TY - JOUR
T1 - Cardiac remodeling in response to chronic iron deficiency
T2 - Role of the erythropoietin receptor
AU - Naito, Yoshiro
AU - Sawada, Hisashi
AU - Oboshi, Makiko
AU - Iwasaku, Toshihiro
AU - Okuhara, Yoshitaka
AU - Morisawa, Daisuke
AU - Eguchi, Akiyo
AU - Hirotani, Shinichi
AU - Mano, Toshiaki
AU - Tsujino, Takeshi
AU - Masuyama, Tohru
N1 - Publisher Copyright:
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2015/6/6
Y1 - 2015/6/6
N2 - 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.
AB - 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.
KW - anemia
KW - cardiac remodeling
KW - erythropoietin
KW - erythropoietin receptor
KW - iron deficiency
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U2 - 10.1097/HJH.0000000000000547
DO - 10.1097/HJH.0000000000000547
M3 - Article
C2 - 25715089
AN - SCOPUS:84929456817
SN - 0263-6352
VL - 33
SP - 1267
EP - 1275
JO - Journal of Hypertension
JF - Journal of Hypertension
IS - 6
ER -