title: Impaired expression of duodenal iron transporters in Dahl salt-sensitive heart failure rats.
abstract: OBJECTIVE
  Anemia is common in patients with heart failure and several factors have been thought to cause anemia in heart failure. Despite vigorous studies, the mechanism underlying the pathophysiology of anemia in heart failure is unknown. We investigated the iron regulating system in Dahl salt-sensitive heart failure rats to elucidate the mechanism of anemia in heart failure.
  
  
  METHODS
  Dahl salt-sensitive rats were provided either a normal or high-salt diet to initiate heart failure progression. A further subset of Dahl salt-sensitive rats underwent an iron-deficient diet to induce iron deficiency anemia (IDA).
  
  
  RESULTS
  Dahl salt-sensitive rats, which develop diastolic heart failure, gradually showed hypertension and anemia after 8 weeks of high-salt diet. Although serum iron levels were decreased, erythropoietin levels were increased in the IDA and heart failure groups. Hepatic expression of hepcidin, a central regulator of iron metabolism, was downregulated in both IDA and heart failure groups. Duodenal cytochrome b (Dcyt-b), divalent metal transporter 1 (DMT-1), and ferroportin are the crucial regulators of intestinal iron transport and absorption. Duodenal expression levels of these molecules were markedly upregulated in the IDA group, but not in the heart failure group. Moreover, intestinal expression of hypoxia-inducible factor-2α, a critical regulator of the transcription of Dcyt-b and DMT-1, was upregulated in the IDA group, but not in the heart failure group.
  
  
  CONCLUSIONS
  Duodenal iron transporters expression was impaired in Dahl heart failure rats. Our data suggest that impaired duodenal iron absorption may occur in Dahl heart failure rats. Understanding the mechanism of abnormal iron regulating system may lead to new therapeutic strategies in anemia with heart failure.
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan. ynaito@hyo-med.ac.jp
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Naito
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsujino
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimori
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sawada
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Akahori
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirotani
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Ohyanagi
authors.forename: Tohru
authors.initials: T
authors.lastname: Masuyama
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D007501:Iron