Non-canonical Wnt signalling modulates the endothelial shear stress flow sensor in vascular remodelling
- London Research Institute, United Kingdom
- The University of Edinburgh, United Kingdom
- Faculdade de Medicina Universidade de Lisboa, Portugal
- Cincinnati Children's Hospital Medical Center, United States
- Vesalius Research Center, Belgium
- National Institutes of Health, United States
- University College London, United Kingdom
- Cited 45
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Abstract
Endothelial cells respond to molecular and physical forces in development and vascular homeostasis. Deregulation of endothelial responses to flow-induced shear is believed to contribute to many aspects of cardiovascular diseases including atherosclerosis. However, how molecular signals and shear-mediated physical forces integrate to regulate vascular patterning is poorly understood. Here we show that endothelial non-canonical Wnt signalling regulates endothelial sensitivity to shear forces. Loss of Wnt5a/Wnt11 renders endothelial cells more sensitive to shear, resulting in axial polarization and migration against flow at lower shear levels. Integration of flow modelling and polarity analysis in entire vascular networks demonstrates that polarization against flow is achieved differentially in artery, vein, capillaries and the primitive sprouting front. Collectively our data suggest that non-canonical Wnt signalling stabilizes forming vascular networks by reducing endothelial shear sensitivity, thus keeping vessels open under low flow conditions that prevail in the primitive plexus.
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Ethics
Animal experimentation: Animal procedures were performed in accordance with the United Kingdom Home Office Animal Act 1986 under the authority of project license PPL 80/2391.
Reviewing Editor
- Ewa Paluch, University College London, United Kingdom
Publication history
- Received: March 26, 2015
- Accepted: February 3, 2016
- Accepted Manuscript published: February 4, 2016 (version 1)
- Version of Record published: March 11, 2016 (version 2)
Copyright
© 2016, Franco et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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