The cardiovascular effects of erythropoietin

Cardiovascular Research

Volumn 59, Issue 3, 2003, Pages 538-548

  Smith, Kyle J ^a   Bleyer, Anthony J ^a   Little, William C ^a   Sane, David C ^a  

^a WAKE FOREST SCHOOL OF MEDICINE   (United States)

Author keywords

Angiogenesis; Endothelial function; Platelets; Renal function; Thrombosis embolism

Indexed keywords

CYTOKINE RECEPTOR; ERYTHROPOIETIN RECEPTOR; JANUS KINASE 2; MEMBRANE PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; PROTEIN DERIVATIVE; PROTEIN EPOR; RECOMBINANT ERYTHROPOIETIN; STAT5 PROTEIN; UNCLASSIFIED DRUG;

AMINO ACID SUBSTITUTION; ANEMIA; ANGIOGENESIS; APOPTOSIS; CARDIOVASCULAR EFFECT; CARDIOVASCULAR SYSTEM; CELL PROLIFERATION; CHRONIC KIDNEY DISEASE; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG SAFETY; DRUG SYNTHESIS; ENDOTHELIUM CELL; ERYTHROPOIESIS; EXERCISE TOLERANCE; HEART DISEASE; HEART FAILURE; HEART LEFT VENTRICLE HYPERTROPHY; HEART MUSCLE CELL; HUMAN; HYPERTENSION; MITOGENESIS; MOLECULAR MECHANICS; PLASMA HALF LIFE; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REDUCTION; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; THROMBOCYTE ACTIVATION; THROMBUS;

ANEMIA; CARDIOVASCULAR SYSTEM; CELL DIVISION; ENDOTHELIUM, VASCULAR; ERYTHROPOIETIN; ERYTHROPOIETIN, RECOMBINANT; GTP-BINDING PROTEIN ALPHA SUBUNITS, GS; HEART FAILURE, CONGESTIVE; HUMANS; HYPERTENSION; KIDNEY FAILURE, CHRONIC; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, CARDIAC; NERVE TISSUE PROTEINS; PLATELET ACTIVATION; RECEPTORS, ERYTHROPOIETIN; THROMBOSIS;

EID: 1642395912     PISSN: 00086363     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0008-6363(03)00468-1     Document Type: Review

References (130)

