Regulation of Endothelial Activation and Vascular Inflammation by Shear Stress - Bioanalysis Advanced Materials Methods and Devices - page 78

In a biomedical context shear stress is typically expressed in units of dynes/cm 2 .
Physiological arterial-level shear stress is variable, due to anatomical variation and
pulsatility, but is approximately 15 dynes/cm 2 [ 18 ]. The magnitude of the shear

stress may also be estimated in most of the vasculature by Poiseuille's law which
states that shear stress is proportional to blood flow viscosity, and inversely
proportional to the third power of the internal radius [ 13 ]. A change in the
physiological amount of shear stress has been implicated in the pathogenesis of
cardiovascular diseases. As pointed out by Cunningham and Gotlieb, three aspects
of the way in which shear stress affects the endothelial surface can be distinguished.
First, laminar flow gives the straightforward steady Poiseuille's flow effect (aver-
aged over the physiological pulsatory cycle). Second, oscillatory flow, expresses
cycle-to-cycle variations, which are normally zero or very low. Third, there are
local regions of disrupted flow comprising separation, recirculation and reattach-
ment [ 9 ]. Indeed in a combined numerical and in vitro study it was demonstrated
that oscillatory low shear stress present in recirculation zones can lead to a signifi-
cant activation of endothelial cells by enhancing ICAM-1 expression [ 34 ].
Shear stress, or rather, lower levels of shear stress have long been associated
with the development of atherosclerosis. Atherosclerosis is a multifactorial disorder
caused by genetic and environmental factors such as cholesterol, obesity, hyperten-
sion, diabetes, and smoking. It is the primary cause of morbidity and mortality
worldwide. The pathogenesis of atherosclerosis involves biochemical and bio-
mechanical changes in the arterial walls. Atherosclerosis is a chronic inflammatory
disease that involves complex interactions between various modified lipoproteins,
monocyte-derived macrophages, T lymphocytes, endothelial cells, and smooth
muscle cells [ 25 ]. Atherosclerotic lesions occur predominantly in areas such as
inner curvatures of the coronary arteries where there is lower shear stress compared
to the average physiological shear stress levels and also in areas that demonstrate
bifurcations where the shear stress is oscillatory [ 6 , 22 ].
At physiological levels of shear stress, the endothelial cells elongate and orient
themselves parallel to the direction of the flow [ 17 ]. However, at lower levels of shear
stress, the endothelial cells are found to being more rounded in shape [ 17 ]. Interest-
ingly, such a rounded endothelial cell morphology has been observed in atheroscle-
rotic lesions, and this is consistent with the finding that atherosclerosis develops at
branches and bends that are exposed to lower levels of shear stress [ 6 , 22 ].

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6.2 Signalling Pathways Involved in Shear Stress Mediated
Endothelial Activation and Inflammation

Dysfunction of endothelial cells has been believed to be one of the main factors in
initiating the pathogenesis of atherosclerosis [ 25 ]. This dysfunction in turn can lead
to changes in gene expression by the endothelial cells. Various signalling pathways
have been implicated in being upregulated or downregulated following endothelial