The Protective Role Of Estrogen On Endothelial And Glycocalyx Barriers Following Shock Conditions: A Microfluidic Study
lawrence diebel, *Madison Wheaton, *David Liberati
wayne state university school of medicine, detroit, MI
Sexual dimorphism has been demonstrated after major trauma and hemorrhage with protective effects related to female gender and/or estrogen. Traumatic endotheliopathy is an important component of trauma induced coagulopathy (TIC). Components of endothelial barrier dysfunction include endothelial glycocalyx (EG) degradation as well as endothelial cellular (EC) injury. A survival benefit in TIC for females is described. This was studied in an in vitro model under flow conditions.
METHODS: Human umbilical vein endothelial cell (HUVEC) monolayers were established in microfluidic flow devices. After overnight perfusion cell monolayers were subjected to normoxic (21% O2) or hypoxic (1% O2) perfusion for 90 minutes. HUVEC cells were then treated with either estrogen (E2, 400 pg/ml), testosterone (DHT, 10 ng/ml) or media alone for 60 minutes. Endothelial activation/injury was indexed by soluble thrombomodulin (sTM) and glycocalyx degradation by syndecan-1 (syn-1) shedding as well as measurement of the glycocalyx layer thickness. The coagulation phenotype of HUVEC was indexed by the relative values of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) activity.
RESULTS: Please see attached table.
CONCLUSIONS: Estrogen but not DHT treatment mitigated the adverse effects of shock on endothelial and glycocalyx barrier properties. Our biomimetic model suggests a beneficial effect of estrogen administration following trauma hemorrhagic shock on the glycocalyx and endothelial barriers.
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