Atrial fibrillation in heart failure is associated with high levels of circulating microRNA-199a-5p and 22-5p and a defective regulation of intracellular calcium and cell-to-cell communication

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• dc.contributor.author Garcia-Elias Heras, Anna
• dc.contributor.author Tajes Orduña, Marta
• dc.contributor.author Yañez Bisbe, Laia
• dc.contributor.author Enjuanes Grau, Cristina
• dc.contributor.author Comín Colet, Josep
• dc.contributor.author Serra, Selma A.
• dc.contributor.author Fernández-Fernández, José Manuel, 1967-
• dc.contributor.author Aguilar-Agon, Kathryn W.
• dc.contributor.author Reilly, Svetlana
• dc.contributor.author Martí Almor, Julio
• dc.contributor.author Benito Villabriga, Begoña
• dc.date.accessioned 2021-10-20T06:29:10Z
• dc.date.available 2021-10-20T06:29:10Z
• dc.date.issued 2021
• dc.description.abstract MicroRNAs (miRNAs) participate in atrial remodeling and atrial fibrillation (AF) promotion. We determined the circulating miRNA profile in patients with AF and heart failure with reduced ejection fraction (HFrEF), and its potential role in promoting the arrhythmia. In plasma of 98 patients with HFrEF (49 with AF and 49 in sinus rhythm, SR), differential miRNA expression was determined by high-throughput microarray analysis followed by replication of selected candidates. Validated miRNAs were determined in human atrial samples, and potential arrhythmogenic mechanisms studied in HL-1 cells. Circulating miR-199a-5p and miR-22-5p were significantly increased in HFrEF patients with AF versus those with HFrEF in SR. Both miRNAs, but particularly miR-199a-5p, were increased in atrial samples of patients with AF. Overexpression of both miRNAs in HL-1 cells resulted in decreased protein levels of L-type Ca2+ channel, NCX and connexin-40, leading to lower basal intracellular Ca2+ levels, fewer inward currents, a moderate reduction in Ca2+ buffering post-caffeine exposure, and a deficient cell-to-cell communication. In conclusion, circulating miR-199a-5p and miR-22-5p are higher in HFrEF patients with AF, with similar findings in human atrial samples of AF patients. Cells exposed to both miRNAs exhibited altered Ca2+ handling and defective cell-to-cell communication, both findings being potential arrhythmogenic mechanisms.
• dc.description.sponsorship This work was funded by the following grants, awarded to B.B.: Sociedad Española de Cardiología, Sección de Arritmias y Electrofisiología 2012; Sociedad Española de Cardiología, Sección de Insuficiencia Cardíaca 2013; Fondo Investigación Sanitaria (FIS)—Instituto Carlos III 2013 (PI13/01830); and Societat Catalana de Cardiologia 2016. Awarded to K.W.A-A. and S.R.: British Heart Foundation (BHF) Intermediate Research Fellowship. Awarded to J.M.F.F.: grant from the Spanish Ministry of Science and Innovation (RTI2018-094809-B-I00). “María de Maeztu” Programme for Units of Excellence in R&D to the Departament de Ciències Experimentals i de la Salut (MDM-2014-0370) and FEDER (Fondo Europeo de Desarrollo Regional) also contributed to this work.
• dc.format.mimetype application/pdf
• dc.identifier.citation Garcia-Elias A, Tajes M, Yañez-Bisbe L, Enjuanes C, Comín-Colet J, Serra SA, Fernández-Fernández JM, Aguilar-Agon KW, Reilly S, Martí-Almor J, Benito B. Atrial fibrillation in heart failure is associated with high levels of circulating microRNA-199a-5p and 22-5p and a defective regulation of intracellular calcium and cell-to-cell communication. Int J Mol Sci. 2021;22(19):10377. DOI: 10.3390/ijms221910377
• dc.identifier.doi http://dx.doi.org/10.3390/ijms221910377
• dc.identifier.issn 1422-0067
• dc.identifier.uri http://hdl.handle.net/10230/48710
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof Int J Mol Sci. 2021;22(19):10377
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-094809-B-I00
• dc.rights © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword HL-1 cells
• dc.subject.keyword L-type calcium channels
• dc.subject.keyword NCX1
• dc.subject.keyword Atrial fibrillation
• dc.subject.keyword Atrial remodeling
• dc.subject.keyword Biomarkers
• dc.subject.keyword Calcium regulation
• dc.subject.keyword Connexin 40
• dc.subject.keyword Heart failure
• dc.subject.keyword microRNA
• dc.title Atrial fibrillation in heart failure is associated with high levels of circulating microRNA-199a-5p and 22-5p and a defective regulation of intracellular calcium and cell-to-cell communication
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion