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Cardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program
Cardiac regeneration post-injury is a tantalizing feature of many lower vertebrates such as fishes and urodeles, but absent in adult humans. Restoration of pumping function is a key endpoint of cardiac regeneration, but very little is known about the biomechanical remodeling process. Here, we quanti...
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/PMC6199254/ https://www.ncbi.nlm.nih.gov/pubmed/30353076 http://dx.doi.org/10.1038/s41598-018-33994-8 |
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author | Yu, Joseph K. Sarathchandra, Padmini Chester, Adrian Yacoub, Magdi Brand, Thomas Butcher, Jonathan T. |
author_facet | Yu, Joseph K. Sarathchandra, Padmini Chester, Adrian Yacoub, Magdi Brand, Thomas Butcher, Jonathan T. |
author_sort | Yu, Joseph K. |
collection | PubMed |
description | Cardiac regeneration post-injury is a tantalizing feature of many lower vertebrates such as fishes and urodeles, but absent in adult humans. Restoration of pumping function is a key endpoint of cardiac regeneration, but very little is known about the biomechanical remodeling process. Here, we quantify and compare the evolution of cellular composition and mechanical stiffness of the zebrafish ventricular myocardium during maturation and following cryoinjury during regeneration to better understand the dynamics of biomechanical remodeling during these two processes. With increasing age, normal myocardial trabecular density and cardiomyocyte fraction increased, while non-myocyte cell fractions decreased. Cell density remained constant during maturation. Cardiomyocyte sarcomeres shortened to a minimum reached at 7.5 months of age, but lengthened with additional age. Concomitantly, ventricular wall stiffness increased up until 7.5 months before plateauing with additional age. Endothelial, myofibroblast/smooth muscle, and cardiomyocyte cell fractions were disrupted following cryoinjury, but were progressively restored to age-specific natural norms by 35 days post infarct (DPI). Infarcted myocardium stiffened immediately following cryoinjury and was a 100-fold greater than non-infarcted tissue by 3 DPI. By 14 DPI, stiffness of the infarcted myocardium had fallen below that of 0 DPI and had completely normalized by 35 DPI. Interestingly, cardiomyocyte sarcomere length increased until 14 DPI, but subsequently shortened to lengths below age-specific natural norms, indicating recovery from a volume overloaded condition. These observations are consistent with the view that regenerating myocardium requires biomechanical stimulation (e.g. strain) to rescue from a volume overloaded condition. Intriguingly, the biomechanical progression of the infarcted adult myocardial wall mirrors that of normal remodeling during aging. The biomechanical progression of the infarcted myocardium targets the values of age-specific norms despite a large divergence in initial conditions. These findings identify a novel biomechanical control of heart regeneration that may orchestrate cellular and tissue level remodeling responses. |
format | Online Article Text |
id | pubmed-6199254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61992542018-10-25 Cardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program Yu, Joseph K. Sarathchandra, Padmini Chester, Adrian Yacoub, Magdi Brand, Thomas Butcher, Jonathan T. Sci Rep Article Cardiac regeneration post-injury is a tantalizing feature of many lower vertebrates such as fishes and urodeles, but absent in adult humans. Restoration of pumping function is a key endpoint of cardiac regeneration, but very little is known about the biomechanical remodeling process. Here, we quantify and compare the evolution of cellular composition and mechanical stiffness of the zebrafish ventricular myocardium during maturation and following cryoinjury during regeneration to better understand the dynamics of biomechanical remodeling during these two processes. With increasing age, normal myocardial trabecular density and cardiomyocyte fraction increased, while non-myocyte cell fractions decreased. Cell density remained constant during maturation. Cardiomyocyte sarcomeres shortened to a minimum reached at 7.5 months of age, but lengthened with additional age. Concomitantly, ventricular wall stiffness increased up until 7.5 months before plateauing with additional age. Endothelial, myofibroblast/smooth muscle, and cardiomyocyte cell fractions were disrupted following cryoinjury, but were progressively restored to age-specific natural norms by 35 days post infarct (DPI). Infarcted myocardium stiffened immediately following cryoinjury and was a 100-fold greater than non-infarcted tissue by 3 DPI. By 14 DPI, stiffness of the infarcted myocardium had fallen below that of 0 DPI and had completely normalized by 35 DPI. Interestingly, cardiomyocyte sarcomere length increased until 14 DPI, but subsequently shortened to lengths below age-specific natural norms, indicating recovery from a volume overloaded condition. These observations are consistent with the view that regenerating myocardium requires biomechanical stimulation (e.g. strain) to rescue from a volume overloaded condition. Intriguingly, the biomechanical progression of the infarcted adult myocardial wall mirrors that of normal remodeling during aging. The biomechanical progression of the infarcted myocardium targets the values of age-specific norms despite a large divergence in initial conditions. These findings identify a novel biomechanical control of heart regeneration that may orchestrate cellular and tissue level remodeling responses. Nature Publishing Group UK 2018-10-23 /pmc/articles/PMC6199254/ /pubmed/30353076 http://dx.doi.org/10.1038/s41598-018-33994-8 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 Yu, Joseph K. Sarathchandra, Padmini Chester, Adrian Yacoub, Magdi Brand, Thomas Butcher, Jonathan T. Cardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program |
title | Cardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program |
title_full | Cardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program |
title_fullStr | Cardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program |
title_full_unstemmed | Cardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program |
title_short | Cardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program |
title_sort | cardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199254/ https://www.ncbi.nlm.nih.gov/pubmed/30353076 http://dx.doi.org/10.1038/s41598-018-33994-8 |
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