Hepcidin in human iron disorders: Diagnostic implications

Clinical Chemistry

Volumn 57, Issue 12, 2011, Pages 1650-1669

  Kroot, Joyce J C ^a   Tjalsma, Harold ^a   Fleming, Robert E ^b   Swinkels, Dorine W ^a  

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^b SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN 2; BONE MORPHOGENETIC PROTEIN 6; C REACTIVE PROTEIN; CD71 ANTIGEN; ERYTHROPOIETIN; FERRITIN; FERROPORTIN; HEMOGLOBIN; HEPCIDIN; HYPOXIA INDUCIBLE FACTOR; INTERLEUKIN 6; IRON; JANUS KINASE; MITOGEN ACTIVATED PROTEIN KINASE; MONOCYTE CHEMOTACTIC PROTEIN 1; RECOMBINANT GROWTH FACTOR; RECOMBINANT OSTEOGENIC PROTEIN 6; SMAD PROTEIN; STAT3 PROTEIN; TOCILIZUMAB; UNCLASSIFIED DRUG;

ANEMIA; ANGIOFOLLICULAR LYMPH NODE HYPERPLASIA; ANTIBODY SPECIFICITY; AUTOCRINE EFFECT; BETA THALASSEMIA; BLOOD VESSEL INJURY; CARDIOVASCULAR RISK; CELL CULTURE; CHRONIC KIDNEY DISEASE; CLINICAL PRACTICE; CONGENITAL DYSERYTHROPOIETIC ANEMIA TYPE 1; CONGENITAL DYSERYTHROPOIETIC ANEMIA TYPE 2; CORONARY ARTERY BYPASS SURGERY; DIAGNOSTIC ACCURACY; DIAGNOSTIC VALUE; DIFFERENTIAL DIAGNOSIS; DISEASE ASSOCIATION; DISEASE SEVERITY; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME LINKED IMMUNOSORBENT ASSAY; ERYTHROPOIESIS; FERRITIN BLOOD LEVEL; GLOMERULUS FILTRATION; HEART FAILURE; HEART INFARCTION; HELICOBACTER INFECTION; HEMOCHROMATOSIS; HEMODIALYSIS; HEPATITIS C VIRUS; HODGKIN DISEASE; HOST RESISTANCE; HUMAN; HYPOXIA; IMMUNE RESPONSE; IMMUNOASSAY; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; INTESTINE CELL; IRON ABSORPTION; IRON BLOOD LEVEL; IRON DEFICIENCY; IRON DEFICIENCY ANEMIA; IRON DEPLETION; IRON METABOLISM; IRON OVERLOAD; IRON RESTRICTION; IRON STORAGE; IRON THERAPY; IRON TRANSPORT; KIDNEY INJURY; KINETICS; LIVER CELL; LUPUS ERYTHEMATOSUS NEPHRITIS; MACROPHAGE; MALARIA; MASS SPECTROMETRY; METABOLIC SYNDROME X; METAL BINDING; MYELODYSPLASTIC SYNDROME; NONHUMAN; OBESITY; PHAGOSOME; PREMENOPAUSE; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN MOTIF; PROTEIN STRUCTURE; PROTEIN SYNTHESIS; REFRACTORY ANEMIA; REVIEW; SIGNAL TRANSDUCTION; SPORTS MEDICINE; TRANSFERRIN BLOOD LEVEL; TREATMENT DURATION; TREATMENT RESPONSE; ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY; URINE LEVEL;

ANIMALS; ANOXIA; ANTIMICROBIAL CATIONIC PEPTIDES; BIOLOGICAL MARKERS; ERYTHROPOIESIS; HUMANS; INFLAMMATION; IRON; IRON METABOLISM DISORDERS; MOLECULAR TARGETED THERAPY; PROTEIN CONFORMATION; REFERENCE VALUES;

EID: 82755195789     PISSN: 00099147     EISSN: 15308561     Source Type: Journal    
DOI: 10.1373/clinchem.2009.140053     Document Type: Review

References (224)

1. Krause A, Neitz S, Magert HJ, Schulz A, Forssmann WG, Schulz-Knappe P, Adermann K. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett 2000;480:147-50.
2. Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, Loreal O. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 2001;276:7811-9.
3. Jordan JB, Poppe L, Haniu M, Arvedson T, Syed R, Li V, et al. Hepcidin revisited, disulfide connectivity, dynamics, and structure. J Biol Chem 2009;284:24155-67.
4. Farnaud S, Patel A, Evans RW. Modelling of a metal-containing hepcidin. Biometals 2006;19:527-33. (Pubitemid 44291046)
5. Farnaud S, Rapisarda C, Bui T, Drake A, Cammack R, Evans RW. Identification of an iron-hepcidin complex. Biochem J 2008;413:553-7.
6. Gerardi G, Biasiotto G, Santambrogio P, Zanella I, Ingrassia R, Corrado M, et al. Recombinant human hepcidin expressed in Escherichia coli isolates as an iron containing protein. Blood Cells Mol Dis 2005;35:177-81. (Pubitemid 41267047)
7. Melino S, Garlando L, Patamia M, Paci M, Petruzzelli R. A metal-binding site is present in the amino terminal region of the bioactive iron regulator hepcidin-25. J Pept Res 2005;66:65-71.
8. Tselepis C, Ford SJ, McKie AT, Vogel W, Zoller H, Simpson RJ, et al. Characterization of the transition-metal-binding properties of hepcidin. Biochem J 2010;427:289-96.
9. Schranz M, Bakry R, Creus M, Bonn G, Vogel W, Zoller H. Activation and inactivation of the iron hormone hepcidin: biochemical characterization of prohepcidin cleavage and sequential degradation to N-terminally truncated hepcidin isoforms. Blood Cells Mol Dis 2009;43:169-79.
10. Valore EV, Ganz T. Posttranslational processing of hepcidin in human hepatocytes is mediated by the prohormone convertase furin. Blood Cells Mol Dis 2008;40:132-8. (Pubitemid 350192311)
11. Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 2001;276:7806-10.
12. Kemna EH, Tjalsma H, Podust VN, Swinkels DW. Mass spectrometry-based hepcidin measurements in serum and urine: analytical aspects and clinical implications. Clin Chem 2007;53:620-8. (Pubitemid 46580231)
13. Kroot JJC, Laarakkers CM, Geurts-Moespot AJ, Grebenchtchikov N, Pickkers P, van Ede AE, et al. Immunochemical and mass-spectrometry-based serum hepcidin assays for iron metabolism disorders. Clin Chem 2010;56:1570-9.
14. Suzuki H, Toba K, Kato K, Ozawa T, Tomosugi N, Higuchi M, et al. Serum hepcidin-20 is elevated during the acute phase of myocardial infarction. Tohoku J Exp Med 2009;218:93-8.
