Upregulation of miR-133b and miR-328 in Patients With Atrial Dilatation: Implications for Stretch-Induced Atrial Fibrillation.

Michela Masè,Flavia Ravelli,Michela Alessandra Denti,Elvira D’Amato,Angelo Graffigna,Margherita Grasso,Manuel Nicolussi Giacomaz,Laura Avogaro,Francesco Tessarolo

doi:10.3389/fphys.2019.01133

Michela Masè, Flavia Ravelli + Show 7 more

Open Access

https://doi.org/10.3389/fphys.2019.01133

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Abstract

Atrial stretch and dilatation are common features of many clinical conditions predisposing to atrial fibrillation (AF). MicroRNAs (miRs) are emerging as potential molecular determinants of AF, but their relationship with atrial dilatation (AD) is poorly understood. The present study was designed to assess the specific miR expression profiles associated with AD in human atrial tissue. The expressions of a preselected panel of miRs, previously described as playing a role in cardiac disease, were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in atrial tissue samples from 30 cardiac surgery patients, who were characterized by different grades of AD and arrhythmic profiles. Our results showed that AD per se was associated with significant up-regulation of miR-328-3p and miR-133b (p < 0.05) with respect to controls, with a fold-change of 1.53 and 1.74, respectively. In a multivariate model including AD and AF as independent variables, miR-328-3p expression was mainly associated with AD grade (p < 0.05), while miR-133b was related to both AD (p < 0.005) and AF (p < 0.05), the two factors exerting opposite modulation effects. The presence of AF was associated with significant (p < 0.05) up-regulation of the expression level of miR-1-3p, miR-21-5p, miR-29a-3p, miR-208b-3p, and miR-590-5p. These results showed the existence of specific alterations of miR expression associated with AD, which may pave the way to future experimental studies to test the involvement of post-transcriptional mechanisms in the stretch-induced formation of a pro-arrhythmic substrate.

Highlights

Atrial fibrillation (AF) is the most frequent sustained cardiac arrhythmia seen in the clinical practice, and is associated with pronounced cardiovascular morbidity and mortality, mostly due to an increased risk of stroke (Chugh et al, 2014)
Echocardiographic data showed the presence of a statistically significant (p < 0.0001) difference in left atrial dilatation (AD) grade, which was significantly higher in AD and atrial fibrillation (AF) groups with respect to the control group
Our results showed that AD per se was associated with up-regulation of miR-328-3p and miR-133b, dilatation produced different expression patterns of these miRs when combined with AF

Summary

Introduction

Atrial fibrillation (AF) is the most frequent sustained cardiac arrhythmia seen in the clinical practice, and is associated with pronounced cardiovascular morbidity and mortality, mostly due to an increased risk of stroke (Chugh et al, 2014). Compelling clinical and experimental evidence demonstrate the contribution of atrial stretch to the different AF mechanisms (Ravelli, 2003; Schotten et al, 2003). Atrial stretch may induce afterdepolarizations promoting focal activity, and may increase the atrial surface, shorten the refractory period and impair conduction, favoring reentrant arrhythmias (Ravelli, 2003). Chronic AD may further contribute to the formation of an electroanatomic substrate by activation of numerous signaling pathways leading to cellular hypertrophy, fibroblast proliferation, and tissue fibrosis (Schotten et al, 2003)

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