Human Erbb2-induced Erk activity robustly stimulates cycling and functional remodeling of rat and human cardiomyocytes

Multiple mitogenic pathways capable of promoting mammalian cardiomyocyte (CM) proliferation have been identified as potential candidates for functional heart repair following myocardial infarction. However, it is unclear whether the effects of these mitogens are species-specific and how they directl...

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Autores principales:	Nicholas Strash, Sophia DeLuca, Geovanni L Janer Carattini, Soon Chul Heo, Ryne Gorsuch, Nenad Bursac
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	cardiomyocyte engineered cardiac tissue proliferation iPSC Erbb2 neonatal rat Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8e568113f8e14154bb83f868392d1564
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spelling	oai:doaj.org-article:8e568113f8e14154bb83f868392d15642021-11-12T14:38:06ZHuman Erbb2-induced Erk activity robustly stimulates cycling and functional remodeling of rat and human cardiomyocytes10.7554/eLife.655122050-084Xe65512https://doaj.org/article/8e568113f8e14154bb83f868392d15642021-10-01T00:00:00Zhttps://elifesciences.org/articles/65512https://doaj.org/toc/2050-084XMultiple mitogenic pathways capable of promoting mammalian cardiomyocyte (CM) proliferation have been identified as potential candidates for functional heart repair following myocardial infarction. However, it is unclear whether the effects of these mitogens are species-specific and how they directly compare in the same cardiac setting. Here, we examined how CM-specific lentiviral expression of various candidate mitogens affects human induced pluripotent stem cell-derived CMs (hiPSC-CMs) and neonatal rat ventricular myocytes (NRVMs) in vitro. In 2D-cultured CMs from both species, and in highly mature 3D-engineered cardiac tissues generated from NRVMs, a constitutively active mutant form of the human gene Erbb2 (cahErbb2) was the most potent tested mitogen. Persistent expression of cahErbb2 induced CM proliferation, sarcomere loss, and remodeling of tissue structure and function, which were attenuated by small molecule inhibitors of Erk signaling. These results suggest transient activation of Erbb2/Erk axis in CMs as a potential strategy for regenerative heart repair.Nicholas StrashSophia DeLucaGeovanni L Janer CarattiniSoon Chul HeoRyne GorsuchNenad BursaceLife Sciences Publications Ltdarticlecardiomyocyteengineered cardiac tissueproliferationiPSCErbb2neonatal ratMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cardiomyocyte engineered cardiac tissue proliferation iPSC Erbb2 neonatal rat Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	cardiomyocyte engineered cardiac tissue proliferation iPSC Erbb2 neonatal rat Medicine R Science Q Biology (General) QH301-705.5 Nicholas Strash Sophia DeLuca Geovanni L Janer Carattini Soon Chul Heo Ryne Gorsuch Nenad Bursac Human Erbb2-induced Erk activity robustly stimulates cycling and functional remodeling of rat and human cardiomyocytes
description	Multiple mitogenic pathways capable of promoting mammalian cardiomyocyte (CM) proliferation have been identified as potential candidates for functional heart repair following myocardial infarction. However, it is unclear whether the effects of these mitogens are species-specific and how they directly compare in the same cardiac setting. Here, we examined how CM-specific lentiviral expression of various candidate mitogens affects human induced pluripotent stem cell-derived CMs (hiPSC-CMs) and neonatal rat ventricular myocytes (NRVMs) in vitro. In 2D-cultured CMs from both species, and in highly mature 3D-engineered cardiac tissues generated from NRVMs, a constitutively active mutant form of the human gene Erbb2 (cahErbb2) was the most potent tested mitogen. Persistent expression of cahErbb2 induced CM proliferation, sarcomere loss, and remodeling of tissue structure and function, which were attenuated by small molecule inhibitors of Erk signaling. These results suggest transient activation of Erbb2/Erk axis in CMs as a potential strategy for regenerative heart repair.
format	article
author	Nicholas Strash Sophia DeLuca Geovanni L Janer Carattini Soon Chul Heo Ryne Gorsuch Nenad Bursac
author_facet	Nicholas Strash Sophia DeLuca Geovanni L Janer Carattini Soon Chul Heo Ryne Gorsuch Nenad Bursac
author_sort	Nicholas Strash
title	Human Erbb2-induced Erk activity robustly stimulates cycling and functional remodeling of rat and human cardiomyocytes
title_short	Human Erbb2-induced Erk activity robustly stimulates cycling and functional remodeling of rat and human cardiomyocytes
title_full	Human Erbb2-induced Erk activity robustly stimulates cycling and functional remodeling of rat and human cardiomyocytes
title_fullStr	Human Erbb2-induced Erk activity robustly stimulates cycling and functional remodeling of rat and human cardiomyocytes
title_full_unstemmed	Human Erbb2-induced Erk activity robustly stimulates cycling and functional remodeling of rat and human cardiomyocytes
title_sort	human erbb2-induced erk activity robustly stimulates cycling and functional remodeling of rat and human cardiomyocytes
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/8e568113f8e14154bb83f868392d1564
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Human Erbb2-induced Erk activity robustly stimulates cycling and functional remodeling of rat and human cardiomyocytes

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