Internal Medicine II, Department of Cardiology, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria.
Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University, 5110 Oberndorf, Austria.
Cells. 2023 Sep 27;12(19):2369. doi: 10.3390/cells12192369.
(1) Background and Objective: MicroRNAs (miRs) are biomarkers for assessing the extent of cardiac remodeling after myocardial infarction (MI) and important predictors of clinical outcome in heart failure. Overexpression of miR-30d-5p appears to have a cardioprotective effect. The aim of the present study was to demonstrate whether miR-30d-5p could be used as a potential therapeutic target to improve post-MI adverse remodeling. (2) Methods and Results: MiR profiling was performed by next-generation sequencing to assess different expression patterns in ischemic vs. healthy myocardium in a rat model of MI. MiR-30d-5p was significantly downregulated ( < 0.001) in ischemic myocardium and was selected as a promising target. A mimic of miR-30d-5p was administered in the treatment group, whereas the control group received non-functional, scrambled siRNA. To measure the effect of miR-30d-5p on infarct area size of the left ventricle, the rats were randomized and treated with miR-30d-5p or scrambled siRNA. Histological planimetry was performed 72 h and 6 weeks after induction of MI. Infarct area was significantly reduced at 72 h and at 6 weeks by using miR-30d-5p (72 h: 22.89 ± 7.66% vs. 35.96 ± 9.27%, p = 0.0136; 6 weeks: 6.93 ± 4.58% vs. 12.48 ± 7.09%, = 0.0172). To gain insight into infarct healing, scratch assays were used to obtain information on cell migration in human umbilical vein endothelial cells (HUVECs). Gap closure was significantly faster in the mimic-treated cells 20 h post-scratching (12.4% more than the scrambled control after 20 h; = 0.013). To analyze the anti-apoptotic quality of miR-30d-5p, the ratio between phosphorylated p53 and total p53 was evaluated in human cardiomyocytes using ELISA. Under the influence of the miR-30d-5p mimic, cardiomyocytes demonstrated a decreased pp53/total p53 ratio (0.66 ± 0.08 vs. 0.81 ± 0.17), showing a distinct tendency ( = 0.055) to decrease the apoptosis rate compared to the control group. (3) Conclusion: Using a mimic of miR-30d-5p underlines the cardioprotective effect of miR-30d-5p in MI and could reduce the risk for development of ischemic cardiomyopathy.
（1）背景和目的：微小 RNA（miRs）是评估心肌梗死后心脏重构程度的生物标志物，也是心力衰竭临床结局的重要预测因子。miR-30d-5p 的过表达似乎具有心脏保护作用。本研究旨在证明 miR-30d-5p 是否可用作改善心肌梗死后不良重构的潜在治疗靶点。（2）方法和结果：通过下一代测序对 miR 图谱进行分析，以评估大鼠 MI 模型中缺血与健康心肌之间的不同表达模式。miR-30d-5p 在缺血心肌中显著下调（<0.001），被选为有前途的靶标。miR-30d-5p 的模拟物在治疗组中给药，而对照组接受非功能的、乱序的 siRNA。为了测量 miR-30d-5p 对左心室梗死面积的影响，将大鼠随机分为 miR-30d-5p 或乱序 siRNA 治疗组。在 MI 诱导后 72 小时和 6 周进行组织学平面图测量。miR-30d-5p 显著减少了 72 小时和 6 周时的梗死面积（72 小时：22.89±7.66%比 35.96±9.27%，p=0.0136；6 周：6.93±4.58%比 12.48±7.09%，p=0.0172）。为了深入了解梗死愈合，划痕实验用于获取人脐静脉内皮细胞（HUVEC）中细胞迁移的信息。划痕后 20 小时，模拟物处理的细胞中缝隙闭合速度明显加快（20 小时后比乱序对照增加 12.4%；p=0.013）。为了分析 miR-30d-5p 的抗凋亡作用，使用 ELISA 评估人心肌细胞中磷酸化 p53 与总 p53 的比值。在 miR-30d-5p 模拟物的影响下，心肌细胞显示出 pp53/总 p53 比值降低（0.66±0.08 比 0.81±0.17），与对照组相比，细胞凋亡率明显降低（p=0.055）。（3）结论：使用 miR-30d-5p 的模拟物强调了 miR-30d-5p 在 MI 中的心脏保护作用，并可能降低缺血性心肌病的发展风险。
