Molecular Control of Cytoskeletal Mechanics by Hemodynamic Forces

Physiology ◽  
2005 ◽  
Vol 20 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Brian P. Helmke
Keyword(s):  
Shear Stress ◽  
Structural Dynamics ◽  
Molecular Level ◽  
Physiological Function ◽  
Primary Transducer ◽  
Molecular Control ◽  
Hemodynamic Forces ◽  
Spatial Gradients ◽  
Cellular Mechanotransduction ◽  
Stress Profiles

The endothelium at the interface between blood and tissue acts as a primary transducer of local hemodynamic forces into signals that maintain physiological function or initiate pathological processes in vessel walls. Rapid intracellular spatial gradients of structural dynamics and signaling molecule activity suggest that mechanical cues at the molecular level guide cellular mechanotransduction and adaptation to shear stress profiles.

Temporal evolution of cell focal adhesions: experimental observations and shear stress profiles

Soft Matter ◽  
2008 ◽  
Vol 4 (12) ◽  
pp. 2410 ◽  
Author(s):  
D. Raz-Ben Aroush ◽  
R. Zaidel-Bar ◽  
A. D. Bershadsky ◽  
H. D. Wagner
Keyword(s):  
Shear Stress ◽  
Temporal Evolution ◽  
Focal Adhesions ◽  
Stress Profiles

scholarly journals MicroRNA-10a is crucial for endothelial response to different flow patterns via interaction of retinoid acid receptors and histone deacetylases

2017 ◽  
Vol 114 (8) ◽  
pp. 2072-2077 ◽  
Author(s):  
Ding-Yu Lee ◽  
Ting-Er Lin ◽  
Chih-I Lee ◽  
Jing Zhou ◽  
Yi-Hsuan Huang ◽  
...  
Keyword(s):  
Shear Stress ◽  
Histone Deacetylases ◽  
Inflammatory Responses ◽  
Nuclear Accumulation ◽  
Hemodynamic Forces ◽  
Endothelial Response ◽  
Vascular Physiology ◽  
Responsive Element ◽  
Retinoid Acid

Histone deacetylases (HDACs) and microRNAs (miRs) have emerged as two important epigenetic factors in the regulation of vascular physiology. This study aimed to elucidate the relationship between HDACs and miRs in the hemodynamic modulation of endothelial cell (EC) dysfunction. We found that miR-10a has the lowest expression among all examined shear-responsive miRs in ECs under oscillatory shear stress (OS), and a relatively high expression under pulsatile shear stress (PS). PS and OS alter EC miR-10a expression to regulate the expression of its direct target GATA6 and downstream vascular cell adhesion molecule (VCAM)-1. PS induces the expression, nuclear accumulation, and association of retinoid acid receptor-α (RARα) and retinoid X receptor-α (RXRα). RARα and RXRα serve as a “director” and an “enhancer,” respectively, to enhance RARα binding to RA-responsive element (RARE) and hence miR-10a expression, thus down-regulating GATA6/VCAM-1 signaling in ECs. In contrast, OS induces associations of “repressors” HDAC-3/5/7 with RARα to inhibit the RARα-directed miR-10a signaling. The flow-mediated miR-10a expression is regulated by Krüppel-like factor 2 through modulation in RARα–RARE binding, with the consequent regulation in GATA6/VCAM-1 in ECs. These results are confirmed in vivo by en face staining on the aortic arch vs. the straight thoracic aorta of rats. Our findings identify a mechanism by which HDACs and RXRα modulate the hormone receptor RARα to switch miR-10a expression and hence the proinflammatory vs. anti-inflammatory responses of vascular endothelium under different hemodynamic forces.

scholarly journals FLUID FLOW AND WALL SHEAR STRESS PROFILES IN MODEL BRANCH OF ABDOMINAL AORTA

Biomechanisms ◽  
1992 ◽  
Vol 11 (0) ◽  
pp. 99-109 ◽  
Author(s):  
Takashi HIROSE ◽  
Akio TANABE ◽  
Kazuo TANISHITA
Keyword(s):  
Shear Stress ◽  
Fluid Flow ◽  
Wall Shear Stress ◽  
Abdominal Aorta ◽  
Stress Profiles ◽  
Wall Shear

scholarly journals Induction of aneurysmogenic high positive wall shear stress gradient by wide angle at cerebral bifurcations, independent of flow rate

2019 ◽  
Vol 131 (2) ◽  
pp. 442-452 ◽  
Author(s):  
Alexandra Lauric ◽  
James E. Hippelheuser ◽  
Adel M. Malek
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Flow Rate ◽  
Stress Gradient ◽  
Dependent Manner ◽  
Parent Vessel ◽  
Spatial Gradients ◽  
Bifurcation Angle ◽  
Wall Shear ◽  
Dynamics Simulations

