Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology

During atrial fibrillation, cardiac tissue undergoes different remodeling processes at different scales from the molecular level to the tissue level. One central player that contributes to both electrical and structural remodeling is the myofibroblast. Based on recent experimental evidence on myofib...

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Autores principales:	Jorge Sánchez, Beatriz Trenor, Javier Saiz, Olaf Dössel, Axel Loewe
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	myofibroblast fibrosis atrial fibrillation calcium handling Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d73a5e4b2b0a43fc80a225f28565ace0
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spelling	oai:doaj.org-article:d73a5e4b2b0a43fc80a225f28565ace02021-11-25T17:08:02ZFibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology10.3390/cells101128522073-4409https://doaj.org/article/d73a5e4b2b0a43fc80a225f28565ace02021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2852https://doaj.org/toc/2073-4409During atrial fibrillation, cardiac tissue undergoes different remodeling processes at different scales from the molecular level to the tissue level. One central player that contributes to both electrical and structural remodeling is the myofibroblast. Based on recent experimental evidence on myofibroblasts’ ability to contract, we extended a biophysical myofibroblast model with Ca<sup>2+</sup> handling components and studied the effect on cellular and tissue electrophysiology. Using genetic algorithms, we fitted the myofibroblast model parameters to the existing in vitro data. In silico experiments showed that Ca<sup>2+</sup> currents can explain the experimentally observed variability regarding the myofibroblast resting membrane potential. The presence of an L-type Ca<sup>2+</sup> current can trigger automaticity in the myofibroblast with a cycle length of 799.9 ms. Myocyte action potentials were prolonged when coupled to myofibroblasts with Ca<sup>2+</sup> handling machinery. Different spatial myofibroblast distribution patterns increased the vulnerable window to induce arrhythmia from 12 ms in non-fibrotic tissue to 22 ± 2.5 ms and altered the reentry dynamics. Our findings suggest that Ca<sup>2+</sup> handling can considerably affect myofibroblast electrophysiology and alter the electrical propagation in atrial tissue composed of myocytes coupled with myofibroblasts. These findings can inform experimental validation experiments to further elucidate the role of myofibroblast Ca<sup>2+</sup> handling in atrial arrhythmogenesis.Jorge SánchezBeatriz TrenorJavier SaizOlaf DösselAxel LoeweMDPI AGarticlemyofibroblastfibrosisatrial fibrillationcalcium handlingBiology (General)QH301-705.5ENCells, Vol 10, Iss 2852, p 2852 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	myofibroblast fibrosis atrial fibrillation calcium handling Biology (General) QH301-705.5
spellingShingle	myofibroblast fibrosis atrial fibrillation calcium handling Biology (General) QH301-705.5 Jorge Sánchez Beatriz Trenor Javier Saiz Olaf Dössel Axel Loewe Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology
description	During atrial fibrillation, cardiac tissue undergoes different remodeling processes at different scales from the molecular level to the tissue level. One central player that contributes to both electrical and structural remodeling is the myofibroblast. Based on recent experimental evidence on myofibroblasts’ ability to contract, we extended a biophysical myofibroblast model with Ca<sup>2+</sup> handling components and studied the effect on cellular and tissue electrophysiology. Using genetic algorithms, we fitted the myofibroblast model parameters to the existing in vitro data. In silico experiments showed that Ca<sup>2+</sup> currents can explain the experimentally observed variability regarding the myofibroblast resting membrane potential. The presence of an L-type Ca<sup>2+</sup> current can trigger automaticity in the myofibroblast with a cycle length of 799.9 ms. Myocyte action potentials were prolonged when coupled to myofibroblasts with Ca<sup>2+</sup> handling machinery. Different spatial myofibroblast distribution patterns increased the vulnerable window to induce arrhythmia from 12 ms in non-fibrotic tissue to 22 ± 2.5 ms and altered the reentry dynamics. Our findings suggest that Ca<sup>2+</sup> handling can considerably affect myofibroblast electrophysiology and alter the electrical propagation in atrial tissue composed of myocytes coupled with myofibroblasts. These findings can inform experimental validation experiments to further elucidate the role of myofibroblast Ca<sup>2+</sup> handling in atrial arrhythmogenesis.
format	article
author	Jorge Sánchez Beatriz Trenor Javier Saiz Olaf Dössel Axel Loewe
author_facet	Jorge Sánchez Beatriz Trenor Javier Saiz Olaf Dössel Axel Loewe
author_sort	Jorge Sánchez
title	Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology
title_short	Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology
title_full	Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology
title_fullStr	Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology
title_full_unstemmed	Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology
title_sort	fibrotic remodeling during persistent atrial fibrillation: in silico investigation of the role of calcium for human atrial myofibroblast electrophysiology
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d73a5e4b2b0a43fc80a225f28565ace0
work_keys_str_mv	AT jorgesanchez fibroticremodelingduringpersistentatrialfibrillationinsilicoinvestigationoftheroleofcalciumforhumanatrialmyofibroblastelectrophysiology AT beatriztrenor fibroticremodelingduringpersistentatrialfibrillationinsilicoinvestigationoftheroleofcalciumforhumanatrialmyofibroblastelectrophysiology AT javiersaiz fibroticremodelingduringpersistentatrialfibrillationinsilicoinvestigationoftheroleofcalciumforhumanatrialmyofibroblastelectrophysiology AT olafdossel fibroticremodelingduringpersistentatrialfibrillationinsilicoinvestigationoftheroleofcalciumforhumanatrialmyofibroblastelectrophysiology AT axelloewe fibroticremodelingduringpersistentatrialfibrillationinsilicoinvestigationoftheroleofcalciumforhumanatrialmyofibroblastelectrophysiology
_version_	1718412744102772736

Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology

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