15. Tomosugi N, Kawabata H, Wakatabe R, Higuchi M, Yamaya H, Umehara H, Ishikawa I. Detection of serum hepcidin in renal failure and inflammation by using ProteinChip System. Blood 2006;108:1381-7. (Pubitemid 44232041)
16. Peters HP, Laarakkers CM, Swinkels DW, Wetzels JF. Serum hepcidin-25 levels in patients with chronic kidney disease are independent of glomerular filtration rate. Nephrol Dial Transplant 2010;25:848-53.
17. Tessitore N, Girelli D, Campostrini N, Bedogna V, Pietro SG, Castagna A, et al. Hepcidin is not useful as a biomarker for iron needs in haemodialysis patients on maintenance erythropoiesis-stimulating agents. Nephrol Dial Transplant 2010;25:3996-4002.
18. Rivera S, Nemeth E, Gabayan V, Lopez MA, Farshidi D, Ganz T. Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs. Blood 2005;106:2196-9. (Pubitemid 41291740)
19. Nemeth E, Preza GC, Jung CL, Kaplan J, Waring AJ, Ganz T. The N-terminus of hepcidin is essential for its interaction with ferroportin: structure-function study. Blood 2006;107:328-33. (Pubitemid 43053559)
20. Peyssonnaux C, Zinkernagel AS, Datta V, Lauth X, Johnson RS, Nizet V. TLR4-dependent hepcidin expression by myeloid cells in response to bacterial pathogens. Blood 2006;107:3727-32.
21. Bekri S, Gual P, Anty R, Luciani N, Dahman M, Ramesh B, et al. Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterology 2006;131:788-96. (Pubitemid 44316823)
22. Nguyen NB, Callaghan KD, Ghio AJ, Haile DJ, Yang F. Hepcidin expression and iron transport in alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 2006;291:L417-25. (Pubitemid 44343718)
23. Merle U, Fein E, Gehrke SG, Stremmel W, Kulaksiz H. The iron regulatory peptide hepcidin is expressed in the heart and regulated by hypoxia and inflammation. Endocrinology 2007;148:2663-8. (Pubitemid 46984791)
24. Kulaksiz H, Fein E, Redecker P, Stremmel W, Adler G, Cetin Y. Pancreatic beta-cells express hepcidin, an iron-uptake regulatory peptide. J Endocrinol 2008;197:241-9. (Pubitemid 351696237)
25. Kulaksiz H, Theilig F, Bachmann S, Gehrke SG, Rost D, Janetzko A, et al. The iron-regulatory peptide hormone hepcidin: expression and cellular localization in the mammalian kidney. J Endocrinol 2005;184:361-70. (Pubitemid 40340171)
26. Gnana-Prakasam JP, Martin PM, Mysona BA, Roon P, Smith SB, Ganapathy V. Hepcidin expression in mouse retina and its regulation via lipopolysaccharide/ Toll-like receptor-4 pathway independent of Hfe. Biochem J 2008;411:79-88. (Pubitemid 351482349)
27. Isoda M, Hanawa H, Watanabe R, Yoshida T, Toba K, Yoshida K, et al. Expression of the peptide hormone hepcidin increases in cardiomyocytes under myocarditis and myocardial infarction. J Nutr Biochem 2010;21:749-56.
28. Peslova G, Petrak J, Kuzelova K, Hrdy I, Halada P, Kuchel PW, et al. Hepcidin, the hormone of iron metabolism, is bound specifically to alpha-2-macroglobulin in blood. Blood 2009;113:6225-36.
29. Ganz T, Olbina G, Girelli D, Nemeth E, Westerman M. Immunoassay for human serum hepcidin. Blood 2008;112:4292-7.
30. Swinkels DW, Girelli D, Laarakkers C, Kroot J, Campostrini N, Kemna EH, Tjalsma H. Advances in quantitative hepcidin measurements by time-of-flight mass spectrometry. PLoS ONE 2008;3:e2706.
31. Ashby DR, Gale DP, Busbridge M, Murphy KG, Duncan ND, Cairns TD, et al. Plasma hepcidin levels are elevated but responsive to erythropoietin therapy in renal disease. Kidney Int 2009;75:976-81.
32. Costa E, Swinkels DW, Laarakkers CM, Rocha-Pereira P, Rocha S, Reis F. et al. Hepcidin serum levels and resistance to recombinant human erythropoietin therapy in haemodialysis patients. Acta Haematol 2009;122:226-9.
33. Sumboonnanonda A, Malasit P, Tanphaichitr VS, Ong-ajyooth S, Sunthornchart S, Pattanakitsakul S. et al. Renal tubular function in beta-thalassemia. Pediatr Nephrol 1998;12:280-3.
34. Wan L, Bellomo R, Di GD, Ronco C. The pathogenesis of septic acute renal failure. Curr Opin Crit Care 2003;9:496-502. (Pubitemid 37518649)
35. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM. et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004;306:2090-3. (Pubitemid 40007660)
36. De Domenico I, Ward DM, Nemeth E, Vaughn MB, Musci G, Ganz T, Kaplan J. The molecular basis of ferroportin-linked hemochromatosis. Proc Natl Acad Sci U S A 2005;102:8955-60. (Pubitemid 40881060)
37. Delaby C, Pilard N, Goncalves AS, Beaumont C, Canonne-Hergaux F. The presence of the iron exporter ferroportin at the plasma membrane of macrophages is enhanced by iron loading and downregulated by hepcidin. Blood 2005;106:3979-84. (Pubitemid 41739041)
38. Ramey G, Deschemin JC, Durel B, Canonne-Hergaux F, Nicolas G, Vaulont S. Hepcidin targets ferroportin for degradation in hepatocytes. Haematologica 2010;95:501-4.
39. Sow FB, Florence WC, Satoskar AR, Schlesinger LS, Zwilling BS, Lafuse WP. Expression and localization of hepcidin in macrophages: a role in host defense against tuberculosis. J Leukoc Biol 2007;82:934-45. (Pubitemid 47511054)
40. De Domenico I, Zhang TY, Koening CL, Branch RW, London N, Lo E, et al. Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice. J Clin Invest 2010;120:2395-405.
41. Theurl I, Theurl M, Seifert M, Mair S, Nairz M, Rumpold H, et al. Autocrine formation of hepcidin induces iron retention in human monocytes. Blood 2008;111:2392-9. (Pubitemid 351451452)
42. Keel SB, Abkowitz JL. The microcytic red cell and the anemia of inflammation. N Engl J Med 2009;361:1904-6.
43. De Domenico I, Nemeth E, Nelson JM, Phillips JD, Ajioka RS, Kay MS, et al. The hepcidin-binding site on ferroportin is evolutionarily conserved. Cell Metab 2008;8:146-56.
44. Hentze MW, Muckenthaler MU, Galy B, Camaschella C. Two to tango: regulation of Mammalian iron metabolism. Cell 2010;142:24-38.
