Skip to main content

Advertisement

SpringerLink
Log in

Do non-hemopoietic effects of erythropoietin play a beneficial role in heart failure?

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Erythropoietin (EPO) is not solely a hormone charged with regulating the proliferation and differentiation of erythroid cells. Indeed, EPO is synthesized locally by many cells, especially under conditions of stress or injury. In these paracrine/autocrine settings, EPO plays a crucial protective–restorative role, activating cytoprotection (e.g., in the brain, heart, and kidney), reducing inflammatory responses, preserving vascular integrity, and mobilizing stem cells, including proliferation and differentiation of endothelial progenitor cells. EPO administration prevents cardiac myocyte apoptosis and decreases infarct size in several studies using rodent models of myocardial infarction. Recently, some key steps of the signaling pathways by which EPO confers cardioprotection have been identified. The striking finding distilled from work by numerous independent investigators is that EPO mediates protection in the heart (as well as other tissues) by multiple pathways that are not redundant. The following actions proven to play a role in protection from acute cardiac injury can exert a beneficial effect in chronic heart failure (HF): (a) antiapoptotic effect, (b) mobilization of endothelial progenitor cells from bone marrow, and (c) anti-hypertrophic effects. The evidences discussed herein provide a strong basis for the ongoing clinical trials testing EPO in chronic HF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Brines M, Cerami A (2005) Emerging biological roles for erythropoietin in the nervous system. Nat Rev Neurosci 6:484–494

    Article  PubMed  CAS  Google Scholar 

  2. Wu H, Lee SH, Gao J, Liu X, Iruela-Arispe ML (1999) Inactivation of erythropoietin leads to defects in cardiac morphogenesis. Development 126:3597–3605

    PubMed  CAS  Google Scholar 

  3. Anagnostou A, Lee ES, Kessimian N, Levinson R, Steiner M (1990) Erythropoietin has a mitogenic and positive chemotactic effect on endothelial cells. Proc Natl Acad Sci USA 87:5978–5982

    Article  PubMed  CAS  Google Scholar 

  4. Konishi Y, Chui D, Hirose H, Kunishita T, Tabira T (1993) Trophic effect of erythropoietin and other hemapoietic factors on central colinergic neurons in vivo and in vitro. Brain Res 609:29–35

    Article  PubMed  CAS  Google Scholar 

  5. Masuda S, Okano M, Yamagishi K, Nagao M, Ueda M, Sasaki R (1994) A novel site of erythropoietin production. Oxygen dependent production in cultured rat astrocytes. J Biol Chem 269:19488–19493

    PubMed  CAS  Google Scholar 

  6. Sakanaka M, Wen TC, Matsuda S, Masuda S, Morishita E, Nagao M, Sasaki R (1998) In vivo evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci USA 95:4635–4640

    Article  PubMed  CAS  Google Scholar 

  7. Brines ML, Ghezzi P, Keenan S, Agnello D, de Lanerolle NC, Cerami C, Itri LM, Cerami A (2000) Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci USA 97:10526–10531

    Article  PubMed  CAS  Google Scholar 

  8. Siren AL, Fratelli M, Brines M, Goemans C, Casagrande S, Lewczuk P, Keenan S, Gleiter C, Pasquali C, Capobianco A, Mennini T, Heumann R, Cerami A, Ehrenreich H, Ghezzi P (2001) Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci USA 98:4044–4049

    Article  PubMed  CAS  Google Scholar 

  9. Brines M, Cerami A (2006) Discovering erythropoietin’s extra-hematopoietic functions: biology and clinical promise. Kidney Int 70:246–250

    Article  PubMed  CAS  Google Scholar 

  10. Lipsic E, Schoemaker RG, van der Meer P, Voors AA, van Veldhuisen DJ, van Gilst WH (2006) Protective effects of erythropoietin in cardiac ischemia. J Am Coll Cardiol 48:2161–2167

