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The role of beta-adrenergic system remodeling in human heart failure: A mechanistic investigation

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The role of beta-adrenergic system remodeling in human heart failure: A mechanistic investigation

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Nombre: Mora-Fenoll;Gong;Sobie ...
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dc.contributor.author Mora-Fenoll, María Teresa es_ES
dc.contributor.author Gong, Jingqi Q. X. es_ES
dc.contributor.author Sobie, Eric A. es_ES
dc.contributor.author Trenor Gomis, Beatriz Ana es_ES
dc.date.accessioned 2021-03-05T04:32:44Z
dc.date.available 2021-03-05T04:32:44Z
dc.date.issued 2021-04 es_ES
dc.identifier.issn 0022-2828 es_ES
dc.identifier.uri http://hdl.handle.net/10251/163196
dc.description.abstract [EN] ß-adrenergic receptor antagonists (ß-blockers) are extensively used to improve cardiac performance in heart failure (HF), but the electrical improvements with these clinical treatments are not fully understood. The aim of this study was to analyze the electrophysiological effects of ß-adrenergic system remodeling in heart failure with reduced ejection fraction and the underlying mechanisms. We used a combined mathematical model that integrated ß-adrenergic signaling with electrophysiology and calcium cycling in human ventricular myocytes. HF remodeling, both in the electrophysiological and signaling systems, was introduced to quantitatively analyze changes in electrophysiological properties due to the stimulation of ß-adrenergic receptors in failing myocytes. We found that the inotropic effect of ß-adrenergic stimulation was reduced in HF due to the altered Ca2+ dynamics resulting from the combination of structural, electrophysiological and signaling remodeling. Isolated cells showed proarrhythmic risk after sympathetic stimulation because early afterdepolarizations appeared, and the vulnerability was greater in failing myocytes. When analyzing coupled cells, ß-adrenergic stimulation reduced transmural repolarization gradients between endocardium and epicardium in normal tissue, but was less effective at reducing these gradients after HF remodeling. The comparison of the selective activation of ß-adrenergic isoforms revealed that the response to ß2-adrenergic receptors stimulation was blunted in HF while ß1-adrenergic receptors downstream effectors regulated most of the changes observed after sympathetic stimulation. In conclusion, this study was able to reproduce an altered ß-adrenergic activity on failing myocytes and to explain the mechanisms involved. The derived predictions could help in the treatment of HF and guide in the design of future experiments. es_ES
dc.description.sponsorship 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), by the "Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020" from the Ministerio de Ciencia e Innovación y Universidades (PID2019-104356RB-C41/AEI/10.13039/5011000110 33), and by the "Programa de Ayudas de Investigación y Desarrollo (PAID-01-17)" from the Universitat Politècnica de València. es_ES
dc.language Inglés es_ES
dc.publisher Elsevier es_ES
dc.relation.ispartof Journal of Molecular and Cellular Cardiology es_ES
dc.rights Reconocimiento - No comercial - Sin obra derivada (by-nc-nd) es_ES
dc.subject Electrophysiology es_ES
dc.subject Simulation es_ES
dc.subject Heart failure es_ES
dc.subject SS-Adrenergic signaling es_ES
dc.subject.classification TECNOLOGIA ELECTRONICA es_ES
dc.title The role of beta-adrenergic system remodeling in human heart failure: A mechanistic investigation es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1016/j.yjmcc.2020.12.004 es_ES
dc.relation.projectID info:eu-repo/grantAgreement/UPV//PAID-01-17/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//DPI2016-75799-R/ES/TECNOLOGIAS COMPUTACIONALES PARA LA OPTIMIZACION DE TERAPIAS PERSONALIZADAS DE PATOLOGIAS AURICULARES Y VENTRICULARES/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104356RB-C41/ES/MODELO MULTIESCALA DE PATOLOGIAS CARDIACAS Y OPTIMIZACION DE TERAPIAS PERSONALIZADAS/ es_ES
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica es_ES
dc.description.bibliographicCitation Mora-Fenoll, MT.; Gong, JQX.; Sobie, EA.; Trenor Gomis, BA. (2021). The role of beta-adrenergic system remodeling in human heart failure: A mechanistic investigation. Journal of Molecular and Cellular Cardiology. 153:14-25. https://doi.org/10.1016/j.yjmcc.2020.12.004 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.1016/j.yjmcc.2020.12.004 es_ES
dc.description.upvformatpinicio 14 es_ES
dc.description.upvformatpfin 25 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 153 es_ES
dc.identifier.pmid 33326834 es_ES
dc.relation.pasarela S\427224 es_ES
dc.contributor.funder Agencia Estatal de Investigación es_ES
dc.contributor.funder European Regional Development Fund es_ES
dc.contributor.funder Universitat Politècnica de València es_ES
dc.contributor.funder Ministerio de Ciencia, Innovación y Universidades es_ES
dc.contributor.funder Ministerio de Economía y Competitividad es_ES
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