45. Ramos E, Kautz L, Rodriguez R, Hansen M, Gabayan V, Ginzburg Y, et al. Evidence for distinct pathways of hepcidin regulation by acute and chronic iron loading in mice. Hepatology 2011;53:1333-41.
46. Corradini E, Meynard D, Wu Q, Chen S, Ventura P, Pietrangelo A, Babitt JL. Serum and liver iron differently regulate the bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway in mice. Hepatology 2011;54:273-84.
47. Babitt JL, Huang FW, Wrighting DM, Xia Y, Sidis Y, Samad TA, et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet 2006;38:531-9.
48. Finberg KE, Whittlesey RL, Fleming MD, Andrews NC. Down-regulation of Bmp/Smad signaling by Tmprss6 is required for maintenance of systemic iron homeostasis. Blood 2010;115:3817-26.
49. Silvestri L, Pagani A, Nai A, De D, I, Kaplan J, Camaschella C. The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab 2008;8:502-11.
50. Nicolas G, Viatte L, Bennoun M, Beaumont C, Kahn A, Vaulont S. Hepcidin, a new iron regulatory peptide. Blood Cells Mol Dis 2002;29:327-35.
51. Pinto JP, Ribeiro S, Pontes H, Thowfeequ S, Tosh D, Carvalho F, Porto G. Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C/EBPalpha. Blood 2008;111:5727-33.
52. Ashby DR, Gale DP, Busbridge M, Murphy KG, Duncan ND, Cairns TD, et al. Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin. Haematologica 2010;95:505-8.
53. Vokurka M, Krijt J, Sulc K, Necas E. Hepcidin mRNA levels in mouse liver respond to inhibition of erythropoiesis. Physiol Res 2006;55:667-74. (Pubitemid 46021227)
54. Pak M, Lopez MA, Gabayan V, Ganz T, Rivera S. Suppression of hepcidin during anemia requires erythropoietic activity. Blood 2006;108:3730-5. (Pubitemid 44864551)
55. Tanno T, Bhanu NV, Oneal PA, Goh SH, Staker P, Lee YT, et al. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med 2007;13:1096-101. (Pubitemid 47517510)
56. Tanno T, Porayette P, Sripichai O, Noh SJ, Byrnes C, Bhupatiraju A, et al. Identification of TWSG1 as a second novel erythroid regulator of hepcidin expression in murine and human cells. Blood 2009;114:181-6.
57. Chou ST, Weiss MJ. Diseased red blood cells topple iron balance. Nat Med 2007;13:1020-1. (Pubitemid 47517495)
58. Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I, et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 2002;110:1037-44.
59. Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 2004;113:1271-6. (Pubitemid 39069926)
60. Peyssonnaux C, Zinkernagel AS, Schuepbach RA, Rankin E, Vaulont S, Haase VH, et al. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J Clin Invest 2007;117:1926-32. (Pubitemid 47036326)
61. Silvestri L, Pagani A, Camaschella C. Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis. Blood 2008;111:924-31.
62. Lakhal S, Schoedel J, Townsend AR, Pugh CW, Ratcliffe PJ, Mole DR. Regulation of type II transmembrane serine proteinase TMPRSS6 by hypoxia-inducible factors: new link between hypoxia signalling and iron homeostasis. J Biol Chem 2011;286:4090-7.
63. Mastrogiannaki M, Matak P, Keith B, Simon MC, Vaulont S, Peyssonnaux C. HIF-2alpha, but not HIF-1alpha, promotes iron absorption in mice. J Clin Invest 2009;119:1159-66.
64. Wrighting DM, Andrews NC. Interleukin-6 induces hepcidin expression through STAT3. Blood 2006;108:3204-9.
65. Verga Falzacappa MV, Vujic SM, Kessler R, Stolte J, Hentze MW, Muckenthaler MU. STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation. Blood 2007;109:353-8. (Pubitemid 46053077)
66. Pietrangelo A, Dierssen U, Valli L, Garuti C, Rump A, Corradini E, et al. STAT3 is required for IL-6-gp130-dependent activation of hepcidin in vivo. Gastroenterology 2007;132:294-300. (Pubitemid 46108739)
67. Vecchi C, Montosi G, Zhang K, Lamberti I, Duncan SA, Kaufman RJ, Pietrangelo A. ER stress controls iron metabolism through induction of hepcidin. Science 2009;325:877-80.
68. Oliveira SJ, Pinto JP, Picarote G, Costa VM, Carvalho F, Rangel M, et al. ER stress-inducible factor CHOP affects the expression of hepcidin by modulating C/EBPalpha activity. PLoS ONE 2009;4:e6618.
69. Bridle K, Cheung TK, Murphy T, Walters M, Anderson G, Crawford DG, Fletcher LM. Hepcidin is down-regulated in alcoholic liver injury: implications for the pathogenesis of alcoholic liver disease. Alcohol Clin Exp Res 2006;30:106-12. (Pubitemid 43341402)
70. Harrison-Findik DD. Role of alcohol in the regulation of iron metabolism. World J Gastroenterol 2007;13:4925-30. (Pubitemid 47496823)
71. Kemna EH, Kartikasari AE, van Tits LJ, Pickkers P, Tjalsma H, Swinkels DW. Regulation of hepcidin: Insights from biochemical analyses on human serum samples. Blood Cells Mol Dis 2008;40:339-46. (Pubitemid 351508446)
72. Lasocki S, Millot S, Andrieu V, Letteron P, Pilard N, Muzeau F, et al. Phlebotomies or erythropoietin injections allow mobilization of iron stores in a mouse model mimicking intensive care anemia. Crit Care Med 2008;36:2388-94.
73. Huang H, Constante M, Layoun A, Santos MM. Contribution of STAT3 and SMAD4 pathways to the regulation of hepcidin by opposing stimuli. Blood 2009;113:3593-9.
74. Darshan D, Frazer DM, Wilkins SJ, Anderson GJ. Severe iron deficiency blunts the response of the iron regulatory gene Hamp and proinflammatory cytokines to lipopolysaccharide. Haematologica 2010;95:1660-7.
75. Theurl I, Aigner E, Theurl M, Nairz M, Seifert M, Schroll A, et al. Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications. Blood 2009;113:5277-86.
76. Roy CN, Custodio AO, de Graaf J, Schneider S, Akpan I, Montross LK, et al. An Hfe-dependent pathway mediates hyposideremia in response to lipopolysaccharide-induced inflammation in mice. Nat Genet 2004;36:481-5. (Pubitemid 38620032)
77. Constante M, Jiang W, Wang D, Raymond VA, Bilodeau M, Santos MM. Distinct requirements for Hfe in basal and induced hepcidin levels in iron overload and inflammation. Am J Physiol Gastrointest Liver Physiol 2006;291:G229-37. (Pubitemid 44024682)
78. van Deuren M, Kroot JJ, Swinkels DW. Time-course analysis of serum hepcidin, iron and cytokines in a C282Y homozygous patient with Schnitzler's syndrome treated with IL-1 receptor antagonist. Haematologica 2009;94:1297-300.
