Effects of Disturbed Flow On Endothelial Cells

1998 ◽  
Vol 120 (1) ◽  
pp. 2-8 ◽  
Author(s):  
J.-J. Chiu ◽  
D. L. Wang ◽  
S. Chien ◽  
R. Skalak ◽  
S. Usami
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Flow Direction ◽  
Arterial System ◽  
Shear Stresses ◽  
Stress Distributions ◽  
Complex Flow ◽  
Local Flow ◽  
Atherosclerotic Lesions

Atherosclerotic lesions tend to localize at curvatures and branches of the arterial system, where the local flow is often disturbed and irregular (e.g., flow separation, recirculation, complex flow patterns, and nonuniform shear stress distributions). The effects of such flow conditions on cultured human umbilical vein endothelial cells (HUVECs) were studied in vitro by using a vertical-step flow channel (VSF). Detailed shear stress distributions and flow structures have been computed by using the finite volume method in a general curvilinear coordinate system. HUVECs in the reattachment areas with low shear stresses were generally rounded in shape. In contrast, the cells under higher shear stresses were significantly elongated and aligned with the flow direction, even for those in the area with reversed flow. When HUVECs were subjected to shearing in VSF, their actin stress fibers reorganized in association with the morphological changes. The rate of DNA synthesis in the vicinity of the flow reattachment area was higher than that in the laminar flow area. These in vitro experiments have provided data for the understanding of the in vivo responses of endothelial cells under complex flow environments found in regions of prevalence of atherosclerotic lesions.

scholarly journals Activation of integrin α5 mediated by flow requires its translocation to membrane lipid rafts in vascular endothelial cells

2016 ◽  
Vol 113 (3) ◽  
pp. 769-774 ◽  
Author(s):  
Xiaoli Sun ◽  
Yi Fu ◽  
Mingxia Gu ◽  
Lu Zhang ◽  
Dan Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Density Lipoprotein ◽  
Membrane Lipid ◽  
Local Flow ◽  
Atherosclerotic Lesions ◽  
Integrin Α5

Local flow patterns determine the uneven distribution of atherosclerotic lesions. Membrane lipid rafts and integrins are crucial for shear stress-regulated endothelial function. In this study, we investigate the role of lipid rafts and integrin α5 in regulating the inflammatory response in endothelial cells (ECs) under atheroprone versus atheroprotective flow. Lipid raft proteins were isolated from ECs exposed to oscillatory shear stress (OS) or pulsatile shear stress, and then analyzed by quantitative proteomics. Among 396 proteins redistributed in lipid rafts, integrin α5 was the most significantly elevated in lipid rafts under OS. In addition, OS increased the level of activated integrin α5 in lipid rafts through the regulation of membrane cholesterol and fluidity. Disruption of F-actin-based cytoskeleton and knockdown of caveolin-1 prevented the OS-induced integrin α5 translocation and activation. In vivo, integrin α5 activation and EC dysfunction were observed in the atheroprone areas of low-density lipoprotein receptor-deficient (Ldlr−/−) mice, and knockdown of integrin α5 markedly attenuated EC dysfunction in partially ligated carotid arteries. Consistent with these findings, mice with haploinsufficency of integrin α5 exhibited a reduction of atherosclerotic lesions in the regions under atheroprone flow. The present study has revealed an integrin- and membrane lipid raft-dependent mechanotransduction mechanism by which atheroprone flow causes endothelial dysfunction.

The Elongation and Orientation of Cultured Endothelial Cells in Response to Shear Stress

1985 ◽  
Vol 107 (4) ◽  
pp. 341-347 ◽  
Author(s):  
M. J. Levesque ◽  
R. M. Nerem
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Cell Elongation ◽  
Vascular Endothelial Cells ◽  
Flow Direction ◽  
Flow Chamber ◽  
Shear Stresses ◽  
Cell Alignment ◽  
Aortic Endothelial Cells ◽  
Time Required

Vascular endothelial cells appear to be aligned with the flow in the immediate vicinity of the arterial wall and have a shape which is more ellipsoidal in regions of high shear and more polygonal in regions of low shear stress. In order to study quantitatively the nature of this response, bovine aortic endothelial cells grown on Thermanox plastic coverslips were exposed to shear stress levels of 10, 30, and 85 dynes/cm2 for periods up to 24 hr using a parallel plate flow chamber. A computer-based analysis system was used to quantify the degree of cell elongation with respect to the change in cell angle of orientation and with time. The results show that (i) endothelial cells orient with the flow direction under the influence of shear stress, (ii) the time required for cell alignment with flow direction is somewhat longer than that required for cell elongation, (iii) there is a strong correlation between the degree of alignment and endothelial cell shape, and (iv) endothelial cells become more elongated when exposed to higher shear stresses.

