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The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870949/ https://www.ncbi.nlm.nih.gov/pubmed/33558521 http://dx.doi.org/10.1038/s41467-021-21178-4 |
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author | Jiang, Fan Yin, Kunlun Wu, Kun Zhang, Mingmin Wang, Shiqiang Cheng, Heping Zhou, Zhou Xiao, Bailong |
author_facet | Jiang, Fan Yin, Kunlun Wu, Kun Zhang, Mingmin Wang, Shiqiang Cheng, Heping Zhou, Zhou Xiao, Bailong |
author_sort | Jiang, Fan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7870949 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78709492021-02-11 The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction Jiang, Fan Yin, Kunlun Wu, Kun Zhang, Mingmin Wang, Shiqiang Cheng, Heping Zhou, Zhou Xiao, Bailong Nat Commun Article 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. Nature Publishing Group UK 2021-02-08 /pmc/articles/PMC7870949/ /pubmed/33558521 http://dx.doi.org/10.1038/s41467-021-21178-4 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Jiang, Fan Yin, Kunlun Wu, Kun Zhang, Mingmin Wang, Shiqiang Cheng, Heping Zhou, Zhou Xiao, Bailong The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction |
title | The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction |
title_full | The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction |
title_fullStr | The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction |
title_full_unstemmed | The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction |
title_short | The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction |
title_sort | mechanosensitive piezo1 channel mediates heart mechano-chemo transduction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870949/ https://www.ncbi.nlm.nih.gov/pubmed/33558521 http://dx.doi.org/10.1038/s41467-021-21178-4 |
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