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识别新冠病毒相关心力衰竭中的潜在生物学过程和关键靶点。

Identifying potential biological processes and key targets in COVID-19-associated heart failure.

作者信息

Li Jia, Guo Zhifu, Song Xiaowei

机构信息

Department of Cardiology, Changhai Hospital, Naval Medical University, Shanghai, China.

出版信息

Heliyon. 2023 Jul 25;9(8):e18575. doi: 10.1016/j.heliyon.2023.e18575. eCollection 2023 Aug.

DOI:10.1016/j.heliyon.2023.e18575
PMID:37554802
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10404953/
Abstract

Novel coronavirus pneumonia (COVID-19) is a new type of viral pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has spread rapidly and become a global pandemic. Heart failure (HF) is the ultimate period of the development of various cardiovascular diseases. There are several research have found that SARS-CoV-2 infection may induce cardiac complications including enhanced cardiac stress biomarkers and heart failure. Our research aims at identifying underlying biological processes and key targets in COVID-19-associated heart failure via bioinformatics analysis. A total of three heart failure datasets and three COVID-19 datasets were obtained using the Gene Expression Omnibus (GEO) database. Batch effects cross each sample were eliminated with surrogate variable analysis algorithm. Then, we identified key modules of COVID-19 datasets and heart failure datasets through weighted gene co-expression network analysis. HF-associated as well as COVID-19-associated key modules were intersected for determining the shared genes of COVID-19-associated heart failure. The pivotal genes associated with COVID-19-related heart failure were determined by intersecting the shared genes with the HF-associated hub genes selected through WGCNA. Furthermore, we conducted GO as well as KEGG enrichment analysis on shared genes of COVID-19-associated heart failure. Two COVID-19-associated key modules as well as three HF-associated key modules were determined. In addition, eleven shared genes for COVID-19-associated heart failure were determined. In conclusion, our work screened two critical genes, namely PYGM and BLM, which may be possible intervention targets for COVID-19-associated heart failure. According to functional enrichment results, the shared genes of COVID-19-associated heart failure showed high enrichment in starch and sucrose metabolism, homologous recombination, Fanconi anemia pathway, and insulin resistance indicate the probably biological processes linked to COVID-19-associated heart failure. These results provided further insights in possible interventional and therapeutic targets of COVID-19-associated heart failure.

摘要

新型冠状病毒肺炎(COVID-19)是由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的一种新型病毒性肺炎,它迅速传播并成为全球大流行疾病。心力衰竭(HF)是各种心血管疾病发展的终末期。有多项研究发现,SARS-CoV-2感染可能诱发心脏并发症,包括心脏应激生物标志物升高和心力衰竭。我们的研究旨在通过生物信息学分析确定COVID-19相关性心力衰竭潜在的生物学过程和关键靶点。使用基因表达综合数据库(GEO)获得了总共三个心力衰竭数据集和三个COVID-19数据集。采用替代变量分析算法消除每个样本间的批次效应。然后,通过加权基因共表达网络分析确定COVID-19数据集和心力衰竭数据集的关键模块。对HF相关以及COVID-19相关的关键模块进行交集分析,以确定COVID-19相关性心力衰竭的共享基因。通过将共享基因与通过WGCNA选择的HF相关枢纽基因进行交集分析,确定与COVID-19相关性心力衰竭相关的关键基因。此外,我们对COVID-19相关性心力衰竭的共享基因进行了基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。确定了两个COVID-19相关关键模块以及三个HF相关关键模块。此外,确定了11个COVID-19相关性心力衰竭的共享基因。总之,我们的研究筛选出了两个关键基因,即磷酸化糖原磷酸化酶(PYGM)和布卢姆综合征解旋酶(BLM),它们可能是COVID-19相关性心力衰竭的潜在干预靶点。根据功能富集结果,COVID-19相关性心力衰竭的共享基因在淀粉和蔗糖代谢、同源重组、范科尼贫血途径以及胰岛素抵抗方面表现出高度富集,这表明这些可能是与COVID-19相关性心力衰竭相关的生物学过程。这些结果为COVID-19相关性心力衰竭可能的干预和治疗靶点提供了进一步的见解。

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