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Kardiale Protektion und Regeneration

Klinische Translation der Erythropoietintherapie nach Myokardischämie

Cardiac protection and regeneration

Clinical translation of erythropoietin therapy after myocardial ischemia

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Zeitschrift für Herz-,Thorax- und Gefäßchirurgie Aims and scope

Zusammenfassung

Erythropoietin (EPO) ist ein hypoxieinduziertes Wachstumshormon mit pleiotropischem Wirkungsprofil. Die EPO-vermittelten Haupteffekte nach myokardialer Ischämie umfassen Apoptoseinhibition, Entzündungsmodifikation, Angiogenese und Reverse Remodeling. Darüber hinaus erscheinen Synergismen mit stammzellassoziierter Kardioregeneration sowie die Induktion intrakardialer Proliferation therapeutisch nutzbar. Infolge wiederholten Nachweises therapeutischer Effizienz tritt EPO zunehmend in den Fokus des klinischen Interesses. Nachfolgender Beitrag erläutert mögliche Indikationen, translationale Richtlinien sowie Risiken während präklinischer und klinischer Studien. Applikationsdosierungen, -zeitpunkte, -routen und EPO-Derivate wurden entsprechend mittels systematischer Literaturrecherche (Medline Datenbank) und eigener Studien gegeneinander evaluiert.

Abstract

Erythropoietin (EPO) is a hypoxia-inducible growth factor with a pleiotropic profile. Following myocardial ischemia, EPO-mediated main effects include inhibition of apoptosis, modification of inflammation, angiogenesis, and reverse remodeling. Furthermore, synergism with stem cell-related cardiac repair and the induction of intracardiac proliferation might exert therapeutic potency. As a result of repeated reports of therapeutic efficiency, EPO has increasingly been the focus of clinical interest. Possible indications, translational guidelines, and risks during preclinical and clinical trials are summarized. Dosing, timing, and routes of application as well as EPO derivatives were evaluated using the data from a systematic review (database: Medline) and our own investigations.

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Literatur

  1. Ren G, Michael LH, Entman ML, Frangogiannis NG (2002) Morphological characteristics of the microvasculature in healing myocardial infarcts. J Histochem Cytochem 50:71–79

    CAS  PubMed  Google Scholar 

  2. Hao X, Silva EA, Månsson-Broberg A et al (2007) Angiogenetic effects of sequential release of VEGF-A165 and PDGF-BB with alginate hydrogels after myocardial infarction. Cardiovasc Res 75:178–185

    Article  CAS  PubMed  Google Scholar 

  3. Yerebakan C, Kaminski A, Liebold A, Steinhoff G (2007) Safety of intramyocardial stem cell therapy for the ischemic myocardium: results of the Rostock trial after 5-year follow-up. Cell Transplant 16:935–940

    Article  PubMed  Google Scholar 

  4. Abdel-Latif A, Bolli R, Tleyjeh IM et al (2007) Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med 167:989–997

    Article  PubMed  Google Scholar 

  5. Schächinger V, Erbs S, Elsässer A et al (2006) Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 355:1210–1221

    Article  PubMed  Google Scholar 

  6. Richmond TD, Chohan M, Barbar DL (2005) Turning cells red: signal transduction mediated by erythropoietin. Trends Cell Biol 15:146–155

    Article  CAS  PubMed  Google Scholar 

  7. Liu X, **e W, Liu P et al (2006) Mechanism of the cardioprotection of rhEPO pretreatment on suppressing the inflammatory response in ischemia-reperfusion. Life Sci 78:2255–2264

    Article  CAS  PubMed  Google Scholar 

  8. Moon C, Krawczyk M, Ahn D et al (2003) Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci U S A 100:11612–11617

    Article  CAS  PubMed  Google Scholar 

  9. Li Y, Takemura G, Okada H et al (2006) Reduction of inflammatory cytokine expression and oxidative damage by erythropoietin in chronic heart failure. Cardiovasc Res 71:684–694

    Article  CAS  PubMed  Google Scholar 

  10. Van der Meer P, Lipsic E, Henning RH et al (2005) Erythropoietin induces neovascularization and improves cardiac function in rats with heart failure after myocardial infarction. J Am Coll Cardiol 46:125–133

    Article  Google Scholar 

  11. Klopsch C, Furlani D, Gaebel R et al (2009) Intracardiac injection of Erythropoietin induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model. J Cell Mol Med 13:664–679

    Article  CAS  PubMed  Google Scholar 

  12. Stein A, Knodler M, Makowski M et al (2010) Local erythropoietin and endothelial progenitor cells improve regional cardiac function in acute myocardial infarction. BMC Cardiovasc Disord 10:43

