基于生物信息学分析花生四烯酸代谢在缺血性心脏病中的作用  

Role of Aarachidonic Acid Metabolism in Ischemic Heart Disease Based on Bioinformatics Analysis

作　　者：杨雪剑 陈虹[1] 王淼[1] YANG Xuejian;CHEN Hong;WANG Miao(State Key Laboratory of Cardiovascular Disease,National Center for Cadiovascular Diseases,Fuwai Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100037,China)

机构地区：[1]中国医学科学院北京协和医学院阜外医院,国家心血管病中心,心血管疾病国家重点实验室,北京市100037

出　　处：《中国分子心脏病学杂志》2023年第6期5720-5728,共9页Molecular Cardiology of China

基　　金：国家重点研发计划主动健康和老龄化科技应对重点专项基金(2020YFC2008000);国家自然科学基金重点国际合作基金(82320108002,92149305)。

摘　　要：目的 基于生物信息学分析缺血性心脏病(IHD)患者花生四烯酸代谢通路(AMP)基因差异表达情况,并探讨AMP基因在IHD发生与发展中的作用。方法 对IHD患者和健康对照者心脏组织转录组数据进行分析以鉴定差异表达基因,并运用机器学习算法筛选与IHD相关的AMP关键基因。这些核心基因被用于IHD诊断模型的开发和验证,并结合单细胞转录组数据进一步研究这些基因在IHD中的功能。结果 转录组数据分析显示,AMP基因在IHD中表达失调,并且鉴定出5个核心基因:PLA2G2A、CYP2J2、ACE、GPX3和EPHX2。基于这5个核心基因构建的模型在训练集和验证集中均表现出良好的诊断性能。这些核心基因主要在成纤维细胞和心肌细胞中表达,并与多种炎症因子及M2型巨噬细胞浸润高度相关。结论 PLA2G2A、CYP2J2、ACE、GPX3和EPHX2可作为IHD的诊断标志物,并与IHD中免疫细胞浸润密切相关。这些发现将为深入研究IHD疾病机制及开发靶向药物提供参考。Objective To investigate the expression and influence of genes associated with arachidonic acid metabolism pathway(AMP) on ischemic heart disease(IHD).Methods Firstly,transcriptome expression profiles were procured from three distinct raw datasets pertinent to IHD.Leveraging advanced machine learning techniques,we identified the pivotal hub genes associated with AMP within the context of IHD.We developed and rigorously validated a diagnostic model designed to predict the occurrence of IHD.Moreover,our insights were further extended through single-cell RNA analysis,particularly sc RNA sequencing data.Results Our investigation uncovered dysregulation of AMP genes in the context of IHD.Five pivotal hub genes(PLA2G2A,CYP2J2,ACE,GPX3,and EPHX2) were successfully identified.Integration of these hub genes into a diagnostic model exhibited compelling clinical utility in IHD diagnosis.Based on the sc RNA-seq,we found that the hub genes had relatively higher expression in fibroblast and cardiomyocyte.Conclusions Five hub genes(PLA2G2A,CYP2J2,ACE,GPX3,and EPHX2) can serve as excellent diagnostic biomarkers for IHD and are closely associated with immune cell infiltration in IHD.The transcriptional activity of the identified hub genes stands out as a promising prospective diagnostic marker for individuals afflicted with IHD.

关 键 词：缺血性心脏病 花生四烯酸 生物信息学 

分 类 号：R541[医药卫生—心血管疾病] Q811.4[医药卫生—内科学]