Format

Send to

Choose Destination
Sci Rep. 2019 Mar 18;9(1):4738. doi: 10.1038/s41598-019-40959-y.

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

Author information

1
Department Mechanical Engineering, University College London, London, UK.
2
Department Bioengineering, Imperial College London, London, UK.
3
SEMS, Queen Mary University London, London, UK.
4
Department Pathology and Immunology, University of Geneva, Geneva, Switzerland.
5
Department Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland.
6
Department Medicine, University of Sheffield, Sheffield, UK.
7
Department Bioengineering, Imperial College London, London, UK. r.krams@qmul.ac.uk.
8
SEMS, Queen Mary University London, London, UK. r.krams@qmul.ac.uk.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center