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Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo

Baeriswyl, DC; Prionisti, I; Peach, T; Tsolkas, G; Chooi, KY; Vardakis, J; Morel, S; ... Krams, R; + view all (2019) Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo. Scientific Reports , 9 , Article 4738. 10.1038/s41598-019-40959-y. Green open access

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Abstract

Intracranial aneurysms are associated with disturbed velocity patterns, and chronic inflammation, but the relevance for these findings are currently unknown. Here, we show that (disturbed) shear stress induced by vortices is a sufficient condition to activate the endothelial NF-kB pathway, possibly through a mechanism of mechanosensor de-activation. We provide evidence for this statement through in-vitro live cell imaging of NF-kB in HUVECs exposed to different flow conditions, stochastic modelling of flow induced NF-kB activation and induction of disturbed flow in mouse carotid arteries. Finally, CFD and immunofluorescence on human intracranial aneurysms showed a correlation similar to the mouse vessels, suggesting that disturbed shear stress may lead to sustained NF-kB activation thereby offering an explanation for the close association between disturbed flow and intracranial aneurysms.

Type: Article
Title: Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-019-40959-y
Publisher version: http://doi.org/10.1038/s41598-019-40959-y
Language: English
Additional information: Copyright © The Author(s) 2019. Open Access, This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10071550
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