Effects of Steady Spatial Wall Shear Stress Gradients on Endothelial Cell Morphology in Three-Dimensional Models

2007 ◽  
Author(s):  
Leonie Rouleau ◽  
Monica Farcas ◽  
Jean-Claude Tardif ◽  
Rosaire Mongrain ◽  
Richard Leask
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Wall Shear Stress ◽  
Cell Morphology ◽  
Flow Direction ◽  
Stress Gradient ◽  
Spatial Gradient ◽  
Stress Gradients ◽  
Wall Shear

Endothelial cell (EC) dysfunction has been linked to atherosclerosis through their response to hemodynamic forces. Flow in stenotic vessels creates complex spatial gradients in wall shear stress. In vitro studies examining the effect of shear stress on endothelial cells have used unrealistic and simplified models, which cannot reproduce physiological conditions. The objective of this study was to expose endothelial cells to the complex shear shear pattern created by an asymmetric stenosis. Endothelial cells were grown and exposed for different times to physiological steady flow in straight dynamic controls and in idealized asymmetric stenosis models. Cells subjected to 1D flow aligned with flow direction and had a spindle-like shape when compared to static controls. Endothelial cell morphology was noticeable different in the regions with a spatial gradient in wall shear stress, being more randomly oriented and of cobblestone shape. This occurred despite the presence of an increased magnitude in shear stress. No other study to date has described this morphology in the presence of a positive wall shear stress gradient or gradient of significant shear magnitude. This technique provides a more realistic model to study endothelial cell response to spatial and temporal shear stress gradients that are present in vivo and is an important advancement towards a better understanding of the mechanisms involved in coronary artery disease.

Endothelial Cell Morphologic Response to Asymmetric Stenosis Hemodynamics: Effects of Spatial Wall Shear Stress Gradients

2010 ◽  
Vol 132 (8) ◽  
Author(s):  
Leonie Rouleau ◽  
Monica Farcas ◽  
Jean-Claude Tardif ◽  
Rosaire Mongrain ◽  
Richard L. Leask
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Wall Shear Stress ◽  
Atherosclerotic Plaque ◽  
Morphological Changes ◽  
Stress Gradients ◽  
Spatial Gradients ◽  
Wall Shear

Endothelial cells are known to respond to hemodynamic forces. Their phenotype has been suggested to differ between atheroprone and atheroprotective regions of the vasculature, which are characterized by the local hemodynamic environment. Once an atherosclerotic plaque has formed in a vessel, the obstruction creates complex spatial gradients in wall shear stress. Endothelial cell response to wall shear stress may be linked to the stability of coronary plaques. Unfortunately, in vitro studies of the endothelial cell involvement in plaque stability have been limited by unrealistic and simplified geometries, which cannot reproduce accurately the hemodynamics created by a coronary stenosis. Hence, in an attempt to better replicate the spatial wall shear stress gradient patterns in an atherosclerotic region, a three dimensional asymmetric stenosis model was created. Human abdominal aortic endothelial cells were exposed to steady flow (Re=50, 100, and 200 and τ=4.5 dyn/cm2, 9 dyn/cm2, and 18 dyn/cm2) in idealized 50% asymmetric stenosis and straight/tubular in vitro models. Local morphological changes that occur due to magnitude, duration, and spatial gradients were quantified to identify differences in cell response. In the one dimensional flow regions, where flow is fully developed and uniform wall shear stress is observed, cells aligned in flow direction and had a spindlelike shape when compared with static controls. Morphological changes were progressive and a function of time and magnitude in these regions. Cells were more randomly oriented and had a more cobblestone shape in regions of spatial wall shear stress gradients. These regions were present, both proximal and distal, at the stenosis and on the wall opposite to the stenosis. The response of endothelial cells to spatial wall shear stress gradients both in regions of acceleration and deceleration and without flow recirculation has not been previously reported. This study shows the dependence of endothelial cell morphology on spatial wall shear stress gradients and demonstrates that care must be taken to account for altered phenotype due to geometric features. These results may help explain plaque stability, as cells in shoulder regions near an atherosclerotic plaque had a cobblestone morphology indicating that they may be more permeable to subendothelial transport and express prothrombotic factors, which would increase the risk of atherothrombosis.

