Masè Michela, Grasso Margherita, Avogaro Laura, Nicolussi Giacomaz Manuel, D'Amato Elvira, Tessarolo Francesco, Graffigna Angelo, Denti Michela Alessandra, Ravelli Flavia
Laboratory of Biophysics and Biosignals, University of Trento, Trento, Italy.
Healthcare Research and Innovation Program, Bruno Kessler Foundation, Trento, Italy.
Front Physiol. 2019 Sep 10;10:1133. doi: 10.3389/fphys.2019.01133. eCollection 2019.
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 was associated with significant up-regulation of miR-328-3p and miR-133b ( < 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 ( < 0.05), while miR-133b was related to both AD ( < 0.005) and AF ( < 0.05), the two factors exerting opposite modulation effects. The presence of AF was associated with significant ( < 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.
心房扩张是许多易引发心房颤动（AF）的临床病症的常见特征。微小RNA（miR）正逐渐成为AF潜在的分子决定因素，但其与心房扩张（AD）的关系却鲜为人知。本研究旨在评估与人类心房组织中AD相关的特定miR表达谱。通过逆转录定量聚合酶链反应（RT-qPCR）对30例心脏手术患者心房组织样本中预先选定的一组miR的表达进行定量，这些患者具有不同程度的AD和心律失常特征，而这些miR先前被描述为在心脏疾病中发挥作用。我们的结果显示，与对照组相比，AD与miR-328-3p和miR-133b的显著上调相关（<0.05），倍数变化分别为1.53和1.74。在一个将AD和AF作为自变量的多变量模型中，miR-328-3p表达主要与AD分级相关（<0.05），而miR-133b与AD（<0.005）和AF（<0.05）均相关，这两个因素发挥相反的调节作用。AF的存在与miR-1-3p、miR-21-5p、miR-29a-3p、miR-208b-3p和miR-590-5p表达水平的显著上调相关（<0.05）。这些结果表明存在与AD相关的miR表达的特定改变，这可能为未来的实验研究铺平道路，以测试转录后机制在拉伸诱导的促心律失常底物形成中的作用。