1. Moreno F., Sanz-Guajardo D., López-Gómez J.M., Jofre R., Valderrábano F. Increasing the hematocrit has a beneficial effect on quality of life and is safe in selected hemodialysis patients. J Am Soc Nephrol. 11:2000;335-342.
2. Eknoyan G., Levin N. Clinical practice guidelines: final guideline summaries from the work groups of the national kidney foundation-dialysis outcomes quality initiative. 1997;National Kidney Foundation, New York.
3. Beguin Y. A risk-benefit assessment of epoetin in the management of anaemia associated with cancer. Drug Safety. 19:1998;269-282.
4. Adamson J.W., Schuster M., Allen S., Haley N.R. Effectiveness of recombinant human erythropoietin therapy in myelodysplastic syndromes. Acta Haematol. 87:(supp1 1):1992;20-24.
5. Phibbs R.H., Shannon K.M., Mentzer W.C. Potential for treatment of anaemia of prematurity with recombinant human erythropoietin: preliminary results. Acta Haematol. 87:(suppl 1):1992;28-33.
6. Feagan B.G., Wong C.J., Kirkley A., et al. Erythropoietin with iron supplementation to prevent allogeneic blood transfusion in total hip joint arthroplasty. A randomized, controlled trial. Ann Intern Med. 133:2000;845-854.
7. Corwin H.L., Gettingrer A., Pearl R.G., et al. Efficacy of recombinant human erythropoietin in critically ill patients. J Am Med Assoc. 288:2002;2827-2835.
8. Cotter D.J., Thamer M., Kimmel P.L., Sadler J.H. Secular trends in recombinant erythropoietin therapy among the U.S. hemodialysis population: 1990-1996. Kidney Int. 54:1998;2129-2139.
9. Macdougall I.C. Novel erythropoiesis stimulating protein. Semin Nephrol. 20:2000;375-381.
10. Noris M., Remuzzi G. Uremic bleeding: closing the circle after 30 years of controversies? Blood. 94:1999;2569-2574.
11. Ozaki K., Leonard W.J. Cytokine and cytokine receptor pleiotropy and redundancy. J Biol Chem. 277:2002;29355-29358.
12. Gabrilove J. Overview: erythropoiesis, anemia, and the impact of erythropoietin. Semin Hematol. 37:(Suppl 6):2000;1-3.
13. Koury S.T., Bondurant M.C., Koury M.J. Localization of erythropoietin synthesizing cells in murine kidneys by in situ hybridization. Blood. 71:1988;524-527.
14. Dame C., Fahnenstich H., Freitag P., Hofmann D., Abdul-Nour T., Bartmann P., Fandrey J. Erythropoietin mRNA in human fetal and neonatal tissue. Blood. 92:1998;3218-3225.
15. Vogt C., Pentz S., Rich I.N. A role for the macrophage in normal hemopoiesis: III. In vitro and in vivo erythropoietin gene expression in macrophages detected by in situ hybridization. Exp Hematol. 17:1989;391-397.
16. Conrad K.P., Benyo D.F., Westerhausen-Larsen A., Miles T.M. Expression of erythropoietin by the human placenta. FASEB J. 10:1996;760-768.
17. Juul S.E., Zhao Y., Dame J.B., Du Y., Hutson A.D., Christensen R.D. Origin and fate of erythropoietin in human milk. Pediatr Res. 48:2000;660-667.
18. Marti H.H., Wenger R.H., Rivas L.A., et al. Erythropoietin gene expression in human, monkey and murine brain. Eur J Neurosci. 8:1996;666-676.
19. Abramowicz M. Darbepoetin (Aranesp) - A long-acting erythropoietin. Med Lett. 43:2001;109-110.
20. Casadevall N., Nataf J., Viron B., et al. Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med. 346:2002;469-475.
21. Bazan J.F. Structural design and molecular evolution of a cytokine receptor superfamily. Proc Natl Acad Sci USA. 87:1990;6934-6938.
22. Witthuhn A., Quelle F.W., Silvennoinen O., et al. JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell. 74:1993;227-236.
23. Gouilleux F., Pallard C., Dusanter-Fourt I., et al. Prolactin, growth hormone, erythropoietin and granulocyte-macrophage colony stimulating factor induce MGF-Stat5 DNA binding activity. EMBO J. 14:1995;2005-2013.
24. Bao H., Jacobs-Helber S.M., Lawson A.E., Penta K., Wickrema A., Sawyer S.T. 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. 93:1999;3757-3773.
