急性新发房颤中循环miRNA及其靶向mRNA网络
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Circulating miRNAs in acute new-onset atrial fibrillation and their target mRNA network
背景与目的
微小RNA（miRNA）与房颤的发病机制密切相关，并且反映疾病的发生与发展。我们的试验研究观察到新发房颤病人、房颤控制良好的病人及正常窦性心律病人有6种miRNA，而miRNA还可以与mRNA相互作用。
方 法
当急性新发房颤病人（N=5）出现不规则快速颤动节律时，在急诊室采集其血浆。房颤控制良好（N=16）及窦性心律（N=15）病人的血液样本在预约心电图检查后采集。
结 果
RT-PCR分析miR-21, miR-133a, miR-133b, miR-150, miR-328, and miR-499的表达。通过IPA数据库和TargetScan数据库确定了这些miRNA的前30个mRNA靶点，并寻找心血管过程中的miRNA-mRNA相互作用。与房颤控制良好和窦性心律病人相比，急性新房颤中miR-133b(1.4倍)，miR-328 (2.0倍),和 miR-499 (2.3倍)的表达增加。与急性新发AF和窦性心律相比，房颤控制良好病人的miR-21的表达下降了（0.6倍）。miRNA-mRNA相互作用证明SMAD7和FASLG基因是miR-21, miR-133b, 和miR-499的靶点，并且与AF直接相关，参与细胞凋亡和纤维化。
结 论
miRNA的表达不同取决于AF发生条件，急性新发房颤患者的miRNA表达要高于房颤控制良好的病人。miRNA监测可能在临床上评估病人的治疗有效性，从而对房颤早发现早监测，以降低与房颤相关的其他心血管事件风险。
原始文献摘要
Da S A, Jng D A, de Oliveira K M, et al. Circulating miRNAs in acute new-onset atrial fibrillation and their target mRNA network[J]. J Cardiovasc Electrophysiol, 2018.
Background: MicroRNAs (miRNAs) are involved in the pathogenesis of atrial fibrillation (AF), acting on development and progression. Our pilot study investigated the expression of six miRNAs and their miRNA-mRNA interactions in patients with acute new-onset AF, well- controlled AF, and normal sinus rhythm (controls).
Methods and results: Plasma of acute new-onset AF patients (n=5) was collected in the emergency room when patients presented with irregular and fast-atrial fibrillation rhythm. Samples from well-controlled AF (n=16) and control (n=15) patients were collected during medical appointments following an ECG. Expression of miR-21, miR-133a, miR-133b, miR- 150, miR-328, and miR-499 was analyzed by real-time PCR. Ingenuity Pathway Analysis and the TargetScan database identified the top 30 mRNA targets of these miRNA, seeking the miRNA mRNA interactions in cardiovascular process. Increased expression of miR-133b (1.4-fold), miR-328 (2.0-fold), and miR-499 (2.3-fold) was observed in patients with acute new-onset AF, compared with well-controlled AF and control patients. Decreased expression of miR-21 was seen in patients with well-controlled AF compared to those with acute new- onset AF and controls (0.6-fold). The miRNA-mRNA interaction demonstrated that SMAD7 and FASLG genes were the targets of miR-21, miR-133b, and miR-499 and were directly related to AF, being involved in apoptosis and fibrosis.
Conclusion: The miRNAs had different expression profiles dependent on the AF condition, with higher expression in the acute new-onset AF than well-controlled AF. Clinically, this may contribute to an effective assessment for patients, leading to early detection of AF and monitoring to reduce the risk of other serious cardiovascular events.
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