Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts

[EN] Heart failure (HF) is characterized, among other factors, by a progressive loss of contractile function and by the formation of an arrhythmogenic substrate, both aspects partially related to intracellular Ca2+ cycling disorders. In failing hearts both electrophysiological and structural remodel...

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Autores: Mora-Fenoll, María Teresa|||0000-0002-8069-2486, Ferrero De Loma-Osorio, José María|||0000-0003-4200-9225, Trenor Gomis, Beatriz Ana|||0000-0001-9166-6112, Gomez, Juan F., Morley, Gregory
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Politècnica de València (UPV)
Repositorio:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Idioma:inglés
OAI Identifier:oai:riunet.upv.es:10251/146434
Acceso en línea:https://riunet.upv.es/handle/10251/146434
Access Level:acceso abierto
Palabra clave:Sarcoplasmic-Reticulum Ca2+
Action-Potential dynamics
Electrical alternans
Cardiac alternans
Ventricular myocytes
Cellular alternans
Conduction
Model
Repolarization
Tissue
TECNOLOGIA ELECTRONICA
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oai_identifier_str oai:riunet.upv.es:10251/146434
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts
title Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts
spellingShingle Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts
Mora-Fenoll, María Teresa|||0000-0002-8069-2486
Sarcoplasmic-Reticulum Ca2+
Action-Potential dynamics
Electrical alternans
Cardiac alternans
Ventricular myocytes
Cellular alternans
Conduction
Model
Repolarization
Tissue
TECNOLOGIA ELECTRONICA
title_short Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts
title_full Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts
title_fullStr Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts
title_full_unstemmed Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts
title_sort Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts
dc.creator.none.fl_str_mv Mora-Fenoll, María Teresa|||0000-0002-8069-2486
Ferrero De Loma-Osorio, José María|||0000-0003-4200-9225
Trenor Gomis, Beatriz Ana|||0000-0001-9166-6112
Gomez, Juan F.
Morley, Gregory
author Mora-Fenoll, María Teresa|||0000-0002-8069-2486
author_facet Mora-Fenoll, María Teresa|||0000-0002-8069-2486
Ferrero De Loma-Osorio, José María|||0000-0003-4200-9225
Trenor Gomis, Beatriz Ana|||0000-0001-9166-6112
Gomez, Juan F.
Morley, Gregory
author_role author
author2 Ferrero De Loma-Osorio, José María|||0000-0003-4200-9225
Trenor Gomis, Beatriz Ana|||0000-0001-9166-6112
Gomez, Juan F.
Morley, Gregory
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Ingeniería Electrónica
Escuela Técnica Superior de Ingeniería Aeroespacial y Diseño Industrial
Escuela Técnica Superior de Ingeniería Industrial
Centro de Investigación e Innovación en Bioingeniería
Universitat Politècnica de València
Ministerio de Economía y Competitividad
Repositorio Institucional de la Universitat Politècnica de València Riunet
dc.subject.none.fl_str_mv Sarcoplasmic-Reticulum Ca2+
Action-Potential dynamics
Electrical alternans
Cardiac alternans
Ventricular myocytes
Cellular alternans
Conduction
Model
Repolarization
Tissue
TECNOLOGIA ELECTRONICA
topic Sarcoplasmic-Reticulum Ca2+
Action-Potential dynamics
Electrical alternans
Cardiac alternans
Ventricular myocytes
Cellular alternans
Conduction
Model
Repolarization
Tissue
TECNOLOGIA ELECTRONICA
description [EN] Heart failure (HF) is characterized, among other factors, by a progressive loss of contractile function and by the formation of an arrhythmogenic substrate, both aspects partially related to intracellular Ca2+ cycling disorders. In failing hearts both electrophysiological and structural remodeling, including fibroblast proliferation, contribute to changes in Ca2+ handling which promote the appearance of Ca2+ alternans (Ca-alt). Ca-alt in turn give rise to repolarization alternans, which promote dispersion of repolarization and contribute to reentrant activity. The computational analysis of the incidence of Ca2+ and/or repolarization alternans under HF conditions in the presence of fibroblasts could provide a better understanding of the mechanisms leading to HF arrhythmias and contractile function disorders. Methods and findings The goal of the present study was to investigate in silico the mechanisms leading to the formation of Ca-alt in failing human ventricular myocytes and tissues with disperse fibroblast distributions. The contribution of ionic currents variability to alternans formation at the cellular level was analyzed and the results show that in normal ventricular tissue, altered Ca2+ dynamics lead to Ca-alt, which precede APD alternans and can be aggravated by the presence of fibroblasts. Electrophysiological remodeling of failing tissue alone is sufficient to develop alternans. The incidence of alternans is reduced when fibroblasts are present in failing tissue due to significantly depressed Ca2+ transients. The analysis of the underlying ionic mechanisms suggests that Ca-alt are driven by Ca2+-handling protein and Ca2+ cycling dysfunctions in the junctional sarcoplasmic reticulum and that their contribution to alternans occurrence depends on the cardiac remodeling conditions and on myocyte-fibroblast interactions. Conclusion It can thus be concluded that fibroblasts modulate the formation of Ca-alt in human ventricular tissue subjected to heart failure-related electrophysiological remodeling. Pharmacological therapies should thus consider the extent of both the electrophysiological and structural remodeling present in the failing heart.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-06-18
