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Title: Role of chronic shear stress in endothelial form and function
Author: Potter, Claire
ISNI:       0000 0004 2737 0378
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Endothelial cells in vivo exist in a dynamic environment, subject to the physical forces of blood flow as it is regulated through the cardiac cycle. Arguably, the most important force endothelial cells are subject to is shear stress, the frictional force of blood flow across the cell surface. Areas of the vasculature that experience laminar shear stress appear resistant to the development of atherosclerotic plaques, whereas those that experience low shear stress, due to complex patterns of blood flow, appear susceptible. In vitro study of the effects of chronic shear stress on the endothelium has been somewhat limited, due to the methods of modelling shear stress available, which are for the most part only suitable for culture for up to 24 hours. I have validated an orbital shaker method of modelling two flow environments seen in the vasculature, unidirectional flow and non-directional flow, with associated shear stress profiles, for chronic time periods of up to 7 days. I have shown clear differences between the two environments in terms of endothelial cell morphology and protein expression and identified many ways in which sheared cells differ from their static counterparts, in terms of morphology, protein expression, vascular mediator release and transcriptional profile. Shear stress appears to be a protective force, inhibiting expression of inflammatory mediators and significantly altering response to inflammatory stimulus. The orbital shaker may prove a useful model for in vitro study of the endothelium in a situation similar to that of physiological conditions.
Supervisor: Gorelik, Julia ; Mitchell, Jane ; Wienberg, Peter Sponsor: British Heart Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral