A theory for how Aquaporin-1 and transmural pressure influence the mechanics of and the transport through the artery wall
Item
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Title
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A theory for how Aquaporin-1 and transmural pressure influence the mechanics of and the transport through the artery wall
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Identifier
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d_2009_2013:1562311db25e:11502
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identifier
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12000
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Creator
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Joshi, Shripad D.,
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Contributor
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David S. Rumschitzki
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Date
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2012
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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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Chemical engineering
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Abstract
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In the first part of Chapter 2, we improve on Huang et al.'s (36) intimal compression theory by implementing the exact fenestral boundary conditions in a finite difference method, rather than the approximate ones used previously due to computational restrictions, and use it to explain the experimentally observed variations (100, 2, 78, 62) in hydraulic conductivities of intact rabbit and rat artery wall with transmural pressure. Our model results explain the hydraulic conductivity data very well. It confirms that, as the transmural pressure increases, the degree of intimal compression increases and the resulting fenestral blockage significantly lowers Lp of the intact artery wall.;The second part of Chapter 2 proposes a new theory to explain the pressure-dependent effect, observed experimentally by Nguyen et al. (62), of AQP1-blocking on the Lp of rat aorta. Our hypothesis is that chemical blocking of AQP1s leads to a decrease in the average pressure in the intima, resulting in a higher force/area on the endothelium. This force compresses the intima and induces fenestra blockage at much lower overall transmural pressures. To assess this new theory, we extend Huang et al.'s (36) filtration model to include transcellular water flow through AQP1s. The results agree well with Nguyen et al.'s (62) experimental data and suggest that the Lp of the intact artery wall indeed decreases with AQP1 blocking (i.e., by decreasing transcellular water transport). This agreement corroborates the significance of AQP1s in the overall water transport across the vessel wall. The model predicts that AQPs contribute at least 30% to the phenomenological endothelial LP at low transmural pressures and to the intrinsic endothelial Lp. Further, we found that the force acting on the endothelium with functioning AQP1s at 60 mmHg, which gives a partially decompressed intima, is same as that acting on endothelium at 43 mmHg with blocked AQPs. Predictions are also presented to show how the increase in endothelial expression of AQP1s can increase the overall hydraulic conductivity of the vessel wall and shift the dynamic range over which the Lp drops significantly with pressure to higher transmural pressures. These findings suggest that AQP1 up-regulation, leading to higher wall Lp, can increase low density lipoprotein's (LDL) drainage from the sub-endothelial intima (SI) and thus might be beneficial in inhibiting pre-atherosclerotic LDL binding to SI matrix.;In Chapter 3, we have extended our filtration theory to include the mass transfer of oncotically active small solutes like albumin. This addition nonlinearly couples the mass transfer, the fluid flow and the wall mechanics. We employ finite difference methods to simultaneously solve the steady filtration and mass-transfer problem as a long-time solution of a fictitious unsteady problem. The model reveals the surprising finding that, due to media filtration, the steady albumin concentration in the SI is in fact higher than in the glycocalyx (GX). This results in higher oncotic pressure in the SI that sucks water from the lumen into, rather than pushing it out of the SI. We find that endothelial AQP1 up-regulation increases the overall driving force across the EC and the total Lp of the vessel wall than that predicted by our filtration based model. Surprisingly, the model predicts that GX degrading enzymes cause a significant decrease in the overall driving force across the EC that ultimately reduces the water flux across the vessel wall.;Chapter 4 investigates the effects of endothelial aquaporin-1 (AQP1) up-regulation, and the resulting increase in transcellular and thus overall transmural water flux, on the tracer concentration inside the arterial wall at various transmural pressures. We combine the predictions from our earlier local filtration model with Zeng et al.'s (131) 2-D macromolecular transport model and include the changes in macromolecular transport properties like the retardation coefficient, the available volume fraction and the diffusion coefficient with pressure induced intimal deformation. Our findings suggest a pressure-dependent decrease in intimal tracer concentration with increasing endothelial AQP1 expression, with the greatest effect observed at higher transmural pressures. These predictions are amenable to experimental verification and suggest AQP1 up-regulation as a potential route for mitigating pre-atherosclerotic lesion formation. (Abstract shortened by UMI.).
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Engineering
