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Highly variable contractile performance correlates with myocyte content in trabeculae from failing human hearts
Heart failure (HF) is defined by compromised contractile function and is associated with changes in excitation-contraction (EC) coupling and cardiomyocyte organisation. Tissue level changes often include fibrosis, while changes within cardiomyocytes often affect structures critical to EC coupling, i...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811450/ https://www.ncbi.nlm.nih.gov/pubmed/29440728 http://dx.doi.org/10.1038/s41598-018-21199-y |
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author | Munro, Michelle L. Shen, Xin Ward, Marie Ruygrok, Peter N. Crossman, David J. Soeller, Christian |
author_facet | Munro, Michelle L. Shen, Xin Ward, Marie Ruygrok, Peter N. Crossman, David J. Soeller, Christian |
author_sort | Munro, Michelle L. |
collection | PubMed |
description | Heart failure (HF) is defined by compromised contractile function and is associated with changes in excitation-contraction (EC) coupling and cardiomyocyte organisation. Tissue level changes often include fibrosis, while changes within cardiomyocytes often affect structures critical to EC coupling, including the ryanodine receptor (RyR), the associated protein junctophilin-2 (JPH2) and the transverse tubular system architecture. Using a novel approach, we aimed to directly correlate the influence of structural alterations with force development in ventricular trabeculae from failing human hearts. Trabeculae were excised from explanted human hearts in end-stage failure and immediately subjected to force measurements. Following functional experiments, each trabecula was fixed, sectioned and immuno-stained for structural investigations. Peak stress was highly variable between trabeculae from both within and between failing hearts and was strongly correlated with the cross-sectional area occupied by myocytes (MCSA), rather than total trabecula cross-sectional area. At the cellular level, myocytes exhibited extensive microtubule densification which was linked via JPH2 to time-to-peak stress. Trabeculae fractional MCSA variability was much higher than that in adjacent free wall samples. Together, these findings identify several structural parameters implicated in functional impairment in human HF and highlight the structural variability of ventricular trabeculae which should be considered when interpreting functional data. |
format | Online Article Text |
id | pubmed-5811450 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58114502018-02-16 Highly variable contractile performance correlates with myocyte content in trabeculae from failing human hearts Munro, Michelle L. Shen, Xin Ward, Marie Ruygrok, Peter N. Crossman, David J. Soeller, Christian Sci Rep Article Heart failure (HF) is defined by compromised contractile function and is associated with changes in excitation-contraction (EC) coupling and cardiomyocyte organisation. Tissue level changes often include fibrosis, while changes within cardiomyocytes often affect structures critical to EC coupling, including the ryanodine receptor (RyR), the associated protein junctophilin-2 (JPH2) and the transverse tubular system architecture. Using a novel approach, we aimed to directly correlate the influence of structural alterations with force development in ventricular trabeculae from failing human hearts. Trabeculae were excised from explanted human hearts in end-stage failure and immediately subjected to force measurements. Following functional experiments, each trabecula was fixed, sectioned and immuno-stained for structural investigations. Peak stress was highly variable between trabeculae from both within and between failing hearts and was strongly correlated with the cross-sectional area occupied by myocytes (MCSA), rather than total trabecula cross-sectional area. At the cellular level, myocytes exhibited extensive microtubule densification which was linked via JPH2 to time-to-peak stress. Trabeculae fractional MCSA variability was much higher than that in adjacent free wall samples. Together, these findings identify several structural parameters implicated in functional impairment in human HF and highlight the structural variability of ventricular trabeculae which should be considered when interpreting functional data. Nature Publishing Group UK 2018-02-13 /pmc/articles/PMC5811450/ /pubmed/29440728 http://dx.doi.org/10.1038/s41598-018-21199-y Text en © The Author(s) 2018 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 Munro, Michelle L. Shen, Xin Ward, Marie Ruygrok, Peter N. Crossman, David J. Soeller, Christian Highly variable contractile performance correlates with myocyte content in trabeculae from failing human hearts |
title | Highly variable contractile performance correlates with myocyte content in trabeculae from failing human hearts |
title_full | Highly variable contractile performance correlates with myocyte content in trabeculae from failing human hearts |
title_fullStr | Highly variable contractile performance correlates with myocyte content in trabeculae from failing human hearts |
title_full_unstemmed | Highly variable contractile performance correlates with myocyte content in trabeculae from failing human hearts |
title_short | Highly variable contractile performance correlates with myocyte content in trabeculae from failing human hearts |
title_sort | highly variable contractile performance correlates with myocyte content in trabeculae from failing human hearts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811450/ https://www.ncbi.nlm.nih.gov/pubmed/29440728 http://dx.doi.org/10.1038/s41598-018-21199-y |
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