Erythropoietin in cardiac disease: new features of an old drug.
Erythropoietin is a haematopoietic hormone with extensive non-haematopoietic effects. The discovery of an erythropoietin receptor outside the haematopoietic system has fuelled the research into the beneficial effects of erythropoietin for various conditions, predominantly in cardiovascular disease. Experimental evidence has revealed the cytoprotective and angiogenic properties of erythropoietin and it seems that the erythropoietin-erythropoietin receptor system provides a powerful backbone against acute and chronic myocardial ischemia, each gaining from the different properties of erythropoietin. Clinical trials in which erythropoietin was titrated to achieve certain haematocrit levels have generated equivocal results. It has been suggested that a (too) high haematocrit is undesirable in cardiovascular disease. We have shown that intermittent (low-dose) erythropoietin administration, that does not increase haematocrit substantially, suffices to activate the beneficial downstream pathways of erythropoietin. We postulate that intermittent administration or a lower than conventional dose of erythropoietin, not only aimed at increasing haemoglobin at high levels, will provide powerful cellular protection and will improve cardiac outcome, without the side effects of erythropoietin associated with increased haematocrit.
Ruifrok
Willem-Peter T
WP
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. w.t.ruifrok@thorax.umcg.nl
de Boer
Rudolf A
RA
Westenbrink
B Daan
BD
van Veldhuisen
Dirk J
DJ
van Gilst
Wiek H
WH
D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D002908:Chronic Disease; D004921:Erythropoietin / Q000009:adverse effects / Q000235:genetics / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use*; D006331:Heart Diseases / Q000188:drug therapy*; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D017467:Receptors, Erythropoietin / Q000187:drug effects / Q000235:genetics; D011994:Recombinant Proteins
D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin