Zhao Xingxing, Jia Yongping, Chen Huanzhen, Yao Hongmei, Guo Wenlin
Department of Cardiology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Exp Ther Med. 2019 Jul;18(1):179-187. doi: 10.3892/etm.2019.7555. Epub 2019 May 8.
Myocardial infarction (MI) is primarily caused by ischemic heart or coronary artery disease and is a major cause of mortality worldwide. Thus, it is necessary to establish reliable biochemical markers for the early diagnosis of MI. MicroRNAs (miRNAs or miR) have been demonstrated to circulate in biological fluids and are enclosed in extracellular vesicles, including exosomes. The current study assessed the differential expression of exosomal miRNAs in the plasma of patients with MI and healthy individuals, and the possible mechanism involved. Plasma-derived exosomes were isolated from patients with MI and healthy control individuals, and vesicles with a membrane were observed using transmission electron microscopy. Furthermore, an exosomal miRNA expression profile was compared between patients with MI and healthy individuals using a miRNA microarray. Significantly differentially expressed miRNAs were validated using reverse transcription-quantitative polymerase chain reaction. To the best of our knowledge, the present study was the first to demonstrate that miR-183 was markedly upregulated in patients with MI compared with healthy individuals. In addition, the relative exosomal miR-183 level increased with the degree of myocardial ischemic injury. Additionally, GO and KEGG analyses demonstrated that miR-183 is primarily involved in cell communication, protein kinase activity regulation and adrenergic signaling in cardiomyocytes. Furthermore, a protein-protein interaction network of all the miR-183 target genes was constructed. The results demonstrated that five core genes ( and ) in the PPI network were also associated with protein kinase activity regulation and adrenergic signaling in cardiomyocytes. Taken together, these data demonstrate that exosomal miR-183 derived from the serum of patients with MI may be a novel diagnostic biomarker involved in the regulation of protein kinase activity. miR-183 may therefore be further developed for clinical use to benefit patients with coronary artery diseases.
心肌梗死（MI）主要由缺血性心脏病或冠状动脉疾病引起，是全球范围内主要的死亡原因。因此，有必要建立可靠的生化标志物用于MI的早期诊断。微小RNA（miRNA或miR）已被证明在生物体液中循环，并包裹在细胞外囊泡中，包括外泌体。本研究评估了MI患者和健康个体血浆中外泌体miRNA的差异表达及其可能的机制。从MI患者和健康对照个体中分离出血浆来源的外泌体，并使用透射电子显微镜观察有膜的囊泡。此外，使用miRNA微阵列比较了MI患者和健康个体之间的外泌体miRNA表达谱。使用逆转录-定量聚合酶链反应验证了差异显著的miRNA。据我们所知，本研究首次证明与健康个体相比，MI患者中miR-183明显上调。此外，外泌体miR-183的相对水平随心肌缺血损伤程度增加而升高。此外，基因本体（GO）和京都基因与基因组百科全书（KEGG）分析表明，miR-183主要参与心肌细胞中的细胞通讯、蛋白激酶活性调节和肾上腺素能信号传导。此外，构建了所有miR-183靶基因的蛋白质-蛋白质相互作用网络。结果表明，蛋白质-蛋白质相互作用网络中的五个核心基因也与心肌细胞中的蛋白激酶活性调节和肾上腺素能信号传导有关。综上所述，这些数据表明来自MI患者血清的外泌体miR-183可能是一种参与蛋白激酶活性调节的新型诊断生物标志物。因此，miR-183可能会进一步开发用于临床应用以造福冠状动脉疾病患者。
