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Publication : Cardiac remodeling in response to chronic iron deficiency: role of the erythropoietin receptor.

First Author  Naito Y Year  2015
Journal  J Hypertens Volume  33
Issue  6 Pages  1267-75
PubMed ID  25715089 Mgi Jnum  J:259751
Mgi Id  MGI:6148152 Doi  10.1097/HJH.0000000000000547
Citation  Naito Y, et al. (2015) Cardiac remodeling in response to chronic iron deficiency: role of the erythropoietin receptor. J Hypertens 33(6):1267-75
abstractText  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.
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