Adaptive response of the heart to long-term anemia induced by iron deficiency
Adaptive response of the heart to long-term anemia induced by iron deficiency
复制标题
DOI：
10.1152/ajpheart.00463.2008
复制
发表时间：
2009-03-01
影响因子：
4.8
通讯作者：
Masuyama, Tohru
中科院分区：
文献类型：
--
作者：
Naito, Yoshiro;Tsujino, Takeshi;Masuyama, Tohru
[10]张文忠，张文忠.心脏对缺铁引起的长期贫血的适应性反应。Am J Physiol Heart Circ Physiol 296：H585-H593，2009.首次发表于2009年1月9日; doi：10.1152/ajpheart.00463.2008。贫血在慢性心力衰竭患者中很常见，是预后不良的独立预测因素。慢性贫血导致左心室（LV）肥大和心力衰竭，但其分子机制仍不清楚。本研究探讨了缺铁性贫血（IDA）诱导心脏重构的分子信号转导机制。用缺铁饲料喂养断乳SD大鼠20 wk，诱导缺铁性贫血（IDA），并探讨心脏重构的分子机制。缺铁饮食最初诱导严重贫血，导致左心室肥大和扩张，保留与血清促红细胞生成素（Epo）浓度增加相关的收缩功能。心脏STAT 3磷酸化和VEGF基因表达增加12周的IDA，引起心脏血管生成。此后，持续性IDA诱导心脏缺氧诱导因子-1 α基因表达上调，并维持心脏VEGF基因表达和心脏血管生成的上调;然而，持续性IDA促进心脏纤维化和肺充血，与12周相比，IDA 20周后血清Epo浓度和心脏STAT 3磷酸化水平降低。血清Epo浓度和心脏STAT 3磷酸化的上调与贫血诱导的心脏肥大的有益适应机制相关，并且随后这些分子的水平降低可能对于长期贫血中从适应性心脏肥大向心功能障碍的转变至关重要。了解心脏对贫血适应不良的机制可能为慢性心力衰竭合并贫血的治疗提供新的策略。
Naito Y, Tsujino T, Matsumoto M, Sakoda T, Ohyanagi M, Masuyama T. Adaptive response of the heart to long-term anemia induced by iron deficiency. Am J Physiol Heart Circ Physiol 296: H585-H593, 2009. First published January 9, 2009; doi:10.1152/ajpheart.00463.2008.-Anemia is common in patients with chronic heart failure and an independent predictor of poor prognosis. Chronic anemia leads to left ventricular (LV) hypertrophy and heart failure, but its molecular mechanisms remain largely unknown. We investigated the mechanisms, including the molecular signaling pathway, of cardiac remodeling induced by iron deficiency anemia (IDA). Weanling Sprague-Dawley rats were fed an iron-deficient diet for 20 wk to induce IDA, and the molecular mechanisms of cardiac remodeling were evaluated. The iron-deficient diet initially induced severe anemia, which resulted in LV hypertrophy and dilation with preserved systolic function associated with increased serum erythropoietin (Epo) concentration. Cardiac STAT3 phosphorylation and VEGF gene expression increased by 12 wk of IDA, causing angiogenesis in the heart. Thereafter, sustained IDA induced upregulation of cardiac hypoxia inducible factor-1 alpha gene expression and maintained upregulation of cardiac VEGF gene expression and cardiac angiogenesis; however, sustained IDA promoted cardiac fibrosis and lung congestion, with decreased serum Epo concentration and cardiac STAT3 phosphorylation after 20 wk of IDA compared with 12 wk. Upregulation of serum Epo concentration and cardiac STAT3 phosphorylation is associated with a beneficial adaptive mechanism of anemia-induced cardiac hypertrophy, and later decreased levels of these molecules may be critical for the transition from adaptive cardiac hypertrophy to cardiac dysfunction in long-term anemia. Understanding the mechanism of cardiac maladaptation to anemia may lead to a new strategy for treatment of chronic heart failure with anemia.