Sepsis & infection

Endothelium-Derived Extracellular Vesicles Expressing Intercellular Adhesion Molecules Reflect Endothelial Permeability and Sepsis Severity

Anesth AnalgPublished Mechanistic study and prospective cross-sectional observational study

Authors' conclusion

EDEVs expressing intercellular adhesion molecules (PECAM+ or VE-cadherin+ EDEVs) may reflect increased endothelial permeability and could be valuable diagnostic and prognostic markers for sepsis.

Study context

Population
Patients with sepsis or septic shock and nonsepsis patients; Human umbilical vein endothelial cells (HUVECs) stimulated with TNF-α
Participants
30 / 30 / 42
Exposure
Septic shock vs sepsis: circulating platelet endothelial cell adhesion molecule (PECAM)+ and vascular endothelial (VE)-cadherin+ endothelium-derived extracellular vesicles (EDEVs)
  • Nonsepsisn = 30
  • Sepsisn = 30reference
  • Septic shockn = 42
Outcome
PECAM+ and VE-cadherin+ EDEVs on admission
Follow-up
On admission
Methodological detailsin vitro HUVEC experiments
  • In vitro HUVEC experiments

Main finding

As reported in the abstract

Average treatment effect (PECAM+ EDEVs)

98 /μL

95% CI 2–270P = 0.043

Septic shock

Average treatment effect (ATE) (VE-cadherin+ EDEVs)

79 /μL

95% CI 19–171P = 0.004

Septic shock

Observational data: associations, not effects.

Further findings

In vitro HUVEC endothelial permeability and EDEV release

TNF-α significantly increased EDEV release and endothelial permeability
Angiopoietin-1 or prostacyclin pretreatment suppressed TNF-α-induced permeability and PECAM+ and VE-cadherin+ EDEV release
Vascular endothelial growth factor (VEGF) pretreatment increased TNF-α-induced permeability and PECAM+ and VE-cadherin+ EDEV release
Permeability-modifying reagents did not affect release of E-selectin, ICAM-1 or VCAM-1 EDEVs

Original publication

Endothelium-Derived Extracellular Vesicles Expressing Intercellular Adhesion Molecules Reflect Endothelial Permeability and Sepsis Severity. Anesth Analg. Published 15 July 2024. doi:10.1213/ane.0000000000006988

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