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
Garcia-Elias, Anna (Vall d'Hebron Institut de Recerca (VHIR))
Tajes, Marta (Hospital del Mar (Barcelona, Catalunya))
Yáñez-Bisbe, Laia (Institut Hospital del Mar d'Investigacions Mèdiques)
Enjuanes, Cristina (Hospital Universitari de Bellvitge)
Comín-Colet, Josep (Universitat de Barcelona. Departament de Ciències Clíniques)
Serra, Selma A. (Universitat Pompeu Fabra)
Fernández-Fernández, José Manuel (Universitat Pompeu Fabra)
Aguilar-Agon, Kathryn W. (University of Oxford)
Reilly, Svetlana (University of Oxford)
Martí-Almor, Julio (Universitat Autònoma de Barcelona. Departament de Medicina)
Benito Villabriga, Begoña (Universitat Autònoma de Barcelona. Departament de Medicina)

Date:	2021
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 Ca 2+ channel, NCX and connexin-40, leading to lower basal intracellular Ca 2+ levels, fewer inward currents, a moderate reduction in Ca 2+ 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 Ca 2+ handling and defective cell-to-cell communication, both findings being potential arrhythmogenic mechanisms.
Grants:	Ministerio de Economía y Competitividad PI13/01830 Agencia Estatal de Investigación RTI2018-094809-B-I00
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Heart failure ; Atrial fibrillation ; Atrial remodeling ; Microrna ; Biomarkers ; HL-1 cells ; Calcium regulation ; L-type calcium channels ; Connexin 40 ; NCX1
Published in:	International journal of molecular sciences, Vol. 22 (september 2021) , ISSN 1422-0067

DOI: 10.3390/ijms221910377
PMID: 34638717

17 p, 2.9 MB

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