Proteomic profiling of plasma extracellular vesicles identifies signatures of innate immunity, coagulation, and endothelial activation in septic patients
Abstract Plasma extracellular vesicles (EVs) are cell-derived lipid particles and reportedly play a role in sepsis pathogenesis. This study aimed to identify EV cargo proteins in septic patients and explore their association with key sepsis pathophysiology. Plasma EVs were subjected to Tandem Mass T...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-06430-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849334884638654464 |
|---|---|
| author | Chanhee Park Taekyung Ryu Rashida Mohamed-Hinds Kyungdo Kim Jin Hyeok Kim Lin Zou Brittney Williams Chan Hyun Na Wei Chao |
| author_facet | Chanhee Park Taekyung Ryu Rashida Mohamed-Hinds Kyungdo Kim Jin Hyeok Kim Lin Zou Brittney Williams Chan Hyun Na Wei Chao |
| author_sort | Chanhee Park |
| collection | DOAJ |
| description | Abstract Plasma extracellular vesicles (EVs) are cell-derived lipid particles and reportedly play a role in sepsis pathogenesis. This study aimed to identify EV cargo proteins in septic patients and explore their association with key sepsis pathophysiology. Plasma EVs were subjected to Tandem Mass Tag (TMT)-based quantitative proteomic analysis. We identified 522 differentially expressed (DE) EV proteins in septic patients (n = 15) compared to the healthy controls (n = 10). The KEGG analysis of the DE proteins revealed multiple functional pathways linked to sepsis, e.g., complement/coagulation, platelet activation, phagosome, inflammation, and neutrophil extracellular trap formation. Weighted Gene Coexpression Network Analysis of 1,642 EV proteins identified nine unique protein modules, some of which were highly correlated with the sepsis diagnosis and diverse endotype markers including organ injury, inflammation, coagulopathy, and endothelial activation, and mortality. ROC analysis revealed a list of novel EV proteins that exhibited strong diagnostic performance. Cell type-specific enrichment analysis revealed the cellular origins of EVs, including immune and epithelial cells, neurons, and glial cells. Thus, the current study discovered complex proteomic signatures in plasma EVs that are closely associated with key pathophysiological responses in sepsis. These findings support the importance of EV cargo proteins in the patients’ immune responses, coagulation, and endothelial activation and lay the foundation for future mechanistic study of plasma EVs and their clinical application as potential diagnostic and prognostic markers. |
| format | Article |
| id | doaj-art-ddc4959b6dd543368e0e08beab6738be |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-ddc4959b6dd543368e0e08beab6738be2025-08-20T03:45:27ZengNature PortfolioScientific Reports2045-23222025-07-0115112010.1038/s41598-025-06430-xProteomic profiling of plasma extracellular vesicles identifies signatures of innate immunity, coagulation, and endothelial activation in septic patientsChanhee Park0Taekyung Ryu1Rashida Mohamed-Hinds2Kyungdo Kim3Jin Hyeok Kim4Lin Zou5Brittney Williams6Chan Hyun Na7Wei Chao8Translational Research Program, Department of Anesthesiology, University of Maryland School of MedicineDepartment of Neurology, Johns Hopkins University School of MedicineTranslational Research Program, Department of Anesthesiology, University of Maryland School of MedicineDepartment of Neurology, Johns Hopkins University School of MedicineDepartment of Neurology, Johns Hopkins University School of MedicineTranslational Research Program, Department of Anesthesiology, University of Maryland School of MedicineTranslational Research Program, Department of Anesthesiology, University of Maryland School of MedicineDepartment of Neurology, Johns Hopkins University School of MedicineTranslational Research Program, Department of Anesthesiology, University of Maryland School of MedicineAbstract Plasma extracellular vesicles (EVs) are cell-derived lipid particles and reportedly play a role in sepsis pathogenesis. This study aimed to identify EV cargo proteins in septic patients and explore their association with key sepsis pathophysiology. Plasma EVs were subjected to Tandem Mass Tag (TMT)-based quantitative proteomic analysis. We identified 522 differentially expressed (DE) EV proteins