title: What is the role of erythropoietin in acute myocardial infarct? Bridging the gap between experimental models and clinical trials.
abstract: Erythropoietin (EPO) is the main hormone that regulates erythropoiesis. Beyond its well-known hematopoietic 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 investigate 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 clinical 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.
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada. francois.roubille@gmail.com
authors.forename: François
authors.initials: F
authors.lastname: Roubille
authors.forename: Fabrice
authors.initials: F
authors.lastname: Prunier
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Barrère-Lemaire
authors.forename: Florence
authors.initials: F
authors.lastname: Leclercq
authors.forename: Christophe
authors.initials: C
authors.lastname: Piot
authors.forename: Ekaterini A
authors.initials: EA
authors.lastname: Kritikou
authors.forename: Eric
authors.initials: E
authors.lastname: Rhéaume
authors.forename: David
authors.initials: D
authors.lastname: Busseuil
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy*
chemical_list: D002316:Cardiotonic Agents; D004921:Erythropoietin