Comprehensive insights into sepsis-induced cardiac dysfunction through proteomics and metabolomics

OBJECTIVE: Sepsis remains a leading cause of mortality worldwide, with cardiac dysfunction contributing substantially to sepsis-related deaths. Due to the unique biology of myocardial tissue, the mechanisms underlying sepsis-induced cardiac injury are incompletely understood. This exploratory study aimed to apply integrated proteomic and metabolomic profiling to characterize molecular alterations in cardiac tissue from a cecal ligation and puncture mouse model of sepsis. RESULTS: Comparative analysis identified 118 significantly altered proteins (75 upregulated and 43 downregulated) and 190 significantly altered metabolites (174 upregulated and 16 downregulated). Integrated pathway and network analyses implicated biological processes including platelet activation, mineral absorption, drug metabolism, terpenoid backbone biosynthesis, and butanoate metabolism. Notably, several previously under-recognized proteins (Prpsap1, Qsox1 and Prph), were identified as differentially expressed and ranked highly in our integrated network analyses, while prostaglandin H2, prostaglandin I2, thromboxane A2 and L-glutamine emerged as central metabolic nodes. These data extend the molecular landscape of septic cardiomyopathy and nominate prioritized candidates for orthogonal validation and mechanistic study.