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.

scholarly journals Investigation of Wall Shear Stress in Cardiovascular Research and in Clinical Practice—From Bench to Bedside

2021 ◽  
Vol 22 (11) ◽  
pp. 5635
Author(s):  
Katharina Urschel ◽  
Miyuki Tauchi ◽  
Stephan Achenbach ◽  
Barbara Dietel
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Cell Function ◽  
Computational Techniques ◽  
Apical Surface ◽  
Cardiovascular Research ◽  
Endothelial Cell Function ◽  
Wall Shear

In the 1900s, researchers established animal models experimentally to induce atherosclerosis by feeding them with a cholesterol-rich diet. It is now accepted that high circulating cholesterol is one of the main causes of atherosclerosis; however, plaque localization cannot be explained solely by hyperlipidemia. A tremendous amount of studies has demonstrated that hemodynamic forces modify endothelial athero-susceptibility phenotypes. Endothelial cells possess mechanosensors on the apical surface to detect a blood stream-induced force on the vessel wall, known as “wall shear stress (WSS)”, and induce cellular and molecular responses. Investigations to elucidate the mechanisms of this process are on-going: on the one hand, hemodynamics in complex vessel systems have been described in detail, owing to the recent progress in imaging and computational techniques. On the other hand, investigations using unique in vitro chamber systems with various flow applications have enhanced the understanding of WSS-induced changes in endothelial cell function and the involvement of the glycocalyx, the apical surface layer of endothelial cells, in this process. In the clinical setting, attempts have been made to measure WSS and/or glycocalyx degradation non-invasively, for the purpose of their diagnostic utilization. An increasing body of evidence shows that WSS, as well as serum glycocalyx components, can serve as a predicting factor for atherosclerosis development and, most importantly, for the rupture of plaques in patients with high risk of coronary heart disease.

Study on Velocity Distribution Estimation Using Blood Pressure Data Based on the Coupled Wave Theory of Elastic Pipes and Fluids

2019 ◽  
Author(s):  
Takeshi Tokunaga ◽  
Koji Mori ◽  
Hiroko Kadowaki ◽  
Takashi Saito
Keyword(s):  
Blood Pressure ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Wall Shear Stress ◽  
Cell Function ◽  
Wave Theory ◽  
Pressure Data ◽  
Endothelial Cell Function ◽  
Blood Pressure Data ◽  
Wall Shear

Abstract Cardiovascular disease that is one of Non-Communicable Disease accounts for about 25% of death in Japan. Prevention of arteriosclerosis that is a main cause of cardiovascular disease is important. Since an early lesions of arteriosclerosis progress as functional change of an endothelial cell that is uniformly distributed on the luminal surface of a blood vessel, an accurate evaluation of the endothelial cell function is important as prevention of the arteriosclerosis. Although Flow-Mediated Dilation (FMD) is widely used as a diagnosis of the endothelial cell function in clinic, it is an evaluation method that uses a static diameter of a blood vessel. Moreover, it isn’t possible to take into account individual difference of a wall shear stress on the endothelial cell. In previous study, it is found that an evoked hyperemic wall shear stress is a major correlate of %FMD. In order to accurately measure the endothelial cell function, it is necessary to simply assess the hyperemic shear stress during FMD. However, it is difficult to non-invasively measure the hyperemic shear stress on the endothelial cell in clinic. In this study, we focused on a blood pressure data that is obtained non-invasively and formulated a relationship between the pressure and a flow velocity based on the coupled wave theory. And we estimated a hyperemic shear stress by using a blood pressure data that is obtained by a tonometry method in experiment that simulate FMD. As a result of estimating the hyperemic shear stress, it reflected characteristics of blood flow in clinic. It may be necessary to consider the hyperemic pressure fluctuation that is waves including low frequency components. Moreover, the hyperemic pressure fluctuation should not be treated as a waveform that has individually different a static pressure in estimation of the hyperemic wall shear stress.

