title: Expression of the peptide hormone hepcidin increases in cardiomyocytes under myocarditis and myocardial infarction.
abstract: The micronutrient iron is an essential component that plays a role in many crucial metabolic reactions. The peptide hormone hepcidin is thought to play a central role in iron homeostasis and its expression is induced by iron overloading and inflammation. Recently, hepcidin has been reported to be expressed also in the heart; however, the kinetics of altered hepcidin expression in diseases of the heart remain unknown. In this study, we examined cardiac expression of hepcidin in rat experimental autoimmune myocarditis (EAM), human myocarditis and rat acute myocardial infarction (AMI). In rat EAM and AMI hearts, hepcidin was expressed in cardiomyocytes; ferroportin, which is a cellular iron exporter bound by hepcidin, was also expressed in various cells. Analysis of the time course of the hepcidin to cytochrome oxidase subunit 6a (Cox6a)2 expression ratio showed that it abruptly increased more than 100-fold in hearts in the very early phase of EAM and in infarcted areas 1 day after MI. The hepcidin/Cox6a2 expression ratio correlated significantly with that of interleukin-6/gamma-actin in both EAM and AMI hearts (r=0.781, P<.0001 and r=0.563, P=.0003). In human hearts with histological myocarditis, the ratio was significantly higher than in those without myocarditis (0.0400+/-0.0195 versus 0.0032+/-0.0017, P=.0045). Hepcidin is strongly induced in cardiomyocytes under myocarditis and MI, conditions in which inflammatory cytokine levels increase and may play an important role in iron homeostasis and free radical generation.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Isoda
authors.forename: Haruo
authors.initials: H
authors.lastname: Hanawa
authors.forename: Ritsuo
authors.initials: R
authors.lastname: Watanabe
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Ken
authors.initials: K
authors.lastname: Toba
authors.forename: Kaori
authors.initials: K
authors.lastname: Yoshida
authors.forename: Mayuko
authors.initials: M
authors.lastname: Kojima
authors.forename: Keita
authors.initials: K
authors.lastname: Otaki
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Hao
authors.forename: Limin
authors.initials: L
authors.lastname: Ding
authors.forename: Komei
authors.initials: K
authors.lastname: Tanaka
authors.forename: Tsugumi
authors.initials: T
authors.lastname: Takayama
authors.forename: Kiminori
authors.initials: K
authors.lastname: Kato
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okura
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Ota
authors.forename: Junichi
authors.initials: J
authors.lastname: Hayashi
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D001483:Base Sequence; D017931:DNA Primers; D004195:Disease Models, Animal; D005260:Female; D064451:Hepcidins; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism*; D009205:Myocarditis / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D023181:Antimicrobial Cationic Peptides; D017931:DNA Primers; C578702:HAMP protein, human; C497442:HIF1A protein, human; C578703:Hamp protein, rat; D064451:Hepcidins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015850:Interleukin-6