79. Hunter HN, 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;277:37597-603.
80. Kulaksiz H, Gehrke SG, Janetzko A, Rost D, Bruckner T, Kallinowski B, Stremmel W. Prohepcidin: expression and cell specific localisation in the liver and its regulation in hereditary haemochromatosis, chronic renal insufficiency, and renal anaemia. Gut 2004;53:735-43. (Pubitemid 38561454)
81. Kemna E, Pickkers P, Nemeth E, van der Hoeven H, Swinkels D. Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood 2005;106:1864-6. (Pubitemid 41208606)
82. Brookes MJ, Sharma NK, Tselepis C, Iqbal TH. Serum pro-hepcidin: measuring active hepcidin or a non-functional precursor? Gut 2005;54:169-70. (Pubitemid 40007239)
83. Roe MA, Spinks C, Heath AL, Harvey LJ, Foxall R, Wimperis J, et al. Serum prohepcidin concentration: no association with iron absorption in healthy men; and no relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients undergoing phlebotomy treatment, or pregnant women. Br J Nutr 2007;97:544-9. (Pubitemid 46662045)
84. Kemna E, Tjalsma H, Laarakkers C, Nemeth E, Willems H, Swinkels D. Novel urine hepcidin assay by mass spectrometry. Blood 2005;106:3268-70. (Pubitemid 41565929)
85. Murphy AT, Witcher DR, Luan P, Wroblewski VJ. Quantitation of hepcidin from human and mouse serum using liquid chromatography tandem mass spectrometry. Blood 2007;110:1048-54. (Pubitemid 47267447)
86. Murao N, Ishigai M, Yasuno H, Shimonaka Y, Aso Y. Simple and sensitive quantification of bioactive peptides in biological matrices using liquid chromatography/selected reaction monitoring mass spectrometry coupled with trichloroacetic acid clean-up. Rapid Commun Mass Spectrom 2007;21:4033-8.
87. Kobold U, Dulffer T, Dangl M, Escherich A, Kubbies M, Roddiger R, Wright JA. Quantification of hepcidin-25 in human serum by isotope dilution micro-HPLC-tandem mass spectrometry. Clin Chem 2008;54:1584-6.
88. Bansal SS, Abbate V, Bomford A, Halket JM, Macdougall IC, Thein SL, Hider RC. Quantitation of hepcidin in serum using ultra-high-pressure liquid chromatography and a linear ion trap mass spectrometer. Rapid Commun Mass Spectrom 2010;24:1251-9.
89. Li H, Rose MJ, Tran L, Zhang J, Miranda LP, James CA, Sasu BJ. Development of a method for the sensitive and quantitative determination of hepcidin in human serum using LC-MS/MS. J Pharmacol Toxicol Methods 2009;59:171-80.
90. Campostrini N, Castagna A, Zaninotto F, Bedogna V, Tessitore N, Poli A, et al. Evaluation of hepcidin isoforms in hemodialysis patients by a proteomic approach based on SELDI-TOF MS. J Biomed Biotechnol 2010;2010:329646.
91. Anderson DS, Heeney MM, Roth U, Menzel C, Fleming MD, Steen H. High-throughput matrix-assisted laser desorption ionization-time-of-flight mass spectrometry method for quantification of hepcidin in human urine. Anal Chem 2010;82:1551-5.
92. Crockett DK, Kushnir MM, Phillips JD, Rockwood AL. Time-of-flight mass spectrometry analysis of the ferroportin-hepcidin binding domain complex for accurate mass confirmation of bioactive hepcidin 25. Clin Chim Acta 2010;411:453-5.
93. Bansal SS, Halket JM, Bomford A, Simpson RJ, Vasavda N, Thein SL, Hider RC. Quantitation of hepcidin in human urine by liquid chromatography-mass spectrometry. Anal Biochem 2008;384:245-53.
94. Altamura S, Kiss J, Blattmann C, Gilles W, Muckenthaler MU. SELDI-TOF MS detection of urinary hepcidin. Biochimie 2009;91:1335-8.
95. Ward DG, Roberts K, Stonelake P, Goon P, Zampronio CG, Martin A, et al. SELDI-TOF-MS determination of hepcidin in clinical samples using stable isotope labelled hepcidin as an internal standard. Proteome Sci 2008;6:28.
96. Busbridge M, Griffiths C, Ashby D, Gale D, Jayantha A, Sanwaiya A, Chapman RS. Development of a novel immunoassay for the iron regulatory peptide hepcidin. Br J Biomed Sci 2009;66:150-7.
97. Grebenchtchikov N, Geurts-Moespot AJ, Kroot JJ, den Heijer M, Tjalsma H, Swinkels DW, Sweep FG. High-sensitive radioimmunoassay for human serum hepcidin. Br J Haematol 2009;146:317-25.
98. Koliaraki V, Marinou M, Vassilakopoulos TP, Vavourakis E, Tsochatzis E, Pangalis GA, et al. A novel immunological assay for hepcidin quantification in human serum. Plos One 2009;4:e4581.
99. Schwarz P, Strnad P, von FG, Janetzko A, Krayenbuhl P, Adler G, Kulaksiz H. A novel monoclonal antibody immunoassay for the detection of human serum hepcidin. J Gastroenterol 2011;46:648-56.
100. Butterfield AM, Luan P, Witcher DR, Manetta J, Murphy AT, Wroblewski VJ, Konrad RJ. A dual-monoclonal sandwich ELISA specific for hepcidin-25. Clin Chem 2010;56:1725-32.
101. Kiernan UA, Tubbs KA, Gruber K, Nedelkov D, Niederkofler EE, Williams P, Nelson RW. High-throughput protein characterization using mass spectrometric immunoassay. Anal Biochem 2002;301:49-56. (Pubitemid 34113677)
102. Nicolardi S, Palmblad M, Dalebout H, Bladergroen M, Tollenaar RA, Deelder AM, van der Burgt YE. Quality control based on isotopic distributions for high-throughput MALDI-TOF and MALDI-FTICR serum peptide profiling. J Am Soc Mass Spectrom 2010;21:1515-25.
103. Bruns DE. The STARD initiative and the reporting of studies of diagnostic accuracy. Clin Chem 2003;49:19-20. (Pubitemid 36078548)
104. ICH Steering Committee. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use: ICH harmonised tripartite guideline text on validation of analytical procedures. http://www.ikev.org/haber/stabilite/cd/08%201.7%20ICH%20Q2A%20for%20CD.pdf (Accessed June 2011).
105. Kroot JJ, Kemna EH, Bansal SS, Busbridge M, Campostrini N, Girelli D, et al. Results of the first international round robin for the quantification of urinary and plasma hepcidin assays: need for standardization. Haematologica 2009;94:1748-52.
