2014


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2014/№4

Anemia in chronic heart failure: Role of hepcidin as a universal regulator of iron metabolism

Solomakhina N. I., Nakhodnova E. S., Ershov V. I.
State Medical University” of the RF Ministry of Health Care, Trubetskaya 8, Bldg. 2, Moscow 119991

Keywords: anemia, hepcidin, treatment, CHF


DOI: 10.18087 / rhfj.2014.4.1931

At present, anemias called “anemia of chronic disease” (ACD) are isolated from the group of iron-deficiency anemias. In ACD, no specific “classic” cause can be identified to classify the anemia as a known clinical and pathogenetic type. Furthermore, ACDs are very heterogeneous in nature and are distinguished by their variable origin and simultaneous contribution of many factors regulating erythropoiesis. This type of anemia is particularly important in CHF which is associated with ACD in many patients according to reports from large epidemiological studies of recent decades. The presence of anemia, which aggravates hypoxia in this patient category, requires both profound studies of its pathogenesis and development of efficient methods for its correction. At present time, researchers are focused on several, most important stages of ACD development, particularly the recently discovered hormone-like protein, hepcidin.
  1. Ершов В. И., Гадаев И. Ю. Анемии. Часть 1. – М.: 2008. – с. 32–34.
  2. Roy CN, Enns CA. Iron homeostasis: new tales from the crypt. Blood. 2000 Dec 15;96 (13):4020–7.
  3. Hunt JR, Roughead ZK. Adaptation of iron absorption in men consuming diets with high or low iron bioavailability. Am J Clin Nutr. 2000 Jan;71 (1):94–102.
  4. Mukhopadhyay CK, Mazumder В, Fox PL. Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron dificiency. J Biol Chem. 2000 Jul 14;275 (28):21048–54.
  5. Park CH, Valore EV, Waring AJ et al. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem. 2001 Mar 16;276 (11):7806–10.
  6. Deicher R, Horl WH. New insights into the regulation of iron homeostasis. Eur J Clin Invest. 2006 May;36 (5):301–9.
  7. Kemna EH, Tjalsma H, Willems HL, Swinkels DW. Hepcidin: from discovery to differential diagnosis. Haematologica. 2008 Jan;93 (1):90–7.
  8. Nemeth E1, Valore EV, Territo M et al. Hepcidin, a putative mediator of anemia of inflammation, is a type II acutephase protein. Blood. 2003 Apr 1;101 (7):2461–3.
  9. Ganz T. Hepcidin in iron metabolism. Curr Opin Hematol. 2004 Jul;11 (4):251–4.
  10. Krause A, Nietz S, Magert H et al. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett. 2000 Sep 1;480 (2-3):147–50.
  11. Swinkels D, Girelli D, Laarakkers C et al. Advances in quantitative hepcidin measurements by time-of-flight mass spectrometry. PLoS One. 2008 Jul 16;3 (7):e2706.
  12. Ganz T. Hepcidin, a key regular of iron metabolism and mediator of anemia of inflammation. Blood. 2003 Aug 1;102 (3):783–8.
  13. Nicolas G, BennounM, Devaux L et al. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci U S A. 2001 Jul 17;98 (15):8780–5.
  14. Pigeon C, Ilyin G, Coursel et al. A new mouse liver:specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem. 2001 Mar 16;276 (11):7811–9.
  15. Roetto A, Papanikolaou G, Politou M et al. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet. 2003 Jan;33 (1):21–2.
  16. Nemeth E, Tuttle M, Powelson J et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004 Dec 17;306 (5704):2090–3.
  17. Young B, Zaritsky J. Hepcidin for clinicians. Clin J Am Soc Nephrol. 2009 Aug;4 (8):1384–7.
  18. Finch C. Regulators of iron balance in humans. Blood. 1994 Sep 15;84 (6):1697–702.
  19. Goswami T, Andrews N. Hereditary hemochromatosis protein,HFE, interaction with transferring receptor 2 suggests a molecular mechanism for mammalian iron sensing. J Biol Chem. 2006 Sep 29;281 (39):28494–8.
