Influence of shear stress magnitude and direction on atherosclerotic plaque composition

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Pedrigi RM, et al. Open Science 2016.pdfPublished version780.64 kBAdobe PDFView/Open
Title: Influence of shear stress magnitude and direction on atherosclerotic plaque composition
Authors: Pedrigi, RM
Mehta, VV
Bovens, SM
Mohri, Z
Poulsen, CB
Gsell, W
Tremoleda, JL
Towhidi, L
De Silva, R
Petretto, E
Krams, R
Item Type: Journal Article
Abstract: The precise flow characteristics that promote different atherosclerotic plaque types remain unclear. We previously developed a blood flow-modifying cuff for ApoE(-/-) mice that induces the development of advanced plaques with vulnerable and stable features upstream and downstream of the cuff, respectively. Herein, we sought to test the hypothesis that changes in flow magnitude promote formation of the upstream (vulnerable) plaque, whereas altered flow direction is important for development of the downstream (stable) plaque. We instrumented ApoE(-/-) mice (n = 7) with a cuff around the left carotid artery and imaged them with micro-CT (39.6 µm resolution) eight to nine weeks after cuff placement. Computational fluid dynamics was then performed to compute six metrics that describe different aspects of atherogenic flow in terms of wall shear stress magnitude and/or direction. In a subset of four imaged animals, we performed histology to confirm the presence of advanced plaques and measure plaque length in each segment. Relative to the control artery, the region upstream of the cuff exhibited changes in shear stress magnitude only (p < 0.05), whereas the region downstream of the cuff exhibited changes in shear stress magnitude and direction (p < 0.05). These data suggest that shear stress magnitude contributes to the formation of advanced plaques with a vulnerable phenotype, whereas variations in both magnitude and direction promote the formation of plaques with stable features.
Issue Date: 19-Oct-2016
Date of Acceptance: 19-Sep-2016
URI: http://hdl.handle.net/10044/1/43093
DOI: http://dx.doi.org/10.1098/rsos.160588
ISSN: 2054-5703
Publisher: Royal Society, The
Journal / Book Title: Royal Society Open Science
Volume: 3
Copyright Statement: © 2016 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, provided the original author and source are credited.
Sponsor/Funder: British Heart Foundation
CHUV
British Heart Foundation
Funder's Grant Number: RG/11/13/29055
CRS113/141811/1
PG/15/49/31595
Keywords: atherosclerosis
biomechanics
endothelial cell
haemodynamics
micro-computed tomography
thin cap fibroatheroma
Publication Status: Published
Conference Place: England
Article Number: 160588
Appears in Collections:Faculty of Engineering
Bioengineering
Institute of Clinical Sciences



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