Erythropoietin and Nonhematopoietic Effects

American Journal of the Medical Sciences

Volumn 353, Issue 1, 2017, Pages 76-81

  Nekoui, Alireza ^a   Blaise, Gilbert ^a  

^a UNIVERSITÉ DE MONTRÉAL   (Canada)

Author keywords

Antiapoptosis; Erythropoietin; Hypoxia inducible factor; Nonhematopoietic; Tissue protection

Indexed keywords

ERYTHROPOIETIN; RECOMBINANT ERYTHROPOIETIN; NEUROPROTECTIVE AGENT;

ANGIOGENESIS; CELL DEATH; COGNITION; DEGENERATIVE DISEASE; DIABETES MELLITUS; HEART LEFT VENTRICLE HYPERTROPHY; HEART PROTECTION; HEMATOPOIESIS; HUMAN; KIDNEY FUNCTION; MEMORY; MENTAL DISEASE; MOLECULAR MECHANICS; NERVE CELL DIFFERENTIATION; NEUROPATHY; NEUROPROTECTION; NONHEMATOPOIETIC EFFECT; NONHUMAN; OBESITY; PROTEIN ANALYSIS; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN SECRETION; RECEPTOR AFFINITY; RETINA NERVE CELL; REVIEW; UPREGULATION; ANIMAL; BLOOD; CARDIOVASCULAR DISEASES; KIDNEY; METABOLISM; NEURODEGENERATIVE DISEASES; PHYSIOLOGY; RETINA;

ANIMALS; CARDIOVASCULAR DISEASES; COGNITION; DIABETES MELLITUS; ERYTHROPOIETIN; HUMANS; KIDNEY; MEMORY; NEOVASCULARIZATION, PHYSIOLOGIC; NEURODEGENERATIVE DISEASES; NEUROPROTECTIVE AGENTS; OBESITY; RETINA;

EID: 85021848572     PISSN: 00029629     EISSN: 15382990     Source Type: Journal    
DOI: 10.1016/j.amjms.2016.10.009     Document Type: Review

References (97)

