血清microRNA 483-5p升高可预测患者术后房颤发生风险
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Elevated serum microRNA 483-5p levels may predict patients at risk of post-operative atrial fibrillation
背景
术后心房颤动（POAF）是最常见的术后心律失常，3名冠状动脉旁路移植术（CABG）患者中就有1名患者会发生。尽管其病因学复杂，但心房基质的改变可能是最主要的预测因素。本研究旨在确定POAF的microRNA标记，并验证循环microRNA为预测术后心律失常的潜在生物标志物。
方 法
前瞻性招募了34名非急诊CABG患者。术中采取右心房活检，并快速冷冻及RNA提取。在手术前24小时和手术后第2天和第4天获得血浆。POAF由Holter记录。组间比较采用t检验或方差分析。受试者工作特征曲线（ROC）用于分析术前血清microRNA与POAF相关程度。
结 果
与窦性心律的患者相比，POAF患者心房肌中有16种microRNA表达差异。miR-208a表达最低 [倍数变化（FC）= 2.458]，而miR-483-5p表达最高（FC = 1.804）。在这些患者中miR-483-5p术前过度表达，ROC分析显示总体预测准确度为78％。
结 论
本研究首次描述了POAF患者心房肌细胞和循环血浆中的microRNA。我们的研究结果表明POAF可能与心房基质差异有关，这种差异诱发心律失常。这项研究强调了miR-483-5p在生物标志物开发中的潜力。现在进一步的工作必须大范围进行前瞻性，有针对性的验证。
原始文献摘要
Abstract
OBJECTIVES: Post-operative atrial fibrillation (POAF) is the commonest post-operative cardiac arrhythmia, affecting 1 in 3 patients undergoing coronary artery bypass grafting (CABG). Although its aetiology is complex, atrial substrate changes may pre-dispose to its onset. This study aims to ascertain the atrial microRNA signature of POAF and determine the potential for circulating microRNA as a pre-operative biomarker for this arrhythmia.
METHODS: Thirty-four patients undergoing non-emergent, on-pump CABG were prospectively recruited. Right atrial biopsies were taken intra-operatively and snap frozen for RNA extraction. Plasma was obtained at 24 h pre-operatively and at 2 and 4 days post-operatively. POAF was defined by continuous Holter recording. Inter-group comparisons were performed using Student’s t-test or analysis of variance as required. Receiver operating characteristic (ROC) analysis was used to determine the diagnostic accuracy of pre-operative serum miRNA as a POAF biomarker.
RESULTS: Sixteen microRNAs were differentially expressed in the atrial myocardium of POAF patients when compared with those maintaining sinus rhythm. miR-208a was the most underexpressed [fold change (FC) = 2.458] and miR-483-5p the most overexpressed (FC = 1.804). miR-483-5p also demonstrated significant overexpression in the pre-operative serum of these patients, with ROC analysis demonstrating an overall predictive accuracy of 78%.
CONCLUSIONS: This study provides the first description of atrial myocardial and circulating plasma microRNA in POAF patients. Our findings suggest POAF may be associated with pre-existing atrial substrate differences predisposing to arrhythmogenesis. Moreover, this study highlights the potential for miR-483-5p in biomarker development. Further work must now perform prospective, targeted validation of these results in a larger patient cohort.
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