106. Forest JC, Burtis CA. Development of reference methods and reference materials. http://www.ifcc.org/index.asp?cat=Publications&scat=eJIFCC- &suba=Vol-13-No-3&subx=Development-Of-Reference-Methods-And-Reference- Materials-by-Jean-Claude-Forest-Carl-A-Burtis&zip=&dove=1&zona= full&numero=&aq=1 (Accessed October 2011).
107. Kroot JJ, Hendriks JC, Laarakkers CM, Klaver SM, Kemna EH, Tjalsma H, Swinkels DW. (Pre) analytical imprecision, between-subject variability, and daily variations in serum and urine hepcidin: implications for clinical studies. Anal Biochem 2009;389:124-9.
108. Zhang X, Jin M, Wu H, Nadasdy T, Nadasdy G, Harris N, et al. Biomarkers of lupus nephritis determined by serial urine proteomics. Kidney Int 2008;74:799-807.
109. Galesloot TE, Vermeulen SH, Geurts-Moespot AJ, Klaver SM, Kroot JJ, van Tienoven D, et al. Serum hepcidin: reference ranges and biochemical correlates in the general population. Blood 2011;117:e218-25.
110. Bayele HK, McArdle H, Srai SK. Cis and trans regulation of hepcidin expression by upstream stimulatory factor. Blood 2006;108:4237-45. (Pubitemid 44913299)
111. Bozzini C, Campostrini N, Trombini P, Nemeth E, Castagna A, Tenuti I, et al. Measurement of urinary hepcidin levels by SELDI-TOF-MS in HFE-hemochromatosis. Blood Cells Mol Dis 2008;40:347-52.
112. Roe MA, Collings R, Dainty JR, Swinkels DW, Fairweather-Tait SJ. Plasma hepcidin concentrations significantly predict interindividual variation in iron absorption in healthy men. Am J Clin Nutr 2009;89:1088-91.
113. Semrin G, Fishman DS, Bousvaros A, Zholudev A, Saunders AC, Correia CE, et al. Impaired intestinal iron absorption in Crohn's disease correlates with disease activity and markers of inflammation. Inflamm Bowel Dis 2006;12:1101-6. (Pubitemid 44847466)
114. Rehu M, Punnonen K, Ostland V, Heinonen S, Westerman M, Pulkki K, Sankilampi U. Maternal serum hepcidin is low at term and independent of cord blood iron status. Eur J Haematol 2010;85:345-52.
115. de Mast Q, Syafruddin D, Keijmel S, Olde RT, Deky O, Asih PB, et al. Increased serum hepcidin and alterations in blood iron parameters associated with asymptomatic P. falciparum and P. vivax malaria. Haematologica 2010;95:1068-74.
116. del Giudice EM, Santoro N, Amato A, Brienza C, Calabro P, Wiegerinck ET, et al. Hepcidin in obese children as a potential mediator of the association between obesity and iron deficiency. J Clin Endocrinol Metab 2009;94:5102-7.
117. Aeberli I, Hurrell RF, Zimmermann MB. Overweight children have higher circulating hepcidin concentrations and lower iron status but have dietary iron intakes and bioavailability comparable with normal weight children. Int J Obes 2009;33:1111-7.
118. Cherian S, Forbes DA, Cook AG, Sanfilippo FM, Kemna EH, Swinkels DW, Burgner DP. An insight into the relationships between hepcidin, anemia, infections and inflammatory cytokines in pediatric refugees: a cross-sectional study. Plos One 2008;3:e4030.
119. Altamura S, D'Alessio F, Selle B, Muckenthaler MU. A novel TMPRSS6 mutation that prevents protease auto-activation causes IRIDA. Biochem J 2010;431:363-71.
120. Tchou I, Diepold M, Pilotto PA, Swinkels D, Neerman-Arbez M, Beris P. Haematologic data, iron parameters and molecular findings in two new cases of iron-refractory iron deficiency anaemia. Eur J Haematol 2009;83:595-602.
121. Van Santen S, de Mast Q, Luty AJ, Wiegerinck ET, van der Ven A, Swinkels DW. Iron homeostasis in mother and child during placental malaria infection. Am J Trop Med Hyg 2011;84:148-51.
122. van Bokhoven MA, van Deursen CT, Swinkels DW. Diagnosis and management of hereditary haemochromatosis. BMJ 2011;342:c7251.
123. Swinkels DW, Janssen MC, Bergmans J, Marx JJ. Hereditary hemochromatosis: genetic complexity and new diagnostic approaches. Clin Chem 2006;52:950-68. (Pubitemid 43794403)
124. Lee PL, Beutler E. Regulation of hepcidin and iron-overload disease. Annu Rev Pathol 2009;4:489-515.
125. van Dijk BA, Laarakkers CM, Klaver SM, Jacobs EM, van Tits LJ, Janssen MC, Swinkels DW. Serum hepcidin levels are innately low in HFE-related haemochromatosis but differ between C282Y-homozygotes with elevated and normal ferritin levels. Br J Haematol 2008;142:979-85.
126. Piperno A, Girelli D, Nemeth E, Trombini P, Bozzini C, Poggiali E, et al. Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis. Blood 2007;110:4096-100. (Pubitemid 350248467)
127. Papanikolaou G, Tzilianos M, Christakis JI, Bogdanos D, Tsimirika K, MacFarlane J, et al. Hepcidin in iron overload disorders. Blood 2005;105:4103-5. (Pubitemid 40656161)
128. Sham RL, Phatak PD, Nemeth E, Ganz T. Hereditary hemochromatosis due to resistance to hepcidin: high hepcidin concentrations in a family with C326S ferroportin mutation. Blood 2009;114:493-4.
129. Drakesmith H, Schimanski LM, Ormerod E, Merryweather-Clarke AT, Viprakasit V, Edwards JP, et al. Resistance to hepcidin is conferred by hemochromatosis-associated mutations of ferroportin. Blood 2005;106:1092-7. (Pubitemid 41076459)
130. Mayr R, Janecke AR, Schranz M, Griffiths WJ, Vogel W, Pietrangelo A, Zoller H. Ferroportin disease: a systematic meta-analysis of clinical and molecular findings. J Hepatol 2010;53:941-9.
131. Wijngaarden P, Hoskam J, Koeken A, Boer JMA, Swinkels DW, Ermens AAM, Cobbaert CM. Primaire hemochromatose door ferroportinegenmutaties: is er een plaats voor hepcidine in de diagnostiek? Ned Tijdschr Klin Chem Labgeneesk 2011;36:6-11.
132. Girelli D, Trombini P, Busti F, Campostrini N, Sandri M, Pelucchi S, et al. A time course of hepcidin response to iron challenge in patients with HFE and TfR2 haemochromatosis. Haematologica 2010;96:500-6.
