Microenvironment Stiffness Amplifies Post-ischemia Heart Regeneration in Response to Exogenous Extracellular Matrix Proteins in Neonatal Mice

The cardiogenesis of the fetal heart is absent in juveniles and adults. Cross-transplantation of decellularized extracellular matrix (dECM) can stimulate regeneration in myocardial infarct (MI) models. We have previously shown that dECM and tissue stiffness have cooperative regulation of heart regen...

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Autores principales:	Xinming Wang, Valinteshley Pierre, Subhadip Senapati, Paul S.-H. Park, Samuel E. Senyo
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	heart regeneration extracellular matrix decellularization microenvironment stiffness myocardial infarction cell cycle activity Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/8f771d133de748fcbbd83b2e32bda4a8
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spelling	oai:doaj.org-article:8f771d133de748fcbbd83b2e32bda4a82021-11-05T09:41:35ZMicroenvironment Stiffness Amplifies Post-ischemia Heart Regeneration in Response to Exogenous Extracellular Matrix Proteins in Neonatal Mice2297-055X10.3389/fcvm.2021.773978https://doaj.org/article/8f771d133de748fcbbd83b2e32bda4a82021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.773978/fullhttps://doaj.org/toc/2297-055XThe cardiogenesis of the fetal heart is absent in juveniles and adults. Cross-transplantation of decellularized extracellular matrix (dECM) can stimulate regeneration in myocardial infarct (MI) models. We have previously shown that dECM and tissue stiffness have cooperative regulation of heart regeneration in transiently regenerative day 1 neonatal mice. To investigate underlying mechanisms of mechano-signaling and dECM, we pharmacologically altered heart stiffness and administered dECM hydrogels in non-regenerative mice after MI. The dECM combined with softening exhibits preserved cardiac function, LV geometry, increased cardiomyocyte mitosis and lowered fibrosis while stiffening further aggravated ischemic damage. Transcriptome analysis identified a protein in cardiomyocytes, CLCA2, confirmed to be upregulated after MI and downregulated by dECM in a mechanosensitive manner. Synthetic knock-down of CLCA2 expression induced mitosis in primary rat cardiomyocytes in the dish. Together, our results indicate that therapeutic efficacy of extracellular molecules for heart regeneration can be modulated by heart microenvironment stiffness in vivo.Xinming WangValinteshley PierreSubhadip SenapatiPaul S.-H. ParkSamuel E. SenyoFrontiers Media S.A.articleheart regenerationextracellular matrixdecellularizationmicroenvironment stiffnessmyocardial infarctioncell cycle activityDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	heart regeneration extracellular matrix decellularization microenvironment stiffness myocardial infarction cell cycle activity Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	heart regeneration extracellular matrix decellularization microenvironment stiffness myocardial infarction cell cycle activity Diseases of the circulatory (Cardiovascular) system RC666-701 Xinming Wang Valinteshley Pierre Subhadip Senapati Paul S.-H. Park Samuel E. Senyo Microenvironment Stiffness Amplifies Post-ischemia Heart Regeneration in Response to Exogenous Extracellular Matrix Proteins in Neonatal Mice
description	The cardiogenesis of the fetal heart is absent in juveniles and adults. Cross-transplantation of decellularized extracellular matrix (dECM) can stimulate regeneration in myocardial infarct (MI) models. We have previously shown that dECM and tissue stiffness have cooperative regulation of heart regeneration in transiently regenerative day 1 neonatal mice. To investigate underlying mechanisms of mechano-signaling and dECM, we pharmacologically altered heart stiffness and administered dECM hydrogels in non-regenerative mice after MI. The dECM combined with softening exhibits preserved cardiac function, LV geometry, increased cardiomyocyte mitosis and lowered fibrosis while stiffening further aggravated ischemic damage. Transcriptome analysis identified a protein in cardiomyocytes, CLCA2, confirmed to be upregulated after MI and downregulated by dECM in a mechanosensitive manner. Synthetic knock-down of CLCA2 expression induced mitosis in primary rat cardiomyocytes in the dish. Together, our results indicate that therapeutic efficacy of extracellular molecules for heart regeneration can be modulated by heart microenvironment stiffness in vivo.
format	article
author	Xinming Wang Valinteshley Pierre Subhadip Senapati Paul S.-H. Park Samuel E. Senyo
author_facet	Xinming Wang Valinteshley Pierre Subhadip Senapati Paul S.-H. Park Samuel E. Senyo
author_sort	Xinming Wang
title	Microenvironment Stiffness Amplifies Post-ischemia Heart Regeneration in Response to Exogenous Extracellular Matrix Proteins in Neonatal Mice
title_short	Microenvironment Stiffness Amplifies Post-ischemia Heart Regeneration in Response to Exogenous Extracellular Matrix Proteins in Neonatal Mice
title_full	Microenvironment Stiffness Amplifies Post-ischemia Heart Regeneration in Response to Exogenous Extracellular Matrix Proteins in Neonatal Mice
title_fullStr	Microenvironment Stiffness Amplifies Post-ischemia Heart Regeneration in Response to Exogenous Extracellular Matrix Proteins in Neonatal Mice
title_full_unstemmed	Microenvironment Stiffness Amplifies Post-ischemia Heart Regeneration in Response to Exogenous Extracellular Matrix Proteins in Neonatal Mice
title_sort	microenvironment stiffness amplifies post-ischemia heart regeneration in response to exogenous extracellular matrix proteins in neonatal mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/8f771d133de748fcbbd83b2e32bda4a8
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Microenvironment Stiffness Amplifies Post-ischemia Heart Regeneration in Response to Exogenous Extracellular Matrix Proteins in Neonatal Mice

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