Abstract | OBJECTIVES: BACKGROUND:
Iron availability influences the pulmonary vascular response to hypoxia in humans and may be significant in the pathogenesis of IPAH. METHODS: RESULTS: Circulating sTfR levels were raised in 63% of IPAH patients, indicating significant iron deficiency. Consistent with this, iron, ferritin, and transferrin saturation levels were reduced and red cell distribution width increased, without overt anemia. Hepcidin correlated inversely with sTfR and positively with increasing ferritin. Hepcidin was inappropriately raised in IPAH independent of the inflammatory marker interleukin-6. EPO levels were also raised and correlated inversely with hepcidin. BMP receptor-type 2 (BMPR2) knockdown in HepG2 cells increased BMP-6-stimulated hepcidin expression. sTfR increased with World Health Organization functional class (p < 0.05), correlated negatively with exercise capacity (p = 0.027), and values >28.1 nmol/l independently predicted survival (p = 0.011). CONCLUSIONS:
Iron deficiency is common in IPAH patients and associated with disease severity and poor clinical outcome. Inappropriately raised hepcidin levels, which impair iron absorption from the gut, may be a factor.
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Authors | Christopher J Rhodes, Luke S Howard, Mark Busbridge, Damien Ashby, Eumorfia Kondili, J Simon R Gibbs, John Wharton, Martin R Wilkins |
Journal | Journal of the American College of Cardiology
(J Am Coll Cardiol)
Vol. 58
Issue 3
Pg. 300-9
(Jul 12 2011)
ISSN: 1558-3597 [Electronic] United States |
PMID | 21737024
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Actins
- Antimicrobial Cationic Peptides
- Bone Morphogenetic Protein 6
- Bone Morphogenetic Proteins
- Growth Differentiation Factor 15
- HAMP protein, human
- Hepcidins
- Interleukin-1
- Receptors, Transferrin
- Erythropoietin
- Ferritins
- Iron
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Topics |
- Actins
(metabolism)
- Adult
- Antimicrobial Cationic Peptides
(blood, metabolism)
- Bone Morphogenetic Protein 6
(pharmacology)
- Bone Morphogenetic Proteins
(metabolism)
- Erythropoietin
(blood)
- Familial Primary Pulmonary Hypertension
- Female
- Ferritins
(blood)
- Growth Differentiation Factor 15
(metabolism)
- Hep G2 Cells
- Hepcidins
- Humans
- Hypertension, Pulmonary
(blood)
- Interleukin-1
(blood)
- Iron
(blood)
- Iron Deficiencies
- Liver
(metabolism)
- Male
- Middle Aged
- Receptors, Transferrin
(blood)
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