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Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo
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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426999/ https://www.ncbi.nlm.nih.gov/pubmed/30894565 http://dx.doi.org/10.1038/s41598-019-40959-y |
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author | Baeriswyl, Daniel C. Prionisti, Ioanna Peach, Tom Tsolkas, Grigoris Chooi, Kok Yean Vardakis, John Morel, Sandrine Diagbouga, Mannekomba R. Bijlenga, Philippe Cuhlmann, Simon Evans, Paul Kwak, Brenda R. Ventikos, Yiannis Krams, Rob |
author_facet | Baeriswyl, Daniel C. Prionisti, Ioanna Peach, Tom Tsolkas, Grigoris Chooi, Kok Yean Vardakis, John Morel, Sandrine Diagbouga, Mannekomba R. Bijlenga, Philippe Cuhlmann, Simon Evans, Paul Kwak, Brenda R. Ventikos, Yiannis Krams, Rob |
author_sort | Baeriswyl, Daniel C. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6426999 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64269992019-03-28 Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo Baeriswyl, Daniel C. Prionisti, Ioanna Peach, Tom Tsolkas, Grigoris Chooi, Kok Yean Vardakis, John Morel, Sandrine Diagbouga, Mannekomba R. Bijlenga, Philippe Cuhlmann, Simon Evans, Paul Kwak, Brenda R. Ventikos, Yiannis Krams, Rob Sci Rep Article 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. Nature Publishing Group UK 2019-03-18 /pmc/articles/PMC6426999/ /pubmed/30894565 http://dx.doi.org/10.1038/s41598-019-40959-y Text en © 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. The 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/. |
spellingShingle | Article Baeriswyl, Daniel C. Prionisti, Ioanna Peach, Tom Tsolkas, Grigoris Chooi, Kok Yean Vardakis, John Morel, Sandrine Diagbouga, Mannekomba R. Bijlenga, Philippe Cuhlmann, Simon Evans, Paul Kwak, Brenda R. Ventikos, Yiannis Krams, Rob Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo |
title | Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo |
title_full | Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo |
title_fullStr | Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo |
title_full_unstemmed | Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo |
title_short | Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo |
title_sort | disturbed flow induces a sustained, stochastic nf-κb activation which may support intracranial aneurysm growth in vivo |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426999/ https://www.ncbi.nlm.nih.gov/pubmed/30894565 http://dx.doi.org/10.1038/s41598-019-40959-y |
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