Department of Preventive Medicine, Shantou University Medical College, 515041 Shantou, Guangdong, China.
Department of Cardiology, People's Hospital of Xinjin District, 611430 Chengdu, Sichuan, China.
Front Biosci (Landmark Ed). 2024 Sep 29;29(10):347. doi: 10.31083/j.fbl2910347.
Angiogenesis plays a critical protective role in myocardial ischemia-reperfusion injury (MIRI); however, therapeutic targeting of associated genes remains constrained. To bridge this gap, we conducted bioinformatics analysis to identify pivotal angiogenesis-related genes in MIRI, potentially applicable for preventive and therapeutic interventions.
We collected two mouse heart I/R expression datasets (GSE61592 and GSE83472) from Gene Expression Omnibus, utilizing the Limma package to identify differentially expressed genes (DEGs). Angiogenesis-related genes (ARGs) were extracted from GeneCards, and their overlap with DEGs produced differentially expressed ARGs (ARDEGs). Further analyses included Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and disease ontology to explore biological functions. Weighted gene correlation network analysis (WGCNA) was used to investigate molecular modules linked to MIRI. Additionally, a protein-protein interaction (PPI) network was constructed to pinpoint hub genes relevant to MIRI. Receiver operating characteristic curves were used to assess the diagnostic efficacy of these hub genes for MIRI. An ischemia-reperfusion injury model was established using human cardiac microvascular endothelial cells (HCMECs), with the expression of hub genes validated within this experimental framework.
We identified 47 ARDEGs, 41 upregulated and 6 downregulated. PPI network analysis revealed suppressor of cytokine signaling 3 (), C-X-C motif chemokine ligand 1 (), interleukin 1 beta (), and matrix metallopeptidase 9 () as hub genes. Receiver operating characteristic (ROC) curve analysis demonstrated strong diagnostic potential for , , , and . validation corroborated the mRNA and protein expression predictions.
Our study highlights the pivotal role of , , , and in MIRI development, their significance in immune cell infiltration, and their diagnostic accuracy. These findings offer valuable insights for MIRI diagnosis and treatment, presenting potential molecular targets for future research.
血管生成在心肌缺血再灌注损伤（MIRI）中起着至关重要的保护作用；然而，相关基因的治疗靶向仍然受到限制。为了弥补这一空白，我们进行了生物信息学分析，以确定 MIRI 中关键的血管生成相关基因，这些基因可能适用于预防和治疗干预。
我们从基因表达综合数据库（GEO）中收集了两个小鼠心脏 I/R 表达数据集（GSE61592 和 GSE83472），利用 Limma 包来识别差异表达基因（DEGs）。从 GeneCards 中提取血管生成相关基因（ARGs），并与 DEGs 进行重叠，得到差异表达的 ARGs（ARDEGs）。进一步的分析包括基因本体论（GO）、京都基因与基因组百科全书（KEGG）和疾病本体论（DO），以探索生物学功能。加权基因相关网络分析（WGCNA）用于研究与 MIRI 相关的分子模块。此外，构建了蛋白质-蛋白质相互作用（PPI）网络，以确定与 MIRI 相关的关键基因。受试者工作特征曲线（ROC）用于评估这些关键基因对 MIRI 的诊断效能。使用人心脏微血管内皮细胞（HCMECs）建立缺血再灌注损伤模型，在此实验框架内验证关键基因的表达。
我们鉴定了 47 个 ARDEGs，其中 41 个上调，6 个下调。PPI 网络分析显示，细胞因子信号转导抑制因子 3（）、C-X-C 基序趋化因子配体 1（）、白细胞介素 1β（）和基质金属蛋白酶 9（）是关键基因。ROC 曲线分析显示，、、、对 MIRI 具有较强的诊断潜力。验证证实了 mRNA 和蛋白表达的预测。
我们的研究强调了、、、在 MIRI 发展中的关键作用，以及它们在免疫细胞浸润中的重要性及其诊断准确性。这些发现为 MIRI 的诊断和治疗提供了有价值的见解，为未来的研究提供了潜在的分子靶点。
