Differentially expressed miRNAs in circulating exosomes between atrial fibrillation and sinus rhythm

Background: Exosomes are small (30–150 nm) membrane vesicles released by cells that transmit intercellular information. As one of the contents of exosomes, microRNAs (miRNAs) may play an important role in the pathogenesis of atrial fibrillation (AF). Exosomal miRNAs potentially function as biomarkers in AF, as shown in many other diseases. Methods: To identify the different expression level of plasma exosomal miRNAs between persistent AF and sinus rhythm (SR) patients, we performed high-throughput sequencing of small RNAs in the exosomes of AF (n=4) and SR (n=4) patients. Target genes of the DE miRNAs were predicted and put into gene ontology analysis and pathway analysis. In the validation phase, we performed quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) of 6 of the DE miRNAs in AF (n=40) and SR (n=20) patients. Univariate and multivariate logistic analysis were used to analyze risk factors of AF. Results: With high-throughput sequencing, we revealed 39 differentially expressed (DE) miRNAs in circulating exosomes. We validated 4 of the DE plasma exosomal miRNAs (miR-483-5p, miR-142-5p, miR-223-3p, miR-223-5p) using qRT-PCR. Univariate logistic analysis shows miR-483-5p, miR-142-5p, miR-223-3p are related with AF, while multivariate logistic analysis suggests miR-483-5p is independently in correlation with AF. Conclusions: This discovery opens up a new perspective in the complicated mechanism underlying AF and the DE plasma exosomal miRNAs exert enormous potential of acting as biomarkers in assessing severity or prognostic of AF and help selecting therapeutic strategy.