    Article  PubMed  CAS  Google Scholar 

  11. Calvillo L, Latini R, Kajstura J, Leri A, Anversa P, Ghezzi P, Salio M, Cerami A, Brines M (2003) Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci USA 100:4802–4806

    Article  PubMed  CAS  Google Scholar 

  12. Parsa CJ, Matsumoto A, Kim J, Riel RU, Pascal LS, Walton GB, Thompson RB, Petrofski JA, Annex BH, Stamler JS, Koch WJ (2003) A novel protective effect of erythropoietin in the infarcted heart. J Clin Invest 112:999–1007

    PubMed  CAS  Google Scholar 

  13. Tramontano AF, Muniyappa R, Black AD, Blendea MC, Cohen I, Deng L, Sowers JR, Cutaia MV, El-Sherif N. (2003) Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an Akt-dependent pathway. Biochem Biophys Res Commun 308:990–994

    Article  PubMed  CAS  Google Scholar 

  14. Cai Z, Semenza GL (2004) Phosphatidylinositol-3-kinase signaling is required for erythropoietin-mediated acute protection against myocardial ischemia/reperfusion injury. Circulation 109:2050–2053

    Article  PubMed  CAS  Google Scholar 

  15. Leist M, Ghezzi P, Grasso G, Bianchi R, Villa P, Fratelli M, Savino C, Bianchi M, Nielsen J, Gerwien J, Kallunki P, Larsen AK, Helboe L, Christensen S, Pedersen LO, Nielsen M, Torup L, Sager T, Sfacteria A, Erbayraktar S, Erbayraktar Z, Gokmen N, Yilmaz O, Cerami-Hand C, Xie QW, Coleman T, Cerami A, Brines M (2004) Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 305:239–242

    Article  PubMed  CAS  Google Scholar 

  16. Moon C, Krawczyk M, Paik D, Coleman T, Brines M, Juhaszova M, Sollott SJ, Lakatta EG, Talan MI (2006) Erythropoietin, modified to not stimulate red blood cell production, retains its cardioprotective properties. J Pharmacol Exp Ther 316:999–1005

    Article  PubMed  CAS  Google Scholar 

  17. Fiordaliso F, Chimenti S, Staszewsky L, Bai A, Carlo E, Cuccovillo I, Doni M, Mengozzi M, Tonelli R, Ghezzi P, Coleman T, Brines M, Cerami A, Latini R (2005) A nonerythropoietic derivative of erythropoietin protects the myocardium from ischemia-reperfusion injury. Proc Natl Acad Sci USA 102:2046–2051

    Article  PubMed  CAS  Google Scholar 

  18. Gao E, Boucher M, Chuprun JK, Zhou RH, Eckhart AD, Koch WJ (2007) Darbepoetin alfa, a long-acting erythropoietin analog, offers novel and delayed cardioprotection for the ischemic heart. Am J Physiol Heart Circ Physiol 293:H60–H68

    Article  PubMed  CAS  Google Scholar 

  19. Frank SJ (2002) Receptor dimerization in GH and erythropoietin action—it takes two to tango, but how? Endocrinology 143:2–10

    Article  PubMed  CAS  Google Scholar 

  20. Jubinsky PT, Krijanovski OI, Nathan DG, Tavernier J, Sieff CA (1997) The beta chain of the interleukin-3 receptor functionally associates with the erythropoietin receptor. Blood 90:1867–1873

    PubMed  CAS  Google Scholar 

  21. Brines M, Grasso G, Fiordaliso F, Sfacteria A, Ghezzi P, Fratelli M, Latini R, Xie QW, Smart J, Su-Rick CJ, Pobre E, Diaz D, Gomez D, Hand C, Coleman T, Cerami A (2004) Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor. Proc Natl Acad Sci USA 101:14907–14912

