Oral butyrate reduces oxidative stress in atherosclerotic lesion sites by a mechanism involving NADPH oxidase down-regulation in endothelial cells
Oral butyrate reduces oxidative stress in atherosclerotic lesion sites by a mechanism involving NADPH oxidase down-regulation in endothelial cells
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DOI：
10.1016/j.jnutbio.2016.05.002
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发表时间：
2016-08-01
影响因子：
5.6
通讯作者：
Alvarez-Leite, Jacqueline I.
中科院分区：
文献类型：
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作者：
Aguilar, Edenil C.;dos Santos, Lana Claudinez;Alvarez-Leite, Jacqueline I.
丁酸盐是一种4碳脂肪酸，具有抗炎和抗氧化特性。已有研究证明，丁酸盐可以通过减少炎症因子来减少动物模型中动脉粥样硬化的发展。然而，其丁酸盐的抗氧化作用在动脉粥样硬化形成中的作用尚未被研究。我们研究了丁酸对ApoE(-/-)小鼠动脉粥样硬化病变和oxLDL刺激的腹膜巨噬细胞和内皮细胞(EA.hy926)的氧化状态、活性氧(ROS)释放和氧化酶(NADPH氧化酶和iNOS)的影响。补充丁酸盐的小鼠主动脉病变面积减少，而主动脉瓣病变面积虽无改变，但超氧化物生成和蛋白质亚硝化减少。酵母多糖刺激后，丁酸组小鼠腹腔巨噬细胞自由基释放量降低。在oxLDL刺激前用丁酸盐处理内皮细胞，CCl-2和超氧阴离子生成量及NADPH氧化酶亚基p22Phox均减少。在巨噬细胞培养中，除了ROS释放减少外，一氧化氮和iNOS的表达也被下调。这些数据表明，丁酸盐对动脉粥样硬化发展的影响的一个机制是减少病变部位的氧化应激。补充丁酸盐可降低与NADPH氧化酶相关的氧化应激和iNOS的表达水平，从而减轻病变部位的内皮功能障碍和巨噬细胞的迁移和激活。(C)2016 Elsevier Inc.保留所有权利。
Butyrate is a 4-carbon fatty acid that has antiinflammatory and antioxidative properties. It has been demonstrated that butyrate is able to reduce atherosclerotic development in animal models by reducing inflammatory factors. However, the contribution of its antioxidative effects of butyrate on atherogenesis has not yet been studied. We investigated the influence of butyrate on oxidative status, reactive oxygen species (ROS) release and oxidative enzymes (NADPH oxidase and iNOS) in atherosclerotic lesions of ApoE(-/-) mice and in oxLDL-stimulated peritoneal macrophages and endothelial cells (EA.hy926). The lesion area in aorta was reduced while in the aortic valve, although lesion area was unaltered, superoxide production and protein nitrosylation were reduced in butyrate-supplemented mice. Peritoneal macrophages from the butyrate group presented a lower free radical release after zymosan stimulus. When endothelial cells were pretreated with butyrate before oxLDL stimulus, the CCL-2 and superoxide ion productions and NADPH oxidase subunit p22phox were reduced. In macrophage cultures, in addition to a reduction in ROS release, nitric oxide and iNOS expression were down-regulated. The data suggest that one mechanism related to the effect of butyrate on atherosclerotic development is the reduction of oxidative stress in the lesion site. The reduction of oxidative stress related to NADPH oxidase and iNOS expression levels associated to butyrate supplementation attenuates endothelium dysfunction and macrophage migration and activation in the lesion site. (C) 2016 Elsevier Inc. All rights reserved.