Early Cellular and Molecular Changes During Hemodynamic Initiation of Intracranial Aneurysms in a Rabbit Model

2010 ◽  
Author(s):  
Ling Gao ◽  
Max Mandelbaum ◽  
Nicholas Liaw ◽  
Sabareesh K. Natarajan ◽  
J. Mocco ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Intracranial Aneurysms ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Stress Gradient ◽  
Rabbit Model ◽  
Apical Region ◽  
Apical Side ◽  
Wall Shear

Hemodynamics constitutes a critical factor in the formation of intracranial aneurysms. However, little is known about how an intracranial arterial wall responds to a hemodynamic insult, and how that response contributes to aneurysm formation. Unlike straight arterial segments (which respond to increased flow by expansive remodeling) and sinuses opposing bifurcation apices (which harbor recirculation flows and are prone to atherosclerotic development), aneurysmal degeneration occurs on the apical side of the bifurcation in the immediate peri-apical region, where flow creates very high wall shear stress (WSS) and wall shear stress gradient (WSSG)1. This results in destructive aneurysmal remodeling, characterized by loss of the internal elastic lamina (IEL) and thinning of the media. It is unknown how the unique hemodynamic conditions of combined high WSS and positive WSSG elicit these morphological changes, how the vascular wall responds to such insult at the molecular level, and what molecular mechanisms are involved.

Intracranial Aneurysms Occur More Frequently at Bifurcation Sites That Typically Experience Higher Hemodynamic Stresses

Neurosurgery ◽  
2013 ◽  
Vol 73 (3) ◽  
pp. 497-505 ◽  
Author(s):  
Jaclyn M. Alfano ◽  
John Kolega ◽  
Sabareesh K. Natarajan ◽  
Jianping Xiang ◽  
Rocco A. Paluch ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Intracranial Aneurysms ◽  
Stress Gradient ◽  
Spatial Gradient ◽  
Impact Zone ◽  
Wall Shear ◽  
A Site ◽  
The Impact ◽  
Hemodynamic Stresses

Abstract BACKGROUND: Intracranial aneurysms (IAs) occur more frequently at certain bifurcations than at others. Hemodynamic stress, which promotes aneurysm formation in animal models, also differs among bifurcations, depending on flow and vessel geometry. OBJECTIVE: To determine whether locations that are more likely to develop IAs experience different hemodynamic stresses that might contribute to higher IA susceptibility. METHODS: We characterized the hemodynamic microenvironment at 10 sites in or around the circle of Willis where IAs commonly occur and examined statistical relationships between hemodynamic factors and the tendency for a site to form IAs. The tendency for each site to develop IAs was quantified on the basis of the site distribution from systematic literature analysis of 19 reports including 26 418 aneurysms. Hemodynamic parameters for these sites were derived from image-based computational fluid dynamics of 114 cerebral bifurcations from 31 individuals. Wall shear stress and its spatial gradient were calculated in the impact zone surrounding the bifurcation apex. Linear and exponential regression analyses evaluated correlations between the tendency for IA formation and the typical hemodynamics of a site. RESULTS: IA susceptibility significantly correlated with the magnitudes of wall shear stress and positive wall shear stress gradient within the hemodynamic impact zone calculated for each site. CONCLUSION: IAs occur more frequently at cerebral bifurcations that typically experience higher hemodynamic shear stress and stronger flow acceleration, conditions previously shown to promote aneurysm initiation in animals.

High Wall Shear Stress and Positive Wall Shear Stress Gradient Trigger the Initiation of Intracranial Aneurysms

2009 ◽  
Author(s):  
Eleni Metaxa ◽  
Markus Tremmel ◽  
Jianping Xiang ◽  
John Kolega ◽  
Max Mandelbaum ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Intracranial Aneurysms ◽  
Potential Role ◽  
Stress Gradient ◽  
Local Flow ◽  
High Wall Shear Stress ◽  
Wall Shear Stress Gradient ◽  
Wall Shear

While the pathogenesis of an intracranial aneurysm (IA) is poorly understood, it has been generally postulated to be related to hemodynamic insult. IAs are predominantly located at apices of arterial bifurcations or outer curves on or near the Circle of Willis, suggesting a potential role of the specific hemodynamics at such locations characterized by high wall shear stress (WSS). Clinically, new IA formation has been observed following local flow increase.

