The role of iron metabolism as a mediator of macrophage inflammation and lipid handling in atherosclerosis.
The role of iron metabolism as a mediator of macrophage inflammation and lipid handling in atherosclerosis.
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DOI：
10.3389/fphar.2014.00195
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发表时间：
2014
影响因子：
5.6
通讯作者：
Finn AV
中科院分区：
文献类型：
--
作者：
Habib A;Finn AV
铁是正常生理过程所需的重要矿物质。虽然它在氧转运和其他重要生理过程中的功能是众所周知的，但对其在炎性疾病如动脉粥样硬化中的作用了解较少。现有的范例表明，铁作为动脉粥样硬化的驱动因素，通过其作为能够引起脂质氧化和组织损伤的促氧化剂的作用。最近，我们和其他人已经确定血红蛋白（Hb）衍生的铁作为一个重要因素，在决定巨噬细胞分化和功能的领域内的斑块出血在人类动脉粥样硬化。Hb相关的巨噬细胞M（Hb）不同于传统的巨噬泡沫细胞，因为它们不含有大量的脂质或炎性细胞因子，其特征在于除了产生抗炎细胞因子如IL-10之外，还高水平表达甘露糖受体（CD 206）和CD 163。尽管铁作为能够通过产生活性氧物质（ROS）如羟基自由基产生脂质过氧化的催化剂的作用是众所周知的，但我们和其他人已经表明，斑块内出血区域中的巨噬细胞表现出减少的细胞内铁和ROS，其触发抗炎细胞因子以及参与胆固醇释放的基因的产生。这些数据表明，操纵巨噬细胞铁本身可能是一个有前途的药理学目标动脉粥样硬化预防通过其对巨噬细胞炎症和脂质代谢的影响。在这篇综述中，我们将总结目前对铁的理解，因为它与斑块炎症和讨论如何进一步探索这一主题可能导致新的治疗动脉粥样硬化。
Iron is an essential mineral needed for normal physiologic processes. While its function in oxygen transport and other important physiologic processes is well known, less is understood about its role in inflammatory diseases such as atherosclerosis. Existing paradigms suggest iron as a driver of atherosclerosis through its actions as a pro-oxidant capable of causing lipid oxidation and tissue damage. Recently we and others have identified hemoglobin (Hb) derived iron as an important factor in determining macrophage differentiation and function in areas of intraplaque hemorrhage within human atherosclerosis. Hb associated macrophages, M(Hb), are distinct from traditional macrophage foam cells because they do not contain large amounts of lipid or inflammatory cytokines, are characterized by high levels of expression of mannose receptor (CD206) and CD163 in addition to producing anti-inflammatory cytokines such as IL-10. Despite the well-known role of iron as an catalyst capable of producing lipid peroxidation through generation of reactive oxygen species (ROS) such as hydroxyl radical, we and others have shown that macrophages in areas of intraplaque hemorrhage demonstrate reduced intracellular iron and ROS which triggers production of anti-inflammatory cytokines as well as genes involved in cholesterol efflux. These data suggest that manipulation of macrophage iron itself may be a promising pharmacologic target for atherosclerosis prevention through its effects on macrophage inflammation and lipid metabolism. In this review we will summarize the current understanding of iron as it relates to plaque inflammation and discuss how further exploration of this subject may lead to new therapies for atherosclerosis.
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影响因子：
37.8
作者：
LIBBY, P
通讯作者：
LIBBY, P
影响因子：
6
作者：
Boyle, Joseph J.;Harrington, Heather A.;Haskard, Dorian O.
通讯作者：
Haskard, Dorian O.
影响因子：
29
作者：
Bouhlel, M. Amine;Derudas, Bruno;Chinetti-Gbaguidi, Giulia
通讯作者：
Chinetti-Gbaguidi, Giulia
影响因子：
37.8
作者：
Ellervik, C;Tybjærg- Hansen, A;Nordestgaard, BG
通讯作者：
Nordestgaard, BG
DOI：
10.1161/atvbaha.110.206433
发表时间：
2010-07
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Nagy E;Eaton JW;Jeney V;Soares MP;Varga Z;Galajda Z;Szentmiklósi J;Méhes G;Csonka T;Smith A;Vercellotti GM;Balla G;Balla J
通讯作者：
Balla J