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STATE-OF-THE-ART PAPER

Protective Effects of Erythropoietin in Cardiac Ischemia

From Bench to Bedside

Erik Lipic, MD, PhD^_*,,_*, Regien G. Schoemaker, PhD^_*, Peter van der Meer, MD, PhD^_*,, Adriaan A. Voors, MD, PhD, Dirk J. van Veldhuisen, MD, PhD, FACC and Wiek H. van Gilst, PhD^_*,

^_* Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Manuscript received April 5, 2006; revised manuscript received August 10, 2006, accepted August 14, 2006.

^_* Reprint requests and correspondence: Dr. Erik Lipic, A. Deusinglaan 1, 9713 AV Groningen, the Netherlands. (Email: e.lipsic{at}dz.nl).

Erythropoietin (EPO) is a hypoxia-induced hormone produced in the kidneys that stimulates hematopoiesis in the bone marrow. However, recent studies have also shown important nonhematopoietic effects of EPO. A functional EPO receptor is found in the cardiovascular system, including endothelial cells and cardiomyocytes. In animal studies, treatment with EPO during ischemia/reperfusion in the heart has been shown to limit the infarct size and the extent of apoptosis. In the longer term, EPO may promote ischemia-induced neovascularization, either by stimulating endothelial cells in situ or by mobilizing endothelial progenitor cells from bone marrow. The effects of EPO in the ischemic heart support the concept of EPO as a pleiotropic, tissue-protective agent for other organs expressing the EPO receptor. We recently performed a first randomized clinical study showing the safety and feasibility of EPO administration in patients with acute myocardial infarction. Future clinical studies are warranted to translate the beneficial effects of EPO from basic experiments to cardiac patients.

Abbreviations and Acronyms   CHF = chronic heart failure   CKD = chronic kidney disease   EPC = endothelial progenitor cell   EPO = erythropoietin   EPO-R = erythropoietin receptor   I/R = ischemia/reperfusion   LV = left ventricle/ventricular   MI = myocardial infarction   rhEPO = recombinant human erythropoietin

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