    Article  PubMed  Google Scholar 

  13. Taniguchi N, Nakamura T, Sawada T et al (2010) Erythropoietin Prevention Trial of Coronary Restenosis and Cardiac Remodeling After ST-Elevated Acute Myocardial Infarction (EPOC-AMI). Circ J. doi:10.1253/circj.CJ-10-0544

  14. Calvillo L, Latini R, Kajstura J et al (2003) Recombinant human erythropoetin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodelling. Proc Natl Acad Sci U S A 15:4802–4806

    Article  Google Scholar 

  15. Parsa CJ, Matsumoto A, Kim J et al (2003) A novel protective effect of erythropoetin in the infarcted heart. J Clin Invest 112:999–1007

    CAS  PubMed  Google Scholar 

  16. Burger D, Xenocostas A, Feng QP (2009) Molecular basis of cardioprotection by erythropoietin. Curr Mol Pharmacol 2:56–69

    Article  CAS  PubMed  Google Scholar 

  17. Nishiya D, Omura T, Shimada K et al (2006) Effects of erythropoietin on cardiac remodeling after myocardial infarction. J Pharmacol Sci 101:31–39

    Article  CAS  PubMed  Google Scholar 

  18. Moon C, Krawczyk M, Paik D et al (2005) Cardioprotection by recombinant human erythropoietin following acute experimental myocardial infarction: dose response and therapeutic window. Cardiovasc Drugs Ther 19:243–250

    Article  CAS  PubMed  Google Scholar 

  19. Prunier F, Pfister O, Hadri L et al (2007) Delayed erythropoietin therapy reduces post-MI cardiac remodeling only at a dose that mobilizes endothelial progenitor cells. Am J Physiol Heart Circ Physiol 292:H522–H529

    Article  CAS  PubMed  Google Scholar 

  20. Fiordaliso F, Chimenti S, Staszewsky L et al (2005) A nonerythropoietic derivative of erythropoietin protects the myocardium from ischemia-reperfusion injury. Proc Natl Acad Sci U S A 102:2046–2051

    Article  CAS  PubMed  Google Scholar 

  21. Ueba H, Brines M, Yamin M et al (2010) Cardioprotection by a nonerythropoietic, tissue-protective peptide mimicking the 3D structure of erythropoietin. Proc Natl Acad Sci U S A 107:14357–14362

    Article  CAS  PubMed  Google Scholar 

  22. Frangogiannis NG, Smith CW, Entman ML (2002) The inflammatory response in myocardial infarction. Cardiovasc Res 53:31–47

    Article  CAS  PubMed  Google Scholar 

  23. Miura T, Shizukuda Y, Ogawa S et al (1991) Effects of early and later reperfusion on healing speed of experimental myocardial infarct. Can J Cardiol 7:146–154

    CAS  PubMed  Google Scholar 

  24. Kaminski A, Ma N, Donndorf P et al (2008) Endothelial NOS is required for SDF-1alpha/CXCR4-mediated peripheral endothelial adhesion of c-kit+ bone marrow stem cells. Lab Invest 88:58–69

    Article  CAS  PubMed  Google Scholar 

  25. Gaebel R, Klopsch C, Furlani D et al (2009) Single high-dose intramyocardial administration of erythropoietin promotes early intracardiac proliferation, proves safety and restores cardiac performance after myocardial infarction in rats. Interact Cardiovasc Thorac Surg 9:20–25

    Article  Google Scholar 

  26. Furlani D, Klopsch C, Gäbel R et al (2008) Intracardiac erythropoietin injection reveals antiinflammatory potential and improved cardiac functions detected by Forced Swim Test. Transplant Proc 40:962–966

    Article  CAS  PubMed  Google Scholar 

  27. Poulsen TD, Andersen LW, Steinbrüchel D et al (2009) Two large preoperative doses of erythropoietin do not reduce the systemic inflammatory response to cardiac surgery. J Cardiothorac Vasc Anesth 23:316–323

    Article  CAS  PubMed  Google Scholar 

  28. Nian M, Lee P, Khaper N, Liu P (2004) Inflammatory cytokines and postmyocardial infarction remodeling. Circ Res 94:1543–1553

    Article  CAS  PubMed  Google Scholar 

  29. Fortuno MA, Ravassa S, Fortuno A et al (2001) Cardiomyocyte apoptotic cell death in arterial hypertension: Mechanism and potential management. Hypertension 38:1406–1412

