Zhang Fang, Geng Lu, Zhang Jing, Han Siliang, Guo Mengya, Xu Yaxin, Chen Chunhong
Department of Cardiology, Affiliated Hospital of Hebei University, No. 212, Yuhua East Road, Baoding, 071000, People's Republic of China.
Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People's Republic of China.
Mol Cell Biochem. 2025 Feb;480(2):1077-1087. doi: 10.1007/s11010-024-05027-8. Epub 2024 May 23.
This study focused on miR-486-5p in atrial fibrillation (AF) evaluating its clinical significance and revealing its regulatory mechanism in cardiac fibroblasts, aiming to explore a novel biomarker for AF. The study enrolled 131 AF patients and 77 non-AF individuals. With the help of polymerase chain reaction (PCR), the expression of miR-486-5p was evaluated. The significance of miR-486-5p in the diagnosis of AF and the occurrence of left atrial fibrosis (LAF) was assessed by receiver operating curve (ROC) and logistic analyses. The regulatory effect and mechanism of miR-486-5p on cardiac fibrosis were investigated in human cardiac fibroblasts treated with angiotensin II. miR-486-5p was significantly upregulated in AF patients and discriminated AF patients from non-AF individuals. Increasing miR-486-5p showed a significant association with decreasing left ventricular ejection fraction (LVEF), increasing left atrial diameter (LAD) and left ventricular end-diastolic diameter (LVEDd), and the high incidence of LAF in AF patients. Moreover, miR-486-5p was identified as a risk factor for LAF and could distinguish AF patients with LAF and without LAF. In cardiac fibroblasts, angiotensin II induced the upregulation of miR-486-5p and promoted cell proliferation, migration, and collagen synthesis. miR-486-5p negatively regulated forkhead box O1 (FOXO1) and its knockdown could reverse the promoted effect of angiotensin II. FOXO1 alleviated the effect of miR-486-5p, and the miR-486-5p/FOXO1 could activate PI3K/Akt signaling. The activation of PI3K/Akt signaling alleviated the enhanced proliferation, migration, and collagen synthesis of cardiac fibroblasts induced by angiotensin II, and its inhibition showed opposite effects. Increased miR-486-5p served as a biomarker for the diagnosis and development prediction of AF. miR-486-5p regulated cardiac fibroblast viability and collagen synthesis via modulating the PI3K/Akt signaling through targeting FOXO1.
本研究聚焦于房颤（AF）中的miR-486-5p，评估其临床意义并揭示其在心脏成纤维细胞中的调控机制，旨在探索一种新的房颤生物标志物。该研究纳入了131例房颤患者和77例非房颤个体。借助聚合酶链反应（PCR）评估miR-486-5p的表达。通过受试者工作特征曲线（ROC）和逻辑分析评估miR-486-5p在房颤诊断及左心房纤维化（LAF）发生中的意义。在用血管紧张素II处理的人心脏成纤维细胞中研究miR-486-5p对心脏纤维化的调控作用及机制。miR-486-5p在房颤患者中显著上调，且能区分房颤患者与非房颤个体。miR-486-5p升高与房颤患者左心室射血分数（LVEF）降低、左心房直径（LAD）和左心室舒张末期直径（LVEDd）增加以及LAF高发显著相关。此外，miR-486-5p被确定为LAF的危险因素，且能区分有LAF和无LAF的房颤患者。在心脏成纤维细胞中，血管紧张素II诱导miR-486-5p上调并促进细胞增殖、迁移和胶原合成。miR-486-5p负向调节叉头框O1（FOXO1），其敲低可逆转血管紧张素II的促进作用。FOXO1减轻了miR-486-5p的作用，且miR-486-5p/FOXO1可激活PI3K/Akt信号通路。PI3K/Akt信号通路的激活减轻了血管紧张素II诱导的心脏成纤维细胞增殖、迁移和胶原合成增强，而其抑制则产生相反作用。miR-486-5p升高可作为房颤诊断和病情发展预测的生物标志物。miR-486-5p通过靶向FOXO1调节PI3K/Akt信号通路来调控心脏成纤维细胞活力和胶原合成。
