Zhong Guofu, Chen Chunxiao, Wu Shixin, Chen Junteng, Han Yue, Zhu Qinghua, Xu Mujuan, Nie Qinqi, Wang Ling
The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China.
Department of Intensive Care Unit, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.
Cardiovasc Diagn Ther. 2023 Jun 30;13(3):534-549. doi: 10.21037/cdt-23-112. Epub 2023 Jun 21.
Dilated cardiomyopathy (DCM) is a severe manifestation or intermediate stage of cardiovascular disease progression with a significantly poor prognosis. Based on a protein interaction network and molecular docking, the present study determined the genes and mechanism of action of angiotensin-converting enzyme inhibitors (ACEIs) in the treatment of DCM, providing a direction for future studies on ACEI drugs for DCM.
This is a retrospective study. DCM samples and healthy controls were downloaded from the GSE42955 dataset, and the targets of the potential active ingredients were obtained from PubChem. Hub genes in ACEIs were analyzed by constructing network models and a protein-protein interaction (PPI) network using the STRING database and Cytoscape software. Molecular docking was performed using Autodock vina software.
Twelve DCM samples and five control samples were finally included. A total of 62 intersected genes were obtained by intersecting the differentially expressed genes with six ACEI target genes. PPI analysis identified 15 intersecting hub genes from these 62 genes. Enrichment analysis showed that the hub genes were associated with T helper type 17 (Th17) cell differentiation as well as the nuclear factor kappa-B (NF-kappa B), interleukin 17 (IL-17), mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF), phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) (PI3K-Akt), and Toll-like receptor signaling pathways. Molecular docking indicated that the compound Benazepril to produce favorable interactions with TNF proteins with a relatively higher score (-8.3).
This study primarily revealed that the preventive and curative effects of ACEI treatment on DCM could be realized through multiple targets and pathways, and its mechanism of action is related to genes such as , vascular endothelial growth factor A (), interleukin 6 (), C-C motif chemokine ligand 2 (), Cyclin D1 (), and AKT serine/threonine kinase 1 (), with immune- and inflammation-related signaling pathways involvement.
扩张型心肌病（DCM）是心血管疾病进展的严重表现或中间阶段，预后极差。基于蛋白质相互作用网络和分子对接，本研究确定了血管紧张素转换酶抑制剂（ACEIs）治疗DCM的基因及作用机制，为未来DCM的ACEI药物研究提供方向。
这是一项回顾性研究。从GSE42955数据集中下载DCM样本和健康对照，从PubChem获取潜在活性成分的靶点。使用STRING数据库和Cytoscape软件构建网络模型和蛋白质-蛋白质相互作用（PPI）网络，分析ACEIs中的枢纽基因。使用Autodock vina软件进行分子对接。
最终纳入12个DCM样本和5个对照样本。通过将差异表达基因与6个ACEI靶点基因相交，共获得62个相交基因。PPI分析从这62个基因中鉴定出15个相交枢纽基因。富集分析表明，枢纽基因与17型辅助性T细胞（Th17）分化以及核因子κB（NF-κB）、白细胞介素17（IL-17）、丝裂原活化蛋白激酶（MAPK）、肿瘤坏死因子（TNF）、磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）（PI3K-Akt）和Toll样受体信号通路相关。分子对接表明，化合物苯那普利与TNF蛋白产生良好相互作用，得分相对较高（-8.3）。
本研究初步揭示，ACEI治疗DCM的防治作用可通过多个靶点和途径实现，其作用机制与血管内皮生长因子A（VEGF-A）、白细胞介素6（IL-6）、C-C基序趋化因子配体2（CCL2）、细胞周期蛋白D1（CCND1）和AKT丝氨酸/苏氨酸激酶1（AKT1）等基因有关，并涉及免疫和炎症相关信号通路。
