Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, C012

Oral Communications

Differential expression profile of microRNAs in patients with atrial dilatation and atrial fibrillation

M. Masè1, M. Grasso2, L. Avogaro2, M. Nicolussi Giacomaz2, F. Tessarolo3, A. Graffigna4, M. A. Denti2, F. Ravelli1

1. Laboratory of Biophysics and Biosignals, University of Trento, Trento, Italy. 2. Centre for Integrative Biology, University of Trento, Trento, Italy. 3. Healthcare Research and Innovation Program, Bruno Kessler Foundation, Trento, Italy. 4. Division of Cardiac Surgery, Santa Chiara Hospital, Trento, Italy.


Atrial fibrillation (AF) is a multi-factorial disease, supported by changes in electrophysiological and structural properties. Abnormal substrates are commonly encountered in different conditions predisposing to AF, whereby atrial stretch plays a key mechanistic role. Despite accumulating evidence supporting the role of stretch in AF [1,2], the precise molecular determinants of stretch-induced changes remain to be fully elucidated. In particular, although the role of microRNAs (miRs) in AF is well-recognized [3], their involvement in stretch-induced remodeling has not been clarified yet. This study aimed to address the issue by quantifying the differential expression profiles of 12 miRs, known for their involvement in cardiac disease and AF, in patients with atrial dilatation and/or AF. Tissue samples from the right atrial appendage were excised from 28 patients (6 females, median age 72.5 years) undergoing cardiac valve replacement. Samples were flash-frozen in pre-chilled liquid isopentane, and stored at −80°C until RNA isolation. After sample processing and homogeneization, total RNA was extracted by miRNeasy mini kit (Qiagen, Italy) and reverse-transcribed by mercury LNATM Universal cDNA Synthesis kit II (Exiqon, Denmark). qPCR assays based on SYBR Green I were performed according to the manifacturer's protocol (Exiqon, Denmark) on the selected miRs. miR expression was normalized to SNORD48 [4]. For the purpose of the study, patients were divided into three groups: control group with normal or mildly dilated left atrium (LA) and no history of AF; atrial dilatation (AD) group with moderately to severely dilated LA and no history of AF; AD+AF group with moderately to severely dilated LA and history of AF >6 months. miR profiling in the three groups pointed out different expression profiles of miRs in atrial stretch and AF. AD was associated with significant up-regulation of miR-328 and miR-133b (fold-change versus control of 1.6 and 2.2, respectively), albeit up-regulation persisted in AD+AF patients only for miR-328 (fold-change 1.9). Further alterations in miR expression were observed in presence of AF, with up-regulation of miR-1, miR-21, miR-29a, miR-208b, and miR-590 (fold-change ranging from 3.8 for miR208b to 10.1 for miR29a). Our results showed that atrial stretch per se was associated with alterations in miR expression in humans. Given the role of miR-328 in L-type Ca2+ channel regulation [5], its up-regulation may be implicated in Ca2+ current reduction leading to atrial remodeling, suggesting the involvement of a post-trascriptional mechanism in stretch pro-arrhythmic effects.

Where applicable, experiments conform with Society ethical requirements