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Publication : The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction.

First Author  Jiang F Year  2021
Journal  Nat Commun Volume  12
Issue  1 Pages  869
PubMed ID  33558521 Mgi Jnum  J:302358
Mgi Id  MGI:6508205 Doi  10.1038/s41467-021-21178-4
Citation  Jiang F, et al. (2021) The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction. Nat Commun 12(1):869
abstractText  The beating heart possesses the intrinsic ability to adapt cardiac output to changes in mechanical load. The century-old Frank-Starling law and Anrep effect have documented that stretching the heart during diastolic filling increases its contractile force. However, the molecular mechanotransduction mechanism and its impact on cardiac health and disease remain elusive. Here we show that the mechanically activated Piezo1 channel converts mechanical stretch of cardiomyocytes into Ca(2+) and reactive oxygen species (ROS) signaling, which critically determines the mechanical activity of the heart. Either cardiac-specific knockout or overexpression of Piezo1 in mice results in defective Ca(2+) and ROS signaling and the development of cardiomyopathy, demonstrating a homeostatic role of Piezo1. Piezo1 is pathologically upregulated in both mouse and human diseased hearts via an autonomic response of cardiomyocytes. Thus, Piezo1 serves as a key cardiac mechanotransducer for initiating mechano-chemo transduction and consequently maintaining normal heart function, and might represent a novel therapeutic target for treating human heart diseases.
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