Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives

Vascular endothelial cells (ECs) are exposed to hemodynamic forces, which modulate EC functions and vascular biology/pathobiology in health and disease. The flow patterns and hemodynamic forces are not uniform in the vascular system. In straight parts of the arterial tree, blood flow is generally laminar and wall shear stress is high and directed; in branches and curvatures, blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress. Sustained laminar flow with high shear stress upregulates expressions of EC genes and proteins that are protective against atherosclerosis, whereas disturbed flow with associated reciprocating, low shear stress generally upregulates the EC genes and proteins that promote atherogenesis. These findings have led to the concept that the disturbed flow pattern in branch points and curvatures causes the preferential localization of atherosclerotic lesions. Disturbed flow also results in postsurgical neointimal hyperplasia and contributes to pathophysiology of clinical conditions such as in-stent restenosis, vein bypass graft failure, and transplant vasculopathy, as well as aortic valve calcification. In the venous system, disturbed flow resulting from reflux, outflow obstruction, and/or stasis leads to venous inflammation and thrombosis, and hence the development of chronic venous diseases. Understanding of the effects of disturbed flow on ECs can provide mechanistic insights into the role of complex flow patterns in pathogenesis of vascular diseases and can help to elucidate the phenotypic and functional differences between quiescent (nonatherogenic/nonthrombogenic) and activated (atherogenic/thrombogenic) ECs. This review summarizes the current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications. Such information can contribute to our understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions.

Download Full-text

Wall Deformation, Wall Shear Stress and Atherosclerosis Around the Intercostal Ostia of C57 Mice

ASME 2007 Summer Bioengineering Conference ◽

10.1115/sbc2007-176636 ◽

2007 ◽

Author(s):

Jin Suo ◽

Dardo E. Ferrara ◽

Robert E. Guldberg ◽

Robert W. Taylor ◽

Don P. Giddens

Keyword(s):

Blood Flow ◽

Shear Stress ◽

Wall Shear Stress ◽

Flow Patterns ◽

Laser Scanning Microscopy ◽

Upstream Region ◽

Disturbed Flow ◽

Wall Deformation ◽

Wall Shear ◽

Blood Flow Patterns

Dorsal surfaces and upstream regions around ostia of aortic branches are favored sites of atherosclerosis. Both asymmetrical stresses in branch walls and disturbed flow patterns have been suggested as contributing to this localization. In the present study, fluorescence images of the thoracic aortic tree of C57 mice were obtained using quantum dot (Qdot) bioconjugate markers for vascular cell adhesion molecule-1 (VCAM-1) and two-photon excitation laser scanning microscopy. The images show that dorsal surfaces and upstream regions of intercostal ostia have a higher intensity of VCAM-1 than the downstream region. We also investigated blood flow patterns and wall shear stress (WSS) in the descending aorta and proximal intercostal branches of C57 mice using micro-CT imaging and ultrasound velocity measurements, combined with computational fluid dynamics (CFD). The latter investigation showed that dynamical wall deformation caused by pulsatile pressure around the ostia induces blood flow patterns which create lower and oscillating WSS in the upstream region and dorsal surface than in the distal region. Comparisons of the Qdot marker and CFD studies demonstrate that the distribution of greater expression of VCAM-1 corresponds with lower and oscillating WSS around the branch ostia. Thus, local wall deformation may contribute to disturbed flow patterns that are known to be associated with increased VCAM-1 expression.

Download Full-text

Evaluation of 3D blood flow patterns and wall shear stress in the normal and dilated thoracic aorta using flow-sensitive 4D CMR

Journal of Cardiovascular Magnetic Resonance ◽

10.1186/1532-429x-14-84 ◽

2012 ◽

Vol 14 (1) ◽

Cited By ~ 110

Author(s):

Jonas Bürk ◽

Philipp Blanke ◽

Zoran Stankovic ◽

Alex Barker ◽

Maximilian Russe ◽

...