    Article  PubMed  CAS  Google Scholar 

  22. van der Meer P, Lipsic E, Henning RH, Boddeus K, van der Velden J, Voors AA, van Veldhuisen DJ, van Gilst WH, Schoemaker RG (2005) Erythropoietin induces neovascularization and improves cardiac function in rats with heart failure after myocardial infarction. J Am Coll Cardiol 46:125–133

    Article  PubMed  Google Scholar 

  23. Cai Z, Manalo DJ, Wei G, Rodriguez ER, Fox-Talbot K, Lu H, Zweier JL, Semenza GL (2003) Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia-reperfusion injury. Circulation 108:79–85

    Article  PubMed  CAS  Google Scholar 

  24. Elliott S, Busse L, Bass MB, Lu H, Sarosi I, Sinclair AM, Spahr C, Um M, Van G, Begley CG (2006) Anti-Epo receptor antibodies do not predict Epo receptor expression. Blood 107(5):1892–1895

    Article  PubMed  CAS  Google Scholar 

  25. Baker JE (2005) Erythropoietin mimics ischemic preconditioning. Vascul Pharmacol 42:233–241

    Article  PubMed  CAS  Google Scholar 

  26. Wojchowski DM, Gregory RC, Miller CP, Pandit AK, Pircher TJ (1999) Signal transduction in the erythropoietin receptor system. Exp Cell Res 253:143–156

    Article  PubMed  CAS  Google Scholar 

  27. Witthuhn BA, Quelle FW, Silvennoinen O, Yi T, Tang B, Miura O, Ihle JN (1993) JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell 74:227–236

    Article  PubMed  CAS  Google Scholar 

  28. Rafiee P, Shi Y, Su J, Pritchard KA Jr, Tweddell JS, Baker JE (2005) Erythropoietin protects the infant heart against ischemia–reperfusion injury by triggering multiple signaling pathways. Basic Res Cardiol 100:187–197

    Article  PubMed  CAS  Google Scholar 

  29. Bao H, Jacobs-Helber SM, Lawson AE, Penta K, Wickrema A, Sawyer ST (1999) Protein kinase B (c-Akt), phosphatidylinositol 3-kinase, and STAT5 are activated by erythropoietin (EPO) in HCD57 erythroid cells but are constitutively active in an EPO-independent, apoptosis-resistant subclone (HCD57-SREI cells). Blood 93:3757–3773

    PubMed  CAS  Google Scholar 

  30. Chong ZZ, Kang JQ, Maiese K (2002) Erythropoietin is a novel vascular protectant through activation of Akt1 and mitochondrial modulation of cysteine proteases. Circulation 106:2973–2979

    Article  PubMed  CAS  Google Scholar 

  31. Juhaszova M, Zorov DB, Kim SH, Pepe S, Fu Q, Fishbein KW, Ziman BD, Wang S, Ytrehus K, Antos CL, Olson EN, Sollott SJ (2004) Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest 113(11):1535–1549

    PubMed  CAS  Google Scholar 

  32. von Lindern M, Parren-van Amelsvoort M, van Dijk T, Deiner E, van den Akker E, van Emst-de Vries S, Willems P, Beug H, Lowenberg B (2000) Protein kinase C alpha controls erythropoietin receptor signaling. J Biol Chem 275:34719–34727

    Article  Google Scholar 

  33. Kawakami M, Iwasaki S, Sato K, Takahashi M (2000) Erythropoietin inhibits calcium-induced neurotransmitter release from clonal neuronal cells. Biochem Biophys Res Commun 279:293–297

    Article  PubMed  CAS  Google Scholar 

  34. Wald MR, Borda ES, Sterin-Borda L (1996) Mitogenic effect of erythropoietin on neonatal rat cardiomyocytes: signal transduction pathways. J Cell Physiol 167:461–468

    Article  PubMed  CAS  Google Scholar 

  35. Shi Y, Rafiee P, Su J, Pritchard KA Jr, Tweddell JS, Baker JE (2004) Acute cardioprotective effects of erythropoietin in infant rabbits are mediated by activation of protein kinases and potassium channels. Basic Res Cardiol 99:173–182