    Article  CAS  PubMed  Google Scholar 

  30. Mihov D, Bogdanov N, Grenacher B et al (2009) Erythropoietin protects from reperfusion-induced myocardial injury by enhancing coronary endothelial nitric oxide production. Eur J Cardiothorac Surg 35:839–846

    Article  PubMed  Google Scholar 

  31. Westenbrink BD, Ruifrok WP, Voors AA et al (2010) Vascular endothelial growth factor is crucial for erythropoietin-induced improvement of cardiac function in heart failure. Cardiovasc Res 87:30–39

    Article  CAS  PubMed  Google Scholar 

  32. Urao N, Okigaki M, Yamada H et al (2006) Erythropoietin-mobilized endothelial progenitors enhance reendothelialization via Akt-endothelial nitric oxide synthase activation and prevent neointimal hyperplasia. Circ Res 98:1405–1413

    Article  CAS  PubMed  Google Scholar 

  33. Regula KM, Rzeszutek MJ, Baetz D et al (2004) Therapeutic opportunities for cell-cycle reentry and cardiac regeneration. Cardiovasc Res 64:395–401

    Article  CAS  PubMed  Google Scholar 

  34. Parsa CJ, Kim J, Riel RU et al (2004) Cardioprotective effects of erythropoietin in the reperfused ischemic heart: a potential role for cardiac fibroblasts. J Biol Chem 279:20655–20662

    Article  CAS  PubMed  Google Scholar 

  35. Potente M, Michaelis UR, Fisslthaler B et al (2002) Cytochrome P450 2C9-induced endothelial cell proliferation involves induction of mitogen-activated protein (MAP) kinase phosphatase-1, inhibition of the c-Jun N-terminal kinase, and up-regulation of cyclin D1. J Biol Chem 277:15671–15676

    Article  CAS  PubMed  Google Scholar 

  36. Qiao M, Shapiro P, Fosbrink M et al (2006) Cell cycle-dependent phosphorylation of the RUNX2 transcription factor by cdc2 regulates endothelial cell proliferation. J Biol Chem 281:7118–7128

    Article  CAS  PubMed  Google Scholar 

  37. Anagnostou A, Lee ES, Kessimian N et al (1990) Erythropoietin has a mitogenic and positive chemotactic effect on endothelial cells. Proc Natl Acad Sci U S A 87:5978–5982

    Article  CAS  PubMed  Google Scholar 

  38. Ledda-Columbano GM, Molotzu F, Pibiri M et al (2006) Thyroid hormone induces cyclin D1 nuclear translocation and DNA synthesis in adult rat cardiomyocytes. FASEB J 20:87–94

    Article  CAS  PubMed  Google Scholar 

  39. Agah R, Kirshenbaum LA, Abdellatif M et al (1997) Adenoviral delivery of E2F-1 directs cell cycle reentry and p53-independent apoptosis in postmitotic adult myocardium in vivo. J Clin Invest 100:2722–2728

    Article  CAS  PubMed  Google Scholar 

  40. Rossini A, Zacheo A, Mocini D et al (2008) HMGB1-stimulated human primary cardiac fibroblasts exert a paracrine action on human and murine cardiac stem cells. J Mol Cell Cardiol 44:683–693

    Article  CAS  PubMed  Google Scholar 

  41. Anversa P, Kajstura J, Leri A, Bolli R (2006) Life and death of cardiac stem cells: a paradigm shift in cardiac biology. Circulation 113:1451–1463

    Article  PubMed  Google Scholar 

  42. Bergmann O, Bhardwaj RD, Bernard S et al (2009) Evidence for cardiomyocyte renewal in humans. Science 324:98–102

    Article  CAS  PubMed  Google Scholar 

  43. Madonna R, Shelat H, Xue Q et al (2009) Erythropoietin protects myocardin-expressing cardiac stem cells against cytotoxicity of tumor necrosis factor-alpha. Exp Cell Res 315:2921–2928

    Article  CAS  PubMed  Google Scholar 

  44. Robey TE, Saiget MK, Reinecke H, Murry CE (2008) Systems approaches to preventing transplanted cell death in cardiac repair. J Mol Cell Cardiol 45:567–581

    Article  CAS  PubMed  Google Scholar 

  45. Leri A, Kajstura J, Anversa P (2005) Cardiac stem cells and mechanisms of myocardial regeneration. Physiol Rev 85:1373–1416

    Article  CAS  PubMed  Google Scholar 

  46. Kalka C, Masuda H, Takahashi T et al (2000) Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A 97:3422–3427

    Article  CAS  PubMed  Google Scholar 

  47. Stamm C, Westphal B, Kleine HD et al (2003) Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 361:45–46

    Article  PubMed  Google Scholar 

  48. George J, Goldstein E, Abashidze A et al (2005) Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner. Cardiovasc Res 68:299–306

