Iron deficiency and raised hepcidin in idiopathic pulmonary arterial hypertension

Journal of the American College of Cardiology

Volumn 58, Issue 3, 2011, Pages 300-309

  Rhodes, Christopher J ^a   Howard, Luke S ^b   Busbridge, Mark ^b   Ashby, Damien ^b   Kondili, Eumorfia ^b   Gibbs, J Simon R ^b   Wharton, John ^a   Wilkins, Martin R ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b NATIONAL HEALTH SERVICE   (United Kingdom)

Author keywords

hepcidin; iron deficiency; pulmonary hypertension; soluble transferrin receptor

Indexed keywords

BONE MORPHOGENETIC PROTEIN 6; BONE MORPHOGENETIC PROTEIN RECEPTOR; BONE MORPHOGENETIC PROTEIN RECEPTOR 2; ERYTHROPOIETIN; FERRITIN; HEPCIDIN; INTERLEUKIN 6; IRON; TRANSFERRIN RECEPTOR;

ADULT; ANEMIA; ARTICLE; CELL STRAIN HEPG2; CONTROLLED STUDY; DISEASE ASSOCIATION; DISEASE SEVERITY; ERYTHROCYTE STRUCTURE; EXERCISE; FEMALE; HUMAN; IRON ABSORPTION; IRON DEFICIENCY; MAJOR CLINICAL STUDY; MALE; MORTALITY; PREDICTION; PREVALENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; PULMONARY HYPERTENSION; SURVIVAL RATE;

ACTINS; ADULT; ANTIMICROBIAL CATIONIC PEPTIDES; BONE MORPHOGENETIC PROTEIN 6; BONE MORPHOGENETIC PROTEINS; ERYTHROPOIETIN; FEMALE; FERRITINS; GROWTH DIFFERENTIATION FACTOR 15; HEP G2 CELLS; HUMANS; HYPERTENSION, PULMONARY; INTERLEUKIN-1; IRON; LIVER; MALE; MIDDLE AGED; RECEPTORS, TRANSFERRIN;

EID: 79960031695     PISSN: 07351097     EISSN: 15583597     Source Type: Journal    
DOI: 10.1016/j.jacc.2011.02.057     Document Type: Article

References (37)

