Estrogen Effects on the Endothelial-Glycocalyx Barrier Under Shock Conditions
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Shock Non Sepsis, Trauma, 2022
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INTRODUCTION: Clinical and animal studies have shown a protective effect of the female sex on outcomes following trauma hemorrhagic shock (T/HS) and other inflammatory conditions. This has been attributed to estrogen (E2) and its menstrual related concentrations. Estrogen impacts endothelial function via membrane and cellular receptors. The endothelial glycocalyx (EGL) layer is a critical component of the endothelial vascular barrier. The impact of estrogen on endothelial and glycocalyx barriers after T/HS are unknown.
METHODS: Human umbilical vein endothelial cell monolayers (HUVEC) were established in microfluidic well plates and subjected to flow. HUVEC were then treated with E2 at variable concentrations (20, 200 or 400 pg/ml), testosterone (DHT, 10 ng/ml) or media alone followed by exposure to hypoxia and epinephrine and reoxygenation (HR + epi). Endothelial activation was indexed by soluble thrombomodulin (sTM); coagulation phenotype by tissue type plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) in the perfusate. Glycocalyx integrity was indexed by shedding of syndecan-1 (syn-1) and hyaluronic acid (HLA) into the perfusate. Glycocalyx thickness was determined using fluorescent imaging and XYZ stack analysis.
RESULTS: HR + epi increased sTM and tPA but decreased PAI-1 (p < 0.05) vs. control. There was an E2 concentration effect that returned these parameters to control values. DHT had no effect. HR + epi increased EGL shedding and diminished its thickness vs. control (p < 0.05). E2 but not DHT protected the EGL barrier in a concentration dependent fashion (p < 0.05 vs. HR + epi, p = ns vs. control at the highest E2 concentration).
CONCLUSIONS: E2 has a concentration dependent protective effect on endothelial and glycocalyx derangement following biomimetic shock conditions. This was associated with a procoagulant profile as it relates to relative tPA and PAI-1 concentrations. These data suggest E2 may protect against trauma induced endotheliopathy.
Meta Tag
Content Type Presentation
Knowledge Area Trauma
Knowledge Area Shock Non Sepsis
Knowledge Level Advanced
Membership Level Select
Tag Shock
Tag Hemorrhage
Tag Surgery
Tag Burns
Year 2022
Dr. Michael Cargi
endothelial glycocalyx barrier
shock conditions
trauma-induced coagulopathy


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