Impaired expression of duodenal iron transporters in Dahl salt-sensitive heart failure rats

Yoshiro Naito, Takeshi Tsujino, Yoshihiro Fujimori, Hisashi Sawada, Hirokuni Akahori, Shinichi Hirotani, Mitsumasa Ohyanagi, Tohru Masuyama

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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. Conclusion: 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.

Original languageEnglish
Pages (from-to)741-748
Number of pages8
JournalJournal of Hypertension
Volume29
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • anemia
  • dahl salt-sensitive rats
  • divalent metal transporter 1
  • heart failure
  • hypoxia-inducible factor-2a
  • iron

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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