Xu Fan, Xie Linfeng, He Jian, Huang Qiuyu, Shen Yanming, Chen Liangwan, Zeng Xiaohong
Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China.
Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, Fujian Province, China.
Heliyon. 2024 Mar 29;10(8):e28029. doi: 10.1016/j.heliyon.2024.e28029. eCollection 2024 Apr 30.
Despite extensive research reveal rheumatoid arthritis (RA) is related to atherosclerosis (AS), common pathogenesis between these two diseases still needs to be explored. In current study, we explored the common pathogenesis between rheumatoid arthritis (RA) and atherosclerosis (AS) by identifying 297 Differentially Expressed Genes (DEGs) associated with both diseases. Through KEGG and GO functional analysis, we highlighted the correlation of these DEGs with crucial biological processes such as the vesicle transport, immune system process, signaling receptor binding, chemokine signaling and many others. Employing Protein-Protein Interaction (PPI) network analysis, we elucidated the associations between DEGs, revealing three gene modules enriched in immune system process, vesicle, signaling receptor binding, Pertussis, and among others. Additionally, through CytoHubba analysis, we pinpointed 11 hub genes integral to intergrin-mediated signaling pathway, plasma membrane, phosphotyrosine binding, chemokine signaling pathway and so on. Further investigation via the TRRUST database identified two key Transcription Factors (TFs), SPI1 and RELA, closely linked with these hub genes, shedding light on their regulatory roles. Finally, leveraging the collective insights from hub genes and TFs, we proposed 10 potential drug candidates targeting the molecular mechanisms underlying RA and AS pathogenesis. Further investigation on xCell revealed that 14 types of cells were all different in both AS and RA. This study underscores the shared pathogenic mechanisms, pivotal genes, and potential therapeutic interventions bridging RA and AS, offering valuable insights for future research and clinical management strategies.
尽管广泛的研究表明类风湿性关节炎（RA）与动脉粥样硬化（AS）有关，但这两种疾病之间的共同发病机制仍有待探索。在当前的研究中，我们通过鉴定297个与这两种疾病相关的差异表达基因（DEG），探索了类风湿性关节炎（RA）和动脉粥样硬化（AS）之间的共同发病机制。通过KEGG和GO功能分析，我们强调了这些DEG与关键生物过程的相关性，如囊泡运输、免疫系统过程、信号受体结合、趋化因子信号传导等。利用蛋白质-蛋白质相互作用（PPI）网络分析，我们阐明了DEG之间的关联，揭示了三个在免疫系统过程、囊泡、信号受体结合、百日咳等方面富集的基因模块。此外，通过CytoHubba分析，我们确定了11个在整合素介导的信号通路、质膜、磷酸酪氨酸结合、趋化因子信号通路等中不可或缺的枢纽基因。通过TRRUST数据库的进一步研究确定了两个关键转录因子（TF），SPI1和RELA，它们与这些枢纽基因密切相关，揭示了它们的调控作用。最后，利用来自枢纽基因和TF的综合见解，我们提出了10种潜在的药物候选物，针对RA和AS发病机制的分子机制。通过xCell的进一步研究表明，在AS和RA中，14种细胞类型均存在差异。这项研究强调了连接RA和AS的共同致病机制、关键基因和潜在的治疗干预措施，为未来的研究和临床管理策略提供了有价值的见解。
