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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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.
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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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