart disease in areas of high wine consumption has led to the widespread belief that wine affords a protective effect. Although moderate drinking of any alcohol helps to reduce the incidence of coronary heart disease, there is no clear evidence that red wine confers an additional benefit. Here we show that red wines(More)
The action of cytokines on the endothelium is a pivotal event in a number of vascular pathologies and inflammatory conditions. Here we have tested the effect of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-2 on endothelial-1 (ET-1) release from cultured bovine aortic endothelial cells. TNF-alpha and IL-1 beta caused(More)
Endothelin-1 (ET-1) is synthesized by a number of cell types, including endothelial, epithelial, and smooth muscle cells. Initial biosynthesis occurs as a protein precursor, preproendothelin-1 (preproET-1). This is processed intracellularly to the inactive intermediate big ET-1, which is hydrolyzed by endothelin-converting enzyme (ECE) to generate ET-1, but(More)
Regular consumption of red wine reduces mortality from coronary heart disease. This observation has been attributed to the anti-thrombotic effects of ethanol and to the antioxidant properties of polyphenolic compounds present in red wine. Here we show that an extract of red wine polyphenols causes a concentration-dependent inhibition of endothelin-1(More)
Reduced endothelium-dependent vasodilator responses with increased synthesis of ET-1 (endothelin-1) are characteristics of endothelial dysfunction in heart failure and are predictive of mortality. Identification of treatments that correct these abnormalities may have particular benefit for patients who become refractory to current regimens. Hawthorn(More)
Subcellular fractionation of the phosphoramidon sensitive membrane-bound endothelin converting enzyme (ECE-1) activity from homogenates of bovine aortic endothelial cells and the human endothelial cell line EA.hy 926, combined with studies of intact cells, shows ECE-1 to be localised primarily to the plasma membrane with the topology of an ectoenzyme. To(More)
Flavonoid-rich diets are associated with a lower mortality from cardiovascular disease. This has been linked to improvements in endothelial function. However, the specific flavonoids, or biologically active metabolites, conferring these beneficial effects have yet to be fully defined. In this experimental study of the effect of flavonoids on endothelial(More)
We have determined the effect on endothelin-1 (ET-1) release of stimulating cultured endothelial cells for 24 h with Ca2+ ionophores. The results obtained using cultured bovine aortic endothelial cells (BAECs) were compared with those using the human endothelial cell line (EA.hy 926). ET-1 was measured using a radioimmunoassay specific for the C-terminal(More)