Glycocalyx Mechanoregulation of Angiopoietin-2 and Post-Traumatic Lung Injury
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2019
- Accession Number
- AD1094152
Entities
People
- Jillian R Richter
Organizations
- University of Alabama at Birmingham