    Article  PubMed  CAS  Google Scholar 

  36. Bartesaghi S, Marinovich M, Corsini E, Galli CL, Viviani B (2005) Erythropoietin: a novel neuroprotective cytokine. Neurotoxicology 26:923–928

    Article  PubMed  CAS  Google Scholar 

  37. Figueroa C, Tarras S, Taylor J, Vojtek AB (2003) Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex. J Biol Chem 278:47922–47927

    Article  PubMed  CAS  Google Scholar 

  38. Maulik N, Sasaki H, Addya S, Das DK (2000) Regulation of cardiomyocyte apoptosis by redox-sensitive transcription factors. FEBS Lett 485:7–12

    Article  PubMed  CAS  Google Scholar 

  39. Liu X, Xie W, Liu P, Duan M, Jia Z, Li W, Xu J (2006) Mechanism of the cardioprotection of rhEPO pretreatment on suppressing the inflammatory response in ischemia-reperfusion. Life Sci 78:2255–2264

    Article  PubMed  CAS  Google Scholar 

  40. Burger D, Lei M, Geoghegan-Morphet N, Lu X, Xenocostas A, Feng Q (2006) Erythropoietin protects cardiomyocytes from apoptosis via up-regulation of endothelial nitric oxide synthase. Cardiovasc Res 72:51–59

    Article  PubMed  CAS  Google Scholar 

  41. Heidbreder M, Frohlich F, Johren O, Dendorfer A, Qadri F, Dominiak P (2003) Hypoxia rapidly activates HIF-3alpha mRNA expression. FASEB J 17:1541–1543

    PubMed  CAS  Google Scholar 

  42. Jung F, Palmer LA, Zhou N, Johns RA (2000) Hypoxic regulation of inducible nitric oxide synthase via hypoxia inducible factor-1 in cardiac myocytes. Circ Res 86:319–325

    PubMed  CAS  Google Scholar 

  43. Mani K, Kitsis RN (2003) Myocyte apoptosis: programming ventricular remodeling. J Am Coll Cardiol 41:761–764

    Article  PubMed  Google Scholar 

  44. Olivetti G, Quaini F, Sala R, Lagrasta C, Corradi D, Bonacina E, Gambert SR, Cigola E, Anversa P (1996) Acute myocardial infarction in humans is associated with activation of programmed myocyte cell death in the surviving portion of the heart. J Mol Cell Cardiol 28:2005–2016

    Article  PubMed  CAS  Google Scholar 

  45. Narula J, Haider N, Virmani R, DiSalvo TG, Kolodgie FD, Hajjar RJ, Schmidt U, Semigran MJ, Dec GW, Khaw BA (1996) Apoptosis in myocytes in end-stage heart failure. N Engl J Med 335:1182–1189

    Article  PubMed  CAS  Google Scholar 

  46. Miao W, Luo Z, Kitsis RN, Walsh K (2000) Intracoronary, adenovirus-mediated Akt gene transfer in heart limits infarct size following ischemia-reperfusion injury in vivo. J Mol Cell Cardiol 32:2397–2402

    Article  PubMed  CAS  Google Scholar 

  47. Chatterjee S, Stewart AS, Bish LT, Jayasankar V, Kim EM, Pirolli T, Burdick J, Woo YJ, Gardner TJ, Sweeney HL (2002) Viral gene transfer of the antiapoptotic factor Bcl-2 protects against chronic postischemic heart failure. Circulation 106:I212–I217

    PubMed  Google Scholar 

  48. Fisher JW (2003) Erythropoietin: physiology and pharmacology update. Exp Biol Med (Maywood) 228:1–14

    CAS  Google Scholar 

  49. Tada H, Kagaya Y, Takeda M, Ohta J, Asaumi Y, Satoh K, Ito K, Karibe A, Shirato K, Minegishi N, Shimokawa H (2006) Endogenous erythropoietin system in non-hematopoietic lineage cells plays a protective role in myocardial ischemia/reperfusion. Cardiovasc Res 71:466–477