1. Babitt, J.L., Lin, H.Y., Mechanisms of anemia in CKD. J Am Soc Nephrol 23:10 (2012), 1631–1634.
2. Eckardt, K.U., Pathophysiology of renal anemia. Clin Nephrol 53:suppl 1 (2000), S2–S8.
3. Taylor, S.K., Is recombinant human erythropoietin (rh-epo) more than just a treatment of anemia in cancer and chemotherapy?. Med Hypotheses 60:1 (2003), 89–93.
4. Handelman, G.J., Levin, N.W., Iron and anemia in human biology: a review of mechanisms. Heart Fail Rev 13:4 (2008), 393–404.
5. Ross, S.D., Allen, I.E., Henry, D.H., et al. Clinical benefits and risks associated with epoetin and darbepoetin in patients with chemotherapy-induced anemia: a systematic review of the literature. Clin Ther 28:6 (2006), 801–831.
6. Sriram, S., Xenocostas, A., Lazo-Langner, A., Erythropoietin in anemia of unknown etiology: a systematic review and meta-analysis. Hematology 21:4 (2016), 234–240.
7. Collister, D., Komenda, P., Hiebert, B., et al. The effect of erythropoietin-stimulating agents on health-related quality of life in anemia of chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med 164:7 (2016), 472–478.
8. Lund, A., Lundby, C., Olsen, N.V., High-dose erythropoietin for tissue protection. Eur J Clin Invest 44:12 (2014), 1230–1238.
9. Messe, S.R., McGarvey, M.L., Bavaria, J.E., et al. A pilot study of darbepoetin alfa for prophylactic neuroprotection in aortic surgery. Neurocrit Care 18:1 (2013), 75–80.
10. Calvillo, L., Latini, R., Kajstura, J., et al. Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci U S A 100:8 (2003), 4802–4806.
11. Campana, W.M., Myers, R.R., Exogenous erythropoietin protects against dorsal root ganglion apoptosis and pain following peripheral nerve injury. Eur J Neurosci 18:6 (2003), 1497–1506.
12. Nekoui, A., Tresierra, V.D., Abdolmohammadi, S., et al. Neuroprotective effect of erythropoietin in postoperation cervical spinal cord injury: case report and review. Anesth Pain Med, 5(6), 2015, e28849.
13. Grasso, G., Sfacteria, A., Cerami, A., et al. Erythropoietin as a tissue-protective cytokine in brain injury: what do we know and where do we go?. Neuroscientist 10:2 (2004), 93–98.
14. Brines, M., Cerami, A., The receptor that tames the innate immune response. Mol Med 18 (2012), 486–496.
15. Edwards, J.K., Anaemia: regulation of renal erythropoietin via HIF. Nat Rev Nephrol, 12(5), 2016, 256.
16. Brines, M., Cerami, A., Discovering erythropoietin׳s extra-hematopoietic functions: biology and clinical promise. Kidney Int 70:2 (2006), 246–250.
17. Bao, H., Jacobs-Helber, S.M., Lawson, A.E., et al. 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 93:11 (1999), 3757–3773.
18. Semenza, G.L., Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology (Bethesda) 24 (2009), 97–106.
19. Semenza, G.L., Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology. Annu Rev Pathol 9 (2014), 47–71.
20. Heyman, S.N., Leibowitz, D., Mor-Yosef, Levi I, et al. Adaptive response to hypoxia and remote ischaemia pre-conditioning: a new hypoxia-inducible factors era in clinical medicine. Acta Physiol (Oxf) 216:4 (2016), 395–406.
21. Alnaeeli, M., Wang, L., Piknova, B., et al. Erythropoietin in brain development and beyond. Anat Res Int, 2012, 2012, 953264.
22. Fan, X., Heijnen, C.J., van der Kooij, M.A., et al. The role and regulation of hypoxia-inducible factor-1alpha expression in brain development and neonatal hypoxic-ischemic brain injury. Brain Res Rev 62:1 (2009), 99–108.
23. Torun, Y.A., Ozdemir, M.A., Ulger, H., et al. Erythropoietin improves brain development in short-term hypoxia in rat embryo cultures. Brain Dev 36:10 (2014), 864–869.
24. Ghaffari, S., Kitidis, C., Zhao, W., et al. AKT induces erythroid-cell maturation of JAK2-deficient fetal liver progenitor cells and is required for Epo regulation of erythroid-cell differentiation. Blood 107:5 (2006), 1888–1891.
25. Zou, Y.R., Zhang, J., Wang, J., et al. Erythropoietin receptor activation protects the kidney from ischemia/reperfusion-induced apoptosis by activating ERK/p53 signal pathway. Transplant Proc 48:1 (2016), 217–221.
26. Sasaki, R., Masuda, S., Nagao, M., Erythropoietin: multiple physiological functions and regulation of biosynthesis. Biosci Biotechnol Biochem 64:9 (2000), 1775–1793.
