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Role of Necroptosis and Immune Infiltration in Atrial Fibrillation: Novel Insights Revealed by Integrated Computational Biology Analyses
  • Danning Wang,
  • Sumin Wu,
  • Ye Zhu
Danning Wang
Fifth Affiliated Hospital of Sun Yat-sen University Cardiovascular Center

Corresponding Author:[email protected]

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Sumin Wu
Fifth Affiliated Hospital of Sun Yat-sen University Department of Nephrology
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Ye Zhu
Fifth Affiliated Hospital of Sun Yat-sen University Department of Nephrology
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Abstract

Background: Atrial fibrillation (AF) is associated with high mortality and morbidity rates. In terms of the underlying pathophysiology, AF is complex and remains unclear. Necroptosis plays an essential role in the pathogenesis of various cardiovascular diseases. This study aims to investigate the role of necroptosis and analyze the interaction between necroptosis and AF. Methods: GSE79768 and GSE41177 from the Gene Expression Omnibus (GEO) database were downloaded, and necroptosis-related differentially expressed genes (NRDEGs) were identified between AF and healthy groups. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were then used to conduct functional enrichment analyses of these genes. The CIBERSORT algorithm was used to reveal the patterns of immune cell infiltration in AF and exam the correlation between hub genes and immune cells to explain the underlying mechanism. Then, a lncRNA-associated ceRNA network was constructed by using Cytoscape underlying the interaction generated from the miRcode, miRTarBase, and TarBase databases. Results: There were a total of 34 DEGs identified. Necroptosis and inflammation were mainly controlled by these DEGs. MAPK8, MAP3K7, CD40, CASP8, MYC, HSP90AA1, BCL2L11and DIABLO were identified as the top 8 hub genes associated with AF. The relationship between AF and the hub genes in patients was further confirmed in the STRING database. The immune cell infiltration analysis indicated that B cells memory, Eosinophil, T cells follicular helper, and Neutrophils were significantly activated in atrial fibrillation. It was found that the hub genes in GSE79768 were strongly correlated with immune cell infiltration. B cells naïve and B cells memory, Plasma cells, and Macrophages M2, T cells CD8 and Mast cells activated, Mast cells resting and Mast cells activated showed a negative correlation (P <0.01), Mast cells activated and Eosinophils, B cells memory and T cells CD4 naïve showed a positive correlation (P <0.01). Finally, 43 lncRNAs were identified in AF. Seven lncRNAs (SLFNL1-AS1, LINC01132, PCBP1-AS1, LINC01816, LINC02035, MYLK-AS1, TERC) regulate the hub-gene through has-mir-34c-5p. Conclusions: MAPK8, MAP3K7, CD40, and CASP8 may act as critical regulators in the necroptosis of cardiomyocytes in AF patients. It involves mechanisms such as humoral immunity, cellular immunity, and inflammatory response, but the fundamental biological function of these genes remains unclear. Our present study may pave the way for further research into the necroptosis of AF.