Keyword(s):

Blood Flow ◽

Shear Stress ◽

Wall Shear Stress ◽

Thoracic Aorta ◽

Flow Patterns ◽

Wall Shear ◽

Blood Flow Patterns

Download Full-text

Non-Newtonian Models for Blood Flow Through an Arterial Stenosis

Volume 1: Advances in Aerospace Technology; Energy Water Nexus; Globalization of Engineering; Posters ◽

10.1115/imece2011-63444 ◽

2011 ◽

Cited By ~ 1

Author(s):

F. Kh. Tazyukov ◽

H. A. Khalaf ◽

Jafar M. Hassan

Keyword(s):

Blood Flow ◽

Shear Stress ◽

Wall Shear Stress ◽

Arterial Stenosis ◽

Stenosed Artery ◽

Two Dimensional Flow ◽

Flow Through ◽

Wall Shear ◽

Volume Method

The problems of non-Newtonian blood flow through a stenosed artery are solved numerically using Finite Volume Method where the non-Newtonian rheology of the flowing blood is characterised by the Generalised Power-law, Carreau-Yasuda and Cross models. In view of the haemodynamical mechanisms related to atherosclerosis formation and the role of the wall shear stress in initiating and further developing of the disease, the investigation is focused on the two-dimensional flow field and in particular on the distribution of the wall shear stress in the vicinity of the stenosis. A comparison is made between the effects of each rheological model on the aforementioned parameters for different Re number.

Download Full-text

Aorta Remodeling Responses to Distinct Atherogenic Stimuli: Hyperten-sion, Hypercholesterolemia and Turbulent Flow/Low Wall Shear Stress

The Open Cardiovascular Medicine Journal ◽

10.2174/1874192400802010041 ◽

2008 ◽

Vol 2 (1) ◽

pp. 41-48 ◽

Cited By ~ 2

Author(s):

Cibele M Prado ◽

Marcos A Rossi

Keyword(s):

Oxidative Stress ◽

Blood Flow ◽

Shear Stress ◽

Laminar Flow ◽

Wall Shear Stress ◽

Normal Diet ◽

Published Data ◽

Hypercholesterolemic Diet ◽

Wall Shear

This review is based on recently published data from our laboratory. We investigated the role of hypertension and laminar flow, hypercholesterolemia and laminar flow and turbulent blood flow/low wall shear stress, and turbulent blood flow/low wall shear stress associated with hypercholesterolemia on aorta remodeling of rats feeding normal diet or hypercholesterolemic diet. Our findings suggest that increased circumferential wall tension due to hypertension plays a key role in the remodeling through biomechanical effects on oxidative stress and increased TGF-β expression; the remodeling observed in the presence of hypercholesterolemia could be initiated by oxidative stress that is involved in several processes of atherogenesis and this remodeling is more pronounced in the presence of turbulent blood flow/low wall shear stress.

Download Full-text

Non-Newtonian Flow Patterns Associated With an Arterial Stenosis

Journal of Biomechanical Engineering ◽

10.1115/1.2894103 ◽

1992 ◽

Vol 114 (4) ◽

pp. 512-514 ◽

Cited By ~ 10

Author(s):

X. Y. Luo ◽

Z. B. Kuang

Keyword(s):

Blood Flow ◽

Shear Stress ◽

Constitutive Equation ◽

Wall Shear Stress ◽

Velocity Profile ◽

Pressure Gradient ◽

Flow Patterns ◽

Arterial Stenosis ◽

Newtonian Flow ◽

Wall Shear

A non-Newtonian constitutive equation for blood has been introduced in this paper. Using this equation, blood flow attributes such as velocity profiles, flowrate, pressure gradient, and wall shear stress in both straight and stenotic (constricted) tubes have been examined. Results showed that compared with Newtonian flow at the same flowrate, the non-Newtonian normally features larger pressure gradient, higher wall shear stress, and different velocity profile, especially in stenotic tube. In addition, the non-Newtonian stenotic flow appears to be more stable than Newtonian flow.

Download Full-text

Association between erythrocyte dynamics and vessel remodelling in developmental vascular networks

10.1101/2020.05.21.106914 ◽

2020 ◽

Cited By ~ 2

Author(s):

Qi Zhou ◽

Tijana Perovic ◽

Ines Fechner ◽

Lowell T. Edgar ◽

Peter R. Hoskins ◽

...

