Phytochemicals and cardio-vascular health

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Flavonoids are common dietary components that have emerged as key target phytochemicals for protecting against cardiovascular disease due to consistent positive outcomes in human trials concerned with their effects on markers of CVD risk. Several cell types play crucial roles in both maintaining healthy vascular function and the development of CVD: platelets, which play a critical role in the processes underlying thrombotic diseases such as myocardial infarction and stroke, vascular endothelial and smooth muscle cells that control vascular tone and blood mononuclear cells that are involved in atherosclerosis and thrombosis. The underlying mechanisms by which flavonoid-rich diets induce potentially beneficial changes in these cells are not understood, in particular (i) the identities of the active metabolites in blood are not known, and (ii) the molecular mechanisms by which these metabolites alter cell / platelet function have not been established. In this project, a systems biology approach will be used to investigate the responses of platelets to dietary flavanols. Proteomics will be combined with a number of functional platelet activity assays to identify key changes in platelet proteins that are related to the observed functional differences to develop a predictive model that will be used to test hypotheses concerned with the anti-haemostatic effects of dietary flavanols. These studies will be performed in humans and in vitro. Complementary studies will be undertaken to establish the effects of flavonoids, their colonic catabolites and the corresponding human conjugates on gene and protein expression in the other cell types important in maintaining vascular health in order to understand the mechanisms involved and to identify the effective metabolites.

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