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Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress.

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TLDR
These studies confirm earlier findings under steady flow conditions that plaques tend to form in areas of low, rather than high, shear stress, but indicate in addition that marked oscillations in the direction of wall shear may enhance atherogenesis.
Abstract
Fluid velocities were measured by laser Doppler velocimetry under conditions of pulsatile flow in a scale model of the human carotid bifurcation. Flow velocity and wall shear stress at five axial and four circumferential positions were compared with intimal plaque thickness at corresponding locations in carotid bifurcations obtained from cadavers. Velocities and wall shear stresses during diastole were similar to those found previously under steady flow conditions, but these quantities oscillated in both magnitude and direction during the systolic phase. At the inner wall of the internal carotid sinus, in the region of the flow divider, wall shear stress was highest (systole = 41 dynes/cm2, diastole = 10 dynes/cm2, mean = 17 dynes/cm2) and remained unidirectional during systole. Intimal thickening in this location was minimal. At the outer wall of the carotid sinus where intimal plaques were thickest, mean shear stress was low (-0.5 dynes/cm2) but the instantaneous shear stress oscillated between -7 and +4 dynes/cm2. Along the side walls of the sinus, intimal plaque thickness was greater than in the region of the flow divider and circumferential oscillations of shear stress were prominent. With all 20 axial and circumferential measurement locations considered, strong correlations were found between intimal thickness and the reciprocal of maximum shear stress (r = 0.90, p less than 0.0005) or the reciprocal of mean shear stress (r = 0.82, p less than 0.001). An index which takes into account oscillations of wall shear also correlated strongly with intimal thickness (r = 0.82, p less than 0.001). When only the inner wall and outer wall positions were taken into account, correlations of lesion thickness with the inverse of maximum wall shear and mean wall shear were 0.94 (p less than 0.001) and 0.95 (p less than 0.001), respectively, and with the oscillatory shear index, 0.93 (p less than 0.001). These studies confirm earlier findings under steady flow conditions that plaques tend to form in areas of low, rather than high, shear stress, but indicate in addition that marked oscillations in the direction of wall shear may enhance atherogenesis.

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Citations
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The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: A “bumper-car” model

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Does low and oscillatory wall shear stress correlate spatially with early atherosclerosis? A systematic review

TL;DR: A systematic review of papers that compare the localization of atherosclerotic lesions with the distribution of haemodynamic indicators calculated using computational fluid dynamics showed that although many articles claim their results conform to the low/oscillatory shear theory, it has been interpreted in different ways.
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Oscillatory shear stress stimulates endothelial production of O2- from p47phox-dependent NAD(P)H oxidases, leading to monocyte adhesion.

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Shear Stress Modulates Expression of Cu/Zn Superoxide Dismutase in Human Aortic Endothelial Cells

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Fluid Shear Stress Stimulates Mitogen-Activated Protein Kinase in Endothelial Cells

TL;DR: It is proposed that flow activates two signal-transduction pathways in endothelial cells, one of which is Ca2+ dependent and involves activation of phospholipase C and increases in intracellular Ca2+.
References
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Journal ArticleDOI

Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress.

TL;DR: It is concluded that in the human carotid bifurcation, regions of moderate to high shear stress, where flow remains unidirectional and axially aligned, are relatively spared of intimal thickening.
Journal ArticleDOI

Atheroma and arterial wall shear. Observation, correlation and proposal of a shear dependent mass transfer mechanism for atherogenesis.

TL;DR: It appears that wall shear rate may be a major controlling factor in the development of atheromatous lesions in man and in animals and a net flux of cholesterol from blood to wall cannot account for the observed normally occurring (quasi-steady state) and experimentally induced atheroma.
Journal ArticleDOI

The dynamic response of vascular endothelial cells to fluid shear stress.

TL;DR: Preliminary studies indicate that certain endothelial cell functions, including fluid endocytosis, cytoskeletal assembly and nonthrombogenic surface properties, also are sensitive to shear stress, which suggests that fluid mechanical forces can directly influence endothelialcell structure and function.
Journal ArticleDOI

Correlation between intimal thickness and fluid shear in human arteries

TL;DR: It is suggested that large excursions of interfacial shear, at levels too low to cause damage, may inhibit intimal thickening.
Journal ArticleDOI

Vascular endothelial morphology as an indicator of the pattern of blood flow.

TL;DR: The results obtained to date suggest that endothelial cell morphology and orientation around a branch vessel may be a natural marker or indicator of the detailed features of blood flow.
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