Eno1 in sepsis-induced coagulopathy: a pleiotropic mechanism hypothesis involving immunomodulation and endothelial dysfunction.

backgroundSeptic-induced coagulopathy (SIC) is a major cause of mortality in sepsis, closely associated with endothelial glycocalyx damage. Enolase 1 (Eno1), a key enzyme in glycolysis, plays a crucial role in sepsis-related systemic inflammation and the maintenance of glycocalyx integrity.

objectiveThis study utilizes multi-omics analysis to investigate the Eno1-regulated network, providing a comprehensive understanding of its molecular mechanisms in SIC.

methodsWe used RNA-seq datasets to identify Eno1-related gene sets through weighted gene co-expression network analysis and validated their biological functions via gene set enrichment analysis.

resultsThrough RNA-seq analysis, we identified gene sets associated with Eno1 involved in immune regulation, endothelial cell apoptosis, coagulation, and glycosaminoglycan metabolism. Immune infiltration analysis revealed that Eno1 modulates SIC pathogenesis by influencing T cells and macrophages, with significant associations with endothelial dysfunction and inflammatory markers. Additionally, we observed that Eno1 regulation of glycolysis is linked to endothelial glycocalyx degradation, contributing to microcirculatory and vascular impairments in SIC. Furthermore, preliminary studies suggest that melatonin treatment may alleviate glycocalyx damage by inhibiting Eno1-mediated glycolytic pathways, offering a potential new therapeutic avenue for intervening in endothelial injury associated with SIC.

conclusionsThis study underscores the critical role of Eno1 in promoting SIC and its potential as both a diagnostic marker and therapeutic target for glycocalyx repair. The multi-omics approach provides valuable insights into the molecular networks regulating SIC, offering new avenues for targeted interventions in sepsis management.