Vascular Cell Physiology Under Shear Flow: Role of Cell Mechanics and Mechanotransduction - Mechanical and Chemical Signaling in Angiogenesis - page 123

range leads to adaptation and changes in the tissue composition, which result
alterations in arterial compliance. When the vessel walls of large arteries harden
due to hypertension, aging or diabetes, their compliance and thus capabilities of
modulating flow pulsatility diminish. Mitchell and colleagues showed that
decreases in large artery distensibility due to ageing lead to increased flow pulse
pressure in downstream arteries [ 10 ]. Decreases in large artery distensibity are
caused by vascular remodeling induced by oxygen deficiency, changes in external
load, disease altering stress-strain relationship within the vascular wall, changes in
arterial pressure, or alterations in smooth muscle tone [ 11 ]. Arterial stiffness is
increasingly recognized as an important component of cardiovascular risk [ 11 ]
because stiffness alters the way that the cardiovascular system responds to stress
and pressure changes. The efficiency of the arterial buffering depends on the
viscoelastic properties of the arterial wall and the vascular diameter.
Modifications in the composition of the arterial wall, known as vascular
remodeling, as well as chronic increases in pulse pressure can lead to reductions in
the arterial compliance or vascular stiffening; therefore, a stiffer artery will require
a higher distending pulse pressure for a given diameter increase [ 12 ]. Character-
istic vascular changes, including intimal hyperplasia/fibrosis, medial hypertrophy,
and extensive extracellular matrix modulation, lead to decreased compliance of the
vasculature and changes in vasoactivity. Vascular stiffening due to increased
smooth muscle hyperplasia and hypertrophy may produce an increase in collagen
fibers and a thinning of elastin fibers, creating less compliant arteries [ 13 ].
In compliant arteries, elastin bears the mechanical load caused by arterial pressure
and circumferential stretch. In stiffer arteries, the elastin in the walls of the conduit
vessels breaks down, resulting in arterial dilation, which further increases the
stress on the vessel wall. Arterial stiffening occurs as the mechanical load is
transferred from elastin to the stiffer collagen fibers. The increase in mechanical
load on the collagen fibers causes an increase in collagen crosslinking, which
results in a stiffer vessel [ 14 ]. Increases in stiffness also increase the downstream
pulsatile tensile and shear stresses. Shear stress is increased as a result of decreased
flow dampening during systole. Thus, more blood is ejected downstream during
systole producing higher peak flows in the systole upstroke of the flow wave. The
tensile stress on the arterial wall increases in proportion to the increase in pulse
pressure. SMCs contribute to arterial stiffness, by transmitting contraction through
the arteries, smooth muscle contraction can effect even the large arteries [ 12 ]. In the
small arteries, contraction of the SMCs can cause large changes in the lumen which
correspond to changes in the peripheral resistance [ 11 ].
Arterial stiffening alters the way that the vascular system can respond to stress
and pressure changes. When the compliance of the vasculature decreases, pulsa-
tions from the heart are not efficiently dampened; this alters the smooth continuous
flow that normally dominates in downstream arteries [ 7 ]. Therefore, arterial
stiffening can increase pulsatile flow in the downstream arteries, which may lead to
further microvascular damage in some vital organs, such as brain and kidney.
In these organs, extensive arterial branching does not exist to dampen the pulsatile
flow before it enters the microvasculature [ 15 ], and thus studies have shown that