Elevated Plasma Levels of Circulating Extracellular miR-320a-3p in Patients with Paroxysmal Atrial Fibrillation

Correspondence: zhelankin.andrey@gmail.com or zhelankin@rcpcm.org; Tel.: +7-910-410-7765
Received: 20 April 2020; Accepted: 13 May 2020; Published: 15 May 2020


Abstract: The potential of extracellular circulating microRNAs (miRNAs) as non-invasive biomarkers
of atrial fibrillation (AF) has been confirmed by a number of recent studies. However, the current
data for some miRNAs are controversial and inconsistent, probably due to pre-analytical and
methodological differences. In this work, we attempted to fulfill the basic pre-analytical requirements
provided for circulating miRNA studies for application to paroxysmal atrial fibrillation (PAF)
research. We used quantitative PCR (qPCR) to determine the relative plasma levels of circulating
miRNAs expressed in the heart or associated with atrial remodeling or fibrillation with reported
altered plasma/serum levels in AF: miR-146a-5p, miR-150-5p, miR-19a-3p, miR-21-5p, miR-29b-3p,
miR-320a-3p, miR-328-3p, miR-375-3p, and miR-409-3p. First, in a cohort of 90 adult outpatient clinic
patients, we found that the plasma level of miR-320a-3p was elevated in PAF patients compared to
healthy controls and hypertensive patients without AF. We further analyzed the impact of medication
therapies on miRNA relative levels and found elevated miR-320a-3p levels in patients receiving
angiotensin-converting-enzyme inhibitors (ACEI) therapy. Additionally, we found that miR-320a-3p,
miR-21-5p, and miR-146a-5p plasma levels positively correlated with the CHA2DS2-Vasc score and
were elevated in subjects with CHA2DS2-Vasc ≥ 2. Our results indicate that, amongst the analyzed
miRNAs, miR-320a-3p may be considered as a potential PAF circulating plasma biomarker, leading
to speculation as to whether this miRNA is a marker of platelet state change due to ACEI therapy.