Systems immunology-based drug repurposing framework to target inflammation in atherosclerosis [Tissue_RNA-seq]. Systems immunology-based drug repurposing framework to target inflammation in atherosclerosis [Tissue_RNA-seq]

we present a novel path to drug repurposing to identify new immunotherapies for ASCVD. The integration of time of-flight mass cytometry (CyTOF) and RNA-sequencing identified unique inflammatory signatures in peripheral blood mononuclear cells (PBMCs) stimulated with ASCVD plasma. By comparing these inflammatory signatures to large-scale gene expression data from the LINCS L1000 dataset, we identified drugs that could reverse this inflammatory response. In conclusion, a systems immunology-driven drug repurposing with pre- clinical validation strategy can aid the development of new cardiovascular immunotherapies. Overall design: Comparative gene expression profiling analysis of RNA-seq data for atherosclerotic patient tissue stimulated with autologous plasma -/+ saracatinib was performed.

本研究提出了一条用于动脉粥样硬化性心血管疾病（Atherosclerotic Cardiovascular Disease, ASCVD）新型免疫疗法发现的药物重定位创新路径。通过整合飞行时间质谱流式细胞术（Time-of-flight mass cytometry, CyTOF）与RNA测序（RNA-sequencing）技术，我们在经ASCVD血浆刺激的外周血单个核细胞（Peripheral Blood Mononuclear Cells, PBMCs）中鉴定出独特的炎症特征。将上述炎症特征与LINCS L1000数据集的大规模基因表达数据进行对比分析，我们筛选出可逆转该炎症反应的候选药物。综上，结合系统免疫学驱动框架与临床前验证策略的药物重定位方法，能够为新型心血管免疫疗法的开发提供有效支撑。整体实验设计：本研究对经自体血浆±萨拉替尼刺激的动脉粥样硬化患者组织的RNA测序数据开展了对比基因表达谱分析。