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Title: The role of mechanical forces in arterial disease
Author: Goodman, Martin Edward
ISNI:       0000 0001 3505 0655
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2008
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Background: Lipid transport and metabolism, especially oxidative modification of Low Density Lipoprotein (LDL), within the intimal layer of the arterial wall is widely accepted as being key in the pathogenesis of cardiovascular disease. Description: A new mathematical model of atherogenesis is developed which links blood flow, shear dependent endothelium permeability and intimal hyperplasia. Key concepts are that excess oxidised LDL (OxLDL) is engulfed by foam cells within the intima layer. This focal accumulation triggers wall thickening (hyperplasia), blood flow is altered and endothelial permeability modified. Hence there is a feed back mechanism between blood flow, wall morphology and metabolism. A localized injury or 'hotspot' is applied to the endothelium, enhancing the influx of LDL, this triggers the development of a lesion shaped indentation. The model is used to explore how this indentation changes over time, its effect on wall shear stress, influx rates of LDL and the sensitivity of these processes to oxidation parameters. The influence of wall thickness and oxidation rates on the accumulation of LDLand OxLDL are investigated using physiologically realistic parameters. Solutions are presented both for axisymmetric and asymmetric cases. Assumptions: LDL transport through the arterial wall is by advection and diffusion, the distribution of LDL at each time step is assumed to be quasi-steady. Blood is modelled as a Newtonian fluid, flow is assumed to be steady and fully developed. An existing linear asymptotic solution is used to solve for wall shear stress. Results: The hotspot injury produces asymmetrical changes extending far downstream by virtue of induced wall shear stress patterns. Increasing the size or lengthening the duration of the injury produces higher levels of OxLDL that persist for longer. This extended retention of OxLDL makes further pro-atherogenic changes more likely. A thicker intima was found to have a greater capacity for hyperplasia.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available