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miR-455-5p 通过靶向细胞因子信号抑制因子 3 来调节心房颤动。

miR-455-5p regulates atrial fibrillation by targeting suppressor of cytokines signaling 3.

机构信息

The Fourth Hospital of Shijiazhuang, Shijiazhuang, 050000, Hebei, China.

Department of Respiratory and Critical Care Medicine, Hengshui People Hospital, Hengshui, 053000, China.

出版信息

J Physiol Biochem. 2021 Aug;77(3):481-490. doi: 10.1007/s13105-021-00808-x. Epub 2021 Apr 1.

Abstract

Atrial fibrillation (AF) is a condition that heart beats quaveringly or irregularly, which causes blood clots, heart failure, stroke, and other heart-related complications. Therefore, early diagnosis and timely preventions are necessary for AF treatment. Compelling evidence indicated that microRNAs (miRNAs) become emerging biomarkers of AF; thus, we aimed to investigate the possibility of miR-455-5p as an AF marker to provide a new strategy for early diagnosis of AF. A minipump containing angiotensin II was implanted into mice to induce AF, and adeno-associated virus (AAV) carrying anti-miR-negative control (NC) or anti-miR-455-5p was injected into the pericardial space of mice respectively. Next, myocytes isolated from wild-type newborn mice were stimulated with angiotensin II and anti-miR-NC or anti-miR-455-5p mimic. The results showed that the expression of miR-455-5p was positively correlated with the severity of AF, and miR-455-5p mimic accelerated the progression of AF by directly binding to its target gene suppressor of cytokines signaling 3 (SOCS3), leading to the activation of signal transducer and activator of transcription 3 (STAT3) signaling pathway. On the contrary, inhibition of miR-455-5p expression effectively ameliorated AF. In conclusion, miR-455-5p might serve as a biomarker of AF.

摘要

心房颤动(AF)是一种心脏跳动不规律或不规则的病症,会导致血栓、心力衰竭、中风和其他与心脏相关的并发症。因此,早期诊断和及时预防对于 AF 的治疗至关重要。有强烈的证据表明,微小 RNA(miRNAs)成为 AF 的新兴生物标志物;因此,我们旨在研究 miR-455-5p 作为 AF 标志物的可能性,为 AF 的早期诊断提供新策略。将含有血管紧张素 II 的微型泵植入小鼠体内以诱导 AF,并分别将携带抗 miR-阴性对照(NC)或抗 miR-455-5p 的腺相关病毒(AAV)注入小鼠的心包腔。接下来,用血管紧张素 II 和抗 miR-NC 或抗 miR-455-5p 模拟物刺激来自野生型新生小鼠的心肌细胞。结果表明,miR-455-5p 的表达与 AF 的严重程度呈正相关,miR-455-5p 模拟物通过直接与靶基因细胞因子信号转导抑制因子 3(SOCS3)结合,加速 AF 的进展,导致信号转导和转录激活因子 3(STAT3)信号通路的激活。相反,抑制 miR-455-5p 的表达可有效改善 AF。总之,miR-455-5p 可能作为 AF 的生物标志物。

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