25. Cheung J.Y., Miller B.A. Molecular mechanisms of erythropoietin signaling. Nephron. 87:2001;215-222.
26. Digicaylioglu M., Lipton S.A. Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-KB signalling cascades. Nature. 412:2001;641-647.
27. Ammarguellat F., Llovera M., Kelly P.A., Goffin V. Low doses of EPO activate MAP kinases but not JAK2-STAT5 in rat vascular smooth muscle cells. Biochem Biophy Res Commun. 284:2001;1031-1038.
28. 2+ channels: Activation by phospholipase C-γ1. Kidney Int. 53:1998;1259-1268.
29. Miller B.A., Cheung J.Y. Mechanisms of erythropoietin signal transduction: involvement of calcium channels. Proc Soc Exp Biol Med. 206:1994;263-267.
30. Fraser J.K., Lin F.K., Berridge M.V. Expression of high affinity receptors for erythropoietin on human bone marrow cells and on the human erythroleukemic cell line, HEL. Exp Hematol. 16:1988;836-842.
31. Fraser J.K., Tan A.S., Lin F.-K., Berridge M.V. Expression of specific high-affinity binding sites for erythropoietin on rat and mouse megakaryocytes. Exp Hematol. 17:1989;10-16.
32. Anagnostou A., Liu Z., Steiner M., et al. Erythropoietin receptor mRNA expression in human endothelial cells. Proc Natl Acad Sci USA. 91:1994;3974-3978.
33. Nagai T., Akizawa T., Kohjiro S., et al. rHuEPO enhances the production of plasminogen activator inhibitor-1 in cultured endothelial cells. Kidney Int. 50:1996;102-107.
34. Anagnostou A., Lee E.S., Kessimian N., Levinson R., Steiner M. Erythropoietin has a mitogenic and positive chemotactic effect on endothelial cells. Proc Natl Acad Sci USA. 87:1990;5978-5982.
35. Ogilvie M., Yu X., Nicolas-Metral V., et al. Erythropoietin stimulates proliferation and interferes with differentiation of myoblasts. J Biol Chem. 275:2000;39754-39761.
36. Masuda S., Nagao M., Takahata K., et al. Functional erythropoietin receptor of the cells with neural characteristics. Comparison with receptor properties of erythroid cells. J Biol Chem. 268:1993;11208-11216.
37. Westenfelder C., Biddle D.L., Baranowski R.L. Human, rat, and mouse kidney cells express functional erythropoietin receptors. Kidney Int. 55:1999;808-820.
38. Arcasoy M.O., Amin K., Karayal A.F., et al. Functional significance of erythropoietin receptor expression in breast cancer. Lab Invest. 82:2002;911-918.
39. Junk A.K., Mammis A., Savitz S.I., et al. Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury. Proc Natl Acad Sci USA. 99:2002;10659-10664.
40. Wu H., Lee S.H., Gao J., Liu X., Iruela-Arispe M.L. Inactivation of erythropoietin leads to defects in cardiac morphogenesis. Development. 126:1999;3597-3605.
41. Baynes R.D., Reddy G.K., Shih Y.J., Skikne B.S., Cook J.D. Serum form of the erythropoietin receptor identified by a sequence-specific peptide antibody. Blood. 82:1993;2088-2095.
42. Harris K.W., Winkelmann J.C. Enzyme-linked immunosorbent assay detects a potential soluble form of the erythropoietin receptor in human plasma. Am J Hematol. 52:1996;8-13.
43. Maeda Y., Sakaguchi M., Naiki Y., et al. Possible involvement of soluble erythropoietin receptor in resistance to erythropoietin in patients with renal anemia. Am J Nephrol. 21:2001;426.
44. Shimizu R., Komatsu N., Miura Y. Dominant negative effect of a truncated erythropoietin receptor (EPOR-T) on erythropoietin-induced erythroid differentiation: possible involvement of EPOR-T in ineffective erythropoiesis of myeloblastic syndrome. Exp Hematol. 27:1999;229-233.
45. Besarab A., Bolton W.K., Browne J.K., et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med. 339:1998;584-590.
46. Muirhead N., Laupacis A., Wong C. Erythropoietin for anemia in haemodialysis patients: results of a maintenance study (the Canadian Erythropoietin Study Group). Nephrol Dial Transplant. 7:1992;811-816.
