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

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

Dunliang Ma  1 , Xianyu Qin  2 , Zhi-An Zhong  3 , Hongtao Liao  3 , Pengyuan Chen  1 , Bin Zhang  3
Affiliations

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

Dunliang Ma et al. Front Cardiovasc Med. .

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).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Workflow used for bioinformatics analyses.
FIGURE 2
FIGURE 2
Overview of WGCNA network construction of all genes (A) Gene modules’ dendrogram plots of all genes; (B) module-trait relationships of four groups in 18 modules. (C–E) Module membership vs. gene significance between three significant modules, including blue module (Pearson cor = 0.9, p < 1e-200), dark green module (cor = 0.9, p = 3.3e-34), and orange module (Pearson cor = 0.79, p < 1e-200); (F) the bubble diagram showing the GO (biological process, BP) function enrichment of genes in sub-modules. The size represents the gene counts, and node colors show the gene expression negative Log10_FDR (false discovery rate).
FIGURE 3
FIGURE 3
Analysis of gene ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and protein-protein interaction (PPI) network of genes in septic cardiomyopathy (SC)-related modules. (A–C) The bubble map showing the GO function (cellular component, CC, and molecular function, MF) and KEGG pathways were constructed by the STRING database. The sizes represent negative Log10 (FDR). (D) The gene PPI network was also constructed based on the STRING database. (E) The plots showing the top 10 higher degree hub genes for SC.
FIGURE 4
FIGURE 4
Immunocyte infiltration analysis and potential immunocyte subtype detection. (A) This diagram shows the immune-related pathways by gene set enrichment analysis (GSEA) analysis. (B) This heatmap shows the immunocyte infiltration difference between SC and control heart samples. (C,D) Box plots presenting significantly infiltrated immunocyte subtypes, neutrophils, and M2 macrophages. (E) This correlated heatmap shows the relationship between immunocytes and hub genes. (F) Intersection between DEGs and hub genes, identifying the key genes, LCN2, and PTX3.
See this image and copyright information in PMC

References

    1. Shankar-Hari M, Phillips G, Levy M, Seymour C, Liu V, Deutschman C, et al. Developing a new definition and assessing new clinical criteria for septic shock: for the third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. (2016) 315:775–87. 10.1001/jama.2016.0289 - DOI - PMC - PubMed
    1. Sharawy N, Lehmann C. New directions for sepsis and septic shock research. J Surg Res. (2015) 194:520–7. 10.1016/j.jss.2014.12.014 - DOI - PubMed
    1. Beesley S, Weber G, Sarge T, Nikravan S, Grissom C, Lanspa M, et al. Septic cardiomyopathy. Crit Care Med. (2018) 46:625–34. 10.1097/CCM.0000000000002851 - DOI - PubMed
    1. Dinh W, Füth R, Nickl W, Krahn T, Ellinghaus P, Scheffold T, et al. Elevated plasma levels of TNF-alpha and interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders. Cardiovasc Diabetol. (2009) 8:58. 10.1186/1475-2840-8-58 - DOI - PMC - PubMed
    1. Mariappan N, Elks C, Sriramula S, Guggilam A, Liu Z, Borkhsenious O, et al. NF-kappaB-induced oxidative stress contributes to mitochondrial and cardiac dysfunction in type II diabetes. Cardiovasc Res. (2010) 85:473–83. 10.1093/cvr/cvp305 - DOI - PMC - PubMed