scholarly journals Genetic correlates of wall shear stress in a patient-specific 3D-printed cerebral aneurysm model

2019 ◽  
Vol 11 (10) ◽  
pp. 999-1003 ◽  
Author(s):  
Michael R Levitt ◽  
Christian Mandrycky ◽  
Ashley Abel ◽  
Cory M Kelly ◽  
Samuel Levy ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Cerebral Aneurysm ◽  
Cell Morphology ◽  
Patient Specific ◽  
Parent Vessel ◽  
3D Printed ◽  
Wall Shear ◽  
Dynamics Simulations

ObjectivesTo study the correlation between wall shear stress and endothelial cell expression in a patient-specific, three-dimensional (3D)-printed model of a cerebral aneurysm.Materials and methodsA 3D-printed model of a cerebral aneurysm was created from a patient’s angiogram. After populating the model with human endothelial cells, it was exposed to media under flow for 24 hours. Endothelial cell morphology was characterized in five regions of the 3D-printed model using confocal microscopy. Endothelial cells were then harvested from distinct regions of the 3D-printed model for mRNA collection and gene analysis via quantitative polymerase chain reaction (qPCR.) Cell morphology and mRNA measurement were correlated with computational fluid dynamics simulations.ResultsThe model was successfully populated with endothelial cells, which survived under flow for 24 hours. Endothelial morphology showed alignment with flow in the proximal and distal parent vessel and aneurysm neck, but disorganization in the aneurysm dome. Genetic analysis of endothelial mRNA expression in the aneurysm dome and distal parent vessel was compared with the proximal parent vessels. ADAMTS-1 and NOS3 were downregulated in the aneurysm dome, while GJA4 was upregulated in the distal parent vessel. Disorganized morphology and decreased ADAMTS-1 and NOS3 expression correlated with areas of substantially lower wall shear stress and wall shear stress gradient in computational fluid dynamics simulations.ConclusionsCreating 3D-printed models of patient-specific cerebral aneurysms populated with human endothelial cells is feasible. Analysis of these cells after exposure to flow demonstrates differences in both cell morphology and genetic expression, which correlate with areas of differential hemodynamic stress.

scholarly journals Neutrophil Adhesion on Endothelial Cells in a Novel Asymmetric Stenosis Model: Effect of Wall Shear Stress Gradients

2010 ◽  
Vol 38 (9) ◽  
pp. 2791-2804 ◽  
Author(s):  
Leonie Rouleau ◽  
Ian B. Copland ◽  
Jean-Claude Tardif ◽  
Rosaire Mongrain ◽  
Richard L. Leask
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Neutrophil Adhesion ◽  
Stress Gradients ◽  
Wall Shear

Intracranial Aneurysms Occur More Frequently at Bifurcation Sites That Typically Experience Higher Hemodynamic Stresses

Neurosurgery ◽  
2013 ◽  
Vol 73 (3) ◽  
pp. 497-505 ◽  
Author(s):  
Jaclyn M. Alfano ◽  
John Kolega ◽  
Sabareesh K. Natarajan ◽  
Jianping Xiang ◽  
Rocco A. Paluch ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Intracranial Aneurysms ◽  
Stress Gradient ◽  
Spatial Gradient ◽  
Impact Zone ◽  
Wall Shear ◽  
A Site ◽  
The Impact ◽  
Hemodynamic Stresses

Abstract BACKGROUND: Intracranial aneurysms (IAs) occur more frequently at certain bifurcations than at others. Hemodynamic stress, which promotes aneurysm formation in animal models, also differs among bifurcations, depending on flow and vessel geometry. OBJECTIVE: To determine whether locations that are more likely to develop IAs experience different hemodynamic stresses that might contribute to higher IA susceptibility. METHODS: We characterized the hemodynamic microenvironment at 10 sites in or around the circle of Willis where IAs commonly occur and examined statistical relationships between hemodynamic factors and the tendency for a site to form IAs. The tendency for each site to develop IAs was quantified on the basis of the site distribution from systematic literature analysis of 19 reports including 26 418 aneurysms. Hemodynamic parameters for these sites were derived from image-based computational fluid dynamics of 114 cerebral bifurcations from 31 individuals. Wall shear stress and its spatial gradient were calculated in the impact zone surrounding the bifurcation apex. Linear and exponential regression analyses evaluated correlations between the tendency for IA formation and the typical hemodynamics of a site. RESULTS: IA susceptibility significantly correlated with the magnitudes of wall shear stress and positive wall shear stress gradient within the hemodynamic impact zone calculated for each site. CONCLUSION: IAs occur more frequently at cerebral bifurcations that typically experience higher hemodynamic shear stress and stronger flow acceleration, conditions previously shown to promote aneurysm initiation in animals.

