Iron regulatory hormone hepcidin decreases in chronic heart failure patients with anemia.

BACKGROUND The etiology of anemia is still unclear in patients with chronic heart failure (CHF). Hepcidin is an iron regulatory peptide that is synthesized in the liver to suppress iron absorption and utilization. Hepcidin synthesis is suppressed by anemia, hypoxia and erythropoiesis, and induced by inflammation. Inflammatory cytokines, such as interleukin-6 (IL-6), increase the synthesis of hepcidin, resulting in anemia of inflammation (AI). The serum hepcidin concentration in CHF patients with anemia was measured in order to better understand anemia in CHF. METHODS AND RESULTS Serum hepcidin-25, erythropoietin (EPO), ferritin and IL-6 concentrations were measured in 61 CHF patients. Among these patients, 36 patients had anemia. A group of 16 patients without cardiac disease or anemia were recruited as controls. Serum IL-6 and EPO were higher and hepcidin-25 was lower in CHF patients with anemia than in controls. Hepcidin-25 correlated with EPO and ferritin but not with IL-6. Results of multivariable regression analysis showed that independent predictors of serum hepcidin-25 included EPO and ferritin but not IL-6. CONCLUSIONS Serum hepcidin-25 concentrations were regulated by iron storage and erythropoiesis but not by IL-6 in CHF patients with anemia. These findings might indicate that AI is a minor cause of anemia in CHF.

[1]  A. Takeshita,et al.  Anemia is an Independent Predictor of Long-Term Adverse Outcomes in Patients Hospitalized With Heart Failure in Japan , 2009 .

[2]  A. Takeshita,et al.  Anemia is an independent predictor of long-term adverse outcomes in patients hospitalized with heart failure in Japan. A report from the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD). , 2009, Circulation journal : official journal of the Japanese Circulation Society.

[3]  S. Srai,et al.  Genetic variation in hepcidin expression and its implications for phenotypic differences in iron metabolism , 2009, Haematologica.

[4]  M. Roth,et al.  Lack of the bone morphogenetic protein BMP6 induces massive iron overload , 2009, Nature Genetics.

[5]  Yin Xia,et al.  BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism , 2009, Nature Genetics.

[6]  N. Hagiwara,et al.  Clinical characteristics and outcome of hospitalized patients with congestive heart failure: results of the HIJC-HF registry. , 2008, Circulation journal : official journal of the Japanese Circulation Society.

[7]  N. Hagiwara,et al.  Clinical Characteristics and Outcome of Hospitalized Patients With Congestive Heart Failure , 2008 .

[8]  G. Karanikas,et al.  Chronic heart failure leads to an expanded plasma volume and pseudoanaemia, but does not lead to a reduction in the body's red cell volume. , 2008, European heart journal.

[9]  K. Matsuo,et al.  Serum hepcidin level and erythropoietic activity after hematopoietic stem cell transplantation , 2008, Haematologica.

[10]  B. Braam,et al.  Mechanisms of Disease: erythropoietin resistance in patients with both heart and kidney failure , 2008, Nature Clinical Practice Nephrology.

[11]  Y. Aso,et al.  Simple and sensitive quantification of bioactive peptides in biological matrices using liquid chromatography/selected reaction monitoring mass spectrometry coupled with trichloroacetic acid clean-up. , 2007, Rapid communications in mass spectrometry : RCM.

[12]  S. Goh,et al.  High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin , 2007, Nature Medicine.

[13]  D. Witcher,et al.  Quantitation of hepcidin from human and mouse serum using liquid chromatography tandem mass spectrometry. , 2007, Blood.

[14]  V. Nizet,et al.  Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). , 2007, The Journal of clinical investigation.

[15]  J. Kanda,et al.  Anti-interleukin 6 receptor antibody tocilizumab reduces the level of serum hepcidin in patients with multicentric Castleman's disease. , 2007, Haematologica.

[16]  S. Ito,et al.  Estimation of glomerular filtration rate by the MDRD study equation modified for Japanese patients with chronic kidney disease , 2007, Clinical and Experimental Nephrology.

[17]  D. Karageorgopoulos,et al.  Etiology of anemia in patients with advanced heart failure. , 2006, Journal of the American College of Cardiology.

[18]  H. Umehara,et al.  Detection of serum hepcidin in renal failure and inflammation by using ProteinChip System. , 2006, Blood.

[19]  T. Ganz,et al.  Iron imports. IV. Hepcidin and regulation of body iron metabolism. , 2006, American journal of physiology. Gastrointestinal and liver physiology.

[20]  E. Nečas,et al.  Hepcidin mRNA levels in mouse liver respond to inhibition of erythropoiesis. , 2006, Physiological research.

[21]  D. Swinkels,et al.  Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. , 2005, Blood.

[22]  Elizabeta Nemeth,et al.  IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. , 2004, The Journal of clinical investigation.

[23]  Matthias W. Hentze,et al.  Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization , 2004 .

[24]  D. Mozaffarian,et al.  Anemia predicts mortality in severe heart failure: the prospective randomized amlodipine survival evaluation (PRAISE). , 2003, Journal of the American College of Cardiology.

[25]  Elizabeta Nemeth,et al.  Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. , 2003, Blood.

[26]  Paul W Armstrong,et al.  Anemia Is Common in Heart Failure and Is Associated With Poor Outcomes: Insights From a Cohort of 12 065 Patients With New-Onset Heart Failure , 2003, Circulation.

[27]  L. Lund,et al.  Hemodilution Is Common in Patients With Advanced Heart Failure , 2003, Circulation.

[28]  M. Loda,et al.  Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. , 2002, Blood.

[29]  Gaël Nicolas,et al.  The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. , 2002, The Journal of clinical investigation.

[30]  D. Tepper.  Anemia Is Associated With Worse Symptoms, Greater Impairment in Functional Capacity, and a Significant Increase in Mortality in Patients With Advanced Heart Failure , 2002 .

[31]  A. Levey,et al.  Prediction equations to estimate glomerular filtration rate: an update , 2001, Current opinion in nephrology and hypertension.

[32]  Bruno Turlin,et al.  A New Mouse Liver-specific Gene, Encoding a Protein Homologous to Human Antimicrobial Peptide Hepcidin, Is Overexpressed during Iron Overload* , 2001, The Journal of Biological Chemistry.

[33]  Christina H. Park,et al.  Hepcidin, a Urinary Antimicrobial Peptide Synthesized in the Liver* , 2001, The Journal of Biological Chemistry.

[34]  I. Pham,et al.  Increased erythropoietin synthesis in patients with COLD or left heart failure is related to alterations in renal haemodynamics , 2001, European journal of clinical investigation.

[35]  S. Anker,et al.  Plasma Cytokine Parameters and Mortality in Patients With Chronic Heart Failure , 2000, Circulation.

[36]  I. Shapira,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. , 2000, Journal of the American College of Cardiology.

[37]  H. Fillit,et al.  Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. , 1990, The New England journal of medicine.