Elevated serum microRNA 483-5p levels may predict patients at risk of post-operative atrial fibrillation.
Elevated serum microRNA 483-5p levels may predict patients at risk of post-operative atrial fibrillation.
复制标题
DOI：
10.1093/ejcts/ezw245
复制
发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Athanasiou T
中科院分区：
文献类型：
--
作者：
Harling L;Lambert J;Ashrafian H;Darzi A;Gooderham NJ;Athanasiou T
术后房颤是最常见的术后心律失常，影响3例冠状动脉搭桥术患者的∼-1。虽然其病因复杂，但心房基质的改变可能是其发病的先兆。本研究旨在确定POAF的心房microRNA特征，并确定循环microRNA作为该心律失常的术前生物标志物的可能性。34名接受非急诊体外循环冠状动脉搭桥术的患者被前瞻性纳入研究对象。术中取右心房活检组织，快速冷冻提取RNA。分别于术前24小时、术后2天、4天采血。采用动态心电图连续描记的方法确定POAF。组间比较按要求使用学生t检验或方差分析。受试者工作特征(ROC)分析用于确定术前血清miRNA作为POAF生物标志物的诊断准确性。16个microRNAs在POAF患者和维持窦性节律的患者的心房心肌中有差异表达。MiR-208A表达最低[倍增(FC)=2.458]，miR-483-5P最高表达(FC=1.804)。MIR-483-5P在这些患者的术前血清中也显示出显著的过度表达，ROC分析显示总体预测准确率为78%。本研究首次对POAF患者的心房心肌和循环血浆microRNA进行了描述。我们的发现提示，POAF可能与预先存在的心房基质差异有关，容易发生心律失常。此外，这项研究强调了miR-483-5P在生物标记物开发中的潜力。进一步的工作现在必须在更大的患者队列中对这些结果进行前瞻性的、有针对性的验证。
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. 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. 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%. 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.