Biomedical Engineering Reference
In-Depth Information
is a pressing need for improved diagnostic criteria to aid clinical decisions:
distinguishing those AAA most at risk of rupture will yield significant improve-
ments in patient healthcare.
To understand the aetiology of AAA requires a thorough understanding of the
underlying biological mechanisms that govern arterial growth and remodelling
(G&R) in both healthy and diseased states [ 13 ]. This is an extremely challenging,
multidisciplinary problem: not only is the function of individual components of the
system elusive, their interactions remain unclear as well. In fact, modelling the
mechanical response of the healthy arterial wall alone poses significant challenges
in itself: it is a highly complex integrated structure [ 14 ]. However, it is envisaged
that models of AAA evolution [ 15 - 18 ] will lead to a greater understanding of the
pathogenesis of the disease and may ultimately yield improved criteria for the
prediction of rupture.
A pre-requisite to modelling AAA evolution is to model the biomechanics and
mechanobiology of the healthy arterial wall. Briefly, the artery, consists of three
layers: intima, media and adventitia. The innermost layer is the intima, this con-
sists of a basement membrane and a lining of endothelial cells (ECs). ECs form a
permeability barrier between the blood flow, the vessel wall and surrounding
tissues, and play a significant role in regulating circulatory functions. An internal
elastic laminae separates the intima from the media. The media consists of a
network of elastin fibres and (approximately) circumferentially orientated vascular
smooth muscle cells (VSMCs) and collagen fibres. The adventitia is an outer
sheath with bundles of collagen fibres, maintained by fibroblast cells [ 19 ],
arranged in helical pitches around the artery. The main load bearing constituents
are elastin and collagen. Collagen is considerably stiffer than elastin; however, for
a healthy large elastic artery, such as the abdominal aorta, at physiological strains
elastin bears most of the load [ 20 ]. This is because collagen is tortuous in nature
[ 21 , 22 ] and acts as a protective sheath to prevent excessive deformation of the
artery.
The structure of the artery is continuously maintained by vascular cells. The
morphology and functionality of the cells are intimately linked to their extracel-
lular mechanical environment. Haemodynamic forces due to the pulsatile blood
flow give rise to cyclic stretching of the extra-cellular matrix (ECM), frictional
forces acting on the inner layer of the arterial wall, normal hydrostatic pressure and
interstitial fluid forces due to the movement of fluid through the ECM. Mecha-
nosensors on the cells convert the mechanical stimuli into chemical signals.
Activation of second messengers (molecules that transduce the signals from the
mechanoreceptors to the nucleus) follows and leads to an increase in the activity of
transcription factors. Binding of the transcriptions factors to the DNA leads to
activation of genes that regulate cell proliferation, apoptosis, differentiation,
morphology, alignment, migration, and synthesis and secretion of various mac-
romolecules [ 23 ]. The living response of the artery acts to ensure it functions in an
optimum manner as mechanical demands change. For instance, in response to
changes in flow, ECs signal VSMCs to constrict/relax to regulate the diameter of
the artery to restore wall shear stress (WSS) to homeostatic levels [ 24 ].
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