Plasma Extracellular Vesicles Multi-Omics Signatures Reveal Dynamic Molecular Rewiring During Sepsis Progression.
- 1Thrombosis Research Center, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People's Republic of China.
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.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.
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BibTeX
@article{zhang2026plasma,
title = {{Plasma Extracellular Vesicles Multi-Omics Signatures Reveal Dynamic Molecular Rewiring During Sepsis Progression.}},
author = {Haiyue Zhang and Shuang Liang and Xinyang Yue and Xiaofei He and Huiru Zhao and Yu Su and Jun Wu},
journal = {International journal of nanomedicine},
year = {2026},
month = oct,
doi = {10.2147/ijn.s622399},
url = {https://europepmc.org/article/MED/42936678},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Plasma Extracellular Vesicles Multi-Omics Signatures Reveal Dynamic Molecular Rewiring During Sepsis Progression.
AU - Haiyue Zhang
AU - Shuang Liang
AU - Xinyang Yue
AU - Xiaofei He
AU - Huiru Zhao
AU - Yu Su
AU - Jun Wu
PY - 2026
DA - 2026/10/22
JO - International journal of nanomedicine
DO - 10.2147/ijn.s622399
UR - https://europepmc.org/article/MED/42936678
AB - 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.
SN - 1176-9114
SN - 1178-2013
ER -