Frequency composition of wall shear stress in animal models of atherosclerosis
View/ Open
Date
27/06/2020Author
Sathasivam, Arunn
Metadata
Abstract
Atherosclerosis and plaque rupture are widely known as multifactorial problems. To
isolate the significance of wall shear stress in these problems, the work of this thesis
explores the hypothesis that the frequency composition of the wall shear stress signal
is associated with the different plaque compositions and disease characteristics in
animal models of atherosclerosis.
In this thesis, a lattice Boltzmann simulation tool was developed to test the hypothesis
with the basic functionality of an existing code being enhanced for blood flow
simulation and wall shear stress calculation. The wall shear stress signals computed
from the simulation tool were analysed in terms of the frequency composition to
recover the harmonic amplitude and phase information. This information was then
used in comparing the different animal models.
Compared to the healthy, non-diseased vessel, disease models are known to result in a
decrease in the time-averaged wall shear stress from the reduction in blood flow rate
and local complex flow patterns. Further to this, the simulation of these models showed
a decrease in the first harmonic amplitude along the length of the vessel. This is a key
result of this thesis as the decreased first harmonic amplitude is associated with an
increase in the expression of adhesion molecules and proinflammatory factors in
endothelial cells. The uniformity in wall shear stress in regions of different plaque
type, however, suggests the dominance of circumferential stretch effects over wall
shear stress effects in the disease process.
Blood flow simulations in the mouse, rabbit and human vessels were also performed
to deduce scaling relationships of the zeroth and first harmonic amplitudes between
mammals. The body mass exponent of the first harmonic amplitude was found to be
higher than that of the zeroth harmonic amplitude. This suggests an increased
significance of the first harmonic component in the wall shear stress signal relative to
the zeroth harmonic amplitude in larger mammals. The absence of plaque rupture in
the atherosclerotic minipig, however, also suggests the dominance of genomic effects
over wall shear stress effects in the disease process.
A key issue in atherosclerosis research is the absence of plaque rupture in the mouse
model. The apparent dominance of circumferential stretch and genomic differences
shown here suggests that the wall shear stress alone cannot explain the lack of plaque
rupture in atherosclerotic mice. How these differences affect plaque composition
would be key in understanding the absence of plaque rupture in mouse models and
how studies in mice can be applied to benefit human treatments.