Cardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program

Abstract 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,...

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Autores principales:	Joseph K. Yu, Padmini Sarathchandra, Adrian Chester, Magdi Yacoub, Thomas Brand, Jonathan T. Butcher
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Cryoinjury Biomechanical Remodeling Cardiomyocyte Sarcomere Sarcomere Length Post-infarction Day (DPI) Medicine R Science Q
Acceso en línea:	https://doaj.org/article/887072574be04d6c86dd4928c7e5f23a
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spelling	oai:doaj.org-article:887072574be04d6c86dd4928c7e5f23a2021-12-02T11:40:26ZCardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program10.1038/s41598-018-33994-82045-2322https://doaj.org/article/887072574be04d6c86dd4928c7e5f23a2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33994-8https://doaj.org/toc/2045-2322Abstract 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.Joseph K. YuPadmini SarathchandraAdrian ChesterMagdi YacoubThomas BrandJonathan T. ButcherNature PortfolioarticleCryoinjuryBiomechanical RemodelingCardiomyocyte SarcomereSarcomere LengthPost-infarction Day (DPI)MedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cryoinjury Biomechanical Remodeling Cardiomyocyte Sarcomere Sarcomere Length Post-infarction Day (DPI) Medicine R Science Q
spellingShingle	Cryoinjury Biomechanical Remodeling Cardiomyocyte Sarcomere Sarcomere Length Post-infarction Day (DPI) Medicine R Science Q Joseph K. Yu Padmini Sarathchandra Adrian Chester Magdi Yacoub Thomas Brand Jonathan T. Butcher Cardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program
description	Abstract 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	article
author	Joseph K. Yu Padmini Sarathchandra Adrian Chester Magdi Yacoub Thomas Brand Jonathan T. Butcher
author_facet	Joseph K. Yu Padmini Sarathchandra Adrian Chester Magdi Yacoub Thomas Brand Jonathan T. Butcher
author_sort	Joseph K. Yu
title	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_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_sort	cardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/887072574be04d6c86dd4928c7e5f23a
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_version_	1718395593000222720

Cardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program

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