REDOX EFFECTS IN A MODEL OF AORTIC TISSUE INJURY

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The major goal is the development of a solid foundation in research techniques related to cell biology and biochemistry. Phase I of the training, which will focus on the development of a model for tissue injury and initial studies characterizing the effects of local reduction-oxidation potentials on both injury and response to injury, will be conducted in the laboratory of Dr. Carl Franzblau, Chairman of the Department of Biochemistry. Phase II, which will also be done under the tutelage of Dr. Franzblau, will focus on the clinically relevant questions of the role of reduction-oxidation environments in ischemia and hypoxia. By developing a cell culture model in which tissue extracellular matrix injury may be assessed, various local physical chemical influences may be studied. Cultured smooth muscle cells, with time, will form a multilayered cell system containing cells embedded in an extracellular matrix in a "hills and valleys" format. If this model is likened to the simplest of tissue specimens, it is hypothesized that injury of the extracellular matrix will provoke cellular responses leading to rapid, normal repair. In an effort to find a proposed method of general control, it is postulated that the local reduction-oxidation potential plays a role not only in the injury but also in the response to that injury. Within the confines of the culture system, a biochemically defined matrix will be produced which, in turn, can be injured in a controlled and measurable manner and ultimately repaired by the cells embedded in the matrix. Preliminary studies have been encouraging that such a system is feasible. The careful definition of this tissue culture system will then allow for the evaluation of the roles played independently or dependently by reduction-oxidation potentials and oxygen in the particular scenario of ischemia and hypoxia. The skills acquired in the first phase of the training program will allow Dr. Bergethon to further refine the techniques relating to measuring and manipulating redox potentials and then apply these techniques to both the smooth muscle culture as well as other cell types in an effort to study if local redox environments can significantly alter the damage done, both functional and mortal, and the subsequent response of cells to the injury.