Wall Shear Stress Measurements in an Arterial Flow Bioreactor

2011 ◽  
Author(s):  
Elizabeth Voigt ◽  
Cara Buchanan ◽  
Jaime Schmieg ◽  
M. Nichole Rylander ◽  
Pavlos Vlachos
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Vascular System ◽  
Vascular Endothelial Cells ◽  
Shear Stresses ◽  
Bulk Flow Rate ◽  
Wall Shear ◽  
Endothelial Cell Response ◽  
And Function

Physiological flow parameters such as pressure and stress inside the vascular system strongly influence the physiology and function of vascular endothelial cells [1]. Variations in the shear stress experienced by endothelial cells affect morphology, alignment with the flow, mechanical strength, rate of proliferation, and gene expression [2]. Although it is known that these factors are dependent on the hemodynamics of the flow, the relationship has not been accurately quantified. In vitro bioreactor flow loops have been developed to simulate vascular flow for tissue conditioning and measurement of the endothelial cell response to varying shear [3–5]; however, wall shear stresses (WSS) have been estimated from the bulk flow rate by assuming Poiseuille flow [2, 6]. Due to the pulsatility of the flow, biochemical interactions, and the typically short vessel length, this assumption is fundamentally incorrect; however, the level of inaccuracy has not been quantified.

The Effects of Shear Stress on Endothelial Cells at Hypothermic Temperatures

2002 ◽  
Author(s):  
John H. Slater ◽  
Shailendra Jain ◽  
Robin N. Coger ◽  
Charles Y. Lee
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Low Flow ◽  
Shear Stresses ◽  
Liver Sinusoids ◽  
Endothelial Cell Cultures ◽  
Shear Stress Response

Hypothermic machine perfusion preservation (MPP) has proven to be a successful technique for hypothermic kidney storage, however this technology has not successfully been applied to the liver. Recent research has indicated that the endothelial cells lining the liver sinusoids display rounding phenomena during MPP that is not fully understood. In order to gain a better understanding of endothelial cell shear stress response and the factors that induce rounding, a temperature-controlled micro-shear chamber has been designed and fabricated. The micro-shear chamber has been used to apply shear stresses, corresponding to those imposed during MPP, to rat liver primary endothelial cell cultures in order to form an understanding of how these stresses affect endothelial cell morphology. The chamber allows for the application of shear stresses ranging from 0.2 ± .01 dynes/cm2 to 2.3 ± 0.3 dynes/cm2, corresponding to what occurs during MPP.] Twenty-four hour in vitro experiments with shear stresses ranging from 0 to 1.49 dynes/cm2 at 4 °C were conducted in order to replicate in vivo conditions of the liver during hypothermic MPP. It has been demonstrated that endothelial cell rounding increases with increasing shear and can be prevented by utilizing low flow rates.

3-D Stress Analysis in Cultured Endothelial Cells Exposed to Fluid Shear Stress

1999 ◽  
Author(s):  
T. Ohashi ◽  
H. Sugawara ◽  
Y. Ishii ◽  
M. Sato
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Cell Surface ◽  
Fluid Shear Stress ◽  
Flow Direction ◽  
Stress Distributions ◽  
Fluid Shear ◽  
Surface Geometry ◽  
Cultured Endothelial Cells

Abstract Under fluid shear stress, applied both in vivo and in vitro, vascular endothelial cells show morphological changes. After applying shear stress, cultured endothelial cells showed elongation and orientation to the flow direction (Kataoka et al., 1998). Moreover, statistical image analysis showed that intercellular F-actin distributions were confirmed to change depending on the shear stress and the flow direction. Thus, the endothelial cell morphology relates closely with the cytoskeletal structures. Intercellular stress distributions in the cells may be also accompanied by the reorganization of cytoskeletal structures. The use of both atomic force microscopy measurements (AFM) of endothelial cell surface topography and computational fluid dynamics of shear stress distributions acting on the cell surface, it has revealed that the surface geometry defined the detailed distribution of shear stress (Davies et al., 1995).

Endothelial Cell Migration in Patient-Specific Models of Intracranial Aneurysm

2010 ◽  
Author(s):  
Liang-Der Jou
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Morphological Changes ◽  
Critical Role ◽  
Endothelial Cell Migration ◽  
Patient Specific ◽  
Shear Stresses ◽  
Wall Shear

Effects of wall shear stress on atherosclerotic disease are widely studied, but its effects on intracranial aneurysms are less clear. In vitro studies have demonstrated that endothelial cells (EC) go through morphological changes under abnormal wall shear stress, and these studies have also shown that abnormal wall shear stresses lead to a non-uniform EC distributions [1, 2]. Since endothelial cells play a critical role in mechanotransduction, a sub-optimal distribution of EC may affect remodeling of vessel wall.

