Role of Chronic Shear Stress in Endothelial Form and Function
Author(s)
Potter, Claire
Type
Thesis or dissertation
Abstract
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.
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.
Date Issued
2013-02
Online Publication Date
2013-05-20T11:29:26Z
Date Awarded
2013-03
Advisor
Gorelik, Julia
Mitchell, Jane
Wienberg, Peter
Sponsor
British Heart Foundation
Publisher Department
National Heart and Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)