- Link:
- http://hdl.handle.net/1969.1/ETD-TAMU-2011-05-9098
- Collection:
-
- Subjects
- Mechanobiology Atomic Force Microscopy Multiscale Modeling Growth and Remodeling ApoE Knockout Mice Immunoflourescence
- Creators:
- Hayenga, Heather Hayenga, Heather Naomi
- Contributor:
- Moore, James E.
- Description
- In order to create informed predictive models that
capture artery dependent responses during atherosclerosis
progression and the long term response to hypertension, one needs
to know the structural, biochemical and mechanical properties as a
function of time in these diseased states. In the case of
hypertension more is known about the mechanical changes; while,
less is known about the structural changes over time. For
atherosclerotic plaques, more is known about the structure and less
about the mechanical properties. We established a congruent
multi-scale model to predict the adapted salient arterial geometry,
structure and biochemical response to an increase in pressure.
Geometrical and structural responses to hypertension were then
quantified in a hypertensive animal model. Eventually this type of
model may be used to predict mechanical changes in complex disease
such as atherosclerosis. Thus for future verification and
implementation we experimentally tested atherosclerotic plaques and
quantified composition, structure and mechanical properties. Using
the theoretical models we can now predict arterial changes in
biochemical concentrations as well as salient features such as
geometry, mass of elastin, smooth muscle, and collagen, and
circumferential stress, in response to hemodynamic loads. Using an
aortic coarctation model of hypertension, we found structural
arterial responses differ in the aorta, coronary and cerebral
arteries. Effects of elevated pressure manifest first in the
central arteries and later in distal muscular arteries. In the
aorta, there is a loss and then increase of cytoskeleton actin
fibers, production of fibrillar collagen and elastin, hyperplasia
or hypertrophy with nuclear polypoid, and recruitment of
hemopoeitic progenitor cells and monocytes. In the muscular
coronary, we see similar changes albeit it appears actin fibers are
recruited and collagen production is only increased slightly in
order to maintain constant the overall ratio of ~55 percent. In the
muscular cerebral artery, despite a temporary loss in actin fibers
there is little structural change. Contrary to hypertensive
arteries, characterizing regional stiffness in atherosclerotic
plaques has not been done before. Therefore, experimental testing
on atherosclerotic plaques of ApoE-/- mice was performed and
revealed nearly homogenously lipidic plaques with a median axial
compressive stiffness value of 1.5 kPa.
- Type
- thesis
- Type
- text
- Format
- application/pdf
- Language
- en_US
- Description
- In order to create informed predictive models that
capture artery dependent responses during atherosclerosis
progression and the long term response to hypertension, one needs
to know the structural, biochemical and mechanical properties as a
function of time in these diseased states. In the case of
hypertension more is known about the mechanical changes; while,
less is known about the structural changes over time. For
atherosclerotic plaques, more is known about the structure and less
about the mechanical properties. We established a congruent
multi-scale model to predict the adapted salient arterial geometry,
structure and biochemical response to an increase in pressure.
Geometrical and structural responses to hypertension were then
quantified in a hypertensive animal model. Eventually this type of
model may be used to predict mechanical changes in complex disease
such as atherosclerosis. Thus for future verification and
implementation we experimentally tested atherosclerotic plaques and
quantified composition, structure and mechanical properties. Using
the theoretical models we can now predict arterial changes in
biochemical concentrations as well as salient features such as
geometry, mass of elastin, smooth muscle, and collagen, and
circumferential stress, in response to hemodynamic loads. Using an
aortic coarctation model of hypertension, we found structural
arterial responses differ in the aorta, coronary and cerebral
arteries. Effects of elevated pressure manifest first in the
central arteries and later in distal muscular arteries. In the
aorta, there is a loss and then increase of cytoskeleton actin
fibers, production of fibrillar collagen and elastin, hyperplasia
or hypertrophy with nuclear polypoid, and recruitment of
hemopoeitic progenitor cells and monocytes. In the muscular
coronary, we see similar changes albeit it appears actin fibers are
recruited and collagen production is only increased slightly in
order to maintain constant the overall ratio of ~55 percent. In the
muscular cerebral artery, despite a temporary loss in actin fibers
there is little structural change. Contrary to hypertensive
arteries, characterizing regional stiffness in atherosclerotic
plaques has not been done before. Therefore, experimental testing
on atherosclerotic plaques of Apolipoprotein E Knockout mice was
performed and revealed nearly homogenously lipidic plaques with a
median axial compressive stiffness value of 1.5
kPa.
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