33. TRYPSIN AND MMP-9 LEVELS INCREASE IN PLASMA AND LUNG AFTER HEMORRHAGIC SHOCK: POTENTIAL MECHANISM FOR MEMBRANE RECEPTOR DAMAGE

Department: Bioengineering
Faculty Advisor(s): Geert Schmid-Schönbein
Award(s): Honorable Mention

Primary Student
Name: Angelina Esther Altshuler
Email: aaltshul@ucsd.edu
Phone: 858-534-2714
Grad Year: 2013

Abstract
Objective: During hemorrhagic shock (HS), the reduced perfusion to the intestine and pancreas results in increased intestinal mucosal permeability, pancreatitis, and potential leakage of serine proteases (i.e. trypsin- a potent matrix metalloproteinase [MMP] activator) into the circulation. These proteases may degrade extracellular domains of vascular endothelial (VE)-cadherin, vascular endothelial growth receptor 2 and 3 (VEGFR-2 and VEGFR-3) in the lung. We hypothesize that after HS, both trypsin and MMP-9 activity is detected in the circulation and in the lung (an organ with early damage in shock) and degrade extracellular receptor components. Methods: Male Wistar rats were grouped into No-HS or HS (N=5). Mean arterial blood pressure of HS animals was reduced to 35 mmHg (2 hr) followed by resuscitation of shed blood (2 hr). Post-HS plasma and lungs were collected. Protease activity in plasma was measured by plate zymography (trypsin-like and MMP-9 specific substrates for plasma) or by gelatin gel zymography (also for lung). Pancreatic trypsin, MMP-9, VE-Cadherin, VEGFR-2, and VEGFR-3 levels were identified by immunoblot. Results: Trypsin-like and MMP-9 activities were elevated in plasma after HS (p<0.05). Post-HS plasma and lungs had elevated levels of pancreatic trypsin and MMP-9 protein levels. There was significant reduction of VE-cadherin, VEGFR-2, and VEGFR-3 in the lung after HS (p<0.05). Conclusion: In HS, trypsin is transported into the systemic circulation and may contribute to MMP-9 activation. Extracellular domains of important membrane receptors are decreased after shock, possibly due to protease activity, contributing to cell dysfunction and organ failure. Supported by GM85072.

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