Cardiac remodeling in response to chronic iron deficiency: role of the erythropoietin receptor.
Cardiac remodeling in response to chronic iron deficiency: role of the erythropoietin receptor.
复制标题
慢性铁缺乏引起的心脏重塑：促红细胞生成素受体的作用。
DOI：
10.1097/hjh.0000000000000547
复制
发表时间：
2015
影响因子：
4.9
通讯作者：
Masuyama T.
中科院分区：
文献类型：
--
作者：
Naito Y;Sawada H;Oboshi M;Iwasaku T;Okuhara Y;Morisawa D;Eguchi A;Hirotani S;Mano T;Tsujino T;Masuyama T.
目的：贫血是心衰患者常见的合并症，缺铁是心衰患者贫血的原因之一。最近的研究表明，单纯缺铁而无明显贫血与心力衰竭患者预后不良有关。因此，为了最大限度地降低心力衰竭患者的死亡率，了解缺铁与心功能之间的联系是很重要的。长期未经治疗的缺铁导致心脏重塑，我们之前报道过促红细胞生成素（Epo）和心脏Epo受体（EpoR）信号可能与心脏重塑有关。然而，EpoR信号与其重塑之间的联系仍有待阐明。在此，我们研究了EpoR信号在慢性缺铁心脏重构中的作用。方法：将野生型小鼠和转基因拯救的EpoR缺失突变小鼠（仅在造血系中表达EpoR）分别饲喂正常和限铁饮食，并研究其分子机制。结果：限铁逐渐诱导小鼠贫血、促红细胞生成素分泌和心肌肥厚。相反，与野生型小鼠相比，饲喂限铁饮食的EpoR - / -限制小鼠表现出贫血、左心室扩张和心功能障碍。有趣的是，缺铁后，EpoR - / -受限小鼠心肌线粒体生物发生发生改变。此外，与野生型小鼠相比，缺铁后EpoR−/−受限小鼠的心脏p53表达增加。结论：这些数据表明EpoR信号与慢性缺铁后的心脏重构有关。
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.