    Article  CAS  PubMed  Google Scholar 

  49. Heeschen C, Aicher A, Lehmann R et al (2003) Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 102:1340–1346

    Article  CAS  PubMed  Google Scholar 

  50. Santhanam AV, d’Uscio LV, Peterson TE, Katusic ZS (2008) Activation of endothelial nitric oxide synthase is critical for erythropoietin-induced mobilization of progenitor cells. Peptides 29:1451–1455

    Article  CAS  PubMed  Google Scholar 

  51. Brunner S, Winogradow J, Huber BC et al (2009) Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR-4/SDF-1 axis. FASEB J 23:351–361

    Article  CAS  PubMed  Google Scholar 

  52. Westenbrink BD, Oeseburg H, Kleijn L et al (2008) Erythropoietin stimulates normal endothelial progenitor cell-mediated endothelial turnover, but attributes to neovascularization only in the presence of local ischemia. Cardiovasc Drugs Ther 22:265–274

    Article  CAS  PubMed  Google Scholar 

  53. Ward MR, Stewart DJ (2008) Erythropoietin and mesenchymal stromal cells in angiogenesis and myocardial regeneration: one plus one equals three? Cardiovasc Res 79:357–359

    Article  CAS  PubMed  Google Scholar 

  54. Copland IB, Jolicoeur EM, Gillis MA, et al (2008) Coupling erythropoietin secretion to mesenchymal stromal cells enhances their regenerative properties. Cardiovasc Res 79:405–415

    Article  CAS  PubMed  Google Scholar 

  55. Zhang D, Zhang F, Zhang Y et al (2007) Combining erythropoietin infusion with intramyocardial delivery of bone marrow cells is more effective for cardiac repair. Transpl Int 20:174–183

    Article  PubMed  Google Scholar 

  56. Zwezdaryk KJ, Coffelt SB, Figueroa YG et al (2007) Erythropoietin, a hypoxia-regulated factor, elicits a pro-angiogenic program in human mesenchymal stem cells. Exp Hematol 35:640–652

    Article  CAS  PubMed  Google Scholar 

  57. Chen L, Cheng FJ, Tang JM (2008) The effect of recombinant human erythropoietin on the migration of bone marrow derived mesenchymal stem cells in vitro. Zhonghua Xue Ye Xue Za Zhi 29:811–814

    PubMed  Google Scholar 

  58. Zeng QB, Cheng FJ, Zhang WG et al (2008) Erythropoietin promotes proliferation of human bone marrow mesenchymal stem cells in vitro. Zhongguo Shi Yan Xue Ye Xue Za Zhi 16:1392–1397

    CAS  PubMed  Google Scholar 

  59. Moon C, Krawczyk M, Lakatta EG, Talan MI (2006) Therapeutic effectiveness of a single vs multiple doses of erythropoietin after experimental myocardial infarction in rats. Cardiovasc Drugs Ther 20:245–251

    Article  CAS  PubMed  Google Scholar 

  60. Lipsic E, Meer P van der, Henning RH et al (2004) Timing of erythropoietin treatment for cardioprotection in ischemia/reperfusion. J Cardiovasc Pharmacol 44:473–479

    Article  CAS  PubMed  Google Scholar 

  61. Schneider C, Jaquet K, Malisius R et al (2007) Attenuation of cardiac remodelling by endocardial injection of erythropoietin: ultrasonic strain-rate imaging in a model of hibernating myocardium. Eur Heart J 28:499–509

    Article  PubMed  Google Scholar 

  62. Palazzuoli A, Silverberg DS, Iovine F et al (2007) Effects of beta-erythropoietin treatment on left ventricular remodeling, systolic function, and B-type natriuretic peptide levels in patients with the cardiorenal anemia syndrome. Am Heart J 154:645

    Article  PubMed  Google Scholar 

  63. Palazzuoli A, Silverberg DS, Calabrò A et al (2009) Beta-erythropoietin effects on ventricular remodeling, left and right systolic function, pulmonary pressure, and hospitalizations in patients affected with heart failure and anemia. J Cardiovasc Pharmacol 53:462–467

    Article  CAS  PubMed  Google Scholar 

  64. Cohen RS, Karlin P, Yushak M et al (2010) The effect of erythropoietin on exercise capacity, left ventricular remodeling, pressure-volume relationships, and quality of life in older patients with anemia and heart failure with preserved ejection fraction. Congest Heart Fail 16:96–103

