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Page 2 of 13 Ahmed et al. Vessel Plus 2018;2:36 I http://dx.doi.org/10.20517/2574-1209.2018.51

link in treatment methods. Common physiological risk factors are hypertension, obesity, a rise in cholesterol
[5]
and diabetes with treatment of each providing a larger scale preventative therapy of CVD . Despite this, the
largest risk factor associated with CVD is ageing, an inevitable process that all individuals undergo.

Ageing causes an increase in CVD incidence and prevalence due to wide array of changes that occurs as a
person becomes older. The cause of ageing requires a diverse and intricate investigation into the crosstalk
[6]
between multiple genetic and environmental (i.e., diet, exercise and smoking) factors . A key modification
observed is the structural and functional alterations within the vasculature. This includes the stiffening
of the arteries, in particular the aorta. The function of the aorta is crucial in converting the large output
of oxygenated blood from the left ventricle into a more controlled flow within the smaller arterioles
[7]
and capillaries . Stiffening ultimately reduces aortic compliance and increases systolic arterial pressure
[8]
that augments the overall vascular resistance . To compensate, the left ventricle adopts a compensatory
mechanism creating a change in the end-systolic volume as well as prolonging systolic contraction. A
direct consequence of this is the thickening of the left ventricle, which causes an aberrant hypertrophic
[9]
physiology . Coupled to this, ageing also causes defects in the repair mechanisms of the vasculature which
[10]
further drives the diseased-phenotypic changes . This, in turn, diminishes the capability of the vascular
system to overcome the increased workload that is generated as a repercussion. Thus, ageing presents as the
most predicative cause of CVD.

ARTERIAL STIFFNESS: CAUSE AND RELEVANCE IN CVD
Arterial stiffness is a predicative biomarker in ageing and CVD, including atherosclerosis, hypertension
and obese populations [11-13] . Normally, pulse pressure expands the elastic arteries, transferring energy from
the blood to the arterial wall and slowing pulse velocity. In conditions of enhanced arterial stiffness, pulse
pressure is no longer able to expand the artery, increasing pulse velocity, and pulse pressure is transmitted
[14]
to the microcirculation of organs such as the heart and lungs . Vessels of the microcirculation are more
fragile, resulting in damage to the microcirculation. The current gold standard method in assessing arterial
[15]
stiffness is pulse wave velocimetry (PWV) . A higher PWV is linked to individuals who have greater risk
[16]
of CVD . As a result, this method can be utilised to provide a predictive analysis of CVD independent of
[17]
standard blood pressure measurements of the brachial artery .
ARTERIAL STRUCTURE
Elastic arteries, including the aorta, are structurally composed of three layers; the tunica intima is the
innermost layer [Figure 1]. It is comprised of a sheet of endothelial cells along with a basal membrane
and collagen fibrils. The tunica media neighbours the tunica intima as the middle layer and is primarily
composed of vascular smooth muscle cells (VSMCs) reinforced with elastin and collagen fibrils. The final
and outermost layer is the tunica adventitia, containing largely connective tissue as a means to provide
[18]
reinforcement to the structure of the aorta . This allows the aorta to act as an “elastic buffering chamber”
[19]
in order to store and transmit blood to the peripheral circulation during systole and diastole, respectively .

This function becomes aberrant when aortic stiffness increases. Stiffness augmentation of the aorta is
ultimately driven by changes in extracellular matrix (ECM) composition, in particular enhanced elastic
degradation as well as augmented collagen deposition [20,21] . All three arterial layers are mechanoresponsive
and remodel during vascular disease progression [22-24] . In this review, we focus on the response of the VSMC
layer to enhanced matrix stiffness. Elastin in small arteries and the aorta allows for vascular distensibility
[21]
and in normal conditions, is found in high abundance within these vessels . However, this dogmatic
view on arterial stiffness was recently found to be misleading, as an in depth analysis of the published data
[25]
on hypertension found collagen levels to be inconsistent . Due to this, several studies have now found
multiple contributing factors towards aortic stiffness, ranging from, but not limited to, mechanical stimuli,
[25]
inflammatory cytokines and compositional changes in the ECM . The existing treatment therapies of aortic