Piezo1 integration of vascular architecture with physiological force

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.

DOI: 10.1038/nature13701

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@inproceedings{Li2014Piezo1IO, title={Piezo1 integration of vascular architecture with physiological force}, author={Jing Li and Bing Hou and Sarka Tumova and Katsuhiko Muraki and Alexander F. Bruns and Melanie J. Ludlow and Alicia Sedo and Adam J. Hyman and Lynn Mckeown and Richard Shih-Hung Young and Nadira Y. Yuldasheva and Yasser Majeed and Lesley A. Wilson and Baptiste Rode and Marc Aaron Bailey and Hyejeong Rosemary Kim and Zhaojun Fu and Deborah AL Carter and Jan Bilton and Helen Imrie and Paul M Ajuh and T. Neil Dear and Richard M Cubbon and Mark T Kearney and Raj Kumar Prasad and Paul C . Evans and Justin FX Ainscough and David Beech}, booktitle={Nature}, year={2014} }