OBJECTIVEEndothelium adapts to wall shear stress (WSS) and is functionally sensitive to positive (aneurysmogenic) and negative (protective) spatial WSS gradients (WSSG) in regions of accelerating and decelerating flow, respectively. Positive WSSG causes endothelial migration, apoptosis, and aneurysmal extracellular remodeling. Given the association of wide branching angles with aneurysm presence, the authors evaluated the effect of bifurcation geometry on local apical hemodynamics.METHODSComputational fluid dynamics simulations were performed on parametric bifurcation models with increasing angles having: 1) symmetrical geometry (bifurcation angle 60°–180°), 2) asymmetrical geometry (daughter angles 30°/60° and 30°/90°), and 3) curved parent vessel (bifurcation angles 60°–120°), all at baseline and double flow rate. Time-dependent and time-averaged apical WSS and WSSG were analyzed. Results were validated on patient-derived models.RESULTSNarrow symmetrical bifurcations are characterized by protective negative apical WSSG, with a switch to aneurysmogenic WSSG occurring at angles ≥ 85°. Asymmetrical bifurcations develop positive WSSG on the more obtuse daughter branch. A curved parent vessel leads to positive apical WSSG on the side corresponding to the outer curve. All simulations revealed wider apical area coverage by higher WSS and positive WSSG magnitudes, with increased bifurcation angle and higher flow rate. Flow rate did not affect the angle threshold of 85°, past which positive WSSG occurs. In curved models, high flow displaced the impingement area away from the apex, in a dynamic fashion and in an angle-dependent manner.CONCLUSIONSApical shear forces and spatial gradients are highly dependent on bifurcation and inflow vessel geometry. The development of aneurysmogenic positive WSSG as a function of angular geometry provides a mechanotransductive link for the association of wide bifurcations and aneurysm development. These results suggest therapeutic strategies aimed at altering underlying unfavorable geometry and deciphering the molecular endothelial response to shear gradients in a bid to disrupt the associated aneurysmal degeneration.

scholarly journals Prevention of Melanoma Extravasation as a New Treatment Option Exemplified by p38/MK2 Inhibition

2020 ◽  
Vol 21 (21) ◽  
pp. 8344
Author(s):  
Peter Petzelbauer
Keyword(s):  
Tumor Cells ◽  
Growth Characteristics ◽  
Cell Surfaces ◽  
Therapeutic Targeting ◽  
Jnk Pathway ◽  
Molecular Control ◽  
Hemodynamic Forces ◽  
Matrix Interactions ◽  
Leukocyte Extravasation ◽  
New Treatment

Melanoma releases numerous tumor cells into the circulation; however, only a very small fraction of these cells is able to establish distant metastasis. Intravascular survival of circulating tumor cells is limited through hemodynamic forces and by the lack of matrix interactions. The extravasation step is, thus, of unique importance to establish metastasis. Similar to leukocyte extravasation, this process is under the control of adhesion molecule pairs expressed on melanoma and endothelial cells, and as for leukocytes, ligands need to be adequately presented on cell surfaces. Based on melanoma plasticity, there is considerable heterogeneity even within one tumor and one patient resulting in a mixture of invasive or proliferative cells. The molecular control for this switch is still ill-defined. Recently, the balance between two kinase pathways, p38 and JNK, has been shown to determine growth characteristics of melanoma. While an active JNK pathway induces a proliferative phenotype with reduced invasive features, an active p38/MK2 pathway results in an invasive phenotype and supports the extravasation step via the expression of molecules capable of binding to endothelial integrins. Therapeutic targeting of MK2 to prevent extravasation might reduce metastatic spread.

PIV Measurements in Square Backward-Facing Step

2007 ◽  
Vol 129 (8) ◽  
pp. 984-990 ◽  
Author(s):  
Mika Piirto ◽  
Aku Karvinen ◽  
Hannu Ahlstedt ◽  
Pentti Saarenrinne ◽  
Reijo Karvinen
Keyword(s):  
Shear Stress ◽  
Reynolds Stress ◽  
Reynolds Shear Stress ◽  
Experimental Tests ◽  
Expansion Ratio ◽  
Spanwise Direction ◽  
Duct Flow ◽  
Backward Facing Step ◽  
Mean Velocity ◽  
Stress Profiles