27. Jelkmann, W., Molecular biology of erythropoietin. Intern Med 43:8 (2004), 649–659.
28. Kretz, A., Happold, C.J., Marticke, J.K., et al. Erythropoietin promotes regeneration of adult CNS neurons via Jak2/Stat3 and PI3K/AKT pathway activation. Mol Cell Neurosci 29:4 (2005), 569–579.
29. Marzo, F., Lavorgna, A., Coluzzi, G., et al. Erythropoietin in heart and vessels: focus on transcription and signalling pathways. J Thromb Thrombolysis 26:3 (2008), 183–187.
30. La Ferla, K., Reimann, C., Jelkmann, W., et al. Inhibition of erythropoietin gene expression signaling involves the transcription factors GATA-2 and NF-kappaB. FASEB J 16:13 (2002), 1811–1813.
31. Imagawa, S., Nakano, Y., Obara, N., et al. A GATA-specific inhibitor (K-7174) rescues anemia induced by IL-1beta, TNF-alpha, or L-NMMA. FASEB J 17:12 (2003), 1742–1744.
32. Elliott, S., Pham, E., Macdougall, I.C., Erythropoietins: a common mechanism of action. Exp Hematol 36:12 (2008), 1573–1584.
33. Maiese, K., Li, F., Chong, Z.Z., New avenues of exploration for erythropoietin. J Am Med Assoc 293:1 (2005), 90–95.
34. Scholz, H., Schurek, H.J., Eckardt, K.U., et al. Role of erythropoietin in adaptation to hypoxia. Experientia 46:11–12 (1990), 1197–1201.
35. Westenfelder, C., Biddle, D.L., Baranowski, R.L., Human, rat, and mouse kidney cells express functional erythropoietin receptors. Kidney Int 55:3 (1999), 808–820.
36. Ammarguellat, F., Llovera, M., Kelly, P.A., et al. Low doses of EPO activate MAP kinases but not JAK2-STAT5 in rat vascular smooth muscle cells. Biochem Biophys Res Commun 284:4 (2001), 1031–1038.
37. Jaquet, K., Krause, K., Tawakol-Khodai, M., et al. Erythropoietin and VEGF exhibit equal angiogenic potential. Microvasc Res 64:2 (2002), 326–333.
38. Akimoto, T., Kusano, E., Muto, S., et al. The effect of erythropoietin on interleukin-1beta mediated increase in nitric oxide synthesis in vascular smooth muscle cells. J Hypertens 17:9 (1999), 1249–1256.
39. Scalera, F., Kielstein, J.T., Martens-Lobenhoffer, J., et al. Erythropoietin increases asymmetric dimethylarginine in endothelial cells: role of dimethylarginine dimethylaminohydrolase. J Am Soc Nephrol 16:4 (2005), 892–898.
40. Kusano, E., Akimoto, T., Inoue, M., et al. Human recombinant erythropoietin inhibits interleukin-1beta-stimulated nitric oxide and cyclic guanosine monophosphate production in cultured rat vascular smooth-muscle cells. Nephrol Dial Transplant 14:3 (1999), 597–603.
41. Akimoto, T., Kusano, E., Ito, C., et al. Involvement of erythropoietin-induced cytosolic free calcium mobilization in activation of mitogen-activated protein kinase and DNA synthesis in vascular smooth muscle cells. J Hypertens 19:2 (2001), 193–202.
42. Jantzie, L.L., Miller, R.H., Robinson, S., Erythropoietin signaling promotes oligodendrocyte development following prenatal systemic hypoxic-ischemic brain injury. Pediatr Res 74:6 (2013), 658–667.
43. Yu, X., Shacka, J.J., Eells, J.B., et al. Erythropoietin receptor signalling is required for normal brain development. Development 129:2 (2002), 505–516.
44. Rangarajan, V., Juul, S.E., Erythropoietin: emerging role of erythropoietin in neonatal neuroprotection. Pediatr Neurol 51:4 (2014), 481–488.
45. Zhu, C., Kang, W., Xu, F., et al. Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy. Pediatrics 124:2 (2009), e218–e226.
46. Zhang, L., Chopp, M., Zhang, R.L., et al. Erythropoietin amplifies stroke-induced oligodendrogenesis in the rat. PLoS One, 5(6), 2010, e11016.
47. Robertson, C.S., Cherian, L., Shah, M., et al. Neuroprotection with an erythropoietin mimetic peptide (pHBSP) in a model of mild traumatic brain injury complicated by hemorrhagic shock. J Neurotrauma 29:6 (2012), 1156–1166.
48. Ohls, R.K., Kamath-Rayne, B.D., Christensen, R.D., et al. Cognitive outcomes of preterm infants randomized to darbepoetin, erythropoietin, or placebo. Pediatrics 133:6 (2014), 1023–1030.
49. Wu, Y.W., Gonzalez, F.F., Erythropoietin: a novel therapy for hypoxic-ischaemic encephalopathy?. Dev Med Child Neurol 57:suppl 3 (2015), 34–39.
50. Hernandez, C., Simo, R., Erythropoietin produced by the retina: its role in physiology and diabetic retinopathy. Endocrine 41:2 (2012), 220–226.