Keyword(s):

Blood Flow ◽

Shear Stress ◽

Wall Shear Stress ◽

Strong Association ◽

Vascular Networks ◽

Vascular Remodelling ◽

Sprouting Angiogenesis ◽

Vessel Regression ◽

Wall Shear

AbstractSprouting angiogenesis is an essential vascularisation mechanism consisting of sprouting and remodelling. The remodelling phase is driven by rearrangements of endothelial cells (ECs) within the post-sprouting vascular plexus. Prior work has uncovered how ECs polarise and migrate in response to flow-induced wall shear stress (WSS). However, the question of how the presence of erythrocytes (well-known as RBCs) and their haemodynamics impact affects vascular remodelling remains unanswered. Here, we devise a computational framework to model cellular blood flow in developmental mouse retina. We demonstrate a previously unreported highly heterogeneous distribution of RBCs in primitive vasculature. Furthermore, we report a strong association between vessel regression and RBC depletion, and identify plasma skimming as the driving mechanism. Live imaging in a developmental zebrafish model confirms this association. Taken together, our results indicate that RBC dynamics are fundamental to establishing the regional WSS differences driving vascular remodelling via their ability to modulate effective viscosity.SummaryRecent studies demonstrate that during sprouting angiogenesis, blood flow provides crucial hydrodynamic cues (e.g. wall shear stress) for the remodelling of primitive plexuses towards a functional network. Notwithstanding, the role of RBCs in this process remains poorly understood. We report on the inherent heterogeneity of RBC perfusion within primitive vasculatures, and uncover a strong association between RBC depletion and vessel regression. Our work indicates the essential role of RBC dynamics in the establishment of regional WSS differences driving vascular remodelling. The RBC-driven process of pruning cell-depleted vessels not only importantly contributes to the optimal patterning of vascular networks during development, but also provides a remodelling mechanism to support clinical findings of microangiopathic complications associated with impaired RBC deformability in diseases such as diabetes mellitus and hypertension.

Download Full-text

A Numerical Study of Blood Flow Patterns in Anatomically Realistic and Simplified End-to-Side Anastomoses

Journal of Biomechanical Engineering ◽

10.1115/1.2798319 ◽

1999 ◽

Vol 121 (3) ◽

pp. 265-272 ◽

Cited By ~ 69

Author(s):

J. A. Moore ◽

D. A. Steinman ◽

S. Prakash ◽

K. W. Johnston ◽

C. R. Ethier

Keyword(s):

Blood Flow ◽

Shear Stress ◽

Wall Shear Stress ◽

Flow Patterns ◽

Geometric Features ◽

Simplified Models ◽

Out Of Plane ◽

Wall Shear ◽

Blood Flow Patterns ◽

Stress Patterns

Purpose: Recently, some numerical and experimental studies of blood flow in large arteries have attempted to accurately replicate in vivo arterial geometries, while others have utilized simplified models. The objective of this study was to determine how much an anatomically realistic geometry can be simplified without the loss of significant hemodynamic information. Method: A human femoral-popliteal bypass graft was used to reconstruct an anatomically faithful finite element model of an end-to-side anastomosis. Nonideal geometric features of the model were removed in sequential steps to produce a series of successively simplified models. Blood flow patterns were numerically computed for each geometry, and the flow and wall shear stress fields were analyzed to determine the significance of each level of geometric simplification. Results: The removal of small local surface features and out-of-plane curvature did not significantly change the flow and wall shear stress distributions in the end-to-side anastomosis. Local changes in arterial caliber played a more significant role, depending upon the location and extent of the change. The graft-to-host artery diameter ratio was found to be a strong determinant of wall shear stress patterns in regions that are typically associated with disease processes. Conclusions: For the specific case of an end-to-side anastomosis, simplified models provide sufficient information for comparing hemodynamics with qualitative or averaged disease locations, provided the “primary” geometric features are well replicated. The ratio of the graft-to-host artery diameter was shown to be the most important geometric feature. “Secondary” geometric features such as local arterial caliber changes, out-of-plane curvature, and small-scale surface topology are less important determinants of the wall shear stress patterns. However, if patient-specific disease information is available for the same arterial geometry, accurate replication of both primary and secondary geometric features is likely required.

Download Full-text