The potential health benefits of marine oils in vascular disease are being intensively investigated, including their effects on platelets, endothelium, macrophages and lipoproteins (LP). There is also great interest in the appearance of atherogenic LP during post-prandial lipemia, and striking effects of the N-3 fatty acids (FA) in marine lipids on post- prandial lipemia are now well-established. However, no studies have yet defined the post-prandial interactions of LP, endothelium and blood elements in humans or how ingestion of marine oils might alter such processes. The object of the proposed research will be to utilize state- of-the-art GC/MS methods and administration of defined test meals to 10 study platelet/vascular interactions during lipoprotein processing in men and women, and how such effects are changed by the acute and chronic ingestion of marine oils; 20 assess the effects of N-3 FA and alpha- tocopherol on the generation of oxidized LP during post-prandial processing by normal and atherosclerotic subjects, as well as the delivery via the bile of oxygenated lipids to the G.I. tract that could be incorporated into nascent chylomicrons, and 3) investigate the transfer of fatty acids, sterols, their oxygenated derivatives, and alpha-tocopherol to monocytes during post-prandial lipemia following ingestion of marine or control oils, and the effects of marine oils and marine-oil enriched LP on human monocyte and macrophage cholesterol ester metabolism, eicosanoid synthesis and chemotaxis. Physiological and pharmacological approaches will be used to define important aspects of platelet/vascular, vascular/lipoprotein, and lipoprotein/monocyte interactions in humans, compare these events in men and women, and determine how they are influenced by marine oils. By doing so, the proposed project directly addresses in vivo several important hypotheses underlying current theories of human atherogenesis, and thereby will define more clearly the potential health benefits of marine oils in Western societies.
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