47. Viron B., Chamma F., Jaar B., Michel C., Mignon F. Thrombosis of angioaccess in haemodialysed patients treated with human recombinant erythropoietin. Nephrol Dial Transplant. 12:1997;368-370.
48. Aranesp™ (darbepoetin alfa), package insert, Amgen.
49. Wolf R.F., Gilmore L.S., Friese P., Downs T., Burstein S.A., Dale G.L. Erythropoietin potentiates thrombus development in a canine arterio-venous shunt model. Thromb Haemost. 77:1997;1020-1024.
50. Tang W.W., Stead R.A., Goodkin D.A. Effects of epoetin alfa on hemostasis in chronic renal failure. Am J Nephrol. 18:1998;263-273.
51. Lage J.M.M., Panizo C., Masdeu J., Rocha E. Cyclist's doping associated with cerebral sinus thrombosis. Neurology. 58:2002;665.
52. Begg T.B., Hearns J.B. Components in blood viscosity. The relative contribution of haematocrit, plasma fibrinogen and other proteins. Clin Sci. 31:1966;87-93.
53. Turitto V.T., Weiss H.J. Red blood cells: their dual role in thrombus formation. Science. 207:1980;541-543.
54. Malyszko J., Malyszko J.S., Borawski J., et al. A study of platelet functions, some hemostatic and fibrinolytic parameters in relation to serotonin in hemodialyzed patients under erythropoietin therapy. Thromb Res. 77:1995;133-143.
55. Akizawa T., Kinugasa E., Kitaoka T., Koshikawa S. Effects of recombinant human erythropoietin and correction of anemia on platelet function in hemodialysis patients. Nephron. 58:1991;400-406.
56. Taylor J.E., McLaren M., Henderson I.S., Belch J.J.F., Stewart W.K. Prothrombotic effect of erythropoietin in dialysis patients. Nephrol Dial Transplant. 7:1992;235-239.
57. Macdougall I.C., Davies M.E., Hallett I., et al. Coagulation in studies and fistula blood flow during erythropoietin therapy in haemodialysis patients. Nephrol Dial Transplant. 6:1991;862-867.
58. Christensson A.G., Danielson B.G., Lethagen S.R. Normalization of haemoglobin concentration with recombinant erythropoietin has minimal effect on blood haemostasis. Nephrol Dial Transplant. 16:2001;313-319.
59. Marchi S.D., Cecchin E., Falleti E., et al. Long-term effects of erythropoietin therapy on fistula stenosis and plasma concentrations of PDGF and MCP-1 in hemodialysis patients. J Am Soc Nephrol. 8:1997;1147-1156.
60. Kooistra M.P., van Es A., Marx J.J.M., Hertsig M.L.A., Struyvenberg A. Low-dose aspirin does not prevent thrombovascular accidents in low-risk haemodialysis patients during treatment with recombinant human erythropoietin. Nephrol Dial Transplant. 9:1994;1115-1120.
61. Taylor J.E., Henderson I.S., Stewart W.K., Belch J.J. Erythropoietin and spontaneous platelet aggregation in haemodialysis patients. Lancet. 338:1991;1361-1362.
62. Zhou X.J., Vaziri N.D. Defective calcium signaling in uraemic platelets and its amelioration with long-term erythropoietin therapy. Nephrol Dial Transplant. 17:2002;992-997.
63. Diaz-Ricart M., Estebanell E., Cases A., et al. Erythropoietin improves signaling through tyrosine phosphorylation in platelets from uremic patients. Thromb Haemost. 82:1999;1312-1317.
64. Roger S.D., Piper J., Tucker B., Raine A.E., Baker L.R., Kovacs I.B. Enhanced platelet reactivity with erythropoietin but not following transfusion in dialysis patients. Nephrol Dial Transplan. 8:1993;213-217.
65. Ando M., Iwata A., Ozeki Y., Tsuchiya K., Akiba T., Nihei H. Circulating platelet-derived microparticles with procoagulant activity may be a potential cause of thrombosis in uremic patients. Kidney Int. 62:2002;1757-1764.
66. Stohlawetz P.J., Dzirio L., Hergovich N., et al. Effects of erythropoietin on platelet reactivity and thrombopoiesis in humans. Blood. 95:2000;2983-2989.
67. Pirisi M., Fabris C., Soardo G., Cecchin E., Toniutto P., Bartoli E. Thrombocytopenia of chronic liver disease corrected by erythropoietin treatment. J Hepatol. 21:1994;376-380.
