Piezo1 integration of vascular architecture with physiological force

Jing Li, Bing Hou, Sarka Tumova, Katsuhiko Muraki, Alexander Bruns, Melanie J. Ludlow, Alicia Sedo, Adam J. Hyman, Lynn McKeown, Richard S. Young, Nadira Y. Yuldasheva, Yasser Majeed, Lesley A. Wilson, Baptiste Rode, Marc A. Bailey, Hyejeong R. Kim, Zhaojun Fu, Deborah A.L. Carter, Jan Bilton, Helen ImriePaul Ajuh, T. Neil Dear, Richard M. Cubbon, Mark T. Kearney, K. Raj Prasad, Paul C. Evans, Justin F.X. Ainscough, David J. Beech

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Abstract

The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca2+ -permeable non-selective cationic channels for detection of noxious mechanical impact. Here we show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezo1 channels as sensors of blood flow was shown by Piezo1 dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer sensitivity to shear stress on otherwise resistant cells. Downstream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezo1 channels function as pivotal integrators in vascular biology.

Original languageEnglish
Pages (from-to)279-282
Number of pages4
JournalNature
Volume515
Issue number7526
DOIs
Publication statusPublished - 13 Nov 2014
Externally publishedYes

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ASJC Scopus subject areas

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Cite this

Li, J., Hou, B., Tumova, S., Muraki, K., Bruns, A., Ludlow, M. J., Sedo, A., Hyman, A. J., McKeown, L., Young, R. S., Yuldasheva, N. Y., Majeed, Y., Wilson, L. A., Rode, B., Bailey, M. A., Kim, H. R., Fu, Z., Carter, D. A. L., Bilton, J., ... Beech, D. J. (2014). Piezo1 integration of vascular architecture with physiological force. Nature, 515(7526), 279-282. https://doi.org/10.1038/nature13701