High Levels of Zinc-Protoporphyrin Identify Iron Metabolic Abnormalities in Pulmonary Arterial Hypertension

Clinical and Translational Science

Volumn 4, Issue 4, 2011, Pages 253-258

  Decker, Ilka ^a   Ghosh, Sudakshina ^b   Comhair, Suzy A ^b   Farha, Samar ^b   Wilson Tang, Wai Hong ^b   Park, Margaret ^b   Wang, Sihe ^b   Lichtin, Alan E ^c   Erzurum, Serpil C ^b  

^a CASE WESTERN RESERVE UNIVERSITY   (United States)

^b LERNER RESEARCH INSTITUTE   (United States)

^c TAUSSIG CANCER INSTITUTE   (United States)

Author keywords

Iron metabolism; Pulmonary arterial hypertension; Zinc protoporphyrin

Indexed keywords

BETA ADRENERGIC RECEPTOR STIMULATING AGENT; BIOCHEMICAL MARKER; CORTICOSTEROID; DIGOXIN; DIURETIC AGENT; ENDOTHELIN RECEPTOR ANTAGONIST; HEMOGLOBIN; PROSTACYCLIN; PROTOPORPHYRIN ZINC; SILDENAFIL; TRANSFERRIN RECEPTOR; WARFARIN;

ADULT; ARTICLE; ASTHMA; CELLULAR DISTRIBUTION; CLINICAL ASSESSMENT; CONTROLLED STUDY; DIAGNOSTIC VALUE; DISEASE ASSOCIATION; DISEASE COURSE; DISEASE SEVERITY; ERYTHROCYTE COUNT; ERYTHROCYTE STRUCTURE; FAMILIAL DISEASE; FEMALE; HEART INDEX; HEMATOCRIT; HEME SYNTHESIS; HEMODYNAMIC MONITORING; HOMEOSTASIS; HUMAN; IDIOPATHIC DISEASE; IRON DEFICIENCY; IRON METABOLISM DISORDER; IRON THERAPY; LEUKOCYTE COUNT; LUNG ARTERY PRESSURE; MAJOR CLINICAL STUDY; MALE; MEAN CORPUSCULAR HEMOGLOBIN; MEAN CORPUSCULAR VOLUME; PRIORITY JOURNAL; PULMONARY HYPERTENSION; SLEEP APNEA SYNDROME; THROMBOCYTE COUNT; VALIDATION PROCESS; WALKING;

ADULT; BLOOD CELL COUNT; BLOOD CELLS; COHORT STUDIES; FEMALE; HUMANS; HYPERTENSION, PULMONARY; IRON; MALE; MIDDLE AGED; PROTOPORPHYRINS; SEVERITY OF ILLNESS INDEX; SLEEP APNEA SYNDROMES;

EID: 80052225606     PISSN: 17528054     EISSN: 17528062     Source Type: Journal    
DOI: 10.1111/j.1752-8062.2011.00301.x     Document Type: Article

References (43)

