The Piezo1 calcium-permeable channel is revealed to have a role in the vascular cellular response to shear stress; a mouse knockout reveals that this channel is also important for normal vascular development. The calcium-permeable ion channel Piezo1 is known to be a sensor for noxious mechanical stimuli. Here David Beech and colleagues identify the channel as an important component in the vascular response to the frictional force or shear stress experienced by the walls of the blood vessel as the blood passes through. They show that Piezo1 channels act as blood flow sensors, important for the alignment of endothelial cells in response to flow. The lack of Piezo1 specifically in endothelial cells leads to abnormal vascular development. These findings have implications for understanding vascular physiology and how it is affected by disease processes such as atherosclerosis and cancer, in which alterations in shear stress and other mechanical forces are common. The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic1,2,3,4,5. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca2+-permeable non-selective cationic channels for detection of noxious mechanical impact6,7,8. 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.

Piezo1 integration of vascular architecture with physiological force