Overexpression of Peroxiredoxin 4 Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice
Overexpression of Peroxiredoxin 4 Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice
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DOI：
10.1089/ars.2012.4549
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发表时间：
2012-11-01
影响因子：
6.6
通讯作者：
Sasaguri, Yasuyuki
中科院分区：
文献类型：
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作者：
Guo, Xin;Yamada, Sohsuke;Sasaguri, Yasuyuki
目的：越来越多的证据表明，血管内氧化分子和活性氧物质的形成增加（即，细胞外空间）在动脉粥样硬化的起始和发展以及不稳定斑块的形成中起关键作用。Peroxiredoxin 4（PRDX 4）是抗氧化剂PRDX家族中唯一已知的分泌型成员。然而，PRDX 4与动脉粥样硬化易感性之间的关系仍不清楚。结果如下：为了确定PRDX 4在高血压诱导的动脉粥样硬化中的作用，我们产生了hPRDX 4转基因（Tg）和载脂蛋白E（apoE）敲除小鼠（hPRDX 4（+/+）/apoE（-/-））。与apoE（-/-）小鼠相比，喂食高胆固醇饮食后，小鼠显示出更少的动脉粥样硬化斑块，更少的T淋巴细胞浸润，更低水平的氧化应激标志物，更少的坏死，更多数量的平滑肌细胞和更多数量的胶原蛋白，导致增厚的纤维帽形成和可能稳定的斑块表型。我们还检测到hPRDX 4（+/+）/apoE（-/-）小鼠比apoE（-/-）小鼠更大的细胞凋亡抑制和Bax表达降低。从hPRDX 4（+/+）供体到apoE（-/-）小鼠的骨髓移植证实了PRDX 4的抗动脉粥样硬化方面，揭示了显著抑制的动脉粥样硬化进展。创新：在这项研究中，我们首次证明PRDX 4抑制了高胆固醇饮食apoE（-/-）小鼠动脉粥样硬化的发展。结论：这些数据表明，PRDX 4是一种抗动脉粥样硬化因子，通过抑制氧化损伤和细胞凋亡，它可以防止脆弱（不稳定）斑块的形成。抗氧化剂。氧化还原信号。17，1362-1375.
Aim: A growing body of evidence has shown that increased formation of oxidized molecules and reactive oxygen species within the vasculature (i.e., the extracellular space) plays a crucial role in the initiation and progression of atherosclerosis and in the formation of unstable plaques. Peroxiredoxin 4 (PRDX4) is the only known secretory member of the antioxidant PRDX family. However, the relationship between PRDX4 and susceptibility to atherosclerosis has remained unclear. Results: To define the role of PRDX4 in hyperlipidemia-induced atherosclerosis, we generated hPRDX4 transgenic (Tg) and apolipoprotein E (apoE) knockout mice (hPRDX4(+/+)/apoE(-/-)). After feeding the mice a high-cholesterol diet, they showed fewer atheromatous plaques, less T-lymphocyte infiltration, lower levels of oxidative stress markers, less necrosis, a larger number of smooth muscle cells, and a larger amount of collagen, resulting in thickened fibrous cap formation and possible stable plaque phenotype as compared with apoE(-/-) mice. We also detected greater suppression of apoptosis and decreased Bax expression in hPRDX4(+/+)/apoE(-/-) mice than in apoE(-/-) mice. Bone marrow transplantation from hPRDX4(+/+) donors to apoE(-/-) mice confirmed the antiatherogenic aspects of PRDX4, revealing significantly suppressed atherosclerotic progression. Innovation: In this study, we demonstrated for the first time that PRDX4 suppressed the development of atherosclerosis in apoE(-/-) mice fed a high-cholesterol diet. Conclusion: These data indicate that PRDX4 is an antiatherogenic factor and, by suppressing oxidative damage and apoptosis, that it may protect against the formation of vulnerable (unstable) plaques. Antioxid. Redox Signal. 17, 1362-1375.