Teng Biyun, Xie Chaozheng, Zhao Yu, Zeng Qiu, Zhan Fangbiao, Feng Yangyang, Wang Zhe
Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Physiol. 2022 Jul 6;13:926508. doi: 10.3389/fphys.2022.926508. eCollection 2022.
Abdominal aortic aneurysm (AAA) is a severe cardiovascular disease that often results in high mortality due to sudden rupture. This paper aims to explore potential molecular mechanisms and effective targeted therapies to prevent and delay AAA rupture. We downloaded two microarray datasets (GSE98278 and GSE17901) from the Gene Expression Omnibus (GEO) database. Differential analysis and single-sample gene set enrichment analysis (ssGSEA) of hypoxia scores were performed on 48 AAA patients in GSE98278. We identified hypoxia- and ruptured AAA-related gene modules using weighted gene coexpression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the R package clusterProfiler. For candidate genes, validation was conducted on the mouse dataset GSE17901. Finally, we predicted drug candidates associated with the hub genes using the HERB Chinese medicine database. Eighty-two differentially expressed genes were screened in the ruptured and stable groups; 103 differentially expressed genes were identified between the high- and low-hypoxia groups; and WGCNA identified 58 differentially expressed genes. Finally, nine candidate genes were screened, including two hub genes (MEDAG and SERPINE1). We identified pathways such as cytokine-cytokine receptor interaction and T-helper 1-type immune response involved in AAA hypoxia and rupture. We predicted 93 traditional Chinese medicines (TCMs) associated with MEDAG and SERPINE1. We identified the hypoxic molecules MEDAG and SERPINE1 associated with AAA rupture. Our study provides an additional direction for the association between hypoxia and AAA rupture.
腹主动脉瘤（AAA）是一种严重的心血管疾病，常因突然破裂导致高死亡率。本文旨在探索潜在的分子机制和有效的靶向治疗方法，以预防和延缓AAA破裂。我们从基因表达综合数据库（GEO）下载了两个微阵列数据集（GSE98278和GSE17901）。对GSE98278中的48例AAA患者进行了缺氧评分的差异分析和单样本基因集富集分析（ssGSEA）。我们使用加权基因共表达网络分析（WGCNA）确定了与缺氧和破裂性AAA相关的基因模块。使用R包clusterProfiler进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。对于候选基因，在小鼠数据集GSE17901上进行了验证。最后，我们使用中药数据库HERB预测了与枢纽基因相关的候选药物。在破裂组和稳定组中筛选出82个差异表达基因；在高缺氧组和低缺氧组之间鉴定出103个差异表达基因；WGCNA鉴定出58个差异表达基因。最后筛选出9个候选基因，包括两个枢纽基因（MEDAG和SERPINE1）。我们确定了参与AAA缺氧和破裂的细胞因子-细胞因子受体相互作用和辅助性T细胞1型免疫反应等途径。我们预测了93种与MEDAG和SERPINE1相关的中药。我们确定了与AAA破裂相关的缺氧分子MEDAG和SERPINE1。我们的研究为缺氧与AAA破裂之间的关联提供了一个新的方向。
