The initiation and growth of extracellular lipid liposomes in arteries and valves.
Item
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Title
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The initiation and growth of extracellular lipid liposomes in arteries and valves.
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Identifier
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AAI9946233
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identifier
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9946233
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Creator
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Yin, Yongyi.
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Contributor
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Mentors: David S. Rumschitzki | Sheldon Weinbaum
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Date
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1999
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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, Biomedical | Engineering, Mechanical | Engineering, Chemical
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Abstract
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There is considerable suggestive evidence that lipoprotein cholesterol, after crossing the arterial endothelium and entering the intima, lodges in extracellular lipid packets (labeled "liposomes") bound to the extracellular matrix. We model the transport of lipoprotein cholesterol and its intimal accumulation and show that the two are quantitatively linked. A single model, with only one adjustable parameter, accounts for liposome accumulation both in the arteries and in the valves of rabbits. This lends support to the hypotheses that the transport and accumulation of lipid are ubiquitous.;Liposomes appear to form by occasional attachment of a low-density lipoprotein (LDL) to the intimal matrix and to grow mainly by appending free LDL. The liposome size distributions observed in chronically hypercholesteremic (WHHL) and in short-term cholesterol-fed rabbits are quite different. We propose a hierarchy of simple, well-stirred nucleation-polymerization models to describe the initiation and growth of extracellular lipid liposomes, all explaining the WHHL data, but none the cholesterol-fed rabbit data. The reason is that short-term feeding produces a local non-uniform intimal history of LDL supply, as a consequence of the focal nature of the transendothelial LDL flow through isolated transient leaky junctions. Even the simplest WHHL model, together with Huang et al.'s macromolecular transport models to describe this intimal non-uniformity, superimposed on a slow uniform transendothelial seepage explain both data sets.;In contrast to arteries, heart valves consist mainly of extracellular matrix surrounded on opposite sides by endothelial monolayers. Thus, the water flow pattern, and the cholesterol delivery, into heart valves differs greatly from that into arteries. We perform HRP experiments which show that macromolecular transport into the valve also proceeds through isolated endothelial leaks and that the interposed region appears to have intima-like layers with large transport parameters. Despite the absence of an internal elastic lamina (EEL) in valves, both the convective-diffusive theory and the experiment produce en face tracer spots almost as large as in the aorta. This theory also explains Tompkins et al.'s low density lipoprotein (LDL) concentration profiles, and, when coupled to the liposome formation and growth models from the artery, the lipid accumulation in valves.
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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.