51. Wang, Q., Pfister, F., Dorn-Beineke, A., et al. Low-dose erythropoietin inhibits oxidative stress and early vascular changes in the experimental diabetic retina. Diabetologia 53:6 (2010), 1227–1238.
52. Mitsuhashi, J., Morikawa, S., Shimizu, K., et al. Intravitreal injection of erythropoietin protects against retinal vascular regression at the early stage of diabetic retinopathy in streptozotocin-induced diabetic rats. Exp Eye Res 106 (2013), 64–73.
53. Zhang, J., Wu, Y., Jin, Y., et al. Intravitreal injection of erythropoietin protects both retinal vascular and neuronal cells in early diabetes. Invest Ophthalmol Vis Sci 49:2 (2008), 732–742.
54. Hassani, V., Homaei, M.M., Shahbazi, A., et al. Human erythropoietin effect in postoperative visual loss following spine surgery: a case report. Anesth Pain Med, 4(2), 2014, e7291.
55. Grasso, G., Sfacteria, A., Erbayraktar, S., et al. Amelioration of spinal cord compressive injury by pharmacological preconditioning with erythropoietin and a nonerythropoietic erythropoietin derivative. J Neurosurg Spine 4:4 (2006), 310–318.
56. Leist, M., Ghezzi, P., Grasso, G., et al. Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 305:5681 (2004), 239–242.
57. Lykissas, M.G., Korompilias, A.V., Vekris, M.D., et al. The role of erythropoietin in central and peripheral nerve injury. Clin Neurol Neurosurg 109:8 (2007), 639–644.
58. Sirén, A.L., Faßhauer, T., Bartels, C., et al. Therapeutic potential of erythropoietin and its structural or functional variants in the nervous system. Neurotherapeutics 6:1 (2009), 108–127.
59. Yin, Z.S., Zhang, H., Gao, W., et al. Erythropoietin promotes functional recovery and enhances nerve regeneration after peripheral nerve injury in rats. AJNR Am J Neuroradiol 31:3 (2010), 509–515.
60. Villa, P., Bigini, P., Mennini, T., et al. Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis. J Exp Med 198:6 (2003), 971–975.
61. Carelli, S., Marfia, G., DiGiulio, A.M., et al. Erythropoietin: recent developments in the treatment of spinal cord injury. Neurol Res Int, 2011, 2011, 453179.
62. Hall, E.D., Springer, J.E., Neuroprotection and acute spinal cord injury: a reappraisal. NeuroRx 1:1 (2004), 80–100.
63. Juul, S.E., Hypothermia plus erythropoietin for neonatal neuroprotection? Commentary on Fan et al and Fang et al. Pediatr Res 73:1 (2013), 10–11.
64. Vinberg, M., Miskowiak, K., Hoejman, P., et al. The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders: a randomised controlled study. PLoS One, 10(5), 2015, e0127629.
65. Loblaw, D.A., Holden, L., Xenocostas, A., et al. Functional and pharmacokinetic outcomes after a single intravenous infusion of recombinant human erythropoietin in patients with malignant extradural spinal cord compression. Clin Oncol (R Coll Radiol) 19:1 (2007), 63–70.
66. Bianchi, R., Buyukakilli, B., Brines, M., et al. Erythropoietin both protects from and reverses experimental diabetic neuropathy. Proc Natl Acad Sci U S A 101:3 (2004), 823–828.
67. Lipton, S.A., Erythropoietin for neurologic protection and diabetic neuropathy. N Engl J Med 350:24 (2004), 2516–2517.
68. Jia, H.B., Jin, Y., Ji, Q., et al. Effects of recombinant human erythropoietin on neuropathic pain and cerebral expressions of cytokines and nuclear factor-kappa B. Can J Anaesth 56:8 (2009), 597–603.
69. Bian, X.X., Yuan, X.S., Qi, C.P., Effect of recombinant human erythropoietin on serum S100B protein and interleukin-6 levels after traumatic brain injury in the rat. Neurol Med Chir (Tokyo) 50:5 (2010), 361–366.
70. Lauria, G., Campanella, A., Filippini, G., et al. Erythropoietin in amyotrophic lateral sclerosis: a pilot, randomized, double-blind, placebo-controlled study of safety and tolerability. Amyotroph Lateral Scler 10:5–6 (2009), 410–415.
71. Ehrenreich, H., Fischer, B., Norra, C., et al. Exploring recombinant human erythropoietin in chronic progressive multiple sclerosis. Brain 130:Pt 10 (2007), 2577–2588.
72. Jang, W., Park, J., Shin, K.J., et al. Safety and efficacy of recombinant human erythropoietin treatment of non-motor symptoms in Parkinson׳s disease. J Neurol Sci 337:1–2 (2014), 47–54.
73. Maurer, M.H., Schabitz, W.R., Schneider, A., Old friends in new constellations—the hematopoetic growth factors G-CSF, GM-CSF, and EPO for the treatment of neurological diseases. Curr Med Chem 15:14 (2008), 1407–1411.