68. Karnicki K., Owen W.G., Miller R.S., McBand R.D.I.I. Factors contributing to individual propensity for arterial thrombosis. Arterioscler Thromb Vasc Biol. 22:2002;1495-1499.
69. Sharpe P.C., Desai Z.R., Morris T.C.M. Increase in mean platelet volume in patients with chronic renal failure treated with erythropoietin. J Clin Pathol. 47:1994;159-161.
70. Martin J.F., Bath P.M.W., Burr M.L. Influence of platelet size on outcome after myocardial infarction. Lancet. 338:1991;1409-1411.
71. Ribatti D., Presta M., Vacca A., et al. Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Blood. 93:1999;2627-2636.
72. Carlini R.G., Dusso A.S., Obialo C.I., Alvarez U.M., Rothstein M. Recombinant human erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells. Kidney Int. 43:1993;1010-1014.
73. Yasuda Y., Masuda S., Chikuma M., Inoue K., Nagao M., Sasaki R. Estrogen-dependent production of erythropoietin in uterus and its implication in uterine angiogenesis. J Biol Chem. 273:1998;25381-25387.
74. Jaquet K., Krause K., Tawakol-Khodai M., Geidel S., Kuck K.-H. Erythropoietin and VEGF exhibit equal angiogenic potential. Microvascular Res. 64:2002;326-333.
75. Carlini R.G., Gupta A., Liapis H., Rothstein M. Endothelin-1 release by erythropoietin involves calcium signaling in endothelial cells. J Cardiovasc Pharmacol. 26:1995;889-892.
76. Haller H., Christel C., Dannenberg L., Thiele P., Lindschau C., Luft F.C. Signal transduction of erythropoietin in endothelial cells. Kidney Int. 50:1996;481-488.
77. Fodinger M., Fritsche-Polanz R., Buchmayer H., et al. Erythropoietin-inducible immediate-early genes in human vascular endothelial cells. J Invest Med. 48:2000;137-149.
78. Sunder-Plassmann G., Hörl W.H. Novel aspects of erythropoietin response in renal failure patients. Nephrol Dial Transplant. 16:(suppl 5):2001;40-44.
79. Noguchi K., Yamashiro S., Matsuzaki T., et al. Effect of 1-week treatment with erythropoietin on the vascular endothelial function in anaesthetized rabbits. Br J Pharmacol. 133:2001;395-405.
80. Wang X.Q., Vaziri N.D. Erythropoietin depresses nitric oxide synthase expression by human endothelial cells. Hypertension. 33:1999;894-899.
81. Shibata J, Hasegawa J, Siemens H-J, et al. Hemostasis and coagulation at a hematocrit of 0.85: functional consequences of erythrocytosis. Blood First Edition Paper, prepublished online February 6, 2003.
82. Wilcox C.S., Deng X., Doll A.H., Snellen H., Welch W.J. Nitric oxide mediates renal vasodilation during erythropoietin-induced polycythemia. Kidney Int. 44:1993;430-435.
83. Heidenreich S., Rahn K.H., Zidek W. Direct vasopressor effect of recombinant human erythropoietin on renal resistance vessels. Kidney Int. 39:1991;259-265.
84. Morakkabati N., Gollnick F., Meyer R., Fandrey J., Jelkmann W. Erythropoietin induces Ca2+ mobilization and contraction in rat mesangial and aortic smooth muscle cultures. Exp Hematol. 24:1996;392-397.
85. 2+ mobilization in cultured rat vascular smooth-muscle cells. Nephrol Dial Transplant. 16:2001;491-499.
86. Akimoto T., Kusano E., Muto S., et al. The effect of erythropoietin on interleukin-1β mediated increase in nitric oxide synthesis in vascular smooth muscle cells. J Hypertens. 17:1999;1249-1256.
87. Hand M.F., Haynes W.G., Johnstone H.A., Anderton J.L., Webb D.J. Erythropoietin enhances vascular responsiveness to norepinephrine in renal failure. Kidney Int. 48:1995;806-813.
88. Kusano E., Akimoto T., Umino T., et al. Modulation of endothelin-1-induced cytosolic free calcium mobilization and mitogen-activated protein kinase activation by erythropoietin in vascular smooth muscle cells. Kidney Blood Press Res. 24:2001;192-200.
