Abstract 15257: Cold Inducible RNA Binding Protein (CIRP) Expression is Regulated by Mild Hypothermia and Elevated by Therapeutic Hypothermia Following Cardiac Arrest
Introduction: Cold Inducible RNA Binding Protein (CIRP) is a novel protein known to alter cellular function specifically in response to mild hypothermia (32°C-34°C). The relationship of CIRP to therapeutic hypothermia protection following cardiac arrest is unknown. We hypothesized that CIRP is increased in the heart and brain in mice treated with therapeutic hypothermia following cardiac arrest and that it is an important regulator of cellular response to mild hypothermia. We further hypothesized that CIRP is a stress-activated protein.
Methods: Anesthetized and ventilated adult female C57BL/6 wild-type mice underwent an 8-min KCL- induced cardiac arrest. After 6 min of arrest, mice were randomized to continue normothermia (NT, 37°C) or hypothermia (TH, 32°C). Cardiopulmonary resuscitation (CPR) was performed until return of spontaneous circulation (ROSC). Mice treated with TH were rewarmed 1 hour following ROSC to 37°C. Tissue samples were collected from the brain and hearts 2 hours after ROSC. Neonatal murine isolated cardiomyocytes and A549 human lung cancer cells were grown in tissue culture and exposed to temperatures ranging from 28-42°C over 24 hours. Cellular and tissue lysates were immunblotted for CIRP. CIRP siRNA was used to knockdown hypothermia induced CIRP and knockdown was confirmed by immunoblotting.
Results: CIRP expression was elevated in the brain and the hearts of mice treated with mild hypothermia 2 hours following cardiac arrest and was associated with increased survival. 32°C was found to induce maximal CIRP expression while 37°C and 42°C had the least expression. However, A549 cancer cells were found to have elevated levels of CIRP at 37°C compared to isolated cardiomyocytes. Knockdown of CIRP with siRNA significantly decreased A549 cellular proliferation at 5 and 7 days.
Conclusion: CIRP is a novel regulator of cellular function that is specifically regulated by mild hypothermia (32°C). CIRP may also be an important stress response protein that can alter cellular function. Finally, CIRP is a promising regulator of therapeutic hypothermia mediated survival following cardiac arrest.
- © 2013 by American Heart Association, Inc.