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.
Highlights
Heart failure (HF), affecting 1–2% of the adult population and up to > 10% of individuals over 70 years, is the cardiovascular disorder associated with the highest morbidity and mortality rates, in the subgroup of patients with reduced ejection fraction [1]
The clinical characteristics of patients included in the discovery phase are shown in Supplementary File, Table S1
Mean left ventricular ejection fraction (LVEF) was around 30%, and New York Heart Association (NYHA) class was similar between patients in permanent atrial fibrillation (AF) and those in sinus rhythm (SR)
Summary
Heart failure (HF), affecting 1–2% of the adult population and up to > 10% of individuals over 70 years, is the cardiovascular disorder associated with the highest morbidity and mortality rates, in the subgroup of patients with reduced ejection fraction [1]. Atrial fibrillation (AF) occurs in 25–40% of patients with HF and reduced ejection fraction (HFrEF) [2] The coexistence of both conditions is facilitated by the common pathogenic mechanisms shared between HF and AF, which promote one another [3,4]. Impaired regulation of intracellular Ca2+, electrical remodeling and the development of fibrosis are seen in the atria of AF patients and in the ventricles of failing hearts [3,4]. These mechanisms favor atrial arrhythmia susceptibility and impaired ventricular contraction [4].
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
