Cardiovascular disease remains a leading cause of death worldwide. Impaired coronary circulation in the heart following a myocardial ischemic episode will lead to compromised hemodynamic function and ultimately cell death. Coronary reperfusion is the only means of limiting infarct size, provided that it occurs early after coronary occlusion, but may paradoxically directly result in tissue injury (lethal reperfusion injury). The management of patients with acute myocardial infarction (AMI) has improved dra matically with the widespread use of thrombolytic and antiplatelet therapy as well as mechanical disruption of the occlusive coronary thrombus or plaque. Even so, attention has turned to adjunctive pharmacologic treatments to enhance myocardial tolerance to ischemia/reperfusion induced stress. This strategy is being pursued in an attempt to further reduce mortality in patients undergoing reperfusion therapy.This project is part of a translational effort dedicated to the development of new therapeutic prot ocols for the identification and validation of novel therapeutic targets in the treatment of acute myocardial ischemia (AMI) and reperfusion injury, in addition to development of novel MRI imaging protocols and sequences to be used in both clinical and ex perimental settings. The project will utilize state-of-the-art technologies in global gene expression analysis, retroviral vector RNAi technology, functional in vivo validation by inducible siRNA transgenic mouse model targeting candidate genes regulated by insulin therapy at reperfusion, and cardiac magnetic resonance imaging. Overall, this research program will provide greater insight into the genetic mechanisms orchestrating insulin pro-survival effects, providing new targets for therapeutic interventi on in the context of ischemia/reperfusion injury in patients and implementation of more advanced and sensitive MRI protocols and sequences for studying progression of AMI in patients.