Centro Malattie Metaboliche del Fegato, Department of Internal Medicine, Università degli Studi, Ospedale Maggiore Policlinico Ca' Granda IRCCS, Milano, Via F Sforza 35, 20122 Milano, Italy.
Arterioscler Thromb Vasc Biol. 2011 Mar;31(3):683-90. doi: 10.1161/ATVBAHA.110.214858. Epub 2010 Dec 23.
Increased body iron stores and hepcidin have been hypothesized to promote atherosclerosis by inducing macrophage iron accumulation and release of cytokines, but direct demonstration in human cells is lacking. The aim of this study was to evaluate the effect of iron on cytokine release in monocytes ex vivo and the correlation with vascular damage and to evaluate the relationship among serum levels of hepcidin, cytokines, and vascular damage in patients with metabolic syndrome alterations.
Manipulation of iron status with ferric ammonium citrate and hepcidin-25 induced monocyte chemoattractant protein (MCP)-1 and interleukin-6 in human differentiating monocytes of patients with hyperferritinemia associated with the metabolic syndrome (n=11), but not in subjects with hemochromatosis or HFE mutations impairing iron accumulation (n=15), and the degree of induction correlated with the presence of carotid plaques, detected by echocolor-Doppler. In monocytes of healthy subjects (n=7), iron and hepcidin increased the mRNA levels and release of MCP-1, but not of interleukin-6. In 130 patients with metabolic alterations, MCP-1 levels, as detected by ELISA, were correlated with hepcidin-25 measured by time-of-flight mass spectrometry (P=0.005) and were an independent predictor of the presence of carotid plaques (P=0.05).
Hepcidin and macrophage iron correlate with MCP-1 release and vascular damage in high-risk individuals with metabolic alterations.
铁储存增加和铁调素被假设通过诱导巨噬细胞铁积累和细胞因子释放来促进动脉粥样硬化，但在人类细胞中缺乏直接证据。本研究旨在评估铁对体外单核细胞细胞因子释放的影响及其与血管损伤的相关性，并评估代谢综合征改变患者血清铁调素、细胞因子和血管损伤之间的关系。
用柠檬酸铁铵和铁调素-25 操纵铁状态，诱导与代谢综合征相关的高血铁蛋白血症患者（n=11）分化中的单核细胞趋化蛋白-1（MCP-1）和白细胞介素-6 的释放，但在血色病或影响铁积累的 HFE 突变患者（n=15）中则没有，诱导程度与颈动脉斑块的存在相关，通过超声彩色多普勒检测。在健康受试者（n=7）的单核细胞中，铁和铁调素增加了 MCP-1 的 mRNA 水平和释放，但白细胞介素-6 则没有。在 130 名代谢改变的患者中，ELISA 检测到的 MCP-1 水平与飞行时间质谱法（time-of-flight mass spectrometry）测定的铁调素-25 相关（P=0.005），且是颈动脉斑块存在的独立预测因子（P=0.05）。
铁调素和巨噬细胞铁与代谢改变的高风险个体的 MCP-1 释放和血管损伤相关。
