Myofibroblast modulation of cardiac myocyte structure and function

Abstract After myocardial infarction, resident fibroblasts (Fb) differentiate towards myofibroblasts (MyoFb), generating the scar tissue and the interstitial fibrosis seen in the adjacent myocardium. Fb and MyoFb have the potential to interact with cardiac myocytes (CMs) but insight into the phenoty...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Chandan K. Nagaraju, Eef Dries, Guillaume Gilbert, Mouna Abdesselem, Nan Wang, Matthew Amoni, Ronald B. Driesen, Karin R. Sipido
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d7d7434f9c4241de92ebb91f7526f189
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d7d7434f9c4241de92ebb91f7526f189
record_format	dspace
spelling	oai:doaj.org-article:d7d7434f9c4241de92ebb91f7526f1892021-12-02T15:09:29ZMyofibroblast modulation of cardiac myocyte structure and function10.1038/s41598-019-45078-22045-2322https://doaj.org/article/d7d7434f9c4241de92ebb91f7526f1892019-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-45078-2https://doaj.org/toc/2045-2322Abstract After myocardial infarction, resident fibroblasts (Fb) differentiate towards myofibroblasts (MyoFb), generating the scar tissue and the interstitial fibrosis seen in the adjacent myocardium. Fb and MyoFb have the potential to interact with cardiac myocytes (CMs) but insight into the phenotype-specific role and mode of interaction is still incomplete. Our objectives are to further define the modulation of CMs by MyoFbs compared to Fbs, as well as the role of direct contact through gap junctions vs. soluble mediators, using Fbs and CMs from pig left ventricle. Fbs were treated to maintain an undifferentiated state (SD-208) or to attain full differentiation to MyoFb (TGF-β1). Fbs and MyoFbs were co-cultured with CMs, with the possibility of direct contact or separated by a Thincert membrane. Only in direct co-culture, both Fbs and MyoFbs were able to decrease CM viability after 2 days. Only MyoFbs induced significant distal spreading of CMs in both direct and indirect co-culture. MyoFbs, but not Fbs, readily made connections with CMs in direct co-culture and connexin 43 expression in MyoFb was higher than in Fb. When coupled to CMs, MyoFbs reduced the CM action potential duration and hyperpolarized the CM resting membrane potential. Uncoupling reversed these effects. In conclusion, MyoFbs, but not Fbs, alter the CM structural phenotype. MyoFbs, but not Fbs, are likely to electrically connect to CMs and thereby modulate the CM membrane potential. These data provide further support for an active role of MyoFbs in the arrhythmogenic substrate after cardiac remodelling.Chandan K. NagarajuEef DriesGuillaume GilbertMouna AbdesselemNan WangMatthew AmoniRonald B. DriesenKarin R. SipidoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chandan K. Nagaraju Eef Dries Guillaume Gilbert Mouna Abdesselem Nan Wang Matthew Amoni Ronald B. Driesen Karin R. Sipido Myofibroblast modulation of cardiac myocyte structure and function
description	Abstract After myocardial infarction, resident fibroblasts (Fb) differentiate towards myofibroblasts (MyoFb), generating the scar tissue and the interstitial fibrosis seen in the adjacent myocardium. Fb and MyoFb have the potential to interact with cardiac myocytes (CMs) but insight into the phenotype-specific role and mode of interaction is still incomplete. Our objectives are to further define the modulation of CMs by MyoFbs compared to Fbs, as well as the role of direct contact through gap junctions vs. soluble mediators, using Fbs and CMs from pig left ventricle. Fbs were treated to maintain an undifferentiated state (SD-208) or to attain full differentiation to MyoFb (TGF-β1). Fbs and MyoFbs were co-cultured with CMs, with the possibility of direct contact or separated by a Thincert membrane. Only in direct co-culture, both Fbs and MyoFbs were able to decrease CM viability after 2 days. Only MyoFbs induced significant distal spreading of CMs in both direct and indirect co-culture. MyoFbs, but not Fbs, readily made connections with CMs in direct co-culture and connexin 43 expression in MyoFb was higher than in Fb. When coupled to CMs, MyoFbs reduced the CM action potential duration and hyperpolarized the CM resting membrane potential. Uncoupling reversed these effects. In conclusion, MyoFbs, but not Fbs, alter the CM structural phenotype. MyoFbs, but not Fbs, are likely to electrically connect to CMs and thereby modulate the CM membrane potential. These data provide further support for an active role of MyoFbs in the arrhythmogenic substrate after cardiac remodelling.
format	article
author	Chandan K. Nagaraju Eef Dries Guillaume Gilbert Mouna Abdesselem Nan Wang Matthew Amoni Ronald B. Driesen Karin R. Sipido
author_facet	Chandan K. Nagaraju Eef Dries Guillaume Gilbert Mouna Abdesselem Nan Wang Matthew Amoni Ronald B. Driesen Karin R. Sipido
author_sort	Chandan K. Nagaraju
title	Myofibroblast modulation of cardiac myocyte structure and function
title_short	Myofibroblast modulation of cardiac myocyte structure and function
title_full	Myofibroblast modulation of cardiac myocyte structure and function
title_fullStr	Myofibroblast modulation of cardiac myocyte structure and function
title_full_unstemmed	Myofibroblast modulation of cardiac myocyte structure and function
title_sort	myofibroblast modulation of cardiac myocyte structure and function
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/d7d7434f9c4241de92ebb91f7526f189
work_keys_str_mv	AT chandanknagaraju myofibroblastmodulationofcardiacmyocytestructureandfunction AT eefdries myofibroblastmodulationofcardiacmyocytestructureandfunction AT guillaumegilbert myofibroblastmodulationofcardiacmyocytestructureandfunction AT mounaabdesselem myofibroblastmodulationofcardiacmyocytestructureandfunction AT nanwang myofibroblastmodulationofcardiacmyocytestructureandfunction AT matthewamoni myofibroblastmodulationofcardiacmyocytestructureandfunction AT ronaldbdriesen myofibroblastmodulationofcardiacmyocytestructureandfunction AT karinrsipido myofibroblastmodulationofcardiacmyocytestructureandfunction
_version_	1718387843026386944

Myofibroblast modulation of cardiac myocyte structure and function

Ejemplares similares