Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice
Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice
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DOI：
10.1007/s00394-014-0749-1
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发表时间：
2015-08-01
影响因子：
5
通讯作者：
Tamaki, Toshiaki
中科院分区：
文献类型：
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作者：
Tajima, Soichiro;Ikeda, Yasumasa;Tamaki, Toshiaki
目的血管紧张素II（ANG II）通过改变铁转运蛋白影响铁代谢，导致细胞和组织铁含量增加。血清铁蛋白是体内铁储存的标志物，在包括高血压在内的各种心血管疾病中升高。然而，相关的铁吸收的变化和铁含量增加的机制在高血压state.Methods C57 BL 6/J小鼠与ANG II治疗产生的高血压模型尚不清楚。将小鼠分为3组：（1）对照组，（2）ANG II处理组，（3）ANG II处理组和ANG II受体阻断剂（ARB）处理组（ANG II-ARB）。在ANG II处理的小鼠中，十二指肠二价金属转运蛋白-1和FPN表达水平增加，肝铁调素mRNA表达和血清铁调素浓度降低。骨形态发生蛋白6和CCAAT/增强子结合蛋白α（铁调素的调节因子）的mRNA表达在ANG II治疗小鼠的肝脏中也下调。在组织铁含量方面，巨噬细胞铁含量和肾铁含量通过ANG II处理增加，并且这些增加与转铁蛋白受体1和FPN的表达减少和铁蛋白的表达增加相关。ANG II治疗引起的这些变化通过ARB的管理得到改善。结论血管紧张素II（ANG II）改变了十二指肠铁转运蛋白的表达，降低了铁调素水平，有助于改变体内铁的分布。
Purpose Angiotensin II (ANG II) has been shown to affect iron metabolism through alteration of iron transporters, leading to increased cellular and tissue iron contents. Serum ferritin, a marker of body iron storage, is elevated in various cardiovascular diseases, including hypertension. However, the associated changes in iron absorption and the mechanism underlying increased iron content in a hypertensive state remain unclear.Methods The C57BL6/J mice were treated with ANG II to generate a model of hypertension. Mice were divided into three groups: (1) control, (2) ANG II-treated, and (3) ANG II-treated and ANG II receptor blocker (ARB)-administered (ANG II-ARB) groups.Results Mice treated with ANG II showed increased serum ferritin levels compared to vehicle-treated control mice. In ANG II-treated mice, duodenal divalent metal transporter-1 and ferroportin (FPN) expression levels were increased and hepatic hepcidin mRNA expression and serum hepcidin concentration were reduced. The mRNA expression of bone morphogenetic protein 6 and CCAAT/enhancer-binding protein alpha, which are regulators of hepcidin, was also down-regulated in the livers of ANG II-treated mice. In terms of tissue iron content, macrophage iron content and renal iron content were increased by ANG II treatment, and these increases were associated with reduced expression of transferrin receptor 1 and FPN and increased expression of ferritin. These changes induced by ANG II treatment were ameliorated by the administration of an ARB.Conclusions Angiotensin II (ANG II) altered the expression of duodenal iron transporters and reduced hepcidin levels, contributing to the alteration of body iron distribution.