International journal of nanomedicine
Plasma Extracellular Vesicles Multi-Omics Signatures Reveal Dynamic Molecular Rewiring During Sepsis Progression
By Zhang H, Liang S, Yue X and 4 others.
Abstract
Background
Sepsis confers persistently high mortality, with risk escalating markedly upon progression to disseminated intravascular coagulation (DIC). Although circulating extracellular vesicles (EVs) have emerged as potential biomarker reservoirs and pathogenic mediators in sepsis-associated DIC (SA-DIC), the molecular mechanisms governing the transition from sepsis through sepsis-induced coagulopathy (SIC) to SA-DIC remain elusive.
Methods
Plasma EVs from healthy controls (n=3) and patients with sepsis, SIC, and SA-DIC (n=6) were collected longitudinally and profiled by multi-omics analysis (miRNome, proteome, and metabolome) using RNA sequencing and LC-MS/MS. Key findings were validated by qRT-PCR and ELISA in an independent longitudinal cohort (n=30). The role of miR-34a-5p in lipopolysaccharide (LPS)-induced inflammatory and procoagulant responses was investigated in human umbilical vein endothelial cells (HUVECs) using miRNA agomirs and antagomirs. In a cecal ligation and puncture (CLP)-induced SA-DIC mouse model, miR-34a-5p agomirs/antagomirs were administered, and coagulation and inflammatory parameters, together with the histopathology of the lung, liver, and intestine, were assessed.