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 (, 100, and 200 and , , and ) 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.
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e-mail: richard.leask@mcgill.ca
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August 2010
Research Papers
Endothelial Cell Morphologic Response to Asymmetric Stenosis Hemodynamics: Effects of Spatial Wall Shear Stress Gradients
Leonie Rouleau,
Leonie Rouleau
Department of Chemical Engineering,
McGill University
, 3610 University, Montreal, QC, H3A 2B2, Canada; Montreal Heart Institute
, Canada
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Monica Farcas,
Monica Farcas
Department of Chemical Engineering,
McGill University
, 3610 University, Montreal, QC, H3A 2B2, Canada
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Jean-Claude Tardif,
Jean-Claude Tardif
Montreal Heart Institute
, Canada
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Rosaire Mongrain,
Rosaire Mongrain
Montreal Heart Institute
, 5000 Bélanger Street, Montreal, QC H1T 1C8, Canada; Department of Mechanical Engineering, McGill University
, Montreal, QC, H3A 2B2, Canada
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Richard L. Leask
Richard L. Leask
PEng
Department of Chemical Engineering,
e-mail: richard.leask@mcgill.ca
McGill University
, 3610 University, Montreal, QC, H3A 2B2, Canada; Montreal Heart Institute
, Canada
Search for other works by this author on:
Leonie Rouleau
Department of Chemical Engineering,
McGill University
, 3610 University, Montreal, QC, H3A 2B2, Canada; Montreal Heart Institute
, Canada
Monica Farcas
Department of Chemical Engineering,
McGill University
, 3610 University, Montreal, QC, H3A 2B2, Canada
Jean-Claude Tardif
Montreal Heart Institute
, Canada
Rosaire Mongrain
Montreal Heart Institute
, 5000 Bélanger Street, Montreal, QC H1T 1C8, Canada; Department of Mechanical Engineering, McGill University
, Montreal, QC, H3A 2B2, Canada
Richard L. Leask
PEng
Department of Chemical Engineering,
McGill University
, 3610 University, Montreal, QC, H3A 2B2, Canada; Montreal Heart Institute
, Canadae-mail: richard.leask@mcgill.ca
J Biomech Eng. Aug 2010, 132(8): 081013 (10 pages)
Published Online: July 29, 2010
Article history
Received:
July 8, 2009
Revised:
May 26, 2010
Posted:
May 31, 2010
Published:
July 29, 2010
Online:
July 29, 2010
Citation
Rouleau, L., Farcas, M., Tardif, J., Mongrain, R., and Leask, R. L. (July 29, 2010). "Endothelial Cell Morphologic Response to Asymmetric Stenosis Hemodynamics: Effects of Spatial Wall Shear Stress Gradients." ASME. J Biomech Eng. August 2010; 132(8): 081013. https://doi.org/10.1115/1.4001891
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