Heart failure (HF) is a rising epidemic and public health burden in modern society. It is of great need to find new biomarkers to ensure a timely diagnosis and to improve treatment and prognosis of the disease. The mouse model of HF was established by thoracic aortic constriction. Color Doppler ultrasound was performed to detect left ventricular end-diastolic diameter. Hematoxylin and eosin staining was conducted to observe the pathological changes of mouse myocardium. The RT-qPCR analysis was performed to detect miR-590-5p and RTN4 expression levels. Western blot was conducted to detect protein levels of the indicated genes. We found that the expression of miR-590-5p was downregulated in cardiac tissues of HF mice. Injection of AAV-miR-590-5p attenuated myocardium hypertrophy and myocyte apoptosis. Additionally, miR-590-5p overexpression promoted viability, inhibited apoptosis, and decreased ANF, BNP and beta-MHC protein levels in H9c2 cell. Mechanistically, miR-590-5p binds to RTN4 3′‐untranslated region, as predicted by starBase online database and evidenced by luciferase reporter assay. Furthermore, miR-590-5p negatively regulates RTN4 mRNA expression and suppresses its translation. The final rescue experiments revealed that miR-590-5p modulated cardiomyocyte phenotypes by binding to RTN4. In conclusion, miR-590-5p modulates myocardium hypertrophy and myocyte apoptosis in HF by downregulating RTN4.

心力衰竭 (HF) 是现代社会日益严重的流行病和公共卫生负担。迫切需要寻找新的生物标志物以确保及时诊断并改善疾病的治疗和预后。采用胸主动脉缩窄法建立心衰小鼠模型。彩色多普勒超声检测左心室舒张末期直径。苏木精伊红染色观察小鼠心肌组织病理变化。进行 RT-qPCR 分析以检测 miR-590-5p 和 RTN4 表达水平。进行蛋白质印迹以检测指定基因的蛋白质水平。我们发现 HF 小鼠心脏组织中 miR-590-5p 的表达下调。注射 AAV-miR-590-5p 可减轻心肌肥大和心肌细胞凋亡。此外，miR-590-5p 过表达促进了 H9c2 细胞的活力，抑制了细胞凋亡，并降低了 ANF、BNP 和 β-MHC 蛋白水平。机制上，miR-590-5p 与 RTN4 3'-非翻译区结合，正如 starBase 在线数据库预测和荧光素酶报告基因分析所证实的那样。此外，miR-590-5p 负调控 RTN4 mRNA 表达并抑制其翻译。最后的拯救实验表明 miR-590-5p 通过与 RTN4 结合来调节心肌细胞表型。总之，miR-590-5p 通过下调 RTN4 来调节 HF 中的心肌肥大和心肌细胞凋亡。此外，miR-590-5p 负调控 RTN4 mRNA 表达并抑制其翻译。最后的拯救实验表明 miR-590-5p 通过与 RTN4 结合来调节心肌细胞表型。总之，miR-590-5p 通过下调 RTN4 来调节 HF 中的心肌肥大和心肌细胞凋亡。此外，miR-590-5p 负调控 RTN4 mRNA 表达并抑制其翻译。最后的拯救实验表明 miR-590-5p 通过与 RTN4 结合来调节心肌细胞表型。总之，miR-590-5p 通过下调 RTN4 来调节 HF 中的心肌肥大和心肌细胞凋亡。