1. S.L. Archer, E.K. Weir, and M.R. Wilkins Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies Circulation 121 2010 2045 2066
2. G.M. Balanos, K.L. Dorrington, and P.A. Robbins Desferrioxamine elevates pulmonary vascular resistance in humans: potential for involvement of HIF-1 J Appl Physiol 92 2002 2501 2507 (Pubitemid 34666376)
3. T.G. Smith, G.M. Balanos, and Q.P. Croft The increase in pulmonary arterial pressure caused by hypoxia depends on iron status J Physiol 586 2008 5999 6005
4. T.G. Smith, N.P. Talbot, and C. Privat Effects of iron supplementation and depletion on hypoxic pulmonary hypertension: two randomized controlled trials JAMA 302 2009 1444 1450
5. C.V. Hampole, A.K. Mehrotra, T. Thenappan, M. Gomberg-Maitland, and S.J. Shah Usefulness of red cell distribution width as a prognostic marker in pulmonary hypertension Am J Cardiol 104 2009 868 872
6. R.A. Krasuski, S.A. Hart, B. Smith, A. Wang, J.K. Harrison, and T.M. Bashore Association of anemia and long-term survival in patients with pulmonary hypertension Int J Cardiol 2010 May 14 [E-pub ahead of print]
7. G. Ruiter, S. Lankhorst, and A. Boonstra Iron deficiency is common in idiopathic pulmonary arterial hypertension Eur Respir J 2010 Sep 30 [E-pub ahead of print]
8. M.W. Hentze, M.U. Muckenthaler, B. Galy, and C. Camaschella Two to tango: regulation of Mammalian iron metabolism Cell 142 2010 24 38
9. C. Atkinson, S. Stewart, and P.D. Upton Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor Circulation 105 2002 1672 1678 (Pubitemid 34298611)
10. R.D. Machado, O. Eickelberg, and C.G. Elliott Genetics and genomics of pulmonary arterial hypertension J Am Coll Cardiol 54 2009 S32 S42
11. B. Andriopoulos Jr., E. Corradini, and Y. Xia BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism Nat Genet 41 2009 482 487
12. L. Kautz, D. Meynard, and A. Monnier Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver Blood 112 2008 1503 1509
13. D. Meynard, L. Kautz, V. Darnaud, F. Canonne-Hergaux, H. Coppin, and M.P. Roth Lack of the bone morphogenetic protein BMP6 induces massive iron overload Nat Genet 41 2009 478 481
14. S. Arndt, U. Maegdefrau, C. Dorn, K. Schardt, C. Hellerbrand, and A.K. Bosserhoff Iron-induced expression of bone morphogenic protein 6 in intestinal cells is the main regulator of hepatic hepcidin expression in vivo Gastroenterology 138 2010 372 382
15. N. Galie, M.M. Hoeper, and M. Humbert Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) Eur Heart J 30 2009 2493 2537
16. M. Busbridge, C. Griffiths, and D. Ashby Development of a novel immunoassay for the iron regulatory peptide hepcidin Br J Biomed Sci 66 2009 150 157
17. J.D. Cook, S. Dassenko, and B.S. Skikne Serum transferrin receptor as an index of iron absorption Br J Haematol 75 1990 603 609 (Pubitemid 20271496)
18. D.R. Ashby, D.P. Gale, and M. Busbridge Plasma hepcidin levels are elevated but responsive to erythropoietin therapy in renal disease Kidney Int 75 2009 976 981
19. S.D. Anker, C.J. Comin, and G. Filippatos Ferric carboxymaltose in patients with heart failure and iron deficiency N Engl J Med 361 2009 2436 2448
20. H.A. Huebers, Y. Beguin, P. Pootrakul, D. Einspahr, and C.A. Finch Intact transferrin receptors in human plasma and their relation to erythropoiesis Blood 75 1990 102 107 (Pubitemid 20031496)
21. M.B. Zimmermann, B. Troesch, R. Biebinger, I. Egli, C. Zeder, and R.F. Hurrell Plasma hepcidin is a modest predictor of dietary iron bioavailability in humans, whereas oral iron loading, measured by stable-isotope appearance curves, increases plasma hepcidin Am J Clin Nutr 90 2009 1280 1287
22. E. Nemeth, S. Rivera, and V. Gabayan IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin J Clin Invest 113 2004 1271 1276 (Pubitemid 39069926)
23. G. Weiss, and L.T. Goodnough Anemia of chronic disease N Engl J Med 352 2005 1011 1023
24. Y. Xia, J.L. Babitt, Y. Sidis, R.T. Chung, and H.Y. Lin Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin Blood 111 2008 5195 5204
25. P.B. Yu, H. Beppu, N. Kawai, E. Li, and K.D. Bloch Bone morphogenetic protein (BMP) type II receptor deletion reveals BMP ligand-specific gain of signaling in pulmonary artery smooth muscle cells J Biol Chem 280 2005 24443 24450 (Pubitemid 40934529)
26. M. Pak, M.A. Lopez, V. Gabayan, T. Ganz, and S. Rivera Suppression of hepcidin during anemia requires erythropoietic activity Blood 108 2006 3730 3735 (Pubitemid 44864551)
27. T. Tanno, N.V. Bhanu, and P.A. Oneal High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin Nat Med 13 2007 1096 1101 (Pubitemid 47517510)
28. D.R. Ashby, D.P. Gale, and M. Busbridge Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin Haematologica 95 2010 505 508
29. P.L. Lee, and E. Beutler Regulation of hepcidin and iron-overload disease Annu Rev Pathol 4 2009 489 515
30. N. Nickel, T. Kempf, and H. Tapken Growth differentiation factor-15 in idiopathic pulmonary arterial hypertension Am J Respir Crit Care Med 178 2008 534 541
31. M. Ivan, K. Kondo, and H. Yang HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing Science 292 2001 464 468 (Pubitemid 32335941)
32. P. Jaakkola, D.R. Mole, and Y.M. Tian Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation Science 292 2001 468 472 (Pubitemid 32335942)
33. K. Brusselmans, V. Compernolle, and M. Tjwa Heterozygous deficiency of hypoxia-inducible factor-2alpha protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia J Clin Invest 111 2003 1519 1527 (Pubitemid 38063284)
34. A.Y. Yu, L.A. Shimoda, and N.V. Iyer Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1alpha J Clin Invest 103 1999 691 696 (Pubitemid 29122422)
35. I. Fijalkowska, W. Xu, and S.A. Comhair Hypoxia inducible-factor1alpha regulates the metabolic shift of pulmonary hypertensive endothelial cells Am J Pathol 176 2010 1130 1138
36. D.O. Okonko, A. Grzeslo, and T. Witkowski Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC-HF: a randomized, controlled, observer-blinded trial J Am Coll Cardiol 51 2008 103 112
37. J.E. Toblli, A. Lombrana, P. Duarte, and F. Di Gennaro Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency J Am Coll Cardiol 50 2007 1657 1665 (Pubitemid 47562670)