Department of Nephrology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey.
Department of Nephrology, Faculty of Medicine, Koc University, Istanbul, Turkey.
Mol Cell Biochem. 2021 Sep;476(9):3365-3381. doi: 10.1007/s11010-021-04168-4. Epub 2021 May 4.
Iron is an essential trace element involved in oxidation-reduction reactions, oxygen transport and storage, and energy metabolism. Iron in excess can be toxic for cells, since iron produces reactive oxygen species and is important for survival of pathogenic microbes. There is a fine-tuning in the regulation of serum iron levels, determined by intestinal absorption, macrophage iron recycling, and mobilization of hepatocyte stores versus iron utilization, primarily by erythroid cells in the bone marrow. Hepcidin is the major regulatory hormone of systemic iron homeostasis and is upregulated during inflammation. Hepcidin metabolism is altered in chronic kidney disease. Ferroportin is an iron export protein and mediates iron release into the circulation from duodenal enterocytes, splenic reticuloendothelial macrophages, and hepatocytes. Systemic iron homeostasis is controlled by the hepcidin-ferroportin axis at the sites of iron entry into the circulation. Hepcidin binds to ferroportin, induces its internalization and intracellular degradation, and thus inhibits iron absorption from enterocytes, and iron release from macrophages and hepatocytes. Recent data suggest that hepcidin, by slowing or preventing the mobilization of iron from macrophages, may promote atherosclerosis and may be associated with increased cardiovascular disease risk. This article reviews the current data regarding the molecular and cellular pathways of systemic and autocrine hepcidin production and seeks the answer to the question whether changes in hepcidin translate into clinical outcomes of all-cause and cardiovascular mortality, and cardiovascular and renal end-points.
铁是一种必需的微量元素，参与氧化还原反应、氧气运输和储存以及能量代谢。过量的铁对细胞是有毒的，因为铁会产生活性氧物种，对致病微生物的生存很重要。血清铁水平的调节非常精细，由肠道吸收、巨噬细胞铁再循环以及肝细胞储存的动员与铁的利用（主要是骨髓中的红细胞）决定。铁调素是调节全身铁稳态的主要激素，在炎症期间上调。慢性肾脏病患者的铁调素代谢发生改变。亚铁转运蛋白是一种铁输出蛋白，介导十二指肠肠上皮细胞、脾脏网状内皮巨噬细胞和肝细胞向循环中释放铁。全身铁稳态由铁进入循环的铁调素-亚铁转运蛋白轴控制。铁调素与亚铁转运蛋白结合，诱导其内化和细胞内降解，从而抑制肠上皮细胞吸收铁，以及巨噬细胞和肝细胞释放铁。最近的数据表明，铁调素通过减缓或阻止巨噬细胞中铁的动员，可能促进动脉粥样硬化，并可能与心血管疾病风险增加有关。本文综述了有关全身和自分泌铁调素产生的分子和细胞途径的最新数据，并试图回答以下问题：铁调素的变化是否转化为全因和心血管死亡率以及心血管和肾脏终点的临床结局。