133. Swinkels DW, Fleming RE. Novel observations in hereditary hemochromatosis: potential implications for clinical strategies. Haematologica 2011;96:485-8.
134. Kattamis A, Papassotiriou I, Palaiologou D, Apostolakou F, Galani A, Ladis V, et al. The effects of erythropoetic activity and iron burden on hepcidin expression in patients with thalassemia major. Haematologica 2006;91:809-12. (Pubitemid 44014549)
135. Gardenghi S, Marongiu MF, Ramos P, Guy E, Breda L, Chadburn A, et al. Ineffective erythropoiesis in beta-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. Blood 2007;109:5027-35. (Pubitemid 46827803)
136. Kearney SL, Nemeth E, Neufeld EJ, Thapa D, Ganz T, Weinstein DA, Cunningham MJ. Urinary hepcidin in congenital chronic anemias. Pediatr Blood Cancer 2007;48:57-63. (Pubitemid 44871594)
137. Origa R, Galanello R, Ganz T, Giagu N, Maccioni L, Faa G, Nemeth E. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica 2007;92:583-8. (Pubitemid 350144260)
138. Tamary H, Shalev H, Perez-Vraham G, Zoldan M, Levi I, Swinkels DW, et al. Elevated growth differentiation factor 15 expression in patients with congenital dyserythropoietic anemia type I. Blood 2008;112:5241-4.
139. Malcovati L, Porta MGD, Laarakkers CM, Galli A, Albertini R, Maffioli M, et al. Erythroid activity, transfusion iron overload, and hepcidin levels in patients with myelodysplastic syndrome. ASH Annu Meeting Abstracts 2008;112:2676.
140. Casanovas G, Swinkels DW, Altamura S, Schwarz K, Laarakkers CM, Gross HJ, et al. Growth differentiation factor 15 in patients with congenital dyserythropoietic anaemia (CDA) type II. J Mol Med 2011.
141. Kroot JJ, Laarakkers CM, Kemna EH, Biemond BJ, Swinkels DW. Regulation of serum hepcidin levels in sickle cell disease. Haematologica 2009;94:885-7.
142. Cuijpers ML, Raymakers RA, Mackenzie MA, de Witte TJ, Swinkels DW. Recent advances in the understanding of iron overload in sideroblastic myelodysplastic syndrome. Br J Haematol 2010;149:322-33.
143. Porter JB. Pathophysiology of transfusional iron overload: contrasting patterns in thalassemia major and sickle cell disease. Hemoglobin 2009;33(Suppl 1):S37-45.
144. Swinkels DW, Drenth JP. Hepcidin in the management of patients with mild non-hemochromatotic iron overload: fact or fiction? J Hepatol 2008;49:680-5.
145. Lin L, Valore EV, Nemeth E, Goodnough JB, Gabayan V, Ganz T. Iron transferrin regulates hepcidin synthesis in primary hepatocyte culture through hemojuvelin and BMP2/4. Blood 2007;110:2182-9. (Pubitemid 47443938)
146. Young MF, Glahn RP, riza-Nieto M, Inglis J, Olbina G, Westerman M, O'Brien KO. Serum hepcidin is significantly associated with iron absorption from food and supplemental sources in healthy young women. Am J Clin Nutr 2009;89:533-8.
147. Zimmermann MB, Troesch B, Biebinger R, Egli I, Zeder C, Hurrell RF. Plasma hepcidin is a modest predictor of dietary iron bioavailability in humans,
148. Finberg KE, Heeney MM, Campagna DR, Aydinok Y, Pearson HA, Hartman KR, et al. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet 2008;40:569-71. (Pubitemid 351601217)
149. Melis MA, Cau M, Congiu R, Sole G, Barella S, Cao A, et al. A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron. Haematologica 2008;93:1473-9.
150. Hartman KR, Barker JA. Microcytic anemia with iron malabsorption: an inherited disorder of iron metabolism. Am J Hematol 1996;51:269-75. (Pubitemid 26116367)
151. Beutler E, Van GC, te Loo DM, Gelbart T, Crain K, Truksa J, Lee PL. Polymorphisms and mutations of human TMPRSS6 in iron deficiency anemia. Blood Cells Mol Dis 2010;44:16-21.
152. Oppenheimer SJ. Iron and its relation to immunity and infectious disease. J Nutr 2001;131:616S-33S.
153. de Mast Q, Nadjm B, Reyburn H, Kemna EH, Amos B, Laarakkers CM, et al. Assessment of urinary concentrations of hepcidin provides novel insight into disturbances in iron homeostasis during malarial infection. J Infect Dis 2009;199:253-62.
154. de Mast Q, van Dongen-Lases EC, Swinkels DW, Nieman AE, Roestenberg M, Druilhe P, et al. Mild increases in serum hepcidin and interleukin-6 concentrations impair iron incorporation in haemoglobin during an experimental human malaria infection. Br J Haematol 2009;145:657-64.
155. Howard CT, McKakpo US, Quakyi IA, Bosompem KM, Addison EA, Sun K, et al. Relationship of hepcidin with parasitemia and anemia among patients with uncomplicated Plasmodium falciparum malaria in Ghana. Am J Trop Med Hyg 2007;77:623-6. (Pubitemid 351844281)
156. Nweneka CV, Doherty CP, Cox S, Prentice A. Iron delocalisation in the pathogenesis of malarial anaemia. Trans R Soc Trop Med Hyg 2010;104:175-84.
157. Cercamondi CI, Egli IM, Ahouandjinou E, Dossa R, Zeder C, Salami L, et al. Afebrile Plasmodium falciparum parasitemia decreases absorption of fortification iron but does not affect systemic iron utilization: a double stable-isotope study in young Beninese women. Am J Clin Nutr 2010;92:1385-92.
158. Sazawal S, Black RE, Ramsan M, Chwaya HM, Stoltzfus RJ, Dutta A, et al. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. Lancet 2006;367:133-43. (Pubitemid 43077129)
159. Drakesmith H, Prentice A. Viral infection and iron metabolism. Nat Rev Microbiol 2008;6:541-52. (Pubitemid 351863367)
160. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005;352:1011-23.
161. Fleming RE, Sly WS. Hepcidin: a putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease. Proc Natl Acad Sci U S A 2001;98:8160-2. (Pubitemid 32678004)
162. Ferrucci L, Semba RD, Guralnik JM, Ershler WB, Bandinelli S, Patel KV, et al. Proinflammatory state, hepcidin, and anemia in older persons. Blood 2010;115:3810-6.
163. Andrews NC. Anemia of inflammation: the cytokine-hepcidin link. J Clin Invest 2004;113:1251-3. (Pubitemid 39069921)
164. Thomas C, Kobold U, Balan S, Roeddiger R, Thomas L. Serum hepcidin-25 may replace the ferritin index in the Thomas plot in assessing iron status in anemic patients. Int J Lab Hematol 2010;33:187-93.
