Endothelium-Derived Extracellular Vesicles Expressing Intercellular Adhesion Molecules Reflect Endothelial...

Area of Science:

• Vascular Biology
• Sepsis Pathophysiology
• Biomarker Discovery

Background:

• Clinical indicators for endothelial permeability in sepsis are lacking.
• Endothelium-derived extracellular vesicles (EDEVs) are emerging biomarkers for endothelial injury.
• Platelet endothelial cell adhesion molecule (PECAM) and VE-cadherin regulate endothelial permeability.

Purpose of the Study:

• To investigate the association between EDEVs expressing PECAM or VE-cadherin and endothelial permeability.
• To evaluate the potential of these EDEVs as biomarkers for sepsis severity.

Main Methods:

• Human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-α, with or without permeability-modifying reagents.
• Endothelial permeability was assessed using dextran assay and transendothelial electrical resistance.
• Circulating EDEV levels (PECAM+, VE-cadherin+) were analyzed in patients with sepsis (n=30), septic shock (n=42), and non-sepsis controls (n=30) via flow cytometry.

Main Results:

• TNF-α stimulation increased HUVEC permeability and EDEV release.
• Angiopoietin-1 and prostacyclin suppressed TNF-α-induced permeability and EDEV release, while VEGF exacerbated it.
• Patients with septic shock exhibited significantly higher levels of PECAM+ and VE-cadherin+ EDEVs compared to sepsis patients, with levels remaining elevated for at least 5 days.

Conclusions:

• EDEVs expressing PECAM and VE-cadherin may serve as indicators of increased endothelial permeability.
• These EDEVs show promise as valuable diagnostic and prognostic markers for sepsis.