Piezo1 integration of vascular architecture with physiological force.

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

    Research output: Contribution to journalArticlepeer-review

    404 Citations (Scopus)


    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 Ca 2+ -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
    Issue number7526
    Publication statusPublished - 13 Nov 2014


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