Concentration of blood-borne agonists at the endothelium

2005 ◽  
Vol 462 (2066) ◽  
pp. 671-688 ◽  
Author(s):  
M.J Plank ◽  
A Comerford ◽  
T David ◽  
D.J.N Wall
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Wall Shear Stress ◽  
Mass Transport ◽  
Vascular Disease ◽  
Cell Function ◽  
Endothelial Cell Function ◽  
Dimensional Flow ◽  
Wall Shear

The delivery of endothelial ligands and macromolecules, such as lipoproteins, from the circulation to the arterial wall is of central importance in modulating endothelial cell function and physiology and, consequently, in the onset of vascular disease. Given the strong spatial correlation between areas of disturbed blood flow and occurrence of atherosclerotic plaque, a detailed understanding of the effects of different fluid flow characteristics on the delivery of factors in the bloodstream to the endothelium is an essential step towards understanding the observed localization of vascular disease to certain focal sites within the vasculature. In this paper, a model of biochemical mass transport in a two-dimensional flow chamber with spatially varying wall shear stress is presented. The advantage of the relatively simple arterial geometry is that all the essential features of blood flow in vivo are captured, but the underlying effects on mass transport, and, hence, on endothelial cell function, are not masked by complex three-dimensional flow. Indeed, it is demonstrated that a previously derived similarity solution, in terms of the shear stress on the endothelial wall, is an asymptotically close approximation to the exact solution to the advection–diffusion equation. The mathematical analysis is then used to identify fundamental links between the wall shear stress and the distribution of chemical species along the endothelium. The physiological implications of these links are discussed, in particular the location of maximum chemical concentration on the endothelium, which is of great significance to the regulation of intracellular signalling and, consequently, endothelial cell function.

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.

High Glucose Alters Endothelial Cell Response to Shear Stress

2009 ◽  
Author(s):  
Steven F. Kemeny ◽  
Alisa Morss Clyne
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Blood Vessels ◽  
Cell Mechanics ◽  
High Glucose ◽  
Fluid Shear Stress ◽  
Cell Function ◽  
Focal Adhesions ◽  
Endothelial Cell Function

Endothelial cells line the walls of all blood vessels, where they maintain homeostasis through control of vascular tone, permeability, inflammation, and the growth and regression of blood vessels. Endothelial cells are mechanosensitive to fluid shear stress, elongating and aligning in the flow direction [1–2]. This shape change is driven by rearrangement of the actin cytoskeleton and focal adhesions [2]. Hyperglycemia, a hallmark of diabetes, affects endothelial cell function. High glucose has been shown to increase protein kinase C, formation of glucose-derived advanced glycation end-products, and glucose flux through the aldose reductase pathway within endothelial cells [3]. These changes are thought to be related to increased reactive oxygen species production [4]. While endothelial cell mechanics have been widely studied in healthy conditions, many disease states have yet to be explored. Biochemical alterations related to high glucose may alter endothelial cell mechanics.

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 The LINC complex is required for endothelial cell adhesion and adaptation to shear stress and cyclic stretch

2021 ◽  
pp. mbc.E20-11-0698
Author(s):  
Kevin B. Denis ◽  
Jolene I. Cabe ◽  
Brooke E. Danielsson ◽  
Katie V. Tieu ◽  
Carl R. Mayer ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
Cell Function ◽  
Dominant Negative ◽  
Cyclic Stretch ◽  
Linc Complex ◽  
Endothelial Cell Function ◽  
Altered Cell

The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex is a structure consisting of nesprin, SUN, and lamin proteins. A principal function of the LINC complex is anchoring the nucleus to the actin, microtubule, and intermediate filament cytoskeletons. The LINC complex is present in nearly all cell types, including endothelial cells. Endothelial cells line the inner most surfaces of blood vessels, and are critical for blood vessel barrier function. In addition, endothelial cells have specialized functions, including adaptation to the mechanical forces of blood flow. Previous studies have shown that depletion of individual nesprin isoforms results in impaired endothelial cell function. To further investigate the role of the LINC complex in endothelial cells we utilized dominant negative KASH (DN-KASH), a dominant negative protein which displaces endogenous nesprins from the nuclear envelope and disrupts nuclear-cytoskeletal connections. Endothelial cells expressing DN-KASH had altered cell-cell adhesion and barrier function, as well as altered cell-matrix adhesion and focal adhesion dynamics. In addition, cells expressing DN-KASH failed to properly adapt to shear stress or cyclic stretch. DN-KASH expressing cells exhibited impaired collective cell migration in wound healing and angiogenesis assays. Our results demonstrate the importance of an intact LINC complex in endothelial cell function and homeostasis. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]

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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