165. Sasu BJ, Li H, Rose MJ, Arvedson TL, Doellgast G, Molineux G. Serum hepcidin but not prohepcidin may be an effective marker for anemia of inflammation (AI). Blood Cells Mol Dis 2010;45:238-45.
166. Swinkels DW, Wetzels JF. Hepcidin: a new tool in the management of anaemia in patients with chronic kidney disease? Nephrol Dial Transplant 2008;23:2450-3.
167. Viatte L, Vaulont S. Hepcidin, the iron watcher. Biochimie 2009;91:1223-8.
168. Zaritsky JJ, Young BY. The utility of multivariate analysis in the study of hepcidin. Kidney Int 2009;76:912-3.
169. Weiss G, Theurl I, Eder S, Koppelstaetter C, Kurz K, Sonnweber T, et al. Serum hepcidin concentration in chronic haemodialysis patients: associations and effects of dialysis, iron and erythropoietin therapy. Eur J Clin Invest 2009;39:883-90.
170. van der Putten K, Jie KE, van den Broek D, Kraaijenhagen RJ, Laarakkers C, Swinkels DW, 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;12:943-50.
171. Valenti L, Girelli D, Valenti GF, Castagna A, Como G, Campostrini N, et al. HFE mutations modulate the effect of iron on serum hepcidin-25 in chronic hemodialysis patients. Clin J Am Soc Nephrol 2009;4:1331-7.
172. Kuragano T, Shimonaka Y, Kida A, Furuta M, Nanami M, Otaki Y, et al. Determinants of hepcidin in patients on maintenance hemodialysis: role of inflammation. Am J Nephrol 2010;31:534-40.
173. Zaritsky J, Young B, Wang HJ, Westerman M, Olbina G, Nemeth E, et al. Hepcidin-a potential novel biomarker for iron status in chronic kidney disease. Clin J Am Soc Nephrol 2009;4:1051-6.
174. Zaritsky J, Young B, Gales B, Wang HJ, Rastogi A, Westerman M, et al. Reduction of serum hepcidin by hemodialysis in pediatric and adult patients. Clin J Am Soc Nephrol 2010;5:1010-4.
175. Ford BA, Eby CS, Scott MG, Coyne DW. Intra-individual variability in serum hepcidin precludes its use as a marker of iron status in hemodialysis patients. Kidney Int 2010;78:769-73.
176. Kato A, Tsuji T, Luo J, Sakao Y, Yasuda H, Hishida A. Association of prohepcidin and hepcidin-25 with erythropoietin response and ferritin in hemodialysis patients Am J Nephrol 2008;28:115-21. (Pubitemid 350126501)
177. Bratescu LO, Barsan L, Munteanu D, Stancu S, Mircescu G. Is hepcidin-25 a clinically relevant parameter for the iron status in hemodialysis patients? J Ren Nutr 2010;20:S77-83.
178. Ho J, Lucy M, Krokhin O, Hayglass K, Pascoe E, Darroch G, et al. Mass spectrometry-based proteomic analysis of urine in acute kidney injury following cardiopulmonary bypass: a nested case-control study. Am J Kidney Dis 2009;53:584-95.
179. Prowle JR, Westerman M, Bellomo R. Urinary hepcidin: an inverse biomarker of acute kidney injury after cardiopulmonary bypass? Curr Opin Crit Care [Epub ahead of print 2010 Aug 21].
180. Tussing-Humphreys LM, Nemeth E, Fantuzzi G, Freels S, Guzman G, Holterman AX, Braunschweig C. Elevated systemic hepcidin and iron depletion in obese premenopausal females. Obesity (Silver Spring) 2010;18:1449-56.
181. Ruivard M, Laine F, Ganz T, Olbina G, Westerman M, Nemeth E, et al. Iron absorption in dysmetabolic iron overload syndrome is decreased and correlates with increased plasma hepcidin. J Hepatol 2009;50:1219-25.
182. Tussing-Humphreys LM, Nemeth E, Fantuzzi G, Freels S, Holterman AX, Galvani C, et al. Decreased serum hepcidin and improved functional iron status 6 months after restrictive bariatric surgery. Obesity 2010;18:2010-6.
183. Amato A, Santoro N, Calabro P, Grandone A, Swinkels DW, Perrone L, Miraglia Del Giudice E. Effect of body mass index reduction on serum hepcidin levels and iron status in obese children. Int J Obes 2010;34:1772-4.
184. Matsumoto M, Tsujino T, Lee-Kawabata M, Naito Y, Akahori H, Sakoda T, et al. Iron regulatory hormone hepcidin decreases in chronic heart failure patients with anemia. Circ J 2010;74:301-6.
185. Divakaran V, Mehta S, Yao D, Hassan S, Simpson S, Wiegerinck E, et al. Hepcidin in anemia of chronic heart failure. Am J Hematol 2011;86:107-9.
186. Kraml PJ, Klein RL, Huang Y, Nareika A, Lopes-Virella MF. Iron loading increases cholesterol accumulation and macrophage scavenger receptor I expression in THP-1 mononuclear phagocytes. Metabolism 2005;54:453-9. (Pubitemid 40410444)
187. Lapenna D, Pierdomenico SD, Ciofani G, Ucchino S, Neri M, Giamberardino MA, Cuccurullo F. Association of body iron stores with low molecular weight iron and oxidant damage of human atherosclerotic plaques. Free Radic Biol Med 2007;42:492-8. (Pubitemid 46162117)
188. Sullivan JL. Macrophage iron, hepcidin, and atherosclerotic plaque stability. Exp Biol Med 2007;232:1014-20. (Pubitemid 47358184)
189. Sullivan JL. Iron in arterial plaque: modifiable risk factor for atherosclerosis. Biochim Biophys Acta 2009;1790:718-23.
190. Barisani D, Pelucchi S, Mariani R, Galimberti S, Trombini P, Fumagalli D, et al. Hepcidin and iron-related gene expression in subjects with Dysmetabolic Hepatic Iron Overload. J Hepatol 2008;49:123-33.
191. Aigner E, Theurl I, Theurl M, Lederer D, Haufe H, Dietze O, et al. Pathways underlying iron accumulation in human nonalcoholic fatty liver disease. Am J Clin Nutr 2008;87:1374-83. (Pubitemid 351679780)
192. Valenti L, Dongiovanni P, Motta BM, Swinkels DW, Bonara P, Rametta R, et al. Serum hepcidin and macrophage iron correlate with MCP-1 release and vascular damage in patients with metabolic syndrome alterations. Arterioscler Thromb Vasc Biol 2011;31:683-90.
193. Sharma S, Nemeth E, Chen YH, Goodnough J, Huston A, Roodman GD, et al. Involvement of hepcidin in the anemia of multiple myeloma. Clin Cancer Res 2008;14:3262-7.
