Dietary Fatty Acid-Induced Oxidative and Inflammatory Environments in Endothelial Cells

  • Toborek, Michal (PI)

Grants and Contracts Details


The development of atherosclerosis is influenced by a number of different factors. In particular, individual lipids, e.g., dietary fatty acids, playa critical role in atherogenesis. Selected fatty acids disrupt endothelial barrier function as well as cause endothelial cell activation and dysfunction. However, specific mechanisms of fatty acid-mediated injury to endothelial cells are not fully understood. The current research proposal is designed to examine molecular mechanisms of injury to endothelial cells induced by major dietary fatty acids, differing in the degree of unsaturation. The main hypothesis of the current research application is that specific dietary fatty acids induce highly individual effects on endothelial cell activation and differently contribute to the development of prooxidative and proinflammatory environments within the vascular endothelium. To test this hypothesis, we will study the involvement of oxidative stress and activation of oxidative stress responsive transcription factors in the inflammatory cascade induced by selected dietary fatty acids in endothelial cells. Specifically, this application will focus on molecular mechanisms of dietary fatty acidinduced inflammatory gene expression. Both cell culture model systems and animaJ studies will be employed in this research proposal. Animal studies will be performed in an atherogenic animal model of apoF/- mice fed diets enriched in dietary lipids. Thus, the present application will allow to study the role of dietary fatty acids at molecular, cellular and animal levels. Because alterations in antioxidant protection may be criticaJ factors in fatty acid-induced endothelial cell dysfunction, adequate antioxidant supplementation may attenuate cellular injury. Based on our preliminary data, we hypothesize that adequate supplementation with vitamin E and N-acetyIcysteine may protect against fatty acid-induced endothelial cell inflammatory response. The long term goals of the present proposal are to determine molecular mechanisms of endothelial cell dysfunction induced by dietary fatty acids. We also will explore mechanisms by which an antioxidant treatment can prevent induction of endothelial dysfunction. Thus, the current research proposal can significantly contribute to the improvement of public health by providing important research data about the role of dietary factors (dietary fatty acids and antioxidants) in the development or prevention of endothelial cell inflammatory response in relationship to atherosclerosis.
Effective start/end date7/1/006/30/04


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