Iron loading increases cholesterol accumulation and macrophage scavenger receptor I expression in THP-1 mononuclear phagocytes
Iron loading increases cholesterol accumulation and macrophage scavenger receptor I expression in THP-1 mononuclear phagocytes
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DOI：
10.1016/j.metabol.2004.10.012
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发表时间：
2005-04-01
影响因子：
9.8
通讯作者：
Lopes-Virella, MF
中科院分区：
文献类型：
--
作者：
Kraml, PJ;Klein, RL;Lopes-Virella, MF
流行病学研究已经证实，高水平的铁体储备与急性冠心病风险的增加有关。为了解释这种联系，有人提出铁催化产生高活性形式的游离氧物种，从而促进低密度脂蛋白(LDL)的氧化，低密度脂蛋白是一种在动脉粥样硬化形成中起关键作用的脂蛋白。然而，很少有研究提供证据来支持这一假设。在本研究中，我们测定了THP-1单核巨噬细胞铁负荷对低密度脂蛋白代谢的影响。我们证明了THP-1细胞的铁负荷促进了培养上清液中低密度脂蛋白共轭二烯的形成。此外，THP-1细胞的铁负荷显著增加了暴露于天然低密度脂蛋白的细胞中胆固醇酯的积累，这表明在细胞与天然低密度脂蛋白孵育过程中，低密度脂蛋白被氧化并被细胞摄取。我们进一步证明，在铁负载的THP-1细胞中，I-125氧化的低密度脂蛋白的降解显著增加。最后，我们证明了铁负荷的THP-1细胞促进了清道夫受体的表达。综上所述，本研究证实了单核巨噬细胞铁负荷导致低密度脂蛋白氧化、细胞胆固醇积聚和清道夫受体表达增加，并支持巨噬细胞铁水平升高促进动脉粥样硬化形成的假说。(C)2005 Elsevier Inc.保留所有权利。
Epidemiological studies have established that a high level of iron body stores is associated with increased risk of acute coronary heart disease. To explain this association, it has been proposed that iron catalyzes the production of highly reactive forms of free oxygen species, and thus, promotes low-density lipoprotein (LDL) oxidation, a lipoprotein that plays a critical role in atherogenesis. However, few studies have provided evidence to support this hypothesis. In the present study, we determined the effect of iron loading of THP-1 mononuclear phagocytes on LDL metabolism. We demonstrated that iron loading of THP-1 cells stimulated conjugated diene formation in LDL in the culture medium. In addition, iron loading of THP-1 cells significantly increased cholesteryl ester accumulation in cells exposed to native LDL, suggesting that during the incubation of the cells with native LDL, the LDL became oxidized and was taken up by the cells. We further demonstrated that the degradation of I-125-oxidized LDL was significantly increased in iron-loaded THP-1 cells. Lastly, we demonstrated that iron loading of THP-1 cells stimulated scavenger receptor expression in these cells. In conclusion, this study demonstrates that loading of mononuclear phagocytes with iron leads to oxidization of LDL, increased cellular cholesterol accumulation and scavenger receptor expression, and supports the hypothesis that increased macrophage iron levels promote atherogenesis. (c) 2005 Elsevier Inc. All rights reserved.