Identification of Fatty Acid Metabolism Disorder-Related Gene Signature in Septic Cardiomyopathy.

BACKGROUND

Septic cardiomyopathy (SCM) is a prevalent complication of sepsis and a primary contributor to mortality in patients with sepsis. Although fatty acid metabolism (FAM) is known to regulate cardiac function, its specific role in the pathogenesis of SCM remains unclear.

METHODS

The SCM datasets were obtained from the NCBI GEO database. Differentially expressed genes (DEGs) were subjected to GO and KEGG pathway analyses. The fatty acid metabolism-related genes were obtained from the MSigDB database. CytoHubba and machine learning algorithms identified hub FAM-DEGs. Associated transcriptional factors and miRNAs of hub FAM-DEGs were predicted using Cytoscape software and miRWalk 3.0 database. The immune infiltration pattern in SCM was analyzed using the ImmuCellAI tool. The relationship between hub FAM-DEGs and immune infiltration abundance was investigated using Spearman method. Hub FAM-DEGs expression levels were validated in clinical samples and mouse models.

RESULTS

Five hub FAM-DEGs associated with SCM were identified, including and . Immune analysis revealed significantly increased infiltrations of granulocytes, monocytes, M1 macrophage and neutrophils in the SCM group. Spearman analysis demonstrated that the hub FAM-DEGs were positively associated with the infiltration of pro-inflammatory immune cells. In Vivo, Down-regulations of Dhcr24 mRNA and protein levels in cardiac tissues were observed in the SCM mouse group. Clinically, the plasma concentration of DHCR24 was significantly decreased in patients with SCM.

CONCLUSION

This study revealed fatty acid metabolism played a crucial role in SCM and identified DHCR24 may act as a potential diagnostic biomarker and therapeutic target in SCM.