Liman Li,1– 3 Tiancong Zhang,1– 3 Chuan Yang,4 Qiang Meng,1– 3 Shuang Wang,1– 3 Yang Fu1– 3 

1Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Sichuan Clinical Research Center for Laboratory Medicine, Chengdu, Sichuan, People’s Republic of China; 3Clinical Laboratory Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China

Correspondence: Yang Fu, Email fuyang827@wchscu.cn

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 Hsd17b7, Dhcr24, Cyp1a1, Ephx1 and Hmgcs2. 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.

Keywords: Sepsis, septic-cardiomyopathy, fatty acid metabolism, DHCR24