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加权基因共表达网络分析（WGCNA）和分子对接确定心脏衰老的关键基因。

WGCNA and molecular docking identify hub genes for cardiac aging.

作者信息

Ping Ping, Guan Lixun, Ning Chaoxue, Liu Qiong, Zhao Yali, Zhu Xiang, Yang Ting, Fu Shihui

机构信息

General Station for Drug and Instrument Supervision and Control, Joint Logistic Support Force of Chinese People's Liberation Army, Beijing, China.

Hematology Department, Hainan Hospital of Chinese People's Liberation Army General Hospital, Sanya, China.

出版信息

Front Cardiovasc Med. 2023 Apr 27;10:1146225. doi: 10.3389/fcvm.2023.1146225. eCollection 2023.

DOI:10.3389/fcvm.2023.1146225
PMID:37180776
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10172467/
Abstract

BACKGROUND

Cardiac aging and ageing-related cardiovascular diseases remain increase medical and social burden. Discovering the molecular mechanisms associated with cardiac aging is expected to provide new perspectives for delaying aging and related disease treatment.

METHODS

The samples in GEO database were divided into older group and younger group based on age. Age-associated differentially expressed genes (DEGs) were identified by limma package. Gene modules significantly associated with age were mined using weighted gene co-expression network analysis (WGCNA). Protein-protein interaction networks (PPI) networks were developed using genes within modules, and topological analysis on the networks was performed to identify hub genes in cardiac aging. Pearson correlation was used to analyze the association among hub genes and immune and immune-related pathways. Molecular docking of hub genes and the anti-aging drug Sirolimus was performed to explore the potential role of hub genes in treating cardiac aging.

RESULTS

We found a generally negative correlation between age and immunity, with a significant negative correlation between age and b_cell_receptor_signaling_pathway, fc_gamma_r_mediated_phagocytosis, chemokine signaling pathway, t-cell receptor signaling pathway, toll_like_receptor_signaling_pathway, and jak_stat_signaling_pathway, respectively. Finally, 10 cardiac aging-related hub genes including LCP2, PTPRC, RAC2, CD48, CD68, CCR2, CCL2, IL10, CCL5 and IGF1 were identified. 10-hub genes were closely associated with age and immune-related pathways. There was a strong binding interaction between Sirolimus-CCR2. CCR2 may be a key target for Sirolimus in the treatment of cardiac aging.

CONCLUSION

The 10 hub genes may be potential therapeutic targets for cardiac aging, and our study provided new ideas for the treatment of cardiac aging.

摘要

背景

心脏衰老及与衰老相关的心血管疾病持续增加医疗和社会负担。探索与心脏衰老相关的分子机制有望为延缓衰老及相关疾病治疗提供新视角。

方法

基于年龄将GEO数据库中的样本分为老年组和年轻组。使用limma软件包鉴定与年龄相关的差异表达基因（DEG）。利用加权基因共表达网络分析（WGCNA）挖掘与年龄显著相关的基因模块。使用模块内的基因构建蛋白质-蛋白质相互作用网络（PPI），并对网络进行拓扑分析以鉴定心脏衰老中的枢纽基因。采用Pearson相关性分析枢纽基因与免疫及免疫相关通路之间的关联。对枢纽基因与抗衰老药物西罗莫司进行分子对接，以探索枢纽基因在治疗心脏衰老中的潜在作用。

结果

我们发现年龄与免疫力之间总体呈负相关，年龄分别与b细胞受体信号通路、FcγR介导的吞噬作用、趋化因子信号通路、T细胞受体信号通路、Toll样受体信号通路和Jak-Stat信号通路之间存在显著负相关。最终，鉴定出10个与心脏衰老相关的枢纽基因，包括LCP2、PTPRC、RAC2、CD48、CD68、CCR2、CCL2、IL10、CCL5和IGF1。10个枢纽基因与年龄和免疫相关通路密切相关。西罗莫司与CCR2之间存在强烈的结合相互作用。CCR2可能是西罗莫司治疗心脏衰老的关键靶点。

结论

这10个枢纽基因可能是心脏衰老的潜在治疗靶点，我们的研究为心脏衰老的治疗提供了新思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56df/10172467/904672092030/fcvm-10-1146225-g010.jpg
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