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

Daniel C. Baeriswyl; Ioanna Prionisti; Tom Peach; Grigoris Tsolkas; Kok Yean Chooi; John Vardakis; Sandrine Morel; Mannekomba R. Diagbouga; Philippe Bijlenga; Simon Cuhlmann; Paul Evans; Brenda R. Kwak; Yiannis Ventikos; Rob Krams

doi:10.1038/s41598-019-40959-y

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

Daniel C. Baeriswyl, Ioanna Prionisti, Tom Peach, Grigoris Tsolkas, Kok Yean Chooi, John Vardakis, Sandrine Morel, Mannekomba R. Diagbouga, Philippe Bijlenga, Simon Cuhlmann, Paul Evans, Brenda R. Kwak, Yiannis Ventikos, Rob Krams

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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.

Original language	English
Article number	4738
Number of pages	14
Journal	Scientific Reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-40959-y
Publication status	Published - 18 Mar 2019
Externally published	Yes

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Baeriswyl, D. C., Prionisti, I., Peach, T., Tsolkas, G., Chooi, K. Y., Vardakis, J., Morel, S., Diagbouga, M. R., Bijlenga, P., Cuhlmann, S., Evans, P., Kwak, B. R., Ventikos, Y., & Krams, R. (2019). Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo. Scientific Reports, 9(1), Article 4738. https://doi.org/10.1038/s41598-019-40959-y

@article{6e5728e084184dc19f1ea90af4b3978c,

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

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.",

author = "Baeriswyl, {Daniel C.} and Ioanna Prionisti and Tom Peach and Grigoris Tsolkas and Chooi, {Kok Yean} and John Vardakis and Sandrine Morel and Diagbouga, {Mannekomba R.} and Philippe Bijlenga and Simon Cuhlmann and Paul Evans and Kwak, {Brenda R.} and Yiannis Ventikos and Rob Krams",

note = "Funding Information: We thank the facility for imaging by light microscopy (FILM), Faculity of Medicine, Imperial College London and in particular Stephen Rothery for his technical support. We thank the Bioimaging core facility, Faculty of Medicine, University of Geneva for technical help. We also would like to thank the ESI Group for allowing the use of the CFD-ACE suite. This work was supported by grants from the Swiss SystemsX.ch initiative, evaluated by the Swiss National Science Foundation (to PB and BRK) and the Foundation Carlos et Elsie De Reuter (to BRK and PB), and by the BHF (RG/11/13/29055) to RK, and a DocMobility stipend from the Swiss National Science Foundation to Daniel Baeriswyl. The Facility for Imaging by Light Microscopy (FILM) at Imperial College London is part-supported by funding from the Wellcome Trust (grant 104931/Z/14/Z) and BBSRC (grant BB/L015129/1). Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = mar,

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doi = "10.1038/s41598-019-40959-y",

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Baeriswyl, DC, Prionisti, I, Peach, T, Tsolkas, G, Chooi, KY, Vardakis, J, Morel, S, Diagbouga, MR, Bijlenga, P, Cuhlmann, S, Evans, P, Kwak, BR, Ventikos, Y & Krams, R 2019, 'Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo', Scientific Reports, vol. 9, no. 1, 4738. https://doi.org/10.1038/s41598-019-40959-y

TY - JOUR

T1 - Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo

AU - Baeriswyl, Daniel C.

AU - Prionisti, Ioanna

AU - Peach, Tom

AU - Tsolkas, Grigoris

AU - Chooi, Kok Yean

AU - Vardakis, John

AU - Morel, Sandrine

AU - Diagbouga, Mannekomba R.

AU - Bijlenga, Philippe

AU - Cuhlmann, Simon

AU - Evans, Paul

AU - Kwak, Brenda R.

AU - Ventikos, Yiannis

AU - Krams, Rob

N1 - Funding Information: We thank the facility for imaging by light microscopy (FILM), Faculity of Medicine, Imperial College London and in particular Stephen Rothery for his technical support. We thank the Bioimaging core facility, Faculty of Medicine, University of Geneva for technical help. We also would like to thank the ESI Group for allowing the use of the CFD-ACE suite. This work was supported by grants from the Swiss SystemsX.ch initiative, evaluated by the Swiss National Science Foundation (to PB and BRK) and the Foundation Carlos et Elsie De Reuter (to BRK and PB), and by the BHF (RG/11/13/29055) to RK, and a DocMobility stipend from the Swiss National Science Foundation to Daniel Baeriswyl. The Facility for Imaging by Light Microscopy (FILM) at Imperial College London is part-supported by funding from the Wellcome Trust (grant 104931/Z/14/Z) and BBSRC (grant BB/L015129/1). Publisher Copyright: © 2019, The Author(s).

PY - 2019/3/18

Y1 - 2019/3/18

N2 - 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.

AB - 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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U2 - 10.1038/s41598-019-40959-y

DO - 10.1038/s41598-019-40959-y

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C2 - 30894565

AN - SCOPUS:85063341966

SN - 2045-2322

VL - 9

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 4738

ER -

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

Abstract

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