Effect of Statins and Wall Shear Stress on Endothelial Cells: Morphology and F-Actin Cytoskeleton Arrangement

2012 ◽  
Author(s):  
Melissa Dick ◽  
Richard L. Leask
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Wall Shear Stress ◽  
Actin Cytoskeleton ◽  
Cell Function ◽  
Endothelial Cell Function ◽  
Wall Shear ◽  
Static Conditions ◽  
Statin Drugs

Wall shear stress and statin drugs have both been shown to influence endothelial cell function. We investigated the effect of statins on the morphology and F-actin cytoskeleton arrangement of endothelial cells with and without wall shear stress. Under static conditions, statins caused cells to become rounded and disorganized the F-actin cytoskeleton. Wall shear stress abrogated the morphological effects, but did not reverse the cytoskeleton disorganization.

Flow Input Waveform Effects on the Temporal and Spatial Wall Shear Stress Gradients in a Femoral Graft-Artery Connector

1996 ◽  
Vol 118 (4) ◽  
pp. 506-510 ◽  
Author(s):  
C. Kleinstreuer ◽  
M. Lei ◽  
J. P. Archie
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Computer Aided Design ◽  
Graft Failure ◽  
Stress Gradient ◽  
Three Dimensional ◽  
Stress Gradients ◽  
Early Graft ◽  
Wall Shear ◽  
Femoral Graft

Employing a validated finite volume code, a computer-aided design of the distal end of a femoral graft-artery junction has been considered to simulate transient three-dimensional blood flow for various flow input waveforms. The study relies on the hypothesis that large sustained wall shear stress gradients play a major role in the rapid recurrence of intimal hyperplasia plus atheroma after bypass surgery, leading to early graft failure. Two new dimensionless parameters have been introduced to correlate flow waveform characteristics with the severity of nonuniform hemodynamics and hence the potential risk for restenosis. The transient and, more importantly, the time-averaged wall shear stress gradient distributions shown, map out the junction areas which are still susceptible to restenosis, especially the toe region. Future geometric modifications will further reduce disturbed flow patterns and hence the probability of graft failure.

Micro-PIV and CFD Studies Show Non-Uniform Wall Shear Stress Distributions Over Endothelial Cells

2010 ◽  
Author(s):  
Sharul S. Dol ◽  
M. Mehdi Salek ◽  
Kayla D. Viegas ◽  
Kristina D. Rinker ◽  
Robert J. Martinuzzi
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Wall Shear Stress ◽  
Cultured Cells ◽  
Flow Chamber ◽  
Shear Stresses ◽  
Stress Distributions ◽  
Micro Piv ◽  
Wall Shear

Wall shear stress acting on arterial walls is an important hemodynamic force determining vessel health. A parallel-plate flow chamber with a 127 μm-thick flow channel is used as an in vitro system to study the fluid mechanics environment. It is essential to know how well this flow chamber performs in emulating physiologic flow regimes especially when cultured cells are present. Hence, the objectives of this work are to computationally and experimentally study the characteristic of the flow chamber in providing a defined flow regime and shear stress to cultured cells and to map wall shear stress distributions in the presence of an endothelial cell layer. Experiments and modeling were performed for the nominal wall shear stresses of 2 and 10 dyn/cm2. Without endothelial cells, the flow field is uniform over 95% of the chamber cross-section and the surfaces are exposed to the target stress level. Using PIV velocity data, the endothelial cell surfaces were re-constructed and flow over these surfaces was then simulated via FLUENT. Once endothelial cells are introduced, local shear variations are large and the velocity profiles are no longer uniform. Due to the velocity distribution between peaks and valleys, the local wall shear stresses range between 47–164% of the nominal values. This study demonstrates the non-uniform shear stress distribution over the cells is non-negligible especially in small vessels or where blockage is important.

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