REVIEW ARTICLE What is the Role of Erythropoietin in Acute Myocardial Infarct? Bridging the Gap Between Experimental Models and Clinical Trials François Roubille & Fabrice Prunier & Stéphanie Barrère-Lemaire & Florence Leclercq & Christophe Piot & Ekaterini A. Kritikou & Eric Rhéaume & David Busseuil & Jean-Claude Tardif Published online: 22 May 2013 # Springer Science+Business Media New York 2013 Abstract Erythropoietin (EPO) is the main hormone that regulates erythropoiesis. Beyond its well-known hemato- poietic action, EPO has diverse cellular effects in non- hematopoietic tissues. It has been shown to inhibit apoptosis by activating pro-survival pathways in the myocardium, to mobilize endothelial progenitor cells and to inhibit migration of inflammatory cells. EPO has also been shown to have potent pro-angiogenic properties. Numerous experimental data support the cardioprotective effects of EPO in animal models of acute myocardial infarct (AMI). However, these findings are not supported by recent clinical trials designed to investi- gate the safety and efficacy of EPO in patients with AMI. In this article, we begin by providing a comprehensive review of the cardioprotective effects of EPO in experimental animal models and the molecular mechanisms underlying these effects. We then discuss the EPO data obtained through clini- cal trials. We compare similarities and differences between the animal and human studies as well as between the different clinical studies in terms of sample size and study design including the dose, the route and the timing of administration as well as confounding factors such as comorbidities and concomitant treatments. Finally, we question the gap between the experimental and the translational clinical data and propose further developments to address these discrepancies and clearly evaluate the role of EPO in the clinical setting of MI. Keywords Erythropoietin . Cardioprotection . Reperfusion injury . Acute myocardial infarction . Experimental models . Clinical trials Abbreviations AAR Area at risk ACE Angiotensin-converting-enzyme inhibitor AMI Acute myocardial infarction ARBs Angiotensin II receptor blockers CABG Coronary artery bypass graft CAD Coronary artery disease ESC European Society of Cardiology EPO Erythropoietin EPO-R EPO receptor ERK Extracellular signal-regulated kinases FGF Fibroblast growth factor G-CSF Granulocyte colony-stimulating factor Hb Hemoglobin HGF Hepatocyte growth factor Electronic supplementary material The online version of this article (doi:10.1007/s10557-013-6461-1) contains supplementary material, which is available to authorized users. F. Roubille (*) Montreal Heart Institute, Université de Montréal, Montreal, Canada e-mail: francois.roubille@gmail.com F. Roubille : F. Leclercq : C. Piot Cardiology Department, University Hospital of Montpellier, Montpellier, France F. Roubille : S. Barrère-Lemaire : C. Piot Inserm, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, INSERM, U661, Universités de Montpellier 1 and 2, Montpellier, France F. Prunier Laboratoire Cardioprotection, Remodelage et Thrombose, Université d’Angers, Angers, France F. Prunier Service de Cardiologie, Centre Hospitalier Universitaire Angers, Angers, France E. A. Kritikou : E. Rhéaume : D. Busseuil : J.<C. Tardif Montreal Heart Institute, Montreal, Quebec, Canada E. Rhéaume : J.<C. Tardif Department of Medicine, Université de Montréal, Montreal, Quebec, Canada Cardiovasc Drugs Ther (2013) 27:315–331 DOI 10.1007/s10557-013-6461-1