89. Barrett J.D., Zhang Z., Zhu J.H., et al. Erythropoietin upregulates angiotensin receptors in cultured rat vascular smooth muscle cells. J Hypertens. 16:1998;1749-1757.
90. Kusano E., Akimoto T., Inoue M., et al. Human recombinant erythropoietin inhibits interleukin-1β-stimulated nitric oxide and cyclic guanosine monophosphate production in cultured rat vascular smooth-muscle cells. Nephrol Dial Transplant. 14:1999;597-603.
91. Goguzev J., Zhu D.L., Herembert T., Ammarguellat F., Marche P., Drueke T. Effect of erythropoietin on DNA synthesis, proto-oncogene expression and phospholipase C activity in rat vascular smooth muscle cells. Biochem Biophys Res Commun. 199:1994;977-983.
92. Carlini R.G., Reyes A.A., Rothstein M. Recombinant human erythropoietin stimulates angiogenesis in vitro. Kidney Int. 47:1995;740-745.
93. Ammarguellat F., Goguzev J., Drueke T.B. Direct effect of erythropoietin on rat vascular smooth-muscle cell via putative erythropoietin receptor. Nephrol Dial Transplant. 11:1996;687-692.
94. Akimoto T., Kusano E., Inaba T., et al. Erythropoietin regulates vascular smooth muscle cell apoptosis by a phosphatidylinositol 3 kinase-dependent pathway. Kidney Int. 58:2000;269-282.
95. Shiojima I., Walsh K. Role of AKT signaling in vascular homeostasis and angiogenesis. Circ Res. 90:2002;1243-1250.
96. Ikegaya N., Yamamoto T., Takeshita A., et al. Elevated erythropoietin receptor and transforming growth factor-β1 expression in stenotic arteriovenous fistulae used for hemodialysis. J Am Soc Nephrol. 11:2000;928-935.
97. Foley R.N., Parfrey P.S., Sarnak M.J. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 32:(Suppl):1998;S112-S119.
98. Maschio G. Erythropoietin and systemic hypertension. Nephrol Dial Transplant. 10:(suppl 2):1995;74-79.
99. Bleyer A.J., Burkart J.M. Seizures: II. Semin Dialysis. 7:1994;41-45.
100. Roger R.D., Fluck R.J., McMahon A.C., Raine A.E.G. Recombinant erythropoietin increases blood pressure in experimental hypertension and uraemia without change in vascular cytosolic calcium. Nephron. 73:1996;212-218.
101. Cirillo M., Laurenzi M., Trevisan M., Stamler J. Hematocrit, Blood Pressure, and Hypertension: The Gubbio Population Study. Hypertension. 20:1992;319-326.
102. Conlon P.J., Kovalik E., Schumm D., Minda S., Schwab S.J. Normalization of hematocrit in hemodialysis patients with cardiac disease does not increase blood pressure. Renal Failure. 22:(4):2000;435-444.
103. Katoh K., Mizuno K., Hashimoto S., et al. Direct evidence for erythropoietin-induced release of endothelin from peripheral vascular tissue. Life Sci. 54:1994;PL253-259.
104. Quaschning T., Ruschizka F., Stallmach T., et al. Eryhropoietin-induced excessive erythrocytosis activates the tissue endothelin system in mice. FASEB J. 17:2003;259-261.
105. Carlini R., Obialo C.I., Rothstein M. Intravenous erythropoietin (rHuEPO) administration increases plasma endothelin and blood pressure in hemodialysis patients. Am J Hypertens. 6:1993;103-107.
106. Brunet P., Lorec A.M., Leonetti F., et al. Plasma endothelin in haemodialysis patients treated with recombinant human erythropoietin. Nephrol Dial Transpl. 9:1994;650-654.
107. Wald M.R., Borda E.S., Sterin-Borda L. Mitogenic effect of erythropoietin on neonatal rat cardiomyocytes: Signal transduction pathways. J Cell Physiol. 167:1996;461-468.
108. Wald M., Gutnisky A., Borda E., Sterin-Borda L. Erythropoietin modified the cardiac action of ouabain in chronically anaemic-uraemic rats. Nephron. 71:1995;190-196.
109. Wagner K.F., Katschinski D.M., Hasegawa J., et al. Chronic inborn erythrocytosis leads to cardiac dysfunction and premature death in mice overexpressing erythropoietin. Blood. 97:2001;536-542.
110. Suzuki N., Ohneda O., Takahashi S., et al. Erythroid-specific expression of the erythropoietin receptor rescued its null mutant mice from lethality. Blood. 100:2002;2279-2288.
