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Heparin: a potent inhibitor of hepcidin expression in vitro and in vivo.
- Source :
-
Blood [Blood] 2011 Jan 20; Vol. 117 (3), pp. 997-1004. Date of Electronic Publication: 2010 Nov 12. - Publication Year :
- 2011
-
Abstract
- Hepcidin is a major regulator of iron homeostasis, and its expression in liver is regulated by iron, inflammation, and erythropoietic activity with mechanisms that involve bone morphogenetic proteins (BMPs) binding their receptors and coreceptors. Here we show that exogenous heparin strongly inhibited hepcidin expression in hepatic HepG2 cells at pharmacologic concentrations, with a mechanism that probably involves bone morphogenetic protein 6 sequestering and the blocking of SMAD signaling. Treatment of mice with pharmacologic doses of heparin inhibited liver hepcidin mRNA expression and SMAD phosphorylation, reduced spleen iron concentration, and increased serum iron. Moreover, we observed a strong reduction of serum hepcidin in 5 patients treated with heparin to prevent deep vein thrombosis, which was accompanied by an increase of serum iron and a reduction of C-reactive protein levels. The data show an unrecognized role for heparin in regulating iron homeostasis and indicate novel approaches to the treatment of iron-restricted iron deficiency anemia.
- Subjects :
- Aged
Aged, 80 and over
Animals
Anticoagulants pharmacology
Anticoagulants therapeutic use
Antimicrobial Cationic Peptides blood
Antimicrobial Cationic Peptides metabolism
Blotting, Western
Bone Morphogenetic Protein 6 pharmacology
C-Reactive Protein metabolism
Female
Fondaparinux
Hep G2 Cells
Heparin analogs & derivatives
Heparin therapeutic use
Heparin, Low-Molecular-Weight pharmacology
Hepcidins
Humans
Interleukin-6 pharmacology
Iron blood
Iron metabolism
Mice
Phosphorylation drug effects
Polysaccharides pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Spleen drug effects
Spleen metabolism
Venous Thrombosis blood
Venous Thrombosis drug therapy
Antimicrobial Cationic Peptides genetics
Gene Expression Regulation drug effects
Heparin pharmacology
Smad Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 117
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 21076043
- Full Text :
- https://doi.org/10.1182/blood-2010-06-289082