Water filtration and macromolecular transport in the artery wall.
Item
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Title
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Water filtration and macromolecular transport in the artery wall.
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Identifier
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AAI9707108
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identifier
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9707108
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Creator
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Huang, Yaqi.
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Contributor
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Advisers: Sheldon Weinbaum | David Rumschitzki
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Date
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1996
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Anatomy | Biophysics, General | Biology, Animal Physiology
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Abstract
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Theoretical and experimental studies are presented in this dissertation to describe water filtration and macromolecular transport in the artery wall, especially in the subendothelial intima, and to reveal the roles that the thin intima and the internal elastic lamina (IEL) with its fenestrae play in modulating this transport. This transport is believed to be closely related to prelesion events associated with atherogenesis.;In Chapter 2 we propose a new model for the growth of cellular level macromolecular leakage spots in the arterial intima. This model differs from previous studies in that we model and calculate in an ab initio manner the intimal transport parameters based on Frank and Fogelman's (1989) ultrastructural observations of the subendothelial proteoglycan matrix. Using a heterogeneous fiber matrix theory the model predicts that the Darcy permeability and macromolecular diffusivity of the subendothelial intima are two orders of magnitude larger than the corresponding values measured in the media. Numerical results show that convection parallel to the endothelium is a very significant transport mechanism for macromolecules in the intima in a large region surrounding the leaky cleft. The predictions for the early-time spread of the HRP leakage spots in the intima and the high LDL concentration region surrounding the leaky cell are in close agreement with the experimental measurements (Chuang et al., 1990; Truskey et al., 1992).;In Chapter 3 we consider for the first time the effect of the intimal compaction on the total hydraulic conductivity of the intact artery wall due to changes in the transmural pressure. Our new hypothesis suggests that the compaction due to pressure loading of the proteoglycan matrix in the arterial intima near fenestral pores of the IEL leads to a narrowing of the pore entrance area and a large decrease in the local intrinsic Darcy permeability of the matrix. To quantitatively assess the feasibility of this mechanism, a local two-dimensional model is proposed to study the filtration flow in the vicinity of the fenestral pores in a compressible intima. This model predict that there is a marked non-linear steepening of the intimal pressure profiles near the fenestral pores, which can cause the endothelial indentations in these regions when the intima thins at higher lumen pressures.;In Chapter 4 we design a new in situ experiment to characterize the IEL's fenestrae in rat aorta, to test whether intimal compression due to transmural pressures occurs and to see if this compression is large enough to account for the observed pressure-induced changes in artery wall hydraulic conductivities (Tedgui and Lever, 1984; Baldwin and Wilson, 1993). Electron micrographs of the aorta sections show that the subendothelial intima is, indeed, very compressible. We have measured a near fourfold intimal compaction in rat thoracic aorta at 100 mm Hg compared to its initial thickness at 0 mm Hg. In both light and electron microscopic observations, we find numerous sites where the endothelium puckers into the fenestral pores at 100 mm Hg. These observations are consistent with the intimal compaction hypothesis and the predictions of our theoretical model.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