    Article  CAS  PubMed  Google Scholar 

  65. Lindahl B, Toss H, Siegbahn A et al (2000) Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during instability in coronary artery disease. N Engl J Med 343:1139–1147

    Article  CAS  PubMed  Google Scholar 

  66. Cokkinos DV, Pantos C (2007) Myocardial protection in man – from research concept to clinical practice. Heart Fail Rev 12:345–362

    Article  CAS  PubMed  Google Scholar 

  67. Reimer KA, Lowe JE, Rasmussen MM, Jennings RB (1977) The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs. Circulation 56:786–794

    CAS  PubMed  Google Scholar 

  68. Bernard SA, Gray TW, Buist MD et al (2002) Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 346:557–563

    Article  PubMed  Google Scholar 

  69. Maio R, Sepodes B, Patel NS et al (2010) Erythropoietin preserves the integrity and quality of organs for transplantation after cardiac death. Shock. doi:10.1097/SHK.0b013e3181e83236

  70. Menasché P (1997) New strategies in myocardial preservation. Curr Opin Cardiol 12:504–514

    Article  PubMed  Google Scholar 

  71. Serruys PW, Morice MC, Kappetein AP et al (2009) Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 360:961–972

    Article  CAS  PubMed  Google Scholar 

  72. Lipsic E, Meer P van der, Voors AA et al (2006) A single bolus of a long-acting erythropoietin analogue darbepoetin alfa in patients with acute myocardial infarction: a randomized feasibility and safety study. Cardiovasc Drugs Ther 20:135–141

    Article  CAS  PubMed  Google Scholar 

  73. Schwartz PJ (1998) Do animal models have clinical value? Am J Cardiol 81:14D–20D

    Article  CAS  PubMed  Google Scholar 

  74. Sweatman J (2003) Good clinical practice: a nuisance, a help or a necessity for clinical pharmacology? Br J Clin Pharmacol 55:1–5

    Article  PubMed  Google Scholar 

  75. Wish JB, Coyne DW (2007) Use of erythropoiesis-stimulating agents in patients with anemia of chronic kidney disease: overcoming the pharmacological and pharmacoeconomic limitations of existing therapies. Mayo Clin Proc 82:1371–1380

    Article  CAS  PubMed  Google Scholar 

  76. Dicato M (2008) Venous thromboembolic events and erythropoiesis-stimulating agents: an update. Oncologist 13(Suppl 3):11–15

    Article  CAS  PubMed  Google Scholar 

  77. Winearls CG (1998) Recombinant human erythropoietin: 10 years of clinical experience. Nephrol Dial Transplant 13(Suppl 2):3–8

    Article  CAS  PubMed  Google Scholar 

  78. Fandrey J, Dicato M (2009) Examining the involvement of erythropoiesis-stimulating agents in tumor proliferation (erythropoietin receptors, receptor binding, signal transduction), angiogenesis, and venous thromboembolic events. Oncologist 14(Suppl 1):34–42

    Article  CAS  PubMed  Google Scholar 

  79. Krapf R, Hulter HN (2009) Arterial hypertension induced by erythropoietin and erythropoiesis-stimulating agents (ESA). Clin J Am Soc Nephrol 4:470–480

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Referenz- und Translationszentrum für kardiale Stammzelltherapie, Universität Rostock, Schillingallee 68, 18057, Rostock, Deutschland

    C. Klopsch, D. Furlani, R. Gäbel, E. Pittermann, C. Yerebakan, A. Kaminski, N. Ma, A. Liebold & G. Steinhoff

  2. Klinik für Herzchirurgie, Universitäres Herzzentrum Rostock, Universität Rostock, Schillingallee 35, 18057, Rostock, Deutschland

    C. Klopsch, D. Furlani, R. Gäbel, E. Pittermann, C. Yerebakan, A. Kaminski, N. Ma, A. Liebold & G. Steinhoff

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  1. C. Klopsch
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  2. D. Furlani
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Correspondence to C. Klopsch.

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Diese Arbeit wurde unterstützt durch das Deutsche Bundesministerium für Bildung und Forschung (Förderungsnummer 0312138 A), das Wirtschaftsministerium Mecklenburg-Vorpommern, Schwerin (Förderungsnummer RTC V220-630-08-TFMV-F/S-035) sowie die Deutsche Forschungsgemeinschaft, Berlin (Förderungsnummer SFB TR37, TPA4).

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Klopsch, C., Furlani, D., Gäbel, R. et al. Kardiale Protektion und Regeneration. Z Herz- Thorax- Gefäßchir 24, 369–375 (2010). https://doi.org/10.1007/s00398-010-0806-x

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