Measurements with both two-dimensional (2D) two-component and three-component stereo particle image velocimetry (PIV) and computation in 2D and three-dimensional (3D) using Reynolds stress turbulence model with commercial code are carried out in a square duct backward-facing step (BFS) in a turbulent water flow at three Reynolds numbers of about 12,000, 21,000, and 55,000 based on the step height h and the inlet streamwise maximum mean velocity U0. The reattachment locations measured at a distance of Δy=0.0322h from the wall are 5.3h, 5.6h, and 5.7h, respectively. The inlet flow condition is fully developed duct flow before the step change with the expansion ratio of 1.2. PIV results show that the mean velocity, root mean square (rms) velocity profiles, and Reynolds shear stress profiles in all the experimental flow cases are almost identical in the separated shear-layer region when they are nondimensionalized by U0. The sidewall effect of the square BFS flow is analyzed by comparing the experimental statistics with direct numerical simulation (DNS) and Reynolds stress model (RSM) data. For this purpose, the simulation is carried out for both 2D BFS and for square BFS having the same geometry in the 3D case as the experimental case at the lowest Reynolds number. A clear difference is observed in rms and Reynolds shear stress profiles between square BFS experimental results and DNS results in 2D channel in the spanwise direction. The spanwise rms velocity difference is about 30%, with experimental tests showing higher values than DNS, while in contrast, turbulence intensities in streamwise and vertical directions show slightly lower values than DNS. However, with the modeling, the turbulence statistical differences between 2D and 3D RSM cases are very modest. The square BFS indicates 0.5h–1.5h smaller reattachment distances than the reattachment lengths of 2D flow cases.

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]

scholarly journals Evaluation of electro-osmotic flow in a nanochannel via semi-analytical method

2012 ◽  
Vol 16 (5) ◽  
pp. 1297-1302 ◽  
Author(s):  
Payam Jalili ◽  
Domairry Ganji ◽  
Bahram Jalili ◽  
Domiri Ganji
Keyword(s):  
Shear Stress ◽  
Analytical Method ◽  
Homotopy Perturbation Method ◽  
Numerical Solutions ◽  
Electrical Potential ◽  
Osmotic Flow ◽  
Homotopy Perturbation ◽  
Stress Profiles ◽  
Electro Osmotic Flow ◽  
Cation Distributions

In this paper, equations due to anion and cation distributions, electrical potential and shear stress profiles in a nanochannel are formed for 1-D electro-osmotic flow, and solved by homotopy perturbation method. Results are compared with numerical solutions.

Multi-Axial Mechanical Stimulation of HUVECs Demonstrates That Combined Loading is not Equivalent to the Superposition of Individual Wall Shear Stress and Tensile Hoop Stress Components

2009 ◽  
Vol 131 (8) ◽  
Author(s):  
Liam T. Breen ◽  
Peter E. McHugh ◽  
Bruce P. Murphy
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Cellular Response ◽  
Umbilical Vein ◽  
Combined Loading ◽  
Hoop Strain ◽  
Hemodynamic Forces ◽  
Testing Period ◽  
Wall Shear

Over the past 25 years, many laboratory based bioreactors have been used to study the cellular response to hemodynamic forces. The vast majority of these studies have focused on the effect of a single isolated hemodynamic force, generally consisting of a wall shear stress (WSS) or a tensile hoop strain (THS). However, investigating the cellular response to a single isolated force does not accurately represent the true in vivo situation, where a number of forces are acting simultaneously. This study used a novel bioreactor to investigate the cellular response of human umbilical vein endothelial cells (HUVECs) exposed to a combination of steady WSS and a range of cyclic THS. HUVECs exposed to a range of cyclic THS (0–12%), over a 12 h testing period, expressed an upregulation of both ICAM-1 and VCAM-1. HUVECs exposed to a steady WSS (0 dynes/cm2 and 25 dynes/cm2), over a 12 h testing period, also exhibited an ICAM-1 upregulation but a VCAM-1 downregulation, where the greatest level of WSS stimulus resulted in the largest upregulation and downregulation of ICAM-1 and VCAM-1, respectively. A number of HUVEC samples were exposed to a high steady WSS (25 dynes/cm2) combined with a range of cyclic THS (0–4%, 0–8%, and 0–12%) for a 12 h testing period. The initial ICAM-1 upregulation, due to the WSS alone, was downregulated with the addition of a cyclic THS. It was observed that the largest THS (0–12%) had the greatest reducing effect on the ICAM-1 upregulation. Similarly, the initial VCAM-1 downregulation, due to the high steady WSS alone, was further downregulated with the addition of a cyclic THS. A similar outcome was observed when HUVEC samples were exposed to a low steady WSS combined with a range of cyclic THS. However, the addition of a THS to the low WSS did not result in an expected ICAM-1 downregulation. In fact, it resulted in a trend of unexpected ICAM-1 upregulation. The unexpected cellular response to the combination of a steady WSS and a cyclic THS demonstrates that such a response could not be determined by simply superimposing the cellular responses exhibited by ECs exposed to a steady WSS and a cyclic THS that were applied in isolation.

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