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://riunet.upv.es/handle/10251/146434
url https://riunet.upv.es/handle/10251/146434
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Universitat Politècnica de València https://doi.org/10.13039/501100004233 PAID-01-17
Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 DPI2016-75799-R TECNOLOGIAS COMPUTACIONALES PARA LA OPTIMIZACION DE TERAPIAS PERSONALIZADAS DE PATOLOGIAS AURICULARES Y VENTRICULARES
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reconocimiento (by)
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reconocimiento (by)
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
instname:Universitat Politècnica de València (UPV)
instname_str Universitat Politècnica de València (UPV)
reponame_str RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
collection RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblastsMora-Fenoll, María Teresa|||0000-0002-8069-2486Ferrero De Loma-Osorio, José María|||0000-0003-4200-9225Trenor Gomis, Beatriz Ana|||0000-0001-9166-6112Gomez, Juan F.Morley, GregorySarcoplasmic-Reticulum Ca2+Action-Potential dynamicsElectrical alternansCardiac alternansVentricular myocytesCellular alternansConductionModelRepolarizationTissueTECNOLOGIA ELECTRONICA[EN] Heart failure (HF) is characterized, among other factors, by a progressive loss of contractile function and by the formation of an arrhythmogenic substrate, both aspects partially related to intracellular Ca2+ cycling disorders. In failing hearts both electrophysiological and structural remodeling, including fibroblast proliferation, contribute to changes in Ca2+ handling which promote the appearance of Ca2+ alternans (Ca-alt). Ca-alt in turn give rise to repolarization alternans, which promote dispersion of repolarization and contribute to reentrant activity. The computational analysis of the incidence of Ca2+ and/or repolarization alternans under HF conditions in the presence of fibroblasts could provide a better understanding of the mechanisms leading to HF arrhythmias and contractile function disorders. Methods and findings The goal of the present study was to investigate in silico the mechanisms leading to the formation of Ca-alt in failing human ventricular myocytes and tissues with disperse fibroblast distributions. The contribution of ionic currents variability to alternans formation at the cellular level was analyzed and the results show that in normal ventricular tissue, altered Ca2+ dynamics lead to Ca-alt, which precede APD alternans and can be aggravated by the presence of fibroblasts. Electrophysiological remodeling of failing tissue alone is sufficient to develop alternans. The incidence of alternans is reduced when fibroblasts are present in failing tissue due to significantly depressed Ca2+ transients. The analysis of the underlying ionic mechanisms suggests that Ca-alt are driven by Ca2+-handling protein and Ca2+ cycling dysfunctions in the junctional sarcoplasmic reticulum and that their contribution to alternans occurrence depends on the cardiac remodeling conditions and on myocyte-fibroblast interactions. Conclusion It can thus be concluded that fibroblasts modulate the formation of Ca-alt in human ventricular tissue subjected to heart failure-related electrophysiological remodeling. Pharmacological therapies should thus consider the extent of both the electrophysiological and structural remodeling present in the failing heart.This work was partially supported by the Plan Estatal de Investigación Científica y Técnica y de Innovación 2013 2016" from the Ministerio de Economía, Industria y Competitividad of Spain and Fondo Europeo de Desarrollo Regional (FEDER) DPI2016-75799-R (AEI/FEDER, UE), and by the Programa de Ayudas de Investigación y Desarrollo (PAID-01-17) from the Universitat Politècnica de València. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Public Library of ScienceDepartamento de Ingeniería ElectrónicaEscuela Técnica Superior de Ingeniería Aeroespacial y Diseño IndustrialEscuela Técnica Superior de Ingeniería IndustrialCentro de Investigación e Innovación en BioingenieríaUniversitat Politècnica de ValènciaMinisterio de Economía y CompetitividadRepositorio Institucional de la Universitat Politècnica de València Riunet20192019-06-18journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://riunet.upv.es/handle/10251/146434reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valénciainstname:Universitat Politècnica de València (UPV)InglésengUniversitat Politècnica de València https://doi.org/10.13039/501100004233 PAID-01-17Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 DPI2016-75799-R TECNOLOGIAS COMPUTACIONALES PARA LA OPTIMIZACION DE TERAPIAS PERSONALIZADAS DE PATOLOGIAS AURICULARES Y VENTRICULARESopen accesshttp://purl.org/coar/access_right/c_abf2Reconocimiento (by)http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:riunet.upv.es:10251/1464342026-06-13T07:49:27Z
score 15,300719

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