College of Medical Technology, Qiqihar Medical University, Qiqihar, China.
Department of Anatomy, Qiqihar Medical University, Qiqihar, China.
Curr HIV Res. 2024;22(5):308-317. doi: 10.2174/011570162X304876240821062047.
HIV-associated pulmonary arterial hypertension (HIV-PAH), a rare and fatal condition within the pulmonary arterial hypertension spectrum, is linked to HIV infection. While ferroptosis, an iron-dependent cell death form, is implicated in various lung diseases, its role in HIVPAH development remains unclear.
Leveraging Gene Expression Omnibus data, we identified differentially expressed genes (DEGs) in pulmonary arterial smooth muscle cells, including HIV-related DEGs (HIV-DEGs) and ferroptosis-related HIV-DEGs (FR-HIV-DEGs). PPI network analysis of FR-HIV-DEGs using CytoHubba in Cytoscape identified hub genes. We conducted functional and pathway enrichment analyses for FR-HIV-DEGs, HIV-DEGs, and hub genes. Diagnostic value assessment of hub genes utilized ROC curve analysis. Key genes were further screened, and external validation was performed. Additionally, we predicted a potential ceRNA regulatory network for key genes.
1372 DEGs were found, of which 228 were HIV-DEGs, and 20 were FR-HIV-DEGs. TP53, IL6, PTGS2, IL1B (downregulated), and PPARG (upregulated) were the five hub genes that were screened. TP53, IL6, and IL1B act as ferroptosis drivers, PTGS2 as a ferroptosis marker, and PPARG as a ferroptosis inhibitor. Enrichment analysis indicated biological processes enriched in "response to oxidative stress" and pathways enriched in "human cytomegalovirus infection." Key genes IL6 and PTGS2 exhibited strong predictive value ROC curve analysis and external validation. The predicted ceRNA regulatory network identified miRNAs (has-mir-335-5p, has-mir-124-3p) targeting key genes and lncRNAs (XIST, NEAT1) targeting these miRNAs.
This study advances our understanding of potential mechanisms in HIV-PAH pathogenesis, emphasizing the involvement of ferroptosis. The findings offer valuable insights for future research in HIV-PAH.
HIV 相关肺动脉高压（HIV-PAH）是肺动脉高压谱中的一种罕见且致命的病症，与 HIV 感染有关。铁死亡是一种与铁相关的细胞死亡形式，与各种肺部疾病有关，但在 HIVPAH 发展中的作用尚不清楚。
利用基因表达综合数据库（GEO）数据，我们鉴定了肺动脉平滑肌细胞中的差异表达基因（DEGs），包括与 HIV 相关的 DEGs（HIV-DEGs）和与铁死亡相关的 HIV-DEGs（FR-HIV-DEGs）。使用 Cytoscape 中的 CytoHubba 对 FR-HIV-DEGs 进行 PPI 网络分析，以识别枢纽基因。我们对 FR-HIV-DEGs、HIV-DEGs 和枢纽基因进行了功能和通路富集分析。利用 ROC 曲线分析评估了枢纽基因的诊断价值。进一步筛选关键基因，并进行外部验证。此外，我们预测了关键基因的潜在 ceRNA 调控网络。
发现了 1372 个 DEGs，其中 228 个是 HIV-DEGs，20 个是 FR-HIV-DEGs。筛选出的 5 个枢纽基因为 TP53、IL6、PTGS2、IL1B（下调）和 PPARG（上调）。TP53、IL6 和 IL1B 作为铁死亡驱动基因，PTGS2 作为铁死亡标志物，PPARG 作为铁死亡抑制剂。富集分析表明，生物过程中富含“对氧化应激的反应”，通路中富含“人巨细胞病毒感染”。关键基因 IL6 和 PTGS2 的 ROC 曲线分析和外部验证均具有较强的预测价值。预测的 ceRNA 调控网络鉴定了针对关键基因的 miRNAs（has-mir-335-5p、has-mir-124-3p）和针对这些 miRNA 的 lncRNAs（XIST、NEAT1）。
本研究深入了解了 HIV-PAH 发病机制中的潜在机制，强调了铁死亡的参与。这些发现为 HIV-PAH 的未来研究提供了有价值的见解。