111. Levin A., Thompson C., Ethier J., et al. Left ventricle mass index increase in early renal disease: Impact of decline in hemoglobin. Am J Kidney Dis. 34:1999;125-134.
112. Greaves S.C., Gamble G.D., Collins J.F., Whalley G.A., Sharpe D.N. Determinants of left ventricle hypertrophy and systolic dysfunction in chronic renal failure. Am J Kidney Dis. 24:1994;768-776.
113. Foley R.N., Parfrey P.S., Harnett J.D., Kent G.M., Murray D.C., Barre P.E. The prognostic importance of left ventricular geometry in uremic cardiomyopathy. J Am Soc Nephrol. 5:1995;2024-2031.
114. Sunder-Plassmann G., Hörl W.H. Effect of Erythropoietin on Cardiovascular Diseases. Am J Kidney Dis. 38:(4):2001;S20-S25.
115. Linde T., Wikstrom B., Andersson L.G., Danielson B.G. Renal anaemia treatment with recombinant human erythropoietin increases cardiac output in patients with ischaemic heart disease. Scand J Urol Nephrol. 30:1996;115-120.
116. Katona M. Erythropoiesis: new dimensions in the treatment of anemia. vol. 3:1991;39-45.
117. Low I., Grutzmacher P., Bergmann M., Schoeppe W. Echocardiographic findings in patients on maintenance hemodialysis substituted with recombinant human erythropoietin. Clin Nephrol. 31:1989;26-30.
118. Low-Friedrich I., Grutzmacher P., Marz W., Bergmann M., Schoeppe W. Therapy with recombinant human erythropoietin reduces cardiac size and improves heart function in chronic hemodialysis patients. Am J Nephrol. 11:1991;54-60.
119. Goldberg N., Lundin A.P., Delano B., Friedman E.A., Stein R.A. Changes in left ventricular size, wall thickness, and function in anemic patients treated with recombinant human erythropoietin. Am Heart J. 124:1992;424-427.
120. Silverberg D.S., Wexler D., Blum M., et al. The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations. J Am Coll Cardiol. 35:2000;1737-1744.
121. Androne A.-S., Katz S.D., Lund L., LaManca J., Hudaihed A., Hryniewicz K., Mancini D.M. Hemodilution is common in patients with advanced heart failure. Circulation. 107:2003;226-229.
122. Horwich T.B., Fonarow G.C., Hamilton M.A., MacLellan W.R., Borenstein J. Anemia is associated with worse symptoms, greater impairment in functional capacity and a significant increase in mortality in patients with advanced heart failure. J Am Coll Cardiol. 39:2002;1780-1786.
123. Ezekowitz J.A., McAlister F.A., Armstrong P.W. Anemia is common in heart failure and is associated with poor outcomes. Insights from a cohort of 12065 patients with new-onset heart failure. Circulation. 107:2003;223-225.
124. Silverberg D.S., Wexler D., Sheps D., et al. The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study. J Am Coll Cardiol. 37:2001;1775-1780.
125. Mancini D.M., Katz S.D., Lang C.C., LaManca J., Hudaihed A., Androne A.-S. Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure. Circulation. 107:2003;294-299.
126. Eckardt K.-U. The CREATE trial - building the evidence. Nephrol Dial Transplant. 16:(suppl 2):2001;16-18.
127. Siren A.L., Ehrenreich H. Erythropoietin - a novel concept for neuroprotection. Eur Arch Psychiatry Clin Neurosci. 251:2001;179-184.
128. Kawakami M., Sekiguchi M., Sato K., Kozaki S., Takahashi M. Erythropoietin receptor-mediated inhibition of exocytotic glutamate release confers neuroprotection during chemical ischemia. J Biol Chem. 276:2001;39469-39475.
129. Miró O., Marrades R.M., Roca J., et al. Skeletal muscle mitochondrial function is preserved in young patients with chronic renal failure. Am J Kidney Dis. 39:2002;1025-1031.
130. Chong Z.Z., Kang J.-Q., Maiese K. Erythropoietin is a novel vascular protectant through activation of Akt1 and mitochondrial modulation of cystein proteases. Circulation. 106:2002;2973-2979.