This project proposes to investigate the role of arachidonic acid metabolites in the control of vessel wall-blood interactions. The regulation of arachidonic acid metabolism, particularly via the lipoxygenase pathway, will be studied in both isolated cell types as well as during direct interactions with other cells. We will examine these reactions in platelets, leukocytes, and the different cellular components of the vessel wall. Initial studies will examine the role of arachidonic acid metabolites in regulating platelet-endothelial interactions. The transfer and utilization of prostaglandin endoperoxides between platelets and cultured endothelial cells will be investigated, with particular emphasis on the modulation of this process by platelet lipoxygenase metabolites. We will also study the effects of endothelial cells and their metabolic products on platelet and leukocyte lipoxygenase. In the second phase of the project, we will investigate the activity of vascular lipoxygenase. Using intact vessel walls of various types and cultured vascular cells, we will examine the production of lipoxygenase metabolites under a variety of experimental conditions, using different stimuli. These lipoxygenase metabolites will be purified, identified, and characterized. Finally, studies will be conducted to investigate the regulation of vascular lipoxygenase by blood cells and to identify any novel lipoxygenase metabolites that are formed as a result of direct metabolic interactions between different cell types. It is anticipated that these studies will elucidate the complex interactions between circulating blood cells and the vessel wall as they involve arachidonic acid metabolism and provide insight into certain disorders of hemostasis and thrombosis.
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