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 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 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.

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

Distribution of Mass Transfer Rate and Wall Shear Stress Behind Simple Rectangular Stenosis in Pulsating Flow

1989 ◽  
Vol 111 (1) ◽  
pp. 47-54 ◽  
Author(s):  
R. Yamaguchi
Keyword(s):  
Mass Transfer ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Transfer Rate ◽  
Schmidt Number ◽  
Fluid Dynamic ◽  
Mass Transfer Rate ◽  
Pulsating Flow ◽  
Flow Through ◽  
Wall Shear

The distributions of mass transfer rate and wall shear stress in sinusoidal laminar pulsating flow through a two-dimensional asymmetric stenosed channel have been studied experimentally and numerically. The distributions are measured by the electrochemical method. The measurement is conducted at a Reynolds number of about 150, a Schmidt number of about 1000, a nondimensional pulsating frequency of 3.40, and a nondimensional flow amplitude of 0.3. It is suggested that the deterioration of an arterial wall distal to stenosis may be greatly enhanced by fluid dynamic effects.

Analysis of Flow and Wall Shear Stress in Curvature Induced Dorsal Aneurysms: Effect of Arterial Curvature

2009 ◽  
Author(s):  
Arun Ramu ◽  
Guo-Xiang Wang
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Fluid Dynamic ◽  
Cerebral Arteries ◽  
Cerebral Aneurysms ◽  
Morbidity Rate ◽  
Mortality And Morbidity ◽  
Wall Shear ◽  
Primary Velocity ◽  
The Impact

Intracranial aneurysms are abnormal enlargement in the walls of cerebral arteries. The rupture of aneurysms is the leading cause of subarachnoid hemorrhage (SAH), with a high mortality and morbidity rate. A majority of saccular cerebral aneurysms occur at sites of arterial bifurcations. However, a good percentage of aneurysms are curvature induced and are found along the cavernous arterial segment. The occurrence of such non branching aneurysms, clinically called dorsal aneurysms, can be related to the increased wall shear stress at the curved arteries. The rupture of aneurysms usually occurs at the dome region, which is subjected to reduced wall shear stress (wss) owing to low re-circulating flow. Hence it is important to understand the impact of arterial curvature on the WSS distribution along the dome of aneurysms. Previously, studies have not taken into account the aspect of low WSS along the dome region. In the present 3-d computational fluid dynamic approach, we investigate the impact of varying arterial curvature on spherical dorsal aneurysms. The primary velocity patterns, the WSS distribution along the dome of the aneurysm and the area of increased WSS have been quantified for steady flow conditions.

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.

Differential Gene Expression of Endothelial Cells Under High Wall Shear Stress and Spatial Gradients

2010 ◽  
Author(s):  
Jennifer Dolan ◽  
Song Liu ◽  
Hui Meng ◽  
John Kolega
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Vessel Wall ◽  
Cerebral Aneurysms ◽  
In Vivo Studies ◽  
Spatial Gradient ◽  
Flow Acceleration ◽  
Spatial Gradients ◽  
Wall Shear

In both human and animal models, cerebral aneurysms tend to develop at the apices of bifurcations in the cerebral vasculature. Due to the focal nature of aneurysm development it has long been speculated that hemodynamics are an important factor in aneurysm susceptibility. The local hemodynamics of bifurcations are complex, being characterized by flow impingement causing a high frictional force on the vessel wall known as wall shear stress (WSS) and significant flow acceleration or deceleration, manifested as the positive or negative spatial gradient of WSS (WSSG). In vivo studies have recently identified that aneurysm initiation occurs at areas of the vessel wall that experience a combination of both high WSS and positive WSSG [1,2]

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