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.

scholarly journals Endothelial Cell Orientation and Polarity Are Controlled by Shear Stress and VEGF Through Distinct Signaling Pathways

2021 ◽  
Vol 11 ◽  
Author(s):  
Anne-Clémence Vion ◽  
Tijana Perovic ◽  
Charlie Petit ◽  
Irene Hollfinger ◽  
Eireen Bartels-Klein ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Flow Direction ◽  
Mutant Mice ◽  
Chemical Stimulus ◽  
Cell Orientation ◽  
Vegfr2 Signaling

Vascular networks form, remodel and mature under the influence of multiple signals of mechanical or chemical nature. How endothelial cells read and interpret these signals, and how they integrate information when they are exposed to both simultaneously is poorly understood. Here, we show using flow-induced shear stress and VEGF-A treatment on endothelial cells in vitro, that the response to the magnitude of a mechanical stimulus is influenced by the concentration of a chemical stimulus, and vice versa. By combining different flow levels and different VEGF-A concentrations, front-rear polarity of endothelial cells against the flow direction was established in a flow and VEGF-A dose-response while their alignment with the flow displayed a biphasic response depending on the VEGF-A dose (perpendicular at physiological dose, aligned at no or pathological dose of VEGF-A). The effect of pharmaceutical inhibitors demonstrated that while VEGFR2 is essential for both polarity and orientation establishment in response to flow with and without VEGF-A, different downstream effectors were engaged depending on the presence of VEGF-A. Thus, Src family inhibition (c-Src, Yes, Fyn together) impaired alignment and polarity without VEGF-A while FAK inhibition modified polarity and alignment only when endothelial cells were exposed to VEGF-A. Studying endothelial cells in the aortas of VEGFR2Y949F mutant mice and SRCiEC–KO mice confirmed the role of VEGFR2 and specified the role of c-SRC in vivo. Endothelial cells of VEGFR2Y949F mutant mice lost their polarity and alignment while endothelial cells from SRCiEC–KO mice only showed reduced polarity. We propose here that VEGFR2 is a sensor able to integrate chemical and mechanical information simultaneously and that the underlying pathways and mechanisms activated will depend on the co-stimulation. Flow alone shifts VEGFR2 signaling toward a Src family pathway activation and a junctional effect (both in vitro and in vivo) while flow and VEGF-A together shift VEGFR2 signaling toward focal adhesion activation (in vitro) both modifying cell responses that govern orientation and polarity.

scholarly journals Disturbed Flow Induces Endothelial Dysfunction by Regulating Thioredoxin-Interacting Protein-Mediated Mitochondrial Energy Homoeostasis

2021 ◽  
Author(s):  
Yongshun Wang ◽  
Jingjin Liu ◽  
Xin Sun ◽  
Jie Yuan ◽  
Huadong Liu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Dysfunction ◽  
Energy Homeostasis ◽  
Glucose Utilization ◽  
Shear Stresses ◽  
No Production ◽  
Disturbed Flow ◽  
Structural Wall

Abstract Endothelial cells are highly sensitive to hemodynamic shear stresses, which act in the blood flow’s direction on the blood vessel’s luminal surface. Endothelial cells on that surface, thusly, are exposed to various physiological and pathological stimuli, such as disturbed flow-induced shear stress, which may exert effects on adaptive vascular diameter or structural wall remodeling. Here we showed that human endothelial cells exposed to disturbed flow exhibited increased levels of thioredoxin-interactive protein (TXNIP) in vitro. On the other hand, deletion of human endothelial TXNIP increased capillary formation, NO production and mitochondrial function, as well as lessened oxidative stress response and endothelial cell inflammation. Additional beneficial impacts from TXNIP deletion were also seen in a glucose utilization study, as reflected by augmented glucose uptake, lactate secretion and extracellular acidification rate. Taken together, our results suggested that TXNIP is a key component involved in mediating shear stress-induced inflammation, energy homeostasis, and glucose utilization, ultimately establishing it as a potentially novel endothelial dysfunction regulator.

FSI SIMULATION OF A HEALTHY CORONARY BIFURCATION FOR STUDYING THE MECHANICAL STIMULI OF ENDOTHELIAL CELLS UNDER DIFFERENT PHYSIOLOGICAL CONDITIONS

2015 ◽  
Vol 15 (05) ◽  
pp. 1550089 ◽  
Author(s):  
HOSSEIN ALI PAKRAVAN ◽  
MOHAMMAD SAID SAIDI ◽  
BAHAR FIROOZABADI
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Flow Direction ◽  
Mechanical Stimuli ◽  
Coronary Bifurcation ◽  
Physiological Conditions ◽  
Atherosclerotic Lesions ◽  
Wall Shear ◽  
And Function

Atherosclerosis is a world-spread and well-known disease. This disease strongly relates to the endothelial cells (ECs) function. Normally, the endothelial cells align in the flow direction in the atheroprotected sites; however, in the case of atheroprone sites these cells orient randomly. The mechanical stimuli such as wall shear stress and strains could determine the morphology and function of the endothelial cells. In the present study, we numerically simulated the left main coronary artery (LCA) and its branches to left anterior descending (LAD) and left circumflex coronary (LCX) artery using fluid–structure interaction (FSI) modeling. The results were presented as longitudinal and circumferential strains of ECs as well as wall shear stress. Wide ranges of heart rate, cardiac motion, systolic and diastolic pressures were considered and their effects on mechanical stimuli were described in detail. The results showed that these factors could greatly influence the risk of atherosclerosis and the location of atherosclerotic lesions.

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