JAMA 293(1): 90-95

New Avenues of Exploration for Erythropoietin

Division of Cellular and Molecular Cerebral Ischemia (Drs Maiese, Li, and Chong); Departments of Neurology and Anatomy & Cell Biology, Center for Molecular Medicine and Genetics, Institute of Environmental Health Sciences (Dr Maiese), Wayne State University School of Medicine, Detroit, Mich.

Corresponding Author: Kenneth Maiese, MD, Department of Neurology, 8C-1 UHC, Wayne State University School of Medicine, 4201 St Antoine, Detroit, MI 48201 (ude.enyaw@8802aa).

Abstract

Discovery that the hormone erythropoietin (EPO) and its receptor play a significant biological role in tissues outside of the hematopoietic system has fueled significant interest in EPO as a novel cytoprotective agent in both neuronal and vascular systems. Erythropoietin is now considered to have applicability in a variety of disorders that include cerebral ischemia, myocardial infarction, and chronic congestive heart failure. Erythropoietin modulates a broad array of cellular processes that include progenitor stem cell development, cellular integrity, and angiogenesis. As a result, cellular protection by EPO is robust and EPO inhibits the apoptotic mechanisms of injury, including the preservation of cellular membrane asymmetry to prevent inflammation. As the investigation into clinical applications for EPO that maximize efficacy and minimize toxicity progresses, a deeper appreciation for the novel roles that EPO plays in the brain and heart and throughout the entire body should be acquired.

Abstract

PRESENTLY, THE HORMONE ERYTHropoietin (EPO) is approved by the US Food and Drug Administration for the treatment of anemia that may result from a variety of conditions, including the anemia associated with chronic renal failure, irrespective of the need for dialysis, and anemia in patients scheduled for elective noncardiovascular surgery, to lessen their requirement for allogenic blood transfusions. In addition, patients who become anemic as a result of chemotherapy administered for nonmyeloid malignancies or during zidovudine treatment of infection with human immunodeficiency virus would fall under the guidelines for the administration of EPO.

In the brief span of approximately a decade, the premise that EPO is required only for erythropoiesis has been altered by studies demonstrating the existence of EPO and its receptor in other organs and tissues outside of the liver and the kidney, such as the brain and heart. We describe herein the unique role and cellular mechanisms of EPO that shape its potential to offer novel therapy for a variety of acute and chronic disorders in both neuronal and vascular systems. To identify studies to include in this discussion, we searched the databases MEDLINE/PubMed, Current Contents/Life Sciences, Chemical Abstracts, and BIOSIS using individual entries and combinations of keywords that included the terms anemia, angiogenesis, apoptosis, brain, cardiomyocyte, cell injury, congestive heart failure, cytokines, erythropoietin, erythropoietin receptor, heart, ischemia, infarction, inflammation, nervous system, programmed cell death, renal disease, stem cells, and vascular disease.

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