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

Author(s):  
Leonie Rouleau ◽  
Joanna Rossi ◽  
Jean-Claude Tardif ◽  
Rosaire Mongrain ◽  
Richard L. Leask

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.

2021 ◽  
Vol 22 (11) ◽  
pp. 5635
Author(s):  
Katharina Urschel ◽  
Miyuki Tauchi ◽  
Stephan Achenbach ◽  
Barbara Dietel

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.


Author(s):  
Risa Robinson ◽  
Lynn Fuller ◽  
Harvey Palmer ◽  
Mary Frame

Blood flow regulation in the microvascular network has been investigated by means of computational fluid dynamics, in vivo particle tracking and microchannel models. It is evident from these studies that shear stress along the wall is a key factor in the communication network that results in blood flow modification, yet current methods for shear stress determination are acknowledged to be imprecise. Micromachining technology allows for the development of implantable shear stress sensors that will enable us to monitor wall shear stress at multiple locations in arteriole bifurcations. In this study, a microchannel was employed as an in vitro model of a microvessel. Thermal shear stress sensors were used to mimic the endothelial cells that line the vessel wall. A three dimensional computational model was created to simulate the system’s thermal response to the constant temperature control circuit and related wall shear stress. The model geometry included a silicon wafer section with all the fabrication layers — silicon dioxide, poly silicon resistor, silicon nitride — and a microchannel with cross section 17 μm × 17 μm. This computational technique was used to optimize the dimensions of the system for a 0.01 Reynolds number flow at room temperature in order to reduce the amount of heat lost to the substrate and to predict and maximize the signal response. Results of the design optimization are presented and the fabrication process discussed.


2009 ◽  
Vol 7 (42) ◽  
pp. 91-103 ◽  
Author(s):  
C. Poelma ◽  
K. Van der Heiden ◽  
B. P. Hierck ◽  
R. E. Poelmann ◽  
J. Westerweel

In order to study the role of blood–tissue interaction in the developing chicken embryo heart, detailed information about the haemodynamic forces is needed. In this study, we present the first in vivo measurements of the three-dimensional distribution of wall shear stress (WSS) in the outflow tract (OFT) of an embryonic chicken heart. The data are obtained in a two-step process: first, the three-dimensional flow fields are measured during the cardiac cycle using scanning microscopic particle image velocimetry; second, the location of the wall and the WSS are determined by post-processing flow velocity data (finding velocity gradients at locations where the flow approaches zero). The results are a three-dimensional reconstruction of the geometry, with a spatial resolution of 15–20 µm, and provides detailed information about the WSS in the OFT. The most significant error is the location of the wall, which results in an estimate of the uncertainty in the WSS values of 20 per cent.


ASAIO Journal ◽  
2018 ◽  
Vol 64 (2) ◽  
pp. 211-217 ◽  
Author(s):  
Amanda K. W. Buck ◽  
Joseph J. Groszek ◽  
Daniel C. Colvin ◽  
Sara B. Keller ◽  
Clark Kensinger ◽  
...  

2010 ◽  
Vol 132 (8) ◽  
Author(s):  
Leonie Rouleau ◽  
Monica Farcas ◽  
Jean-Claude Tardif ◽  
Rosaire Mongrain ◽  
Richard L. Leask

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.


Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2010
Author(s):  
Milos Kasparek ◽  
Ludmila Novakova ◽  
Jan Malik

Vascular access is a lifeline for hemodialysis patients. Its lifetime is affected by many hemodynamic factors such as pressure, flow regime and wall shear stress. During hemodialysis, changes in hemodynamic parameters occur due to the flow from needles inserted into the vascular system. Primarily, there is a change in shear stress that affects the vascular wall. Pathological effects of high or low WSS are known. The effect of jet from a venous needle on hemodynamics parameters was studied, but the influence of the arterial needle on hemodynamics parameters is not sufficiently studied. To understand its possible effects, we performed in vivo and in vitro studies. Methods. In vivo experiment: The existence of flow reversal around the suction needle was visualized in a group of 12 randomly selected patients using ultrasound velocity profiling (Doppler ultrasonography) during hemodialysis. In vitro experiment: The flow field was measured using the stereo particle image velocimetry method (stereo PIV). Two regimes were studied. In the first regime, the fluid in the extracorporeal circuit was pumped by a peristaltic pump. In the second regime, the continuous pump was used in the extracorporeal circuit. The conditions were set to resemble those in vascular access during a hemodialysis session. Flow volume was set to 600 mL/min for vascular access and 200 mL/min for the extracorporeal circuit. Results. The main finding of this study was that the wall in the region of the arterial needle was stressed by backflow through the arterial needle. Since this was a variable, low-shear stress loading, it was one of the risk factors for the development of stenosis. Cyclic flow reversal was apparent in all of the included hemodialysis patients. The stereo PIV in vitro experiment revealed the oscillating character of wall shear stress (WSS) inside the model. High shear stress was documented upstream of the injection point of the arterial needle. An area of very low WSS was detected right behind the injection point during a pulse of the peristaltic pump. The minimal and maximal values of the WSS during a pulse of the peristaltic pump in the observed area were −0.7 Pa and 6 Pa, respectively. The distribution of wall shear stress with the continual pump used in the extracorporeal circuit was similar to the distribution during a pulse of the peristaltic one. However, the WSS values were continual; the WSS did not oscillate. WSS ranged between 4.8 Pa and 1.0 Pa.


The Analyst ◽  
2021 ◽  
Author(s):  
Jingtong Na ◽  
Siyu Hu ◽  
Chundong Xue ◽  
Yanxia Wang ◽  
Kejie Chen ◽  
...  

To reproduce hemodynamic stress microenvironments of endothelial cells in vitro is of vital significance, by which one could exploit quantitative impact of hemodynamic stresses on endothelial function and seek innovative...


2021 ◽  
Author(s):  
Claire A. Dessalles ◽  
Clara Ramón-Lozano ◽  
Avin Babataheri ◽  
Abdul I. Barakat

AbstractIn the microvasculature, blood flow-derived forces are key regulators of vascular structure and function. Consequently, the development of hydrogel-based microvessel-on-chip systems that strive to mimic the in vivo cellular organization and mechanical environment has received great attention in recent years. However, despite intensive efforts, current microvessel- on-chip systems suffer from several limitations, most notably failure to produce physiologically relevant wall strain levels. In this study, a novel microvessel-on-chip based on the templating technique and using luminal flow actuation to generate physiologically relevant levels of wall shear stress and circumferential stretch is presented. Normal forces induced by the luminal pressure compress the surrounding soft collagen hydrogel, dilate the channel, and create large circumferential strain. The fluid pressure gradient in the system drives flow forward and generates realistic pulsatile wall shear stresses. Rigorous characterization of the system reveals the crucial role played by the poroelastic behavior of the hydrogel in determining the magnitudes of the wall shear stress and strain. The experimental measurements are combined with an analytical model of flow in both the lumen and the porous hydrogel to provide an exceptionally versatile user manual for an application-based choice of parameters in microvessels-on-chip. This unique strategy of flow actuation adds a dimension to the capabilities of microvessel-on-chip systems and provides a more general framework for improving hydrogel-based in vitro engineered platforms.Abstract Figure


2011 ◽  
Vol 33 (3) ◽  
pp. 589-597 ◽  
Author(s):  
Erik T. Bieging ◽  
Alex Frydrychowicz ◽  
Andrew Wentland ◽  
Benjamin R. Landgraf ◽  
Kevin M. Johnson ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document