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Disturbed Cyclical Stretch of Endothelial Cells Promotes Nuclear Expression of the Pro-Atherogenic Transcription Factor NF-κB

Pedrigi, RM; Papadimitriou, KI; Kondiboyina, A; Sidhu, S; Chau, J; Patel, MB; Baeriswyl, DC; ... Krams, R; + view all (2017) Disturbed Cyclical Stretch of Endothelial Cells Promotes Nuclear Expression of the Pro-Atherogenic Transcription Factor NF-κB. Annals of Biomedical Engineering , 45 (4) pp. 898-909. 10.1007/s10439-016-1750-z. Green open access

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Abstract

Exposure of endothelial cells to low and multidirectional blood flow is known to promote a pro-atherogenic phenotype. The mechanics of the vessel wall is another important mechano-stimulus within the endothelial cell environment, but no study has examined whether changes in the magnitude and direction of cell stretch can be pro-atherogenic. Herein, we developed a custom cell stretching device to replicate the in vivo stretch environment of the endothelial cell and examined whether low and multidirectional stretch promote nuclear translocation of NF-κB. A fluid–structure interaction model of the device demonstrated a nearly uniform strain within the region of cell attachment and a negligible magnitude of shear stress due to cyclical stretching of the cells in media. Compared to normal cyclical stretch, a low magnitude of cyclical stretch or no stretch caused increased expression of nuclear NF-κB (p = 0.09 and p < 0.001, respectively). Multidirectional stretch also promoted significant nuclear NF-κB expression, comparable to the no stretch condition, which was statistically higher than the low (p < 0.001) and normal (p < 0.001) stretch conditions. This is the first study to show that stretch conditions analogous to atherogenic blood flow profiles can similarly promote a pro-atherogenic endothelial cell phenotype, which supports a role for disturbed vessel wall mechanics as a pathological cell stimulus in the development of advanced atherosclerotic plaques.

Type: Article
Title: Disturbed Cyclical Stretch of Endothelial Cells Promotes Nuclear Expression of the Pro-Atherogenic Transcription Factor NF-κB
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s10439-016-1750-z
Publisher version: http://dx.doi.org/10.1007/s10439-016-1750-z
Language: English
Additional information: Copyright © The Author(s) 2016. Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Keywords: Atherosclerosis, Mechanobiology, Biomechanics, Strain, Shear stress, Fluid–structure interaction, Advanced plaques, Thin cap fibroatheroma, Nuclear factor kappa b
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
URI: https://discovery.ucl.ac.uk/id/eprint/1556151
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