Models for receptor-mediated LDL metabolism and arterial macromolecular transport.
Item
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Title
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Models for receptor-mediated LDL metabolism and arterial macromolecular transport.
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Identifier
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AAI9108196
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identifier
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9108196
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Creator
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Yuan, Fan.
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Contributor
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Advisers: Sheldon Weinbaum | Robert Pfeffer
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Date
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1990
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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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Engineering, Mechanical | Engineering, Biomedical | Biophysics, General
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Abstract
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In this thesis, three mathematical models are proposed. One attempts to study the receptor-mediated cellular regulation of the low density lipoprotein (LDL) metabolism in nonhepatic cells and the other two models greatly extend existing theoretical frameworks for modeling macromolecular transport in the artery wall.;The simplified model for the receptor-mediated LDL metabolism described in Chapter 2 is the first theoretical study to investigate the overall self-adaptive regulation of human fibroblasts and other cells with a native LDL receptor. The model also predicts the basic regulatory behavior of smooth muscle cells (SMCs), i.e., for a slowly increasing LDL concentration in the extracellular medium, the rate of intracellular degradation of LDL first increases and then becomes saturated.;In Chapter 3, an initial attempt is made to extend the leaky junction-cell turnover model proposed in Weinbaum et al. (1985) to include convective transport and a discrete IEL. The model is time-dependent and two dimensional but employs the simple one-dimensional (1-D) continuity relation for the velocity in each wall layer. Unfortunately, this assumption of 1-D continuity relation for the velocity has led to physically spurious results for the subendothelial intima (SI) concentration profiles and the total macromolecular flux entering the artery wall, because the major transport processes in the SI occur parallel rather than normal to the endothelial surface in the vicinity of the leaky cleft exit, due to the unique ultrastructure of the intima. A new view of convective-diffusive transport processes in the arterial intima is thus proposed in Chapter 4 and is described below.;The major conclusions of the new transport model in the intima proposed in Chapter 4 are: (1) it is impossible for the macromolecular concentrations in the SI to be higher than in the lumen unless a sieving structure exists in the intima; (2) 1-D convective-diffusive models can lead to the concentrations in the SI that are higher than in the lumen, and overestimate the macromolecular convective flux entering the artery wall by more than an order of magnitude; (3) the structure of the normal endothelial junction strand varies tremendously as one proceeds from the large arteries to capillaries; and (4) for rabbit aorta (200 {dollar}\mu{dollar}m wall thickness) the new model predicts, (i) 99 percent of the total arterial wall resistance to macromolecular transport resides in the endothelium, (ii) the macromolecular flux entering the artery wall is proportional to the frequency {dollar}\phi{dollar} of the endothelial cells with leaky clefts when {dollar}\phi\leq{dollar} 0.05, and is proportional to the lumen pressure p{dollar}\sb{lcub}\rm L{rcub}{dollar} when p{dollar}\sb{lcub}\rm L{rcub}\geq{dollar} 70 mmHg, and (iii) the growth of the fluorescent leakage spot in the SI is confined to only several cell radii after 2 hrs. of labeling.
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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.
