Zhou Yu, Rui Shibao, Tang Shengxin, Ju Changlin
Department of Emergency, The First Affiliated Hospital of Wannan Medical College, Wuhu, China.
Department of Cardiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, China.
Front Cardiovasc Med. 2022 Apr 13;9:829484. doi: 10.3389/fcvm.2022.829484. eCollection 2022.
Significant reductions in the incidence of cardiac arrhythmia (CA) and sudden cardiac death (SCD), along with amelioration of heart failure, have been reported for treatment with Sacubitril/valsartan (SV). However, its anti-arrhythmic mechanism remains unclear. The current study aims to explore the anti-arrhythmic molecular mechanism of SV. The direct protein targets (DPT) of SV were extracted from DrugBank. The protein-protein interaction (PPI) network of SV DPTs was constructed using STRING, and the indirect protein targets (IPTs) were also identified. A search for arrhythmia-related genes was conducted using GeneCards and the Comparative Toxicogenomics Database (CTD). The DTPs, ITPs, and arrhythmia-related genes from the two datasets were combined in a Venn diagram, and the overlapping genes were identified as core target genes. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses identified the top 20 biological processes and signaling pathways related to disease and the therapeutic effects of SV. The renin-angiotensin system, adrenergic signaling in cardiomyocytes, and gap junction pathways are strongly implicated in the effects of SV on CA. In conclusion, our bioinformatics analyses provided evidence pertaining to the possible antiarrhythmic mechanisms of SV and may contribute to the development of novel drugs for CA.
据报道，沙库巴曲缬沙坦（SV）治疗可显著降低心律失常（CA）的发生率和心源性猝死（SCD），并改善心力衰竭。然而，其抗心律失常机制仍不清楚。本研究旨在探讨SV的抗心律失常分子机制。从DrugBank中提取SV的直接蛋白质靶点（DPT）。使用STRING构建SV DPT的蛋白质-蛋白质相互作用（PPI）网络，并确定间接蛋白质靶点（IPT）。使用GeneCards和比较毒理基因组学数据库（CTD）搜索心律失常相关基因。将两个数据集中的DTP、ITP和心律失常相关基因合并在维恩图中，重叠基因被确定为核心靶基因。基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析确定了与疾病及SV治疗效果相关的前20个生物学过程和信号通路。肾素-血管紧张素系统、心肌细胞中的肾上腺素能信号传导和缝隙连接通路与SV对CA的作用密切相关。总之，我们的生物信息学分析为SV可能的抗心律失常机制提供了证据，并可能有助于开发治疗CA的新药。
