title: The iron regulatory peptide hepcidin is expressed in the heart and regulated by hypoxia and inflammation.
abstract: The peptide hormone hepcidin plays a central role in iron homeostasis. It is predominantly expressed in the liver and regulated by iron, hypoxia, and inflammation. Although it has been shown that iron plays a key pathophysiological role in cardiac diseases, including iron-overload cardiomyopathy, myocardial ischemia-reperfusion injury, and atherosclerosis, very little is known about the putative expression and the role of hepcidin in the heart. In the present study, expression and regulation of hepcidin in rat heart were analyzed. Basal cardiac expression of hepcidin was demonstrated on mRNA and protein level in vivo in a rat model and compared with its regulation in the liver. The cellular localization was analyzed by immunofluorescence microscopy. Sixteen hours after a single injection of turpentine, a more than 2-fold increase of cardiac hepcidin mRNA and a more than 3-fold increase of hepatic hepcidin mRNA was observed. In response to hypoxia, expression of hepcidin in the liver decreased. In contrast, hypoxia resulted in a strong up-regulation of hepcidin expression on mRNA and protein level in the heart, accompanied by an increased immunoreactivity of hepcidin pronounced at the myocardial intercalated disc area. The finding of a regulated expression of the iron-regulatory peptide hormone hepcidin in the heart suggests that hepcidin may have an important role in cardiac diseases.
authors.affiliation: University Hospital Heidelberg, Department of Internal Medicine IV, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Merle
authors.forename: Evelyn
authors.initials: E
authors.lastname: Fein
authors.forename: Sven Gustav
authors.initials: SG
authors.lastname: Gehrke
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
authors.forename: Hasan
authors.initials: H
authors.lastname: Kulaksiz
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D005786:Gene Expression Regulation; D006331:Heart Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D064451:Hepcidins; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D023181:Antimicrobial Cationic Peptides; C578703:Hamp protein, rat; D064451:Hepcidins; D007501:Iron; D010100:Oxygen