scholarly journals An In Vivo Murine Model of Low-Magnitude Oscillatory Wall Shear Stress to Address the Molecular Mechanisms of Mechanotransduction—Brief Report

2010 ◽  
Vol 30 (11) ◽  
pp. 2099-2102 ◽  
Author(s):  
Nick J. Willett ◽  
Robert C. Long ◽  
Kathryn Maiellaro-Rafferty ◽  
Roy L. Sutliff ◽  
Richard Shafer ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Murine Model ◽  
Molecular Mechanisms ◽  
Wall Shear ◽  
Low Magnitude

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.

Numerical Investigation and Prediction of Atherogenic Sites in Branching Arteries

1995 ◽  
Vol 117 (3) ◽  
pp. 350-357 ◽  
Author(s):  
M. Lei ◽  
C. Kleinstreuer ◽  
G. A. Truskey
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Blood Vessels ◽  
Vector Fields ◽  
Stress Gradient ◽  
Western World ◽  
Medium Size ◽  
Wall Shear Stress Gradient ◽  
Shear Stress Gradient ◽  
Wall Shear

Atherosclerosis, a disease of large- and medium-size arteries, is the chief cause of death in the US and most of the western world. It is widely accepted that the focal nature of the disease in arterial bends, junctions, and bifurcations is directly related to locally abnormal hemodynamics, often labeled “disturbed flows.” Employing the aorto-celiac junction of rabbits as a representative atherosclerotic model and considering other branching blood vessels with their distinctive input wave forms, it is suggested that the local wall shear stress gradient (WSSG) is the single best indicator of nonuniform flow fields leading to atherogenesis. Alternative predictors of susceptible sites are briefly evaluated. The results discussed include transient velocity vector fields, wall shear stress gradient distributions, and a new dimensionless parameter for the prediction of the probable sites of stenotic developments in branching blood vessels. Some of the possible underlying biological aspects of atherogenesis due to locally significant |WSSG|-magnitudes are briefly discussed.

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.

scholarly journals Modulating wall shear stress gradient via equilateral triangular channel for in situ cellular adhesion assay

2016 ◽  
Vol 10 (5) ◽  
pp. 054119 ◽  
Author(s):  
Hyung Woo Kim ◽  
Seonjin Han ◽  
Wonkyoung Kim ◽  
Jiwon Lim ◽  
Dong Sung Kim
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Stress Gradient ◽  
Cellular Adhesion ◽  
Adhesion Assay ◽  
Triangular Channel ◽  
Wall Shear Stress Gradient ◽  
Shear Stress Gradient ◽  
Wall Shear

Numerical study of flow fields in an airway closure model

2011 ◽  
Vol 677 ◽  
pp. 483-502 ◽  
Author(s):  
C.-F. TAI ◽  
S. BIAN ◽  
D. HALPERN ◽  
Y. ZHENG ◽  
M. FILOCHE ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Normal Stress ◽  
Numerical Study ◽  
Stress Gradient ◽  
Fluid Motion ◽  
Flow Fields ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Wall Shear

The liquid lining in small human airways can become unstable and form liquid plugs that close off the airways. Direct numerical simulations are carried out on an airway model to study this airway instability and the flow-induced stresses on the airway walls. The equations governing the fluid motion and the interfacial boundary conditions are solved using the finite-volume method coupled with the sharp interface method for the free surface. The dynamics of the closure process is simulated for a viscous Newtonian film with constant surface tension and a passive core gas phase. In addition, a special case is examined that considers the core dynamics so that comparisons can be made with the experiments of Bian et al. (J. Fluid Mech., vol. 647, 2010, p. 391). The computed flow fields and stress distributions are consistent with the experimental findings. Within the short time span of the closure process, there are large fluctuations in the wall shear stress. Furthermore, dramatic velocity changes in the film during closure indicate a steep normal stress gradient on the airway wall. The computational results show that the wall shear stress, normal stress and their gradients during closure can be high enough to injure airway epithelial cells.

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