The purpose of this study was to investigate the regulatory mechanism of miR-450a-2-3p in myocardial fibrosis in patients with atrial fibrillation. For this purpose, the expression profile of GSE55296 was extracted from the GEO database, and differentially expressed lncRNAs were identified. Gene ontology analysis of the target genes of mir-450a-2-3p indicated that there was a regulatory relationship between LINC00636 and miR-450a-2-3p. Further, the expression levels of the analyzed RNAs were confirmed by RT-qPCR. TGF-β1-induced cardiac fibroblasts (CFs) and human umbilical vein endothelial cells (HUVECs) were used to establish a myocardial fibrosis model and endothelium-mesenchymal transformation (EMT) model in vivo. We hypothesized that exosomes containing LINC00636 regulate the expression of miR-450a-2-3p. LINC00636 was positively correlated with the expression of miR-450a-2-3p. The overexpression of miR-450a-2-3p suppressed the MAPK1 expression in CFs, thereby inhibiting the expression of α-SMA, COL1, and COL3 and preventing CF proliferation. In HUVECs, the miR-450a-2-3p overexpression upregulated the expression of VE-Cadherin (VE-Cad) and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) by inhibiting the mitogen-activated protein kinase 1 (MAPK1) expression, whereas the expression levels of vimentin, COL1, and COL3 decreased. These results indicate that LINC00636, which is present in human pericardial fluid, is an antifibrotic molecule that inhibits MAPK1 through the miR-450a-2-3p overexpression and improves cardiac fibrosis in patients with atrial fibrillation.

中文翻译：

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含有LINC00636的外泌体通过人心包液中的miR-450a-2-3p过表达抑制MAPK1并改善心房颤动患者的心脏纤维化

本研究旨在探讨miR-450a-2-3p在心房颤动患者心肌纤维化中的调控机制。为此，从 GEO 数据库中提取 GSE55296 的表达谱，并鉴定出差异表达的 lncRNA。mir-450a-2-3p靶基因的基因本体分析表明LINC00636与miR-450a-2-3p之间存在调控关系。此外，通过 RT-qPCR 确认了分析的 RNA 的表达水平。转化生长因子-β1诱导的心脏成纤维细胞（CFs）和人脐静脉内皮细胞（HUVECs）用于建立体内心肌纤维化模型和内皮-间质转化（EMT）模型。我们假设含有 LINC00636 的外泌体调节 miR-450a-2-3p 的表达。LINC00636 与 miR-450a-2-3p 的表达呈正相关。miR-450a-2-3p 的过表达抑制了 CFs 中 MAPK1 的表达，从而抑制了α的表达-SMA、COL1 和 COL3 并防止 CF 增殖。在 HUVECs 中，miR-450a-2-3p 过表达通过抑制丝裂原活化蛋白激酶 1 (MAPK1) 上调 VE-Cadherin (VE-Cad) 和血小板内皮细胞粘附分子-1 (PECAM-1/CD31) 的表达) 表达，而波形蛋白、COL1 和 COL3 的表达水平下降。这些结果表明存在于人心包液中的 LINC00636 是一种抗纤维化分子，可通过 miR-450a-2-3p 过表达抑制 MAPK1 并改善心房颤动患者的心脏纤维化。