Cardiac remodeling in response to chronic iron deficiency: Role of the erythropoietin receptor

Yoshiro Naito, Hisashi Sawada, Makiko Oboshi, Toshihiro Iwasaku, Yoshitaka Okuhara, Daisuke Morisawa, Akiyo Eguchi, Shinichi Hirotani, Toshiaki Mano, Takeshi Tsujino, Tohru Masuyama

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Objective: Anemia is a common comorbidity of patients with heart failure, and iron deficiency is known as one of the causes of anemia in heart failure. Recent studies have shown that iron deficiency alone, without overt anemia, is associated with poor outcomes in patients with heart failure. Thus, to minimize the mortality in patients with heart failure, it is important to understand the link between iron deficiency and cardiac function. Chronic untreated iron deficiency results in cardiac remodeling, and we have previously reported that erythropoietin (Epo) and cardiac Epo receptor (EpoR) signaling may be associated with its remodeling. However, the link between EpoR signaling and its remodeling remains to be elucidated. Herein, we investigated the role of EpoR signaling on cardiac remodeling in response to chronic iron deficiency. Methods: Wild-type mice and transgene-rescued EpoR-null mutant mice, which express EpoR only in the hematopoietic lineage (EpoR -/- -restricted mice), were fed with either a normal or an iron-restricted diet, and the molecular mechanisms were investigated. Results: Dietary iron restriction gradually induced anemia, Epo secretion, and cardiac hypertrophy in wild-type mice. In contrast, EpoR -/- -restricted mice fed with an iron-restricted diet exhibited anemia, left ventricular dilatation, and cardiac dysfunction compared with wild-type mice. Interestingly, altered cardiac mitochondrial biogenesis was observed in EpoR -/- -restricted mice following iron deficiency. Moreover, cardiac p53 expression was increased in EpoR -/- -restricted mice compared with wild-type mice following iron deficiency. Conclusion: These data indicate that EpoR signaling is associated with cardiac remodeling following chronic iron deficiency.

Original languageEnglish
Pages (from-to)1267-1275
Number of pages9
JournalJournal of Hypertension
Issue number6
StatePublished - Jun 6 2015

Bibliographical note

Publisher Copyright:
© 2015 Wolters Kluwer Health, Inc. All rights reserved.


  • anemia
  • cardiac remodeling
  • erythropoietin
  • erythropoietin receptor
  • iron deficiency

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Cardiac remodeling in response to chronic iron deficiency: Role of the erythropoietin receptor'. Together they form a unique fingerprint.

Cite this