scholarly journals Endothelial cells express a unique transcriptional profile under very high wall shear stress known to induce expansive arterial remodeling

2012 ◽  
Vol 302 (8) ◽  
pp. C1109-C1118 ◽  
Author(s):  
Jennifer M. Dolan ◽  
Fraser J. Sim ◽  
Hui Meng ◽  
John Kolega
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Plasminogen Activator ◽  
Transcriptional Profile ◽  
Arterial Remodeling ◽  
Flow Conditions ◽  
Wall Shear ◽  
Very High

Chronic high flow can induce arterial remodeling, and this effect is mediated by endothelial cells (ECs) responding to wall shear stress (WSS). To assess how WSS above physiological normal levels affects ECs, we used DNA microarrays to profile EC gene expression under various flow conditions. Cultured bovine aortic ECs were exposed to no-flow (0 Pa), normal WSS (2 Pa), and very high WSS (10 Pa) for 24 h. Very high WSS induced a distinct expression profile compared with both no-flow and normal WSS. Gene ontology and biological pathway analysis revealed that high WSS modulated gene expression in ways that promote an anti-coagulant, anti-inflammatory, proliferative, and promatrix remodeling phenotype. A subset of characteristic genes was validated using quantitative polymerase chain reaction: very high WSS upregulated ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motif-1), PLAU (urokinase plasminogen activator), PLAT (tissue plasminogen activator), and TIMP3, all of which are involved in extracellular matrix processing, with PLAT and PLAU also contributing to fibrinolysis. Downregulated genes included CXCL5 and IL-8 and the adhesive glycoprotein THBS1 (thrombospondin-1). Expressions of ADAMTS1 and uPA proteins were assessed by immunhistochemistry in rabbit basilar arteries experiencing increased flow after bilateral carotid artery ligation. Both proteins were significantly increased when WSS was elevated compared with sham control animals. Our results indicate that very high WSS elicits a unique transcriptional profile in ECs that favors particular cell functions and pathways that are important in vessel homeostasis under increased flow. In addition, we identify specific molecular targets that are likely to contribute to adaptive remodeling under elevated flow conditions.

scholarly journals Differential gene expression by endothelial cells under positive and negative streamwise gradients of high wall shear stress

2013 ◽  
Vol 305 (8) ◽  
pp. C854-C866 ◽  
Author(s):  
Jennifer M. Dolan ◽  
Hui Meng ◽  
Fraser J. Sim ◽  
John Kolega
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Fluid Dynamic ◽  
Expression Profiles ◽  
Ki 67 ◽  
Flow Acceleration ◽  
Bilateral Carotid ◽  
Wall Shear

Flow impingement at arterial bifurcations causes high frictional force [or wall shear stress (WSS)], and flow acceleration and deceleration in the branches create positive and negative streamwise gradients in WSS (WSSG), respectively. Intracranial aneurysms tend to form in regions with high WSS and positive WSSG. However, little is known about the responses of endothelial cells (ECs) to either positive or negative WSSG under high WSS conditions. We used cDNA microarrays to profile gene expression in cultured ECs exposed to positive or negative WSSG for 24 h in a flow chamber where WSS varied between 3.5 and 28.4 Pa. Gene ontology and biological pathway analysis indicated that positive WSSG favored proliferation, apoptosis, and extracellular matrix processing while decreasing expression of proinflammatory genes. To determine if similar responses occur in vivo, we examined EC proliferation and expression of the matrix metalloproteinase ADAMTS1 under high WSS and WSSG created at the basilar terminus of rabbits after bilateral carotid ligation. Precise hemodynamic conditions were determined by computational fluid dynamic simulations from three-dimensional angiography and mapped on immunofluorescence staining for the proliferation marker Ki-67 and ADAMTS1. Both proliferation and ADAMTS1 were significantly higher in ECs under positive WSSG than in adjacent regions of negative WSSG. Our results indicate that WSSG elicits distinct EC gene expression profiles and particular biological pathways including increased cell proliferation and matrix processing. Such EC responses may be important in understanding the mechanisms of intracranial aneurysm initiation at regions of high WSS and positive WSSG.

