A multidisciplinary research project is proposed to investigate the role of hemodynamics in the development of arterial disease. Specifically, various disciplines in the areas of bioengineering, biochemistry, surgery, cell biology and veterinary pathology will be joined in an integrated approach to study this complex problem. A novel feature of our research effort is the use of a pulse duplicator apparatus (PDA) for simulation in vitro of realistic vascular hemodynamics. The PDA has been so designed that the relative importance of individual hemodynamic variables such as mean pressure, pulse pressure, pulse rate, flow rate, and transmural pressure to the uptake and distribution of lipoprotein molecules by the arterial wall can be delineated. Experimental results of lipoprotein wall transport will be interpreted and correlated along with companion measurements and detailed calculations of lipid biochemistry, histology, fluorescence microscopy of the cytoskeletal array of intimal actin and myosin, physiological fluid mechanics, and mathematical models of cholesterol uptake. The data of cell biology are important to our long-term objective of furthering current understanding of hemodynamics and arterial disease, since the cytoskeletal array of contractile proteins appears to be important for maintenance of intimal integrity in vivo. In all, the applicants intend to conduct perfusion experiments, laboratory measurements, and bioengineering analyses for a three-year project. Our proposal is supported by preliminary data in the various aforementioned disciplines. It is hoped that the results of the proposed project will provide new information regarding the effects of various hemodynamic patterns on cholesterol deposition in mammalian vessels contributing to atherogenic plaque.
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