0234: Exchange protein directly activated by cAMP (Epac1) knock-down limits cardiomyocytes death during myocardial infarction

Introduction Ischemia/reperfusion is accompanied and influenced by perturbations of the beta adrenergic receptor pathway and act through diverse signaling cascades to modulate cardiac function and remodelling. The Epac-Rap signaling pathway is a potent regulator of Ca(2+) cycling, cardiac hypertrophy, fibrosis. However, their role in determining cell death in the heart remains underexplored. Our aim is to better understand the mechanistic role, if any, of the alterations in Epac signalling pathway that occur during myocardial infarction leading to contractile dysfunction. Methods and Results Myocardial infarction was induced in wild-type (WT) versus Epac-1 (KO) littermates by left anterior descending coronary artery ligation for 24h. We examined the area at risk by Evans blue and infarct size was evaluated by TTC staining. We found the infarct size is significantly decreased in the KO mice compared to the WT animals (53% vs 40%, p Conclusion The lost of Epac-1 confers resistance to ischemic injury, at least in part, via limiting cell death pathway in cardiomyocytes. Further studies are necessary to unveil the mechanism by which Epac-1 promotes cardiomyocytes cell death. Epac-1 pharmacological inhibitors seem to be a good candidate to limit myocardial infarction injury.