Mammalian hibernation is a unique strategy for winter survival in response to limited food supply and harsh climate. The hearts of hibernators exhibit remarkable tolerance and resistance to the ventricular arrhythmias/fibrillation that is observed in non-hibernators at lower body temperature. Hibernating mammals may be a model with unique natural cardioprotection to investigate novel mechanisms involved in myocardial ischemic disease. We observed that hibernating mammals such as woodchucks (Marmota monax) demonstrate a changed phenotype from summer to winter. They exhibit powerful myocardial protection in the winter against ischemia/reperfusion (I/R) injury compared to woodchucks in summer, similar to that elucidated by ischemic preconditioning. In fact, hibernating animals are """"""""prepared"""""""" for winter by evoking their intrinsic cardioprotective mechanisms. Our preliminary results also demonstrate that the cAMP response element binding protein (CREB), a nuclear transcription factor, which regulates the expression of genes important for cell survival and apoptosis, is significantly activated in the woodchuck hearts in winter and even higher during hibernation. We hypothesize that the activation of CREB is a potentially novel molecule mediating this cardioprotection in the hearts of woodchucks in winter. The goal of this proposal is to (1) investigate the importance of CREB in mediating cardioprotection and to identify other key signaling molecules linked to CREB which protect the heart against apoptosis and necrosis following a myocardial ischemic instance;(2) examine whether mechanisms mediating traditional IPC are also involved in the cardioprotection observed in the woodchuck heart in the winter. The long term goal is to reveal the cellular and molecular mechanisms involved in natural resistance to cardiac stresses in hibernating mammals and to uncover the master """"""""switch"""""""" for cardioprotection. The implications for health care are clear: understanding the cardiac adaptive mechanisms in hibernators may suggest new strategies to protect myocardium of non-hibernating animals, especially humans, from cardiac dysfunction induced by hypothermic stresses and myocardial ischemia.PROJECT NARRATIVE: The implications for health care are clear: understanding the cardiac adaptive mechanisms in hibernators may suggest new strategies to protect myocardium of non-hibernating animals, especially humans, from cardiac dysfunction induced by hypothermic stresses and myocardial ischemia.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL091781-03
Application #
7849013
Study Section
Special Emphasis Panel (ZRG1-CVS-A (50))
Program Officer
Lathrop, David A
Project Start
2008-06-01
Project End
2012-05-31
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
3
Fiscal Year
2010
Total Cost
$351,000
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
623946217
City
Newark
State
NJ
Country
United States
Zip Code
07107
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