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.

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.

Analysis of Laminar Mixed Convective Plumes Along Vertical Adiabatic Surfaces

1984 ◽  
Vol 106 (3) ◽  
pp. 552-557 ◽  
Author(s):  
K. V. Rao ◽  
B. F. Armaly ◽  
T. S. Chen
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Leading Edge ◽  
Vertical Surface ◽  
Stream Velocity ◽  
Thermal Source ◽  
Flow Conditions ◽  
Velocity Overshoot ◽  
Wall Shear ◽  
Prandtl Numbers

Laminar mixed forced and free convection from a line thermal source imbedded at the leading edge of an adiabatic vertical surface is analytically investigated for the cases of buoyancy assisting and buoyancy opposing flow conditions. Temperature and velocity distributions in the boundary layer adjacent to the adiabatic surface are presented for the entire range of the buoyancy parameter ξ (x) = Grx/Rex5/2 from the pure forced (ξ(x) = 0) to the pure free (ξ(x) = ∞) convection regime for fluids having Prandtl numbers of 0.7 and 7.0. For buoyancy-assisting flow, the velocity overshoot, the temperature, and the wall shear stress increase as the plume’s strength increases. On the other hand, the velocity overshoot, the wall shear stress, and the temperature decrease as the free-stream velocity increases. For buoyancy opposing flow, the velocity and wall shear stress decrease but the temperature increases as the plume’s strength increases.

scholarly journals Analysis of the wall shear stress in a generic aneurysm under pulsating and transitional flow conditions

2020 ◽  
Vol 61 (2) ◽  
Author(s):  
Andreas Bauer ◽  
Maximilian Bopp ◽  
Suad Jakirlic ◽  
Cameron Tropea ◽  
Axel Joachim Krafft ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Transitional Flow ◽  
Flow Conditions ◽  
Wall Shear

scholarly journals Targeting functionalized nanoparticles to activated endothelial cells under high wall shear stress

2019 ◽  
Vol 5 (2) ◽  
Author(s):  
Hila Zukerman ◽  
Maria Khoury ◽  
Yosi Shammay ◽  
Josué Sznitman ◽  
Noah Lotan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Functionalized Nanoparticles ◽  
High Wall Shear Stress ◽  
Wall Shear

Inflammatory Response of Endothelial Cells to Wall Shear Stress in Three Dimensional Stenotic Models

2009 ◽  
Author(s):  
Leonie Rouleau ◽  
Joanna Rossi ◽  
Jean-Claude Tardif ◽  
Rosaire Mongrain ◽  
Richard L. Leask
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Three Dimensional ◽  
Realistic Model ◽  
In Vitro Models ◽  
Steady Flows ◽  
Wall Shear

Endothelial cells (ECs) are believed to respond differentially to hemodynamic forces in the vascular tree. Once atherosclerotic plaque has formed in a vessel, the obstruction creates complex spatial gradients in wall shear stress (WSS). In vitro models have used mostly unrealistic and simplified geometries, which cannot reproduce accurately physiological conditions. The objective of this study was to expose ECs to the complex WSS pattern created by an asymmetric stenosis. Endothelial cells were grown and exposed for different times to physiological steady flows in straight dynamic controls and in idealized asymmetric stenosis models. Cell morphology was noticeably different in the regions with spatial WSS gradients, being more randomly oriented and of cobblestone shape. Inflammatory molecule expression was also altered by exposure to shear and endothelial nitric oxide synthase (eNOS) was upregulated by its presence. A regional response in terms of inflammation was observed through confocal microscopy. This work provides a more realistic model to study endothelial cell response to spatial and temporal WSS gradients that are present in vivo and is an important advancement towards a better understanding of the mechanisms involved in coronary artery disease.

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.

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