    Article  PubMed  CAS  Google Scholar 

  50. Agnello D, Bigini P, Villa P, Mennini T, Cerami A, Brines ML, Ghezzi P (2002) Erythropoietin exerts an anti-inflammatory effect on the CNS in a model of experimental autoimmune encephalomyelitis. Brain Res 952:128–134

    Article  PubMed  CAS  Google Scholar 

  51. Li Y, Takemura G, Okada H, Miyata S, Maruyama R, Li L, Higuchi M, Minatoguchi S, Fujiwara T, Fujiwara H (2006) Reduction of inflammatory cytokine expression and oxidative damage by erythropoietin in chronic heart failure. Cardiovasc Res 71:684–694

    Article  PubMed  CAS  Google Scholar 

  52. Bahlmann FH, De Groot K, Spandau JM, Landry AL, Hertel B, Duckert T, Boehm SM, Menne J, Haller H, Fliser D (2004) Erythropoietin regulates endothelial progenitor cells. Blood 103:921–926

    Article  PubMed  CAS  Google Scholar 

  53. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Bohm M, Nickenig G (2005) Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 353:999–1007

    Article  PubMed  CAS  Google Scholar 

  54. Valgimigli M, Rigolin GM, Fucili A, Porta MD, Soukhomovskaia O, Malagutti P, Bugli AM, Bragotti LZ, Francolini G, Mauro E, Castoldi G, Ferrari R (2004) CD34+ and endothelial progenitor cells in patients with various degrees of congestive heart failure. Circulation 110:1209–1212

    Article  PubMed  CAS  Google Scholar 

  55. Kissel CK, Lehmann R, Assmus B, Aicher A, Honold J, Fischer-Rasokat U, Heeschen C, Spyridopoulos I, Dimmeler S, Zeiher AM (2007) Selective funcional exhaustion of hematopoietic progenitor cells in the bone marrow of patients with postinfarction heart failure. J Am Coll Cardiol 49:2341–2349

    Article  PubMed  Google Scholar 

  56. Aicher A, Heeschen C, Mildner-Rihm C, Urbich C, Ihling C, Technau-Ihling K, Zeiher AM, Dimmeler S (2003) Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med 9:1370–1376

    Article  PubMed  CAS  Google Scholar 

  57. Landmesser U, Engberding N, Bahlmann F, Schaefer A, Wiencke A, Heineke A, Spiekermann S, Hilfiker-Kleiner D, Templin C, Kotlarz D, Mueller M, Fuchs M, Hornig B, Haller H, Drexler H (2004) Statin-induced improvement of endothelial progenitor cell mobilization, myocardial neovascularization, left ventricular function, and survival after experimental myocardial infarction requires endothelial nitric oxide synthase. Circulation 110:1933–1939

    Article  PubMed  CAS  Google Scholar 

  58. van der Meer P, Lipsic E, Henning RH, de Boer RA, Suurmeijer AJ, van Veldhuisen DJ, van Gilst WH (2004) Erythropoietin improves left ventricular function and coronary flow in an experimental model of ischemia-reperfusion injury. Eur J Heart Fail 6:853–859

    PubMed  Google Scholar 

  59. Westenbrink BD, Lipsic E, van der Meer P, van der Harst P, Oeseburg H, Du Marchie Sarvaas GJ, Koster J, Voors AA, van Veldhuisen DJ, van Gilst WH, Schoemaker RG (2007) Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization. Eur Heart J 28:2018–2027

    Article  PubMed  CAS  Google Scholar 

  60. Hirata A, Minamino T, Asanuma H, Fujita M, Wakeno M, Myoishi M, Tsukamoto O, Okada K, Koyama H, Komamura K, Takashima S, Shinozaki Y, Mori H, Shiraga M, Kitakaze M, Hori M (2006) Erythropoietin enhances neovascularization of ischemic myocardium and improves left ventricular dysfunction after myocardial infarction in dogs. J Am Coll Cardiol 48:176–184

