Glycocalyx Mechanoregulation of Angiopoietin-2 and Post-Traumatic Lung Injury
Technical Report,01 May 2018,30 Apr 2019
University of Alabama at Birmingham Birmingham United States
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Preliminary results from our clinical studies show elevated levels of activated heparanase HPSE in plasma collected from trauma patientsupon arrival to our Level I Trauma Center. Additionally, these patients have elevated levels of Angiopoeitin-2, a well-established biomarkerof endothelial cell EC inflammation. Results from our in vitro studies suggest that degradation of heparan sulfate causes lungmicrovascular EC to produce more Agpt-2, suggestive of a mechanistic linkage between HPSE enzyme activity and dysregulation of Agpt-2levels. Since Agpt-2 increases the permeability of blood vessels and promotes lung injury, blocking the activity of HPSE and preventingAgpt-2 release could be a viable strategy for preventing lung injury in trauma patients. Preliminary data from animal studies show thatblocking HPSE activity with the drug Roneparstat may attenuate pulmonary cytokine production caused by trauma-hemorrhage andresuscitation. These findings are important for the field of trauma research since they address a clinical need for developing therapeuticstrategies that target mechanisms responsible for vascular dysfunction and organ failure in trauma patients.
- Medicine and Medical Research