title: Influence of shear stress magnitude and direction on atherosclerotic plaque composition.
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.
authors.affiliation: Department of Bioengineering , Imperial College London , London , UK.
authors.forename: Ryan M
authors.identifier: 0000-0003-1099-1859
authors.initials: RM
authors.lastname: Pedrigi
authors.affiliation: Department of Bioengineering , Imperial College London , London , UK.
authors.forename: Vikram V
authors.initials: VV
authors.lastname: Mehta
authors.affiliation: Department of Bioengineering , Imperial College London , London , UK.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Bovens
authors.affiliation: Department of Bioengineering , Imperial College London , London , UK.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Mohri
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology , Aarhus , Denmark.
authors.forename: Christian Bo
authors.initials: CB
authors.lastname: Poulsen
authors.affiliation: MRC-Clinical Sciences Centre, Imperial College London, London, UK; Biomedical MRI, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Willy
authors.initials: W
authors.lastname: Gsell
authors.affiliation: MRC-Clinical Sciences Centre, Imperial College London, London, UK; Centre for Trauma Sciences, Queen Mary University of London, London, UK.
authors.forename: Jordi L
authors.initials: JL
authors.lastname: Tremoleda
authors.affiliation: Department of Bioengineering , Imperial College London , London , UK.
authors.forename: Leila
authors.initials: L
authors.lastname: Towhidi
authors.affiliation: National Heart and Lung Institute , Imperial College London , London , UK.
authors.forename: Ranil
authors.initials: R
authors.lastname: de Silva
authors.affiliation: MRC-Clinical Sciences Centre, Imperial College London, London, UK; Duke-NUS Medical School, Singapore, Republic of Singapore.
authors.forename: Enrico
authors.initials: E
authors.lastname: Petretto
authors.affiliation: Department of Bioengineering , Imperial College London , London , UK.
authors.forename: Rob
authors.initials: R
authors.lastname: Krams
keywords: atherosclerosis; biomechanics; endothelial cell; haemodynamics; micro-computed tomography; thin cap fibroatheroma