PDF(Pubmed)
Abstract：
UNASSIGNED: Left ventricular hypertrophy (LVH) is a common consequence of hypertension and can lead to heart failure. The immune response plays an important role in hypertensive LVH; however, there is no comprehensive method to investigate the mechanistic relationships between immune response and hypertensive LVH or to find novel therapeutic targets. This study aimed to screen hub immune-related genes involved in hypertensive LVH as well as to explore immune target-based therapeutic drugs.
UNASSIGNED: RNA-sequencing data from a mouse model generated by angiotensin II infusion were subjected to weighted gene co-expression network analysis (WGCNA) to identify core expression modules. Machine learning algorithms were applied to screen immune-related LVH characteristic genes. Heart structures were evaluated by echocardiography and cardiac magnetic resonance imaging (CMRI). Validation of hub genes was conducted by RT-qPCR and western blot. Using the Connectivity Map database and molecular docking, potential small-molecule drugs were explored.
UNASSIGNED: A total of 1215 differentially expressed genes were obtained, most of which were significantly enriched in immunoregulation and collagen synthesis. WGCNA and multiple machine learning strategies uncovered six hub immune-related genes (Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3) that may accurately predict hypertensive LVH diagnosis. Immune analysis revealed that fibroblasts and macrophages were closely correlated with hypertensive LVH, and hub gene expression was significantly associated with these immune cells. A regulatory network of transcription factor-mRNA and a ceRNA network of miRNA-lncRNA was established. Notably, six hub immune-related genes were significantly increased in the hypertensive LVH model, which were positively linked to left ventricle wall thickness. Finally, 12 small-molecule compounds with the potential to reverse the high expression of hub genes were ruled out as potential therapeutic agents for hypertensive LVH.
UNASSIGNED: This study identified and validated six hub immune-related genes that may play essential roles in hypertensive LVH, providing new insights into the potential pathogenesis of cardiac remodeling and novel targets for medical interventions.
UNASSIGNED: RNA-sequencing data from a mouse model generated by angiotensin II infusion were subjected to weighted gene co-expression network analysis (WGCNA) to identify core expression modules. Machine learning algorithms were applied to screen immune-related LVH characteristic genes. Heart structures were evaluated by echocardiography and cardiac magnetic resonance imaging (CMRI). Validation of hub genes was conducted by RT-qPCR and western blot. Using the Connectivity Map database and molecular docking, potential small-molecule drugs were explored.
UNASSIGNED: A total of 1215 differentially expressed genes were obtained, most of which were significantly enriched in immunoregulation and collagen synthesis. WGCNA and multiple machine learning strategies uncovered six hub immune-related genes (Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3) that may accurately predict hypertensive LVH diagnosis. Immune analysis revealed that fibroblasts and macrophages were closely correlated with hypertensive LVH, and hub gene expression was significantly associated with these immune cells. A regulatory network of transcription factor-mRNA and a ceRNA network of miRNA-lncRNA was established. Notably, six hub immune-related genes were significantly increased in the hypertensive LVH model, which were positively linked to left ventricle wall thickness. Finally, 12 small-molecule compounds with the potential to reverse the high expression of hub genes were ruled out as potential therapeutic agents for hypertensive LVH.
UNASSIGNED: This study identified and validated six hub immune-related genes that may play essential roles in hypertensive LVH, providing new insights into the potential pathogenesis of cardiac remodeling and novel targets for medical interventions.
摘要：
■左心室肥厚（LVH）是高血压的常见后果，可导致心力衰竭。免疫反应在高血压LVH中起重要作用；然而，没有全面的方法来研究免疫反应与高血压LVH之间的机制关系或寻找新的治疗靶点。本研究旨在筛选与高血压LVH相关的中枢免疫相关基因，并探索基于免疫靶标的治疗药物。对来自通过血管紧张素II输注产生的小鼠模型的
RNA测序数据进行加权基因共表达网络分析(WGCNA)以鉴定核心表达模块。应用机器学习算法筛选免疫相关的LVH特征基因。通过超声心动图和心脏磁共振成像（CMRI）评估心脏结构。通过RT-qPCR和蛋白质印迹进行hub基因的验证。使用ConnectivityMap数据库和分子对接，潜在的小分子药物进行了探索。
■共获得1215个差异表达基因，其中大多数在免疫调节和胶原蛋白合成方面显着富集。WGCNA和多种机器学习策略发现了六个中心免疫相关基因（Ankrd1，Birc5，Nuf2，C1qtnf6，Fcgr3和Cdca3），可以准确预测高血压LVH诊断。免疫分析显示成纤维细胞和巨噬细胞与高血压LVH密切相关,和hub基因表达与这些免疫细胞显著相关。建立了转录因子-mRNA的调控网络和miRNA-lncRNA的ceRNA网络。值得注意的是,6个中枢免疫相关基因在高血压LVH模型中显著增加,与左心室壁厚度呈正相关。最后,排除了12种具有逆转hub基因高表达潜力的小分子化合物作为高血压LVH的潜在治疗剂。
■这项研究确定并验证了可能在高血压LVH中起重要作用的六个中枢免疫相关基因，为心脏重塑的潜在发病机制和医学干预提供新的靶点。
RNA测序数据进行加权基因共表达网络分析(WGCNA)以鉴定核心表达模块。应用机器学习算法筛选免疫相关的LVH特征基因。通过超声心动图和心脏磁共振成像（CMRI）评估心脏结构。通过RT-qPCR和蛋白质印迹进行hub基因的验证。使用ConnectivityMap数据库和分子对接，潜在的小分子药物进行了探索。
■共获得1215个差异表达基因，其中大多数在免疫调节和胶原蛋白合成方面显着富集。WGCNA和多种机器学习策略发现了六个中心免疫相关基因（Ankrd1，Birc5，Nuf2，C1qtnf6，Fcgr3和Cdca3），可以准确预测高血压LVH诊断。免疫分析显示成纤维细胞和巨噬细胞与高血压LVH密切相关,和hub基因表达与这些免疫细胞显著相关。建立了转录因子-mRNA的调控网络和miRNA-lncRNA的ceRNA网络。值得注意的是,6个中枢免疫相关基因在高血压LVH模型中显著增加,与左心室壁厚度呈正相关。最后,排除了12种具有逆转hub基因高表达潜力的小分子化合物作为高血压LVH的潜在治疗剂。
■这项研究确定并验证了可能在高血压LVH中起重要作用的六个中枢免疫相关基因，为心脏重塑的潜在发病机制和医学干预提供新的靶点。