194. Maes K, Nemeth E, Roodman GD, Huston A, Esteve F, Freytes C, et al. In anemia of multiple myeloma, hepcidin is induced by increased bone morphogenetic protein 2. Blood 2010;116:3635-44.
195. Hohaus S, Massini G, Giachelia M, Vannata B, Bozzoli V, Cuccaro A, et al. Anemia in Hodgkin's lymphoma: the role of interleukin-6 and hepcidin. J Clin Oncol 2010;28:2538-43.
196. Zucker SD. The swinging pendulum of the anemia of cancer: erythropoietin trumps hepcidin. J Clin Oncol 2011;29:e42.
197. Ukarma L, Johannes H, Beyer U, Zaug M, Osterwalder B, Scherhag A. Hepcidin as a predictor of response to epoetin therapy in anemic cancer patients. Clin Chem 2009;55:1354-60.
198. Peeling P, Dawson B, Goodman C, Landers G, Trinder D. Athletic induced iron deficiency: new insights into the role of inflammation, cytokines and hormones. Eur J Appl Physiol 2008;103:381-91.
199. Roecker L, Meier-Buttermilch R, Brechtel L, Nemeth E, Ganz T. Iron-regulatory protein hepcidin is increased in female athletes after a marathon. Eur J Appl Physiol 2005;95:569-71. (Pubitemid 41762564)
200. Peeling P, Dawson B, Goodman C, Landers G, Wiegerinck ET, Swinkels DW, Trinder D. Cumulative effects of consecutive running sessions on hemolysis, inflammation and hepcidin activity. Eur J Appl Physiol 2009;106:51-9.
201. Peeling P, Dawson B, Goodman C, Landers G, Wiegerinck ET, Swinkels DW, Trinder D. Training surface and intensity: inflammation, hemolysis, and hepcidin expression. Med Sci Sports Exerc 2009;41:1138-45.
202. Troadec MB, Laine F, Daniel V, Rochcongar P, Ropert M, Cabillic F, et al. Daily regulation of serum and urinary hepcidin is not influenced by submaximal cycling exercise in humans with normal iron metabolism. Eur J Appl Physiol 2009;106:435-43.
203. Peeling P. Exercise as a mediator of hepcidin activity in athletes. Eur J Appl Physiol 2010;110:877-83.
204. Nemeth E. Targeting the hepcidin-ferroportin axis in the diagnosis and treatment of anemias. Adv Hematol 2010;2010:750643.
205. Pietrangelo A. Hepcidin in human iron disorders: therapeutic implications. J Hepatol 2011;54:173-81.
206. Nemeth E. Hepcidin biology and therapeutic applications. Expert Rev Hematol 2010;3:153-5.
207. Gardenghi S, Ramos P, Marongiu MF, Melchiori L, Breda L, Guy E, et al. Hepcidin as a therapeutic tool to limit iron overload and improve anemia in beta-thalassemic mice. J Clin Invest 2010;120:4466-77.
208. Babitt JL, Huang FW, Xia Y, Sidis Y, Andrews NC, Lin HY. Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance. J Clin Invest 2007;117:1933-9. (Pubitemid 47036327)
209. Corradini E, Schmidt PJ, Meynard D, Garuti C, Montosi G, Chen S, et al. BMP6 treatment compensates for the molecular defect and ameliorates hemochromatosis in Hfe knockout mice. Gastroenterology 2010;139:1721-9.
210. Semenza GL. Development of novel therapeutic strategies that target HIF-1. Expert Opin Ther Targets 2006;10:267-80.
211. Sasu BJ, Cooke KS, Arvedson TL, Plewa C, Ellison AR, Sheng J, et al. Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia. Blood 2010;115:3616-24.
212. Yu PB, Hong CC, Sachidanandan C, Babitt JL, Deng DY, Hoyng SA, et al. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol 2008;4:33-41. (Pubitemid 350273653)
213. Fatih N, Camberlein E, Island ML, Corlu A, Abgueguen E, Detivaud L, et al. Natural and synthetic STAT3 inhibitors reduce hepcidin expression in differentiated mouse hepatocytes expressing the active phosphorylated STAT3 form. J Mol Med 2010;88:477-86.
214. Song SN, Tomosugi N, Kawabata H, Ishikawa T, Nishikawa T, Yoshizaki K. Down-regulation of hepcidin resulting from long-term treatment with an anti-IL-6 receptor antibody (tocilizumab) improves anemia of inflammation in multicentric Castleman disease. Blood 2010;116:3627-34.
215. Hashizume M, Uchiyama Y, Horai N, Tomosugi N, Mihara M. Tocilizumab, a humanized anti-interleukin-6 receptor antibody, improved anemia in monkey arthritis by suppressing IL-6-induced hepcidin production. Rheumatol Int 2010;30:917-23.
216. Nishimoto N, Kanakura Y, Aozasa K, Johkoh T, Nakamura M, Nakano S, et al. Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. Blood 2005; 106:2627-32. (Pubitemid 41510733)
217. Kawabata H, Tomosugi N, Kanda J, Tanaka Y, Yoshizaki K, Uchiyama T. Anti-interleukin 6 receptor antibody tocilizumab reduces the level of serum hepcidin in patients with multicentric Castleman's disease. Haematologica 2007;92:857-8. (Pubitemid 350155317)
218. Poli M, Girelli D, Campostrini N, Maccarinelli F, Finazzi D, Luscieti S, et al. Heparin: a potent inhibitor of hepcidin expression in vitro and in vivo. Blood 2011;117:997-1004.
219. Xiao JJ, Krzyzanski W, Wang YM, Li H, Rose MJ, Ma M, et al. Pharmacokinetics of anti-hepcidin monoclonal antibody Ab 12B9m and hepcidin in cynomolgus monkeys. AAPS J 2010;12:646-57.
220. Braliou GG, Verga Falzacappa MV, Chachami G, Casanovas G, Muckenthaler MU, Simos G. 2-Oxoglutarate-dependent oxygenases control hepcidin gene expression. J Hepatol 2008;48:801-10.
221. Klaus S, Langsetmo I, Spong S, Gervasi B, Nichols B, Fourney P, et al. Induction of erythropoiesis and iron utilization by the HIF prolyl hydroxylase inhibitor FG-4592 [Abstract]. J Am Soc Nephrol 16, 49A 2005.
222. Tjalsma H, Laarakkers CM, van Swelm RP, Theurl M, Theurl I, Kemna EH, et al. Mass spectrometry analysis of hepcidin peptides in experimental mouse models. PLoS ONE 2011;6:e16762.
223. Janssen MC, Swinkels DW. Hereditary haemochromatosis. Best Pract Res Clin Gastroenterol 2009;23:171-83.
224. Kemna EH, Tjalsma H, Willems HL, Swinkels DW. Hepcidin: from discovery to differential diagnosis. Haematologica 2008;93:90-7. (Pubitemid 351156156)