Systematic analysis of myocardial immune progression in septic cardiomyopathy: Immune-related mechanisms in septic cardiomyopathy

Front Cardiovasc Med. 2023 Feb 24:9:1036928. doi: 10.3389/fcvm.2022.1036928. eCollection 2022.

Abstract

Background: The immune infiltration and molecular mechanisms underlying septic cardiomyopathy (SC) have not been completely elucidated. This study aimed to identify key genes related to SC and elucidate the potential molecular mechanisms.

Methods: The weighted correlation network analysis (WGCNA), linear models for microarray analysis (LIMMA), protein-protein interaction (PPI) network, CIBERSORT, Kyoto Encyclopedia of Genes and Genomes pathway (KEGG), and gene set enrichment analysis (GSEA) were applied to assess the key pathway and hub genes involved in SC.

Results: We identified 10 hub genes, namely, LRG1, LCN2, PTX3, E LANE, TCN1, CLEC4D, FPR2, MCEMP1, CEACAM8, and CD177. Furthermore, we used GSEA for all genes and online tools to explore the function of the hub genes. Finally, we took the intersection between differential expression genes (DEGs) and hub genes to identify LCN2 and PTX3 as key genes. We found that immune-related pathways played vital roles in SC. LCN2 and PTX3 were key genes in SC progression, which mainly showed an anti-inflammatory effect. The significant immune cells in cardiomyocytes of SC were neutrophils and M2 macrophages.

Conclusion: These cells may have the potential to be prognostic and therapeutic targets in the clinical management of SC. Excessive anti-inflammatory function and neutrophil infiltration are probably the primary causes of SC.

Keywords: LCN2; PTX3; gene set enrichment analysis (GSEA); immune infiltration; septic cardiomyopathy; weighted correlation network analysis (WGCNA).