TRAUMA-DERIVED EXTRACELLULAR VESICLES ARE SUFFICIENT TO INDUCE ENDOTHELIAL DYSFUNCTION AND COAGULOPATHY

Area of Science:

• Trauma and hemorrhagic shock research
• Extracellular vesicle (EV) biology
• Coagulation and hemostasis

Background:

• Studies show increased extracellular vesicle (EV) release after trauma, but their biological role remains unclear.
• Extracellular vesicles (EVs) are implicated in various physiological and pathological processes.
• Understanding the specific contribution of trauma-induced EVs to post-injury complications is crucial.

Purpose of the Study:

• To investigate the hypothesis that EVs released after trauma/hemorrhagic shock (HS) contribute to endotheliopathy and coagulopathy.
• To determine if EVs from severely injured patients in shock are sufficient to induce endothelial dysfunction and coagulopathy in vivo.
• To explore potential therapeutic strategies targeting trauma-induced EVs.

Main Methods:

• Adoptive transfer experiments using EVs isolated from trauma/HS patients and minimally injured patients into naive mice.
• Administration of EVs at varying concentrations, followed by assessment of thrombin generation (TAT), syndecan-1 levels, lung vascular permeability, and histopathologic injury.
• Analysis of bronchial alveolar lavage fluid protein and intravascular fibrin deposition in lung tissues.

Main Results:

• EVs from severely injured trauma/HS patients induced significantly higher lung vascular permeability, histopathologic injury, and intravascular fibrin deposition compared to controls.
• Administration of trauma/HS EVs led to elevated plasma TAT and syndecan-1 levels, indicating coagulopathy and endotheliopathy.
• While initial experiments showed lung injury, higher concentrations of trauma/HS EVs confirmed both endotheliopathy and coagulopathy.

Conclusions:

• Trauma/hemorrhagic shock (HS) induces systemic release of extracellular vesicles (EVs).
• These trauma-induced EVs are capable of causing endotheliopathy (elevated syndecan-1, increased permeability) and coagulopathy (increased TAT, intravascular fibrin deposition).
• Targeting trauma-induced EVs may offer a novel therapeutic approach for managing post-trauma complications.