    Article  PubMed  CAS  Google Scholar 

  61. Hamed S, Barshack I, Luboshits G, Wexler D, Deutsch V, Keren G, George J (2006) Erythropoietin improves myocardial performance in doxorubicin-induced cardiomyopathy. Eur Heart J 27:1876–1883

    Article  PubMed  CAS  Google Scholar 

  62. Pfeffer JM, Pfeffer MA, Mirsky I, Braunwald E (1982) Regression of left ventricular hypertrophy and prevention of left ventricular dysfunction by captopril in the spontaneously hypertensive rat. Proc Natl Acad Sci USA 79:3310–3314

    Article  PubMed  CAS  Google Scholar 

  63. Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D; CHOIR Investigators (2006) Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 355:2085–2098

    Article  PubMed  CAS  Google Scholar 

  64. Strippoli GF, Tognoni G, Navaneethan SD, Nicolucci A, Craig JC (2007) Haemoglobin targets: we were wrong, time to move on. Lancet 369(9559):346–350

    Article  PubMed  Google Scholar 

  65. Cotter DJ, Stefanik K, Zhang Y, Thamer M, Scharfstein D, Kaufman J (2004) Hematocrit was not validated as a surrogate end point for survival among epoetin-treated hemodialysis patients. J Clin Epidemiol 57:1086–1095

    Article  PubMed  Google Scholar 

  66. Nishihara M, Miura T, Miki T, Sakamoto J, Tanno M, Kobayashi H, Ikeda Y, Ohori K, Takahashi A, Shimamoto K (2006) Erythropoietin affords additional cardioprotection to preconditioned hearts by enhanced phosphorylation of glycogen synthase kinase-3 beta. Am J Physiol Heart Circ Physiol 291:H748–H755

    Article  PubMed  CAS  Google Scholar 

  67. Kristensen J, Maeng M, Rehling M, Berg JS, Mortensen UM, Nielsen SS, Nielsen TT (2005) Lack of acute cardioprotective effect from preischaemic erythropoietin administration in a porcine coronary occlusion model. Clin Physiol Funct Imaging 25:305–310

    Article  PubMed  CAS  Google Scholar 

  68. Lipsic E, van der Meer P, Henning RH, Suurmeijer AJ, Boddeus KM, van Veldhuisen DJ, van Gilst WH, Schoemaker RG (2004) Timing of erythropoietin treatment for cardioprotection in ischemia/reperfusion. J Cardiovasc Pharmacol 44:473–479

    Article  PubMed  CAS  Google Scholar 

  69. Parsa CJ, Kim J, Riel RU, Pascal LS, Thompson RB, Petrofski JA, Matsumoto A, Stamler JS, Koch WJ (2004) Cardioprotective effects of erythropoietin in the reperfused ischemic heart: a potential role for cardiac fibroblasts. J Biol Chem 279:20655–20662

    Article  PubMed  CAS  Google Scholar 

  70. Moon C, Krawczyk M, Ahn D, Ahmet I, Paik D, Lakatta EG, Talan MI (2003) Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci USA 100:11612–11617

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiovascular Research, Instituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, Milan, 20156, Italy

    Roberto Latini & Fabio Fiordaliso

  2. Department of Medicine, New York Medical College, Valhalla, NY, USA

    Roberto Latini

  3. The Kenneth S. Warren Institute and Warren Pharmaceuticals, Ossining, NY, USA

    Michael Brines

Authors
  1. Roberto Latini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Brines
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fabio Fiordaliso
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roberto Latini.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Latini, R., Brines, M. & Fiordaliso, F. Do non-hemopoietic effects of erythropoietin play a beneficial role in heart failure?. Heart Fail Rev 13, 415–423 (2008). https://doi.org/10.1007/s10741-008-9084-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-008-9084-z

Keywords

Search

Navigation