Department of Cardiology, College of Medicine, Ewha Womans University School of Medicine, Seoul 07985, Republic of Korea.
Department of Otorhinolaryngology‑Head and Neck Surgery, Inha University School of Medicine, Incheon 22332, Republic of Korea.
Mol Med Rep. 2022 May;25(5). doi: 10.3892/mmr.2022.12702. Epub 2022 Mar 29.
MicroRNAs (miRNAs) are small non‑coding RNAs that control patterns of gene expression by inducing the degradation of mRNAs. In addition, miRNAs are known to serve an important role in the pathogenesis of atrial fibrillation (AF). In general, AF is diagnosed using electrocardiography. However, the present study investigated whether specific miRNAs derived from microarray analysis of human urine could regulate AF through the inhibition of calcium handling protein phosphorylation in an AF model. Microarray analysis of the transcriptome in the human urine of patients with paroxysmal supraventricular tachycardia and AF revealed that 7 differentially expressed miRNAs were significantly downregulated (miR‑3613, 6763, 423, 3162, 1180, 6511, 3197) in patients with AF. In addition, quantitative PCR results demonstrated that collagen I, collagen III, fibronectin and TGF‑β, which are fibrosis‑related genes, were upregulated in patients with AF. Furthermore, fibrosis‑related genes were upregulated in angiotensin II‑induced atrial myocytes, which demonstrated that these genes may be targets of miR‑423. In the AF cell model transfected with miR‑423, the expression of calcium handling proteins, including phosphorylated calmodulin‑dependent protein kinase II, was reduced. The transfection of miR‑423 attenuated damage to cardiac cells caused by calcium handling proteins. The findings highlight the importance of calcium handling protein phosphorylation changes in fibrosis‑induced AF and support miR‑423 detection in human urine as a potential novel approach of AF diagnosis.
微小 RNA（miRNA）是一类小的非编码 RNA，通过诱导 mRNA 的降解来控制基因表达的模式。此外，miRNA 已知在心房颤动（AF）的发病机制中发挥重要作用。通常，AF 通过心电图诊断。然而，本研究通过抑制 AF 模型中钙处理蛋白磷酸化，探讨了源自人尿微阵列分析的特定 miRNA 是否可以调节 AF。对阵发性室上性心动过速和 AF 患者人尿中转录组的微阵列分析显示，7 个差异表达的 miRNA 明显下调（miR-3613、6763、423、3162、1180、6511、3197）在 AF 患者中。此外，定量 PCR 结果表明，AF 患者中纤维化相关基因胶原 I、胶原 III、纤连蛋白和 TGF-β上调。此外，血管紧张素 II 诱导的心房心肌细胞中纤维化相关基因上调，表明这些基因可能是 miR-423 的靶点。在转染 miR-423 的 AF 细胞模型中，钙处理蛋白的表达，包括磷酸化钙调蛋白依赖性蛋白激酶 II，减少。miR-423 的转染减轻了钙处理蛋白对心脏细胞的损伤。这些发现强调了钙处理蛋白磷酸化变化在纤维化诱导的 AF 中的重要性，并支持 miR-423 在人尿中的检测作为 AF 诊断的一种潜在新方法。
