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Cardiac sarcomere mechanics in health and disease
The sarcomere is the fundamental structural and functional unit of striated muscle and is directly responsible for most of its mechanical properties. The sarcomere generates active or contractile forces and determines the passive or elastic properties of striated muscle. In the heart, mutations in s...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553709/ https://www.ncbi.nlm.nih.gov/pubmed/34745372 http://dx.doi.org/10.1007/s12551-021-00840-7 |
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author | Crocini, Claudia Gotthardt, Michael |
author_facet | Crocini, Claudia Gotthardt, Michael |
author_sort | Crocini, Claudia |
collection | PubMed |
description | The sarcomere is the fundamental structural and functional unit of striated muscle and is directly responsible for most of its mechanical properties. The sarcomere generates active or contractile forces and determines the passive or elastic properties of striated muscle. In the heart, mutations in sarcomeric proteins are responsible for the majority of genetically inherited cardiomyopathies. Here, we review the major determinants of cardiac sarcomere mechanics including the key structural components that contribute to active and passive tension. We dissect the molecular and structural basis of active force generation, including sarcomere composition, structure, activation, and relaxation. We then explore the giant sarcomere-resident protein titin, the major contributor to cardiac passive tension. We discuss sarcomere dynamics exemplified by the regulation of titin-based stiffness and the titin life cycle. Finally, we provide an overview of therapeutic strategies that target the sarcomere to improve cardiac contraction and filling. |
format | Online Article Text |
id | pubmed-8553709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-85537092021-11-04 Cardiac sarcomere mechanics in health and disease Crocini, Claudia Gotthardt, Michael Biophys Rev Review The sarcomere is the fundamental structural and functional unit of striated muscle and is directly responsible for most of its mechanical properties. The sarcomere generates active or contractile forces and determines the passive or elastic properties of striated muscle. In the heart, mutations in sarcomeric proteins are responsible for the majority of genetically inherited cardiomyopathies. Here, we review the major determinants of cardiac sarcomere mechanics including the key structural components that contribute to active and passive tension. We dissect the molecular and structural basis of active force generation, including sarcomere composition, structure, activation, and relaxation. We then explore the giant sarcomere-resident protein titin, the major contributor to cardiac passive tension. We discuss sarcomere dynamics exemplified by the regulation of titin-based stiffness and the titin life cycle. Finally, we provide an overview of therapeutic strategies that target the sarcomere to improve cardiac contraction and filling. Springer Berlin Heidelberg 2021-10-12 /pmc/articles/PMC8553709/ /pubmed/34745372 http://dx.doi.org/10.1007/s12551-021-00840-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Crocini, Claudia Gotthardt, Michael Cardiac sarcomere mechanics in health and disease |
title | Cardiac sarcomere mechanics in health and disease |
title_full | Cardiac sarcomere mechanics in health and disease |
title_fullStr | Cardiac sarcomere mechanics in health and disease |
title_full_unstemmed | Cardiac sarcomere mechanics in health and disease |
title_short | Cardiac sarcomere mechanics in health and disease |
title_sort | cardiac sarcomere mechanics in health and disease |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553709/ https://www.ncbi.nlm.nih.gov/pubmed/34745372 http://dx.doi.org/10.1007/s12551-021-00840-7 |
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