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Pejcic et al. Vessel Plus 2019;3:32 I http://dx.doi.org/10.20517/2574-1209.2019.18 Page 7 of 12

there were distinct fibre families, directions and dispersion present in the three arterial layers: these
[12]
variations between the layers underlie their different mechanical and functional properties. Sassani et al. utilized
a four fiber microstructure based model to characterize region and layer-specific material properties in
ascending aortic aneurysmal tissue samples; their novel hypothesis that the fibers are able to support
compressive forces provides further insight into the role of elastin and collagen in withstanding mechanical
loads. The aortic wall shows an increase in viscoelastic creep further from the aortic root, which can be
attributed to a decrease in elastin content. Irregular variability in the opening angle was observed over the
length of the vessel, the pattern of which was determined to be similar across both young (less than 40 years
[14]
[37]
of age) and old subjects . Haskett et al. delved into the critical importance of gaining a better structural
model of the aorta through quantification of microstructural and mechanical changes. Specifically, they
looked at anisotropy and extra-cellular matrix microstructure changes as a function of location and age of
the aorta.

Age-dependent effects
Another concept of interest is the age-dependent elastic behaviour of the arterial wall which is closely
related to the histological compositional changes that occur with age. These alterations with age are
[51]
explored by Maceri et al. ; they introduce a multiscale mechanical model that accounts for nanoscale
effects of cross-link stretching, as well as micro- and macroscale mechanisms. This model further supports
experimental evidence regarding the histological alterations in the aortic wall that occur with age, showing
evidence between the influence of cross-link density and stiffness on the elastic modulus. With age, there
is an increase in aortic diameter, thickness, elastin stiffness and collagen cross links and there is a decrease
[52]
in collagen amount, collagen fiber radius and waviness. Carallo et al. concur and describe the effects of
ageing as a change in the arterial wall with an increased collagen presence and reduced elastin function,
leading to a larger and stiffer vessel. Moreover, this increase in aortic stiffness and thickness is greatest
[14]
circumferentially .
[53]
Cavalcante et al. present a comprehensive review on arterial stiffness associated with age and, in
particular, the acceleration of aortic stiffness due to hypertension. They identify arterial stiffness as an
important prognostic factor and emphasize its deleterious effect on the Windkessel function of the aorta.
Moreover, they identify pharmacological and non pharmacological therapies targeted against increased
aortic stiffness. This further highlights the importance of identifying contributing factors that affect vessel
function so that more targeted therapies can be employed. A monotonic decrease in circumferential and
[13]
axial tensile strength of the arterial wall with age is evident as well [13,54,55] . Guinea et al. utilized uniaxial
tensile tests on donor thoracic aortas and found that the tensile strength of the thoracic aorta falls rapidly
[55]
after age 30 and Morrison et al. found that circumferential and longitudinal strain decreased by 50% with
increasing age (patients with a mean age of 68 compared to patients with a mean age of 41). Deveja et al. [56]
found a negative correlation between failure stress and stretch with increasing age in all three layers of the
[57]
ascending aorta and a similar correlation was found by Iliopoulos et al. in tissue samples of patients with
[58]
Sinus of Valsalva aneurysms. Tracy and Eigenbrodt found that a disproportionate increase in vessel wall
thickness with age causes a deviation from the Laplace law: they introduced age specific constants into the
Laplace equation to make their data conform to Laplace expectations. This further highlights the need for a
more comprehensive guideline to assess aneurysm rupture risk, especially in an ageing population, than the
current diameter-based guidelines which were formed on the basis of the Laplace Law.

Hemodynamic effects
Hemodynamics is of particular interest as a potential factor in arterial disease formation and progression.
Dynamic in vitro tests could show the effect of flow on the healthy arterial structure and subsequent
disease formation while still allowing for control of the loading conditions and isolating mechanical
effects. Pulsatile arterial hemodynamics has been explored in numerous studies [52,59,60] . The scope of this