74. Jia, Y., Mo, S.J., Feng, Q.Q., et al. EPO-dependent activation of PI3K/Akt/FoxO3a signalling mediates neuroprotection in in vitro and in vivo models of Parkinson׳s disease. J Mol Neurosci 53:1 (2014), 117–124.
75. Dahan, A., Dunne, A., Swartjes, M., et al. ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Mol Med 19 (2013), 334–345.
76. Merelli, A., Czornyj, L., Lazarowski, A., Erythropoietin: a neuroprotective agent in cerebral hypoxia, neurodegeneration, and epilepsy. Curr Pharm Des 19:38 (2013), 6791–6801.
77. Santos, C.M., New agents promote neuroprotection in Parkinson׳s disease models. CNS Neurol Disord Drug Targets 11:4 (2012), 410–418.
78. Girolamo, F., Coppola, C., Ribatti, D., et al. Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neuropathol Commun, 2, 2014, 84.
79. Hellewell, S.C., Yan, E.B., Alwis, D.S., et al. Erythropoietin improves motor and cognitive deficit, axonal pathology, and neuroinflammation in a combined model of diffuse traumatic brain injury and hypoxia, in association with upregulation of the erythropoietin receptor. J Neuroinflammation, 10, 2013, 156.
80. Hasselblatt, M., Ehrenreich, H., Siren, A.L., The brain erythropoietin system and its potential for therapeutic exploitation in brain disease. J Neurosurg Anesthesiol 18:2 (2006), 132–138.
81. Miskowiak, K.W., Vinberg, M., Harmer, C.J., et al. Erythropoietin: a candidate treatment for mood symptoms and memory dysfunction in depression. Psychopharmacology (Berl) 219:3 (2012), 687–698.
82. Miskowiak, K.W., Vinberg, M., Christensen, E.M., et al. Recombinant human erythropoietin for treating treatment-resistant depression: a double-blind, randomized, placebo-controlled phase 2 trial. Neuropsychopharmacology 39:6 (2014), 1399–1408.
83. Fond, G., Macgregor, A., Attal, J., et al. Treating patients with schizophrenia deficit with erythropoietin?. Psychiatry Clin Neurosci 66:5 (2012), 375–382.
84. Wustenberg, T., Begemann, M., Bartels, C., et al. Recombinant human erythropoietin delays loss of gray matter in chronic schizophrenia. Mol Psychiatry 16:1 (2011), 26–36 1.
85. Ehrenreich, H., Bartels, C., Sargin, D., et al. Recombinant human erythropoietin in the treatment of human brain disease: focus on cognition. J Ren Nutr 18:1 (2008), 146–153.
86. Foskett, A., Alnaeeli, M., Wang, L., et al. The effects of erythropoietin dose titration during high-fat diet-induced obesity. J Biomed Biotechnol, 2011, 2011, 373781.
87. Katz, O., Stuible, M., Golishevski, N., et al. Erythropoietin treatment leads to reduced blood glucose levels and body mass: insights from murine models. J Endocrinol 205:1 (2010), 87–95.
88. Peelman, F., Waelput, W., Iserentant, H., et al. Leptin: linking adipocyte metabolism with cardiovascular and autoimmune diseases. Prog Lipid Res 43:4 (2004), 283–301.
89. Choi, D., Schroer, S.A., Lu, S.Y., et al. Erythropoietin protects against diabetes through direct effects on pancreatic beta cells. J Exp Med 207:13 (2010), 2831–2842.
90. Brines, M., Grasso, G., Fiordaliso, F., et al. Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor. Proc Natl Acad Sci U S A 101:41 (2004), 14907–14912.
91. Lipsic, E., Schoemaker, R.G., van der Meer, P., et al. Protective effects of erythropoietin in cardiac ischemia: from bench to bedside. J Am Coll Cardiol 48:11 (2006), 2161–2167.
92. Heeschen, C., Aicher, A., Lehmann, R., et al. Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 102:4 (2003), 1340–1346.
93. Chong, Z.Z., Kang, J.Q., Maiese, K., Angiogenesis and plasticity: role of erythropoietin in vascular systems. J Hematother Stem Cell Res 11:6 (2002), 863–871.
94. Yamaji, R., Okada, T., Moriya, M., et al. Brain capillary endothelial cells express two forms of erythropoietin receptor mRNA. Eur J Biochem 239:2 (1996), 494–500.
95. Martinez-Estrada, O.M., Rodriguez-Millan, E., Gonzalez-de Vicente, E., et al. Erythropoietin protects the in vitro blood-brain barrier against VEGF-induced permeability. Eur J Neurosci 18:9 (2003), 2538–2544.
96. Urbich, C., Dimmeler, S., Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95:4 (2004), 343–353.
97. Galeano, M., Altavilla, D., Bitto, A., et al. Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds. Crit Care Med 34:4 (2006), 1139–1146.