Journal
BIOCHEMICAL PHARMACOLOGY
Volume 92, Issue 3, Pages 467-475Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2014.09.007
Keywords
Iron absorption and metabolism; Hepcidin; Low-molecular-weight heparins; Anemia of chronic diseases
Categories
Funding
- Fondazione Cariplo, Italy [2012-0570]
- Italian Ministry of Health [RF-2010-2312048]
- [MIUR-PRIN-11]
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Hepcidin is a peptide hormone that controls systemic iron availability and is upregulated by iron and inflammation. Heparins have been shown to be efficient hepcidin inhibitors both in vitro and in vivo, even when their anticoagulant activity has been abolished by chemical reactions of oxidation/reduction (glycol-split). We analyzed a modified heparin type, characterized by a high, almost saturated, sulfation degree and low molecular weight. It inhibited hepcidin expression in hepatic HepG2 cells, and when used in mice, it readily suppressed liver hepcidin mRNA and serum hepcidin, with a significant decrease of spleen iron. This occurred also in inflammation-model, LPS-treated animals, and after heparin chronic 10-day treatments. The heparin had low/absent anticoagulant activity, as tested for factor-Xa and -IIA, APTT and anti Xa. It reduced triglyceride levels in the mice. This heparin acts faster and is more potent than the glycol split-heparins, probably because of its smaller molecular weight and higher sulfation degree. This modified heparin has potential applications for the treatment of diseases with high hepcidin levels. (C) 2014 Elsevier Inc. All rights reserved.
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