Related Experiment Video
Updated: Oct 28, 2026
Isolation, Characterization, and Proteomic Analysis of Plasma-Derived Extracellular Vesicles for Cardiovascular Biomarker Discovery
Published on: January 31, 2025
Plasma Extracellular Vesicles Multi-Omics Signatures Reveal Dynamic Molecular Rewiring During Sepsis Progression
Haiyue Zhang1, Shuang Liang1, Xinyang Yue1
1Thrombosis Research Center, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People's Republic of China.
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.
Results:
Integrated multi-omics analysis identified 112 miRNAs, 525 proteins, and 60 metabolites that were differentially expressed in plasma EVs during sepsis progression, which were enriched in blood coagulation, platelet activation, inflammatory response, energy metabolism and vitamin metabolism. We identified miR-34a-5p as a biomarker for discriminating sepsis, SIC, and SA-DIC. In vitro, miR-34a-5p downregulation attenuated inflammation, reduced thrombomodulin secretion, and increased CD138 and heparan sulfate expression. Consistently, in vivo modulation of miR-34a-5p ameliorated coagulation dysfunction and lung, liver, and intestinal histopathological injury.
Conclusion:
This study provides the first integrative map of plasma EVs molecular reprogramming during sepsis progression, identifying potential diagnostic biomarkers and a candidate therapeutic target.