in septic patients (n = 15) compared to the healthy controls (n = 10). The KEGG analysis of the DE proteins revealed multiple functional pathways linked to sepsis, e.g., complement/coagulation, platelet activation, phagosome, inflammation, and neutrophil extracellular trap formation. Weighted Gene Coexpression Network Analysis of 1,642 EV proteins identified nine unique protein modules, some of which were highly correlated with the sepsis diagnosis and diverse endotype markers including organ injury, inflammation, coagulopathy, and endothelial activation, and mortality. ROC analysis revealed a list of novel EV proteins that exhibited strong diagnostic performance. Cell type-specific enrichment analysis revealed the cellular origins of EVs, including immune and epithelial cells, neurons, and glial cells. Thus, the current study discovered complex proteomic signatures in plasma EVs that are closely associated with key pathophysiological responses in sepsis. These findings support the importance of EV cargo proteins in the patients’ immune responses, coagulation, and endothelial activation and lay the foundation for future mechanistic study of plasma EVs and their clinical application as potential diagnostic and prognostic markers.https://doi.org/10.1038/s41598-025-06430-xSepsisExtracellular vesicles (EVs)Mass spectrometryProteomicsTandem mass Tag (TMT) |
| spellingShingle | Chanhee Park Taekyung Ryu Rashida Mohamed-Hinds Kyungdo Kim Jin Hyeok Kim Lin Zou Brittney Williams Chan Hyun Na Wei Chao Proteomic profiling of plasma extracellular vesicles identifies signatures of innate immunity, coagulation, and endothelial activation in septic patients Scientific Reports Sepsis Extracellular vesicles (EVs) Mass spectrometry Proteomics Tandem mass Tag (TMT) |
| title | Proteomic profiling of plasma extracellular vesicles identifies signatures of innate immunity, coagulation, and endothelial activation in septic patients |
| title_full | Proteomic profiling of plasma extracellular vesicles identifies signatures of innate immunity, coagulation, and endothelial activation in septic patients |
| title_fullStr | Proteomic profiling of plasma extracellular vesicles identifies signatures of innate immunity, coagulation, and endothelial activation in septic patients |
| title_full_unstemmed | Proteomic profiling of plasma extracellular vesicles identifies signatures of innate immunity, coagulation, and endothelial activation in septic patients |
| title_short | Proteomic profiling of plasma extracellular vesicles identifies signatures of innate immunity, coagulation, and endothelial activation in septic patients |
| title_sort | proteomic profiling of plasma extracellular vesicles identifies signatures of innate immunity coagulation and endothelial activation in septic patients |
| topic | Sepsis Extracellular vesicles (EVs) Mass spectrometry Proteomics Tandem mass Tag (TMT) |
| url | https://doi.org/10.1038/s41598-025-06430-x |
| work_keys_str_mv | AT chanheepark proteomicprofilingofplasmaextracellularvesiclesidentifiessignaturesofinnateimmunitycoagulationandendothelialactivationinsepticpatients AT taekyungryu proteomicprofilingofplasmaextracellularvesiclesidentifiessignaturesofinnateimmunitycoagulationandendothelialactivationinsepticpatients AT rashidamohamedhinds proteomicprofilingofplasmaextracellularvesiclesidentifiessignaturesofinnateimmunitycoagulationandendothelialactivationinsepticpatients AT kyungdokim proteomicprofilingofplasmaextracellularvesiclesidentifiessignaturesofinnateimmunitycoagulationandendothelialactivationinsepticpatients AT jinhyeokkim proteomicprofilingofplasmaextracellularvesiclesidentifiessignaturesofinnateimmunitycoagulationandendothelialactivationinsepticpatients AT linzou proteomicprofilingofplasmaextracellularvesiclesidentifiessignaturesofinnateimmunitycoagulationandendothelialactivationinsepticpatients AT brittneywilliams proteomicprofilingofplasmaextracellularvesiclesidentifiessignaturesofinnateimmunitycoagulationandendothelialactivationinsepticpatients AT chanhyunna proteomicprofilingofplasmaextracellularvesiclesidentifiessignaturesofinnateimmunitycoagulationandendothelialactivationinsepticpatients AT weichao proteomicprofilingofplasmaextracellularvesiclesidentifiessignaturesofinnateimmunitycoagulationandendothelialactivationinsepticpatients |