1. Adir Y, Humbert M. Pulmonary hypertension in patients with chronic myeloproliferative disorders. Eur Respir J. 2010; 35: 1396-1406.
2. Hickey MM, Richardson T, Wang T, Mosqueira M, Arguiri E, Yu H, Yu QC, Solomides CC, Morrisey EE, Khurana TS, Christofidou-Solomidou M., and Simon M.C. The von Hippel-Lindau Chuvash mutation promotes pulmonary hypertension and fibrosis in mice. J Clin Invest. 2010; 120: 827-839.
3. Rich S, Hart K. Familial pulmonary hypertension in association with an abnormal hemoglobin. Insights into the pathogenesis of primary pulmonary hypertension. Chest. 1991; 99: 1208-1210.
4. Smith TG, Balanos GM, Croft QP, Talbot NP, Dorrington KL, Ratcliffe PJ, Robbins PA. The increase in pulmonary arterial pressure caused by hypoxia depends on iron status. J Physiol. 2008; 586: 5999-6005.
5. Smith TG, Talbot NP, Privat C, Rivera-Ch M, Nickol AH, Ratcliffe PJ, Dorrington KL, Leon-Velarde F, Robbins, PAEffects of iron supplementation and depletion on hypoxic pulmonary hypertension: two randomized controlled trials. JAMA. 2009; 302: 1444-1450.
6. Fagan KA. Selected Contribution: pulmonary hypertension in mice following intermittent hypoxia. J Appl Physiol. 2001; 90: 2502-2507.
7. Farber HW, Loscalzo J. Pulmonary arterial hypertension. N Engl J Med. 2004; 351: 1655-1665.
8. McLaughlin VV, McGoon MD.Pulmonary arterial hypertension. Circulation. 2006; 114: 1417-1431.
9. Weitzenblum E, Chaouat A, Canuet M, Kessler R.Pulmonary hypertension in chronic obstructive pulmonary disease and interstitial lung diseases. Semin Respir Crit Care Med. 2009; 30: 458-470.
10. Krasuski RA, Hart SA, Smith B, Wang A, Harrison JK, Bashore TM. Association of anemia and long-term survival in patients with pulmonary hypertension. 2010 May 14 [Epub ahead of print].
11. Ruiter G, Lankhorst S, Boonstra A, Postmus PE, Zweegman S, Westerhof N, van der Laarse WJ, Vonk-Noordegraaf A. Iron deficiency is common in idiopathic pulmonary arterial hypertension. Eur Respir J. 2011; 37:1386-1391.
12. Labbe RF, Vreman HJ, Stevenson DK. Zinc protoporphyrin: a metabolite with a mission. Clin Chem. 1999; 45: 2060-2072.
13. Hastka J, Lasserre JJ, Schwarzbeck A, Hehlmann R.Central role of zinc protoporphyrin in staging iron deficiency. Clin Chem. 1994; 40: 768-773.
14. Hastka J, Lasserre JJ, Schwarzbeck A, Strauch M, Hehlmann R.Zinc protoporphyrin in anemia of chronic disorders. Blood. 1993; 81: 1200-1204.
15. Simonneau G, Galie N, Rubin LJ, Langleben D, Seeger W, Domenighetti G, Gibbs S, Lebrec D, Speich R, Beghetti, M., et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2004; 43: 5S-12S.
16. Ghamra ZW, Dweik RA.Primary pulmonary hypertension: an overview of epidemiology and pathogenesis. Cleve Clin J Med. 2003; 70(Suppl 1): S2-S8.
17. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep. 1999; 22: 667-689.
18. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide. Am J Respir Crit Care Med 2005; 171: 912-930.
19. Kircher BJ, Himelman RB, Schiller NB.Noninvasive estimation of right atrial pressure from the inspiratory collapse of the inferior vena cava. Am J Cardiol. 1990; 66: 493-496.
20. Hampole CV, Mehrotra AK, Thenappan T, Gomberg-Maitland M, Shah SJ.Usefulness of red cell distribution width as a prognostic marker in pulmonary hypertension. Am J Cardiol. 2009; 104: 868-872.
21. Stuehr DJ, Tejero J, Haque MMStructural and mechanistic aspects of flavoproteins: electron transfer through the nitric oxide synthase flavoprotein domain. Febs J. 2009; 276: 3959-3974.
22. Archer SL, Marsboom G, Kim GH, Zhang HJ, Toth PT, Svensson EC, Dyck JR, Gomberg-Maitland M, Thebaud B, Husain AN, et al. Epigenetic attenuation of mitochondrial superoxide dismutase 2 in pulmonary arterial hypertension: a basis for excessive cell proliferation and a new therapeutic target. Circulation. 2010; 121: 2661-2671.
23. Fijalkowska I, Xu W, Comhair SA, Janocha AJ, Mavrakis LA, Krishnamachary B, Zhen L, Mao T, Richter A, Erzurum SC, et al. Hypoxia inducible-factor1alpha regulates the metabolic shift of pulmonary hypertensive endothelial cells. Am J Pathol. 2010; 176: 1130-1138.
