Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, China.
Tongji University School of Medicine, Shanghai, China.
Int J Cardiol. 2022 Feb 15;349:115-122. doi: 10.1016/j.ijcard.2021.11.084. Epub 2021 Dec 6.
Work stress and its contribution to cardiovascular diseases are well documented in recent years, but its molecular mechanisms are still not clear. In this study, we aimed to explore the potential pathophysiological mechanisms of stress-induced heart injury in mouse models.
The RNA- and miRNA- sequencing profiles from five stress-treated mice and five control mice were performed. After normalization, differentially expressed genes (DEGs) and miRNAs (DEmiRs) were identified using the edgeR method. Then, based on the functional enrichment analysis and protein-protein interaction (PPI) network, as well as miRNA-mRNA interactome, the core DEGs and DEmiRs associated with stress-induced heart injury were marked and validated by qPCR, and the DEmiR targets were validated in vitro.
A total of 293 genes and 29 miRNAs were identified as DEGs and DEmiRs respectively, and Alb, Stat1, C3, Irf7, Usp18 were hub genes in the PPI network. The enrichment pathways were related to inflammation and immune, coagulation, oxidative phosphorylation, vascular development, cell cycle and extracellular matrix (ECM), which likely mediated the biological injury processes or reflected the results of damage. The target DEGs of DEmiRs were clustered in angiogenesis, immune system process and ECM. After the validation in vitro, we found that miR-29b-3p mimics could down-regulate the expression of its predicted targets, Pxdn and Col15a1.
The findings revealed a molecular basis from the gene and miRNA level for the heart injury associated with stress. miR-29b-3p, as a potential target to repair stress-induced ECM disorder in heart, deserves further study.
近年来，工作压力及其对心血管疾病的贡献已得到充分证实，但压力导致心脏损伤的分子机制仍不清楚。在这项研究中，我们旨在探索应激诱导的小鼠模型心脏损伤的潜在病理生理机制。
对五例应激处理的小鼠和五例对照小鼠的 RNA 和 miRNA 测序谱进行了分析。在归一化后，使用 edgeR 方法鉴定差异表达基因（DEGs）和 miRNA（DEmiRs）。然后，基于功能富集分析和蛋白质-蛋白质相互作用（PPI）网络以及 miRNA-mRNA 互作网络，通过 qPCR 标记和验证与应激诱导的心脏损伤相关的核心 DEGs 和 DEmiRs，并在体外验证 DEmiR 的靶标。
共鉴定出 293 个基因和 29 个 miRNA 分别作为 DEGs 和 DEmiRs，并且在 PPI 网络中 Alb、Stat1、C3、Irf7 和 Usp18 是核心基因。富集途径与炎症和免疫、凝血、氧化磷酸化、血管发育、细胞周期和细胞外基质（ECM）有关，这可能介导了生物学损伤过程或反映了损伤的结果。DEmiR 的靶基因 DEGs 聚类在血管生成、免疫系统过程和 ECM 中。在体外验证后，我们发现 miR-29b-3p 模拟物可以下调其预测靶基因 Pxdn 和 Col15a1 的表达。
这些发现从基因和 miRNA 水平揭示了与应激相关的心脏损伤的分子基础。miR-29b-3p 作为一种潜在的修复应激诱导的心脏 ECM 紊乱的靶标，值得进一步研究。
