The Ph.D. Program of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
Clinical Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan.
Int J Mol Sci. 2022 Jan 24;23(3):1281. doi: 10.3390/ijms23031281.
Myocardial infarction (MI) is a multifactorial global disease, recognized as one of the leading causes of cardiovascular morbidity and mortality. Timely and correct diagnoses and effective treatments could significantly reduce incidence of complications and improve patient prognoses. In this study, seven unconventional differentially expressed genes (DEGs) (MAN2A2, TNFRSF12A, SPP1, CSNK1D, PLAUR, PFKFB3, and CXCL16, collectively termed the MTSCPPC signature) were identified through integrating DEGs from six MI microarray datasets. The pathological and theranostic roles of the MTSCPPC signature in MI were subsequently analyzed. We evaluated interactions of the MTSCPPC signature with ovatodiolide, a bioactive compound isolated from (L.) Kuntze, using in silico molecular docking tools and compared it to specific inhibitors of the members of the MTSCPPC signature. Single-cell transcriptomic analysis of the public databases revealed high expression levels of the MTSCPPC signature in immune cells of adult human hearts during an MI event. The MTSCPPC signature was significantly associated with the cytokine-cytokine receptor interactions, chemokine signaling, immune and inflammatory responses, and metabolic dysregulation in MI. Analysis of a micro (mi)RNA regulatory network of the MTSCPPC signature suggested post-transcriptional activation and the roles of miRNAs in the pathology of MI. Our molecular docking analysis suggested a higher potential for ovatodiolide to target MAN2A2, CSNK1D, and TNFRSF12A. Collectively, the results derived from the present study further advance our understanding of the complex regulatory mechanisms of MI and provide a potential MI theranostic signature with ovatodiolide as a therapeutic candidate.
心肌梗死（MI）是一种多因素的全球性疾病，被认为是心血管发病率和死亡率的主要原因之一。及时、正确的诊断和有效的治疗可以显著降低并发症的发生率，改善患者的预后。在这项研究中，通过整合六个 MI 微阵列数据集的差异表达基因（DEG），鉴定了七个非常规差异表达基因（DEG）（MAN2A2、TNFRSF12A、SPP1、CSNK1D、PLAUR、PFKFB3 和 CXCL16，统称为 MTSCPPC 特征）。随后分析了 MTSCPPC 特征在 MI 中的病理和治疗作用。我们使用计算机分子对接工具评估了 MTSCPPC 特征与从 （L.）Kuntze 中分离出的生物活性化合物 ovatodiolide 的相互作用，并将其与 MTSCPPC 特征成员的特定抑制剂进行了比较。对公共数据库的单细胞转录组分析显示，在人类心脏发生 MI 事件期间，MTSCPPC 特征在免疫细胞中的表达水平较高。MTSCPPC 特征与细胞因子-细胞因子受体相互作用、趋化因子信号、免疫和炎症反应以及 MI 中的代谢失调显著相关。对 MTSCPPC 特征的 micro（mi）RNA 调控网络的分析表明，MAN2A2、CSNK1D 和 TNFRSF12A 的转录后激活和 miRNA 在 MI 病理中的作用。我们的分子对接分析表明，ovatodiolide 靶向 MAN2A2、CSNK1D 和 TNFRSF12A 的潜力更高。综上所述，本研究的结果进一步加深了我们对 MI 复杂调控机制的理解，并提供了一个潜在的 MI 治疗特征，以 ovatodiolide 作为治疗候选物。
