Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
Mol Med Rep. 2018 Apr;17(4):5658-5665. doi: 10.3892/mmr.2018.8620. Epub 2018 Feb 20.
MicroRNA-210 (miRNA-210) has been reported to be associated with angiogenesis and may serve important roles in acute myocardial infarction (AMI), which remain unclear. The present study sought to evaluate the efficacy of miRNA‑210 in AMI and to examine the potential associated mechanisms. AMI models were established in Sprague‑Dawley rats. The expression of miRNA‑210 was upregulated via transfection with lentivirus‑mediated agonists and quantitative analysis was performed using the reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Immunoblotting and RT‑qPCR were separately used to detect the expression levels of hepatocyte growth factor (HGF) in heart samples, while only the protein expression level of β‑myosin heavy chain (β‑MHC) was assessed. The expression of HGF in human umbilical vein endothelial cells under hypoxic conditions was silenced by transfecting with small interfering RNA, as demonstrated by the determination of associated protein expression levels. The microvessel density (MVD) of the infarcted myocardium was selected to be the angiogenesis efficacy endpoint, which was evaluated by platelet endothelial cell adhesion molecule immunostaining. Markedly increased expression of HGF was observed among the AMI rats receiving miRNA‑210 agonists, demonstrated via quantitative analyses using RT‑qPCR or western blotting. Promotion of angiogenesis was observed with the increased MVD. Improved cardiac function in the rats was subsequently noted, as they exhibited improved left ventricular fractional shortening and left ventricular ejection fraction percentages, which may result from improved cardiac contractility indicated by attenuating the increase in β‑MHC protein expression. Overexpression of miRNA‑210 appeared to be an advantageous therapeutic tool for treating AMI, primarily due to its promoting effects on angiogenesis in the infarcted myocardium by stimulating HGF expression and inducing improved left ventricular remodeling, leading to improved cardiac function.
微小 RNA-210(miRNA-210)已被报道与血管生成有关,并且在急性心肌梗死(AMI)中可能具有重要作用,但作用机制尚不清楚。本研究旨在评估 miRNA-210 在 AMI 中的疗效,并研究其潜在的相关机制。采用慢病毒介导的激动剂转染建立 Sprague-Dawley 大鼠 AMI 模型,并通过逆转录-定量聚合酶链反应(RT-qPCR)对 miRNA-210 的表达进行定量分析。免疫印迹和 RT-qPCR 分别用于检测心脏样本中肝细胞生长因子(HGF)的表达水平,而仅评估β-肌球蛋白重链(β-MHC)的蛋白表达水平。通过转染小干扰 RNA 沉默缺氧条件下人脐静脉内皮细胞中 HGF 的表达,通过检测相关蛋白表达水平进行验证。通过血小板内皮细胞黏附分子免疫染色选择梗死心肌的微血管密度(MVD)作为血管生成疗效终点。通过 RT-qPCR 或 Western blot 定量分析发现,接受 miRNA-210 激动剂的 AMI 大鼠 HGF 的表达明显增加。观察到 MVD 增加,表明血管生成得到促进。随后发现大鼠的心脏功能得到改善,表现为左室短轴缩短率和左室射血分数百分比增加,这可能是由于心肌收缩力改善(表现为β-MHC 蛋白表达增加减少)所致。miRNA-210 的过表达似乎是治疗 AMI 的有利治疗工具,主要是因为它通过刺激 HGF 表达和诱导改善的左室重构,从而促进梗死心肌中的血管生成,从而改善心脏功能。