Interaction of Se, fatty acids and a polymorphism in GPX4 in modulation of vascular function. (360G-Wellcome-083358_Z_07_Z)

Incidence of vascular disease in humans can be influenced either beneficially or adversely by diet. Dietary fats can modulate vascular function and in particular, polyunsaturated fatty acids (PUFA), which have potentially beneficial effects, may have their function modulated by dietary selenium. This study aims to explore the molecular mechanisms through which selenium-containing proteins, and in particular, glutathione peroxidases can influence the metabolism of PUFA to promote formation of pro ducts in vascular cells that may be help prevent or decrease vascular disease. We propose that phospholipid hydroperoxide glutathione peroxidase (GPX4) has a critical role in eicosanoid metabolism and that this is influenced by a novel single nucleotide polymorphism (SNP) in GPX4. Thus, lipoxygenase activities and eicosanoid metabolism may be modulated by both dietary selenium through the peroxidases and through levels of PUFA in monocytes and endothelial cells. The effect of dietary releva nt levels of selenium and PUFA on endothelial-monocyte function/dysfunction will be assessed in genotyped cells and correlated with their effects on eicosanoid profiles and changes in gene and protein expression. Throughout this work we intend to gain insight not only into the interaction of dietary components with vascular health but crucially the role that genotype plays in this interaction.