  20. Hunter HN1, Fulton DB, Ganz T, Vogel HJ. The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis. J Biol Chem. 2002 Oct 4;277 (40):37597–603.
  21. Kemna E, Pickkers P, Nemeth E et al. Time course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood. 2005 Sep 1;106 (5):1864–6.
  22. Nemeth E, Rivera S, Gabayan V et al. IL 6 mediates hypoferremia in inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004 May;113 (9):1271–6.
  23. Wrighting D, Andrews N. Interleukin 6 induces hepcidin expression through STAT3. Blood. 2006 Nov 1;108 (9):3204–9.
  24. Means RT Jr, Krantz SB. Inhibition of human erythroid colony:forming units by gamma interferon can be corrected by recombinant human erythropoietin. Blood. 1991 Nov 15;78 (10):2564–7.
  25. Jelkmann W. Proin flammatory cytokines lowering erythropoietin Production. J Interferon Cytokine Res. 1998 Aug;18 (8):555–9.
  26. Nicolasа G, Chauvet C, Viatte L et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest. 2002 Oct;110 (7):1037–44.
  27. Nicolas G, Viatte L, Bennoun M et al. Hepcidin, a new iron regulatory peptide. Blood Cells Mol Dis. 2002 Nov-Dec;29 (3):327–35.
  28. Pak M, Lopez M, Gabayan V et al. Suppression of hepcidin during anemia requires erythropoietic activity. Blood. 2006 Dec 1;108 (12):3730–5.
  29. Патрушева Ю. С., Куличенко Т. В. Гепцидин: основной регулятор обмена железа и новый диагностический маркер. Журнал вопросы диагностики в педиатрии. 2009;1 (1):18–24.
  30. Fleming RE, Sly WS. Ferroprotein mutation in autosomal dominant hemochromatosis: loss of function, gain in understanding. J Clin Invest. 2001 Aug;108 (4):521–2.
  31. Nicolas G, Weinstein DA, Nemeth EС et al. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci U S A. 2002 Apr 2;99 (7):4596–601.
  32. Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: in sights from a cohort of 12065 patients with new-onset heart failure. Circulation. 2003 Jan 21;107 (2):223–5.
  33. Левина А. А., Казюкова Т. В., Цветаева Н. В. и др. Гепсидин как регулятор гомеостаза железа. Педиатрия. 2008;87 (1):67–74.
  34. Horwich TB, Fonarow GC, Hamilton MA et al. 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. 2002 Jun 5;39 (11):1780–6.
  35. Mancini DM, Katz SD, Lang CC et al. Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure. Circulation. 2003 Jan 21;107 (2):294–9.
  36. Besarab A, Hörl WH, Silverberg D. Iron metabolism, iron deficiency, thrombocytosis, and the cardiorenal anemia syndrome. Oncologist. 2009;14 (Suppl 1):22–33.
  37. Van der Putten K, Jie K. E, van den Broek D et al. Hepcidin-25 is a marker of the response rather than resistance to exogenous erythropoietin in chronic kidney disease chronic heart failure patients. Eur J Heart Fail. 2010 Sep;12 (9):943–50.
  38. Martínez-Ruiz A, Tornel-Osorio PL, Sánchez-Más J et al. Soluble TNFα receptor type I and hepcidin as determinants of development of anemia in the long-term follow-up of heart failure patients. Clin Biochem. 2012 Nov;45 (16-17):1455–8.
  39. Divakaran V, Mehta S, Yao D, Hassan S et al. Hepcidin in anemia of chronic heart failure. Am J Hematol. 2011 Jan;86 (1):107–9.
  40. Matsumoto M, Tsujino T, Lee-Kawabata M et al. Iron regulatory hormone hepcidin decreases in chronic heart failure patients with anemia. Circ J. 2010 Feb;74 (2):301–6.
  41. Напалков Д. А, Панферов А. С, Головенко Е. Н. Особенности обмена железа у пациентов с хронической сердечной недостаточностью. Кардиология и сердечно-сосудистая хирургия: науч.‑практ. журнал. 2009;2 (6):65–69.
Solomakhina N. I., Nakhodnova E. S., Ershov V. I. Anemia in chronic heart failure: Role of hepcidin as a universal regulator of iron metabolism. Russian Heart Failure Journal. 2014;85 (4):254–260

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