24. Kaneko FT, Arroliga AC, Dweik RA, Comhair SA, Laskowski D, Oppedisano R, Thomassen MJ Erzurum SC.Biochemical reaction products of nitric oxide as quantitative markers of primary pulmonary hypertension. Am J Respir Crit Care Med. 1998; 158: 917-923.
25. Machado RF, Londhe Nerkar MV, Dweik RA, Hammel J, Janocha A, Pyle J, Laskowski D, Jennings C, Arroliga AC, Erzurum SC.Nitric oxide and pulmonary arterial pressures in pulmonary hypertension. Free Radic Biol Med. 2004; 37: 1010-1017.
26. Ozkan M, Dweik RA, Laskowski D, Arroliga AC, Erzurum SC.High levels of nitric oxide in individuals with pulmonary hypertension receiving epoprostenol therapy. Lung. 2001; 179: 233-243.
27. Xu W, Kaneko FT, Zheng S, Comhair SA, Janocha AJ, Goggans T, Thunnissen FB, Farver C, Hazen SL, Jennings C C., et al. Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension. Faseb J. 2004; 18: 1746-1748.
28. Xu W, Koeck T, Lara AR, Neumann D, DiFilippo FP, Koo M, Janocha AJ, Masri FA, Arroliga AC, Jennings C. et al. Alterations of cellular bioenergetics in pulmonary artery endothelial cells. Proc Natl Acad Sci U S A. 2007; 104: 1342-1347.
29. Weiss G, Goodnough LT.Anemia of chronic disease. N Engl J Med. 2005; 352: 1011-1023.
30. Asosingh K, Aldred MA, Vasanji A, Drazba J, Sharp J, Farver C, Comhair SA, Xu W, Licina L, Huang L, et al. Circulating angiogenic precursors in idiopathic pulmonary arterial hypertension. Am J Pathol. 2008; 172: 615-627.
31. Aytekin M, Comhair SA, de la Motte C, Bandyopadhyay SK, Farver CF, Hascall VC, Erzurum SC, Dweik RA.High levels of hyaluronan in idiopathic pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. 2008; 295: L789-L799.
32. Dorfmuller P, Perros F, Balabanian K, Humbert M.Inflammation in pulmonary arterial hypertension. Eur Respir J. 2003; 22: 358-363.
33. Soon E, Holmes AM, Treacy CM, Doughty NJ, Southgate L, Machado RD, Trembath RC, Jennings S, Barker L, Nicklin P, et al. Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension. Circulation. 2010; 122: 920-927.
34. Soon E, Treacy CM, Toshner MR, Mackenzie-Ross R, Manglam V, Busbridge M, Sinclair-McGarvie M, Arnold J, Sheares KK, Morrell NW, Pepke-Zaba J. Unexplained iron deficiency in idiopathic and heritable pulmonary arterial hypertension. Thorax. 2011; 66: 326-332.
35. Punnonen K, Irjala K, Rajamaki ASerum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood. 1997; 89: 1052-1057.
36. Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Luscher TF, Bart B, Banasiak W, Niegowska J, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009; 361: 2436-2448.
37. Comin-Colet J, Ruiz S, Cladellas M, Rizzo M, Torres A, Bruguera J.A pilot evaluation of the long-term effect of combined therapy with intravenous iron sucrose and erythropoietin in elderly patients with advanced chronic heart failure and cardio-renal anemia syndrome: influence on neurohormonal activation and clinical outcomes. J Card Fail. 2009; 15: 727-735.
38. Patel KV, Ferrucci L, Ershler WB, Longo DL, Guralnik JM.Red blood cell distribution width and the risk of death in middle-aged and older adults. Arch Intern Med. 2009; 169: 515-523.
39. Perlstein TS, Weuve J, Pfeffer MA, Beckman JA.Red blood cell distribution width and mortality risk in a community-based prospective cohort. Arch Intern Med. 2009; 169: 588-594.
40. Bakouboula, B., Morel, O., Faure, A., Zobairi, F., Jesel, L., Trinh, A., Zupan, M., Canuet, M., Grunebaum, L., Brunette, A., et al. Procoagulant membrane microparticles correlate with the severity of pulmonary arterial hypertension. Am J Respir Crit Care Med. 2008; 177: 536-543.
41. Can MM, Tanboga IH, Demircan HC, Ozkan A, Koca F, Keles N, Sonmez K, Kaymaz C, Serebruany V.Enhanced hemostatic indices in patients with pulmonary arterial hypertension: an observational study. Thromb Res. 2010; 126: 280-282.
42. Singer ST, Kuypers FA, Styles L, Vichinsky EP, Foote D, Rosenfeld H.Pulmonary hypertension in thalassemia: association with platelet activation and hypercoagulable state. Am J Hematol. 2006; 81: 670-675.
43. Villagra J, Shiva S, Hunter LA, Machado RF, Gladwin MT, Kato GJPlatelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension, and nitric oxide scavenging by cell-free hemoglobin. Blood 2007; 110: 2166-2172.