Circulating extracellular vesicles are associated with the clinical outcomes of sepsis
IntroductionSepsis is associated with endothelial cell (EC) dysfunction, increased vascular permeability and organ injury, which may lead to mortality, acute respiratory distress syndrome (ARDS) and acute renal failure (ARF). There are no reliable biomarkers to predict these sepsis complications at...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1150564/full |
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| author | Pengfei Li Yan Wu Andrew J. Goodwin Bethany Wolf Perry V. Halushka Perry V. Halushka Hongjun Wang Basilia Zingarelli Hongkuan Fan |
| author_facet | Pengfei Li Yan Wu Andrew J. Goodwin Bethany Wolf Perry V. Halushka Perry V. Halushka Hongjun Wang Basilia Zingarelli Hongkuan Fan |
| author_sort | Pengfei Li |
| collection | DOAJ |
| description | IntroductionSepsis is associated with endothelial cell (EC) dysfunction, increased vascular permeability and organ injury, which may lead to mortality, acute respiratory distress syndrome (ARDS) and acute renal failure (ARF). There are no reliable biomarkers to predict these sepsis complications at present. Recent evidence suggests that circulating extracellular vesicles (EVs) and their content caspase-1 and miR-126 may play a critical role in modulating vascular injury in sepsis; however, the association between circulating EVs and sepsis outcomes remains largely unknown.MethodsWe obtained plasma samples from septic patients (n=96) within 24 hours of hospital admission and from healthy controls (n=45). Total, monocyte- or EC-derived EVs were isolated from the plasma samples. Transendothelial electrical resistance (TEER) was used as an indicator of EC dysfunction. Caspase-1 activity in EVs was detected and their association with sepsis outcomes including mortality, ARDS and ARF was analyzed. In another set of experiments, total EVs were isolated from plasma samples of 12 septic patients and 12 non-septic critical illness controls on days 1, and 3 after hospital admission. RNAs were isolated from these EVs and Next-generation sequencing was performed. The association between miR-126 levels and sepsis outcomes such as mortality, ARDS and ARF was analyzed.ResultsSeptic patients with circulating EVs that induced EC injury (lower transendothelial electrical resistance) were more likely to experience ARDS (p<0.05). Higher caspase-1 activity in total EVs, monocyte- or EC-derived EVs was significantly associated with the development of ARDS (p<0.05). MiR-126-3p levels in EC EVs were significantly decreased in ARDS patients compared with healthy controls (p<0.05). Moreover, a decline in miR-126-5p levels from day 1 to day 3 was associated with increased mortality, ARDS and ARF; while decline in miR-126-3p levels from day 1 to day 3 was associated with ARDS development.ConclusionsEnhanced caspase-1 activity and declining miR-126 levels in circulating EVs are associated with sepsis-related organ failure and mortality. Extracellular vesicular contents may serve as novel prognostic biomarkers and/or targets for future therapeutic approaches in sepsis. |
| first_indexed | 2024-04-09T16:06:33Z |
| format | Article |
| id | doaj.art-9ce235785a274d49a2d79eae8dd14ba7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T16:06:33Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9ce235785a274d49a2d79eae8dd14ba72023-04-25T05:19:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11505641150564Circulating extracellular vesicles are associated with the clinical outcomes of sepsisPengfei Li0Yan Wu1Andrew J. Goodwin2Bethany Wolf3Perry V. Halushka4Perry V. Halushka5Hongjun Wang6Basilia Zingarelli7Hongkuan Fan8Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United StatesDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United StatesDivision of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Medical University of South Carolina, Charleston, SC, United StatesDepartment of Public Health Sciences, Medical University of South Carolina, Charleston, SC, United StatesDepartment of Medicine, Medical University of South Carolina, Charleston, SC, United StatesDepartment of Pharmacology, Medical University of South Carolina, Charleston, SC, United StatesDepartments of Surgery, Medical University of South Carolina, Charleston, SC, United StatesDivision of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United StatesIntroductionSepsis is associated with endothelial cell (EC) dysfunction, increased vascular permeability and organ injury, which may lead to mortality, acute respiratory distress syndrome (ARDS) and acute renal failure (ARF). There are no reliable biomarkers to predict these sepsis complications at present. Recent evidence suggests that circulating extracellular vesicles (EVs) and their content caspase-1 and miR-126 may play a critical role in modulating vascular injury in sepsis; however, the association between circulating EVs and sepsis outcomes remains largely unknown.MethodsWe obtained plasma samples from septic patients (n=96) within 24 hours of hospital admission and from healthy controls (n=45). Total, monocyte- or EC-derived EVs were isolated from the plasma samples. Transendothelial electrical resistance (TEER) was used as an indicator of EC dysfunction. Caspase-1 activity in EVs was detected and their association with sepsis outcomes including mortality, ARDS and ARF was analyzed. In another set of experiments, total EVs were isolated from plasma samples of 12 septic patients and 12 non-septic critical illness controls on days 1, and 3 after hospital admission. RNAs were isolated from these EVs and Next-generation sequencing was performed. The association between miR-126 levels and sepsis outcomes such as mortality, ARDS and ARF was analyzed.ResultsSeptic patients with circulating EVs that induced EC injury (lower transendothelial electrical resistance) were more likely to experience ARDS (p<0.05). Higher caspase-1 activity in total EVs, monocyte- or EC-derived EVs was significantly associated with the development of ARDS (p<0.05). MiR-126-3p levels in EC EVs were significantly decreased in ARDS patients compared with healthy controls (p<0.05). Moreover, a decline in miR-126-5p levels from day 1 to day 3 was associated with increased mortality, ARDS and ARF; while decline in miR-126-3p levels from day 1 to day 3 was associated with ARDS development.ConclusionsEnhanced caspase-1 activity and declining miR-126 levels in circulating EVs are associated with sepsis-related organ failure and mortality. Extracellular vesicular contents may serve as novel prognostic biomarkers and/or targets for future therapeutic approaches in sepsis.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1150564/fullsepsisextracellular vesiclescaspase-1miR-126vascular injuryARDS (acute respiratory distress syndrome) |
| spellingShingle | Pengfei Li Yan Wu Andrew J. Goodwin Bethany Wolf Perry V. Halushka Perry V. Halushka Hongjun Wang Basilia Zingarelli Hongkuan Fan Circulating extracellular vesicles are associated with the clinical outcomes of sepsis Frontiers in Immunology sepsis extracellular vesicles caspase-1 miR-126 vascular injury ARDS (acute respiratory distress syndrome) |
| title | Circulating extracellular vesicles are associated with the clinical outcomes of sepsis |
| title_full | Circulating extracellular vesicles are associated with the clinical outcomes of sepsis |
| title_fullStr | Circulating extracellular vesicles are associated with the clinical outcomes of sepsis |
| title_full_unstemmed | Circulating extracellular vesicles are associated with the clinical outcomes of sepsis |
| title_short | Circulating extracellular vesicles are associated with the clinical outcomes of sepsis |
| title_sort | circulating extracellular vesicles are associated with the clinical outcomes of sepsis |
| topic | sepsis extracellular vesicles caspase-1 miR-126 vascular injury ARDS (acute respiratory distress syndrome) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1150564/full |
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