RRC ID 32721
Author Naito Y, Sawada H, Oboshi M, Iwasaku T, Okuhara Y, Morisawa D, Eguchi A, Hirotani S, Mano T, Tsujino T, Masuyama T.
Title Cardiac remodeling in response to chronic iron deficiency: role of the erythropoietin receptor.
Journal J Hypertens
Abstract 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.
Volume 33(6)
Pages 1267-75
Published 2015-6-1
DOI 10.1097/HJH.0000000000000547
PMID 25715089
MeSH Anemia, Iron-Deficiency / complications* Animals Chronic Disease Disease Models, Animal Erythropoietin / metabolism Heart Failure / etiology* Heart Failure / pathology* Iron Deficiencies* Male Mice Mice, Knockout Myocardium / pathology* Receptors, Erythropoietin / genetics Receptors, Erythropoietin / physiology* Signal Transduction / drug effects
IF 4.171
Times Cited 5
Mice RBRC00985