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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL034739-03
Application #
3348004
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1985-09-30
Project End
1988-09-29
Budget Start
1987-09-30
Budget End
1988-09-29
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Greisler, H P; Joyce, K A; Kim, D U et al. (1992) Spatial and temporal changes in compliance following implantation of bioresorbable vascular grafts. J Biomed Mater Res 26:1449-61
Johnson, G A; Borovetz, H S; Anderson, J L (1992) A model of pulsatile flow in a uniform deformable vessel. J Biomech 25:91-100
Healy, A M; Herman, I M (1992) Density-dependent accumulation of basic fibroblast growth factor in the subendothelial matrix. Eur J Cell Biol 59:56-67
Healy, A M; Herman, I M (1992) Preparation of fluorescent basic fibroblast growth factor: localization in living retinal microvascular endothelial cells. Exp Eye Res 55:663-9
Ligush Jr, J; Labadie, R F; Berceli, S A et al. (1992) Evaluation of endothelium-derived nitric oxide mediated vasodilation utilizing ex vivo perfusion of an intact vessel. J Surg Res 52:416-21
Mandarino, W A; Berceli, S A; Sheppeck, R A et al. (1992) Experimental determination of velocity profiles and wall shear rate along the rabbit aortoiliac bifurcation: relationship to vessel wall low-density lipoprotein (LDL) metabolism. J Biomech 25:985-93
Hoock, T C; Newcomb, P M; Herman, I M (1991) Beta actin and its mRNA are localized at the plasma membrane and the regions of moving cytoplasm during the cellular response to injury. J Cell Biol 112:653-64
Marquez-Sterling, N; Herman, I M; Pesacreta, T et al. (1991) Immunolocalization of the vacuolar-type (H+)-ATPase from clathrin-coated vesicles. Eur J Cell Biol 56:19-33

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