Exploring the Genetic Landscape of Sepsis-Induced Cardiomyopathy: A Comprehensive Analysis

Abstract Background: Sepsis poses a severe threat in critical care, often leading to septic cardiomyopathy. This study aimed to explore the genes related to mitochondrial damage in septic cardiomyopathy, observe their changes during sepsis, and analyze the possible pathogenesis of this disease. Methods: Bioinformatics methods were used to identify differentially expressed genes (DEGs) and enrichment pathways associated with mitochondrial damage in patients with septic cardiomyopathy. Subsequently, clinical specimens and cardiomyocytes were verified and compared to clarify the expression of these genes and their change trend in the pathogenesis of septic myocardial injury to explore the possible relationship between these genes and septic myocardial mitochondrial dysfunction. Results: In this study, using diverse datasets, 398 differentially expressed genes (DEGs) related to sepsis were identified, and 11 key genes (GNAS, MRPL2, TIMM17b, SLC25A3, SDHA, PRPF6, LMF2, IMMT, CS, UCP2, and CASP2) were significantly associated with these genes. Functional analysis highlighted the importance of the TIM23 complex in septic mitochondrial injury. Real-time fluorescence quantitative PCR was performed on 11 genes and TIMM23 expression in 24-48 hours in clinical specimens, and the expression of TIMM17b and TIMM23 was increased in the sepsis group, while the expression of the other 10 DEGs was decreased. Further verification via cell experiments revealed that the expression of 11 DEGs and 5 TIM23 complex member genes, TIMM23, TIMM17A, TIMM44, PAM16 and TIMM50, increased in the 6-hour group, while their expression decreased significantly in the 24-hour group; moreover, the expression of only TIMM17b was still greater than that in the normal control group. The expression of other genes was lower than or close to that of the normal control group. Conclusion: This integrative study not only provides a comprehensive overview of DEGs associated with sepsis but also emphasizes the importance of the TIM23 complex. The identified genes and pathways offer potential targets for further mechanistic studies and therapeutic interventions in the context of sepsis-related complications.