Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages
Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages
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DOI：
10.1016/j.bbrc.2013.01.014
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发表时间：
2013-02-08
影响因子：
3.1
通讯作者：
Araki, Eiichi
中科院分区：
文献类型：
--
作者：
Kinoshita, Hiroyuki;Matsumura, Takeshi;Araki, Eiichi
巨噬细胞产生活性氧（ROS）和其他促炎物质在动脉粥样硬化中起重要作用。Apocynin（4-羟基-3-甲氧基-苯乙酮）是一种众所周知的NADPH氧化酶抑制剂，具有抗炎作用，包括抑制ROS的产生。然而，罗布麻素对动脉粥样硬化进展的抑制作用尚不清楚。因此，我们利用载脂蛋白e缺陷（apoE(-/-)）小鼠和体外小鼠腹腔巨噬细胞研究了夹竹桃素的抗动脉粥样硬化作用。在动脉粥样硬化易发apoE（-/-）小鼠中，夹带素抑制动脉粥样硬化的进展，降低动脉粥样硬化病变中4-羟基壬烯醛阳性区域，降低主动脉单核细胞趋化蛋白-1 （MCP-1）和白细胞介素-6 (IL-6) mRNA表达。在小鼠腹腔巨噬细胞中，罗布麻素抑制ox - ldl诱导的ROS生成，抑制MCP-1、IL-6和粒细胞/巨噬细胞集落刺激因子mRNA表达，抑制细胞增殖。此外，免疫组织化学研究显示，夹竹桃素可减少apoE（-/-）小鼠动脉粥样硬化病变中增殖细胞核抗原阳性巨噬细胞的数量。这些结果表明，罗布麻苷抑制动脉粥样硬化病变的形成，至少部分是通过使巨噬细胞失活。因此，罗布麻素可能是一种潜在的治疗材料，以防止动脉粥样硬化的进展。(C) 2013爱思唯尔公司版权所有。
Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages plays an important role in atherogenesis. Apocynin (4-hydroxy-3-methoxy-acetophenone), which is well known as a NADPH oxidase inhibitor, has anti-inflammatory effects including suppression of the generation of ROS. However, the suppressive effects of apocynin on the progression of atherosclerosis are not clearly understood. Thus, we investigated anti-atherosclerotic effects of apocynin using apolipoprotein E-deficient (apoE(-/-)) mice in vivo and in mouse peritoneal macrophages in vitro. In atherosclerosis-prone apoE(-/-) mice, apocynin suppressed the progression of atherosclerosis, decreased 4-hydroxynonenal-positive area in atherosclerotic lesions, and mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in aorta. In mouse peritoneal macrophages, apocynin suppressed the Ox-LDL-induced ROS generation, mRNA expression of MCP-1, IL-6 and granulocyte/macrophage colony-stimulating factor, and cell proliferation. Moreover, immunohistochemical studies revealed that apocynin decreased the number of proliferating cell nuclear antigen-positive macrophages in atherosclerotic lesions of apoE(-/-) mice. These results suggested that apocynin suppressed the formation of atherosclerotic lesions, at least in part, by inactivation of macrophages. Therefore, apocynin may be a potential therapeutic material to prevent the progression of atherosclerosis. (C) 2013 Elsevier Inc. All rights reserved.