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 Imrie & 8 others Paul Ajuh, T. Neil Dear, Richard M. Cubbon, Mark T. Kearney, K. Raj Prasad, Paul C. Evans, Justin F. X. Ainscough, David J. Beech

    Research output: Contribution to journalLetter

    226 Citations (Scopus)

    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 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)279-82
    Number of pages4
    JournalNature
    Volume515
    Issue number7526
    DOIs
    Publication statusPublished - 13 Nov 2014

    Fingerprint

    Blood Vessels
    Endothelial Cells
    Calcium
    Haploinsufficiency
    Cell Polarity
    Protein Subunits
    Sensory Receptor Cells
    Peptide Hydrolases

    Keywords

    • Animals
    • Embryo, Mammalian
    • Endothelial Cells
    • Female
    • Friction
    • Hemorheology
    • Ion Channels
    • Male
    • Mice
    • Stress, Mechanical

    Cite this

    Li, J., Hou, B., Tumova, S., Muraki, K., Bruns, A., Ludlow, M. J., ... Beech, D. J. (2014). Piezo1 integration of vascular architecture with physiological force. Nature, 515(7526), 279-82. https://doi.org/10.1038/nature13701
    Li, Jing ; Hou, Bing ; Tumova, Sarka ; Muraki, Katsuhiko ; Bruns, Alexander ; Ludlow, Melanie J. ; Sedo, Alicia ; Hyman, Adam J. ; McKeown, Lynn ; Young, Richard S. ; Yuldasheva, Nadira Y. ; Majeed, Yasser ; Wilson, Lesley A. ; Rode, Baptiste ; Bailey, Marc A. ; Kim, Hyejeong R. ; Fu, Zhaojun ; Carter, Deborah A. L. ; Bilton, Jan ; Imrie, Helen ; Ajuh, Paul ; Dear, T. Neil ; Cubbon, Richard M. ; Kearney, Mark T. ; Prasad, K. Raj ; Evans, Paul C. ; Ainscough, Justin F. X. ; Beech, David J. / Piezo1 integration of vascular architecture with physiological force. In: Nature. 2014 ; Vol. 515, No. 7526. pp. 279-82.
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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 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.",
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    author = "Jing Li and Bing Hou and Sarka Tumova and Katsuhiko Muraki and Alexander Bruns and Ludlow, {Melanie J.} and Alicia Sedo and Hyman, {Adam J.} and Lynn McKeown and Young, {Richard S.} and Yuldasheva, {Nadira Y.} and Yasser Majeed and Wilson, {Lesley A.} and Baptiste Rode and Bailey, {Marc A.} and Kim, {Hyejeong R.} and Zhaojun Fu and Carter, {Deborah A. L.} and Jan Bilton and Helen Imrie and Paul Ajuh and Dear, {T. Neil} and Cubbon, {Richard M.} and Kearney, {Mark T.} and Prasad, {K. Raj} and Evans, {Paul C.} and Ainscough, {Justin F. X.} and Beech, {David J.}",
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    Li, J, Hou, B, Tumova, S, Muraki, K, Bruns, A, Ludlow, MJ, Sedo, A, Hyman, AJ, McKeown, L, Young, RS, Yuldasheva, NY, Majeed, Y, Wilson, LA, Rode, B, Bailey, MA, Kim, HR, Fu, Z, Carter, DAL, Bilton, J, Imrie, H, Ajuh, P, Dear, TN, Cubbon, RM, Kearney, MT, Prasad, KR, Evans, PC, Ainscough, JFX & Beech, DJ 2014, 'Piezo1 integration of vascular architecture with physiological force', Nature, vol. 515, no. 7526, pp. 279-82. https://doi.org/10.1038/nature13701

    Piezo1 integration of vascular architecture with physiological force. / Li, Jing; Hou, Bing; Tumova, Sarka; Muraki, Katsuhiko; Bruns, Alexander; Ludlow, Melanie J.; Sedo, Alicia; Hyman, Adam J.; McKeown, Lynn; Young, Richard S.; Yuldasheva, Nadira Y.; Majeed, Yasser; Wilson, Lesley A.; Rode, Baptiste; Bailey, Marc A.; Kim, Hyejeong R.; Fu, Zhaojun; Carter, Deborah A. L.; Bilton, Jan; Imrie, Helen; Ajuh, Paul; Dear, T. Neil; Cubbon, Richard M.; Kearney, Mark T.; Prasad, K. Raj; Evans, Paul C.; Ainscough, Justin F. X.; Beech, David J.

    In: Nature, Vol. 515, No. 7526, 13.11.2014, p. 279-82.

    Research output: Contribution to journalLetter

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    T1 - Piezo1 integration of vascular architecture with physiological force

    AU - Li, Jing

    AU - Hou, Bing

    AU - Tumova, Sarka

    AU - Muraki, Katsuhiko

    AU - Bruns, Alexander

    AU - Ludlow, Melanie J.

    AU - Sedo, Alicia

    AU - Hyman, Adam J.

    AU - McKeown, Lynn

    AU - Young, Richard S.

    AU - Yuldasheva, Nadira Y.

    AU - Majeed, Yasser

    AU - Wilson, Lesley A.

    AU - Rode, Baptiste

    AU - Bailey, Marc A.

    AU - Kim, Hyejeong R.

    AU - Fu, Zhaojun

    AU - Carter, Deborah A. L.

    AU - Bilton, Jan

    AU - Imrie, Helen

    AU - Ajuh, Paul

    AU - Dear, T. Neil

    AU - Cubbon, Richard M.

    AU - Kearney, Mark T.

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    AU - Ainscough, Justin F. X.

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    N2 - 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.

    AB - 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.

    KW - Animals

    KW - Embryo, Mammalian

    KW - Endothelial Cells

    KW - Female

    KW - Friction

    KW - Hemorheology

    KW - Ion Channels

    KW - Male

    KW - Mice

    KW - Stress, Mechanical

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    Li J, Hou B, Tumova S, Muraki K, Bruns A, Ludlow MJ et al. Piezo1 integration of vascular architecture with physiological force. Nature. 2014 Nov 13;515(7526):279-82. https://doi.org/10.1038/nature13701