Abstract TP432: Glyco-proteomic Study of Therapeutic Hypothermia in Global Ischemic Brain Injury Post Cardiac Arrest
Background: Global ischemic brain injury post cardiac arrest is prevalent with dismal prognosis -- less than 10% survive to hospital discharge. Therapeutic hypothermia (TH) is an efficacious neuroprotective treatment, protects against multi-organ damage, doubles the chance of good neurologic outcome and decreases mortality by 25%, but is grossly underutilized (<5%). We use a glyco-proteomic approach to better understand and predict TH response, because: 1) glycosylation is one of the most important and common extracellular post-translational modifications in immunity and coagulation, and is crucial in TH-related side effects such as sepsis and bleeding; 2) it occurs rapidly over the time window of treatment; and 3) it can be used to focus proteomic profiling by targeting specific plasma signals.
Methods: Lectin array and various lectin immunoblots were used to study plasma glycosylation patterns of TH patients (n=30; 24 hrs post cardiac arrest) with good vs poor clinical outcome (evaluated at 3 months post event). To identify and enrich candidate plasma proteins with potential clinical utility, specific lectin affinity chromatography and LC-MS/MS were performed.
Results: Plasma glycosylation patterns differ dramatically with respect to clinical outcome in TH-treated patients. On screening lectin blots (figure), whereas SBA showed little change, RCA (decreased around 35-100kD - in box) and ConA (increased around 40-150kD - in box) were different in a wide range of MW, and WGA identified unique banding around 100kD (in box) in TH responders. In lectin affinity pull-down, more than 400 specific glycoproteins were identified showing significant changes with respect to TH outcome.
Conclusion: A glyco-proteomic approach is promising to help predict neurologic outcome, select TH responders, and triage hypothermic therapy in global ischemic brain injury patients post cardiac arrest. Further studies are under way to investigate these exploratory findings.
- © 2012 by American Heart Association, Inc.