MicroRNA-135a Regulates Sodium-Calcium Exchanger Gene Expression and Cardiac Electrical Activity
Abstract Background Complete atrioventricular block (CAVB) causes arrhythmogenic remodeling and increases the risk of Torsades de Pointes (TdP) arrhythmias. MicroRNAs (miRNAs) are key regulators of gene-expression that contribute to cardiac remodeling. Objective To assess miRNA changes after complet...
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Veröffentlicht in: | Heart rhythm 2017-05, Vol.14 (5), p.739-748 |
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Sprache: | eng |
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Zusammenfassung: | Abstract Background Complete atrioventricular block (CAVB) causes arrhythmogenic remodeling and increases the risk of Torsades de Pointes (TdP) arrhythmias. MicroRNAs (miRNAs) are key regulators of gene-expression that contribute to cardiac remodeling. Objective To assess miRNA changes after complete atrioventricular block (CAVB) and identify novel candidates potentially involved in arrhythmogenic cardiac remodeling. Methods CAVB was induced in mice via His bundle ablation. Expression of microRNAs was evaluated by pan-miRNA microarray with qPCR confirmation, on samples obtained 24 hours and 4 weeks post-CAVB. MiRNA target-prediction algorithms were used to identify potential target genes. Targets confirmed by luciferase assays in HEK293 cells were followed up with overexpression studies in neonatal rat ventricular myocytes (NRVMs) to evaluate regulation using RT-qPCR, Western blots, cell shortening measurements and fura-2 Ca2+ fluorescence imaging. Results Of >400 miRNAs assayed, only miRNA-135a was altered at 24 hours, downregulated 78% (p |
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ISSN: | 1547-5271 1556-3871 |
DOI: | 10.1016/j.hrthm.2017.01.045 |