补体成分C5a的过表达加速了载脂蛋白E基因敲除小鼠动脉粥样硬化的发展。
Overexpression of complement component C5a accelerates the development of atherosclerosis in ApoE-knockout mice.
作者信息
An Guipeng, Li Bo, Liu Xiaoman, Zhang Mingxiang, Gao Fei, Zhao Yuxia, An Fengshuang, Zhang Yun, Zhang Cheng
机构信息
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, China.
Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong, China.
出版信息
Oncotarget. 2016 Aug 30;7(35):56060-56070. doi: 10.18632/oncotarget.11180.
BACKGROUND
In this study, we investigated the direct effect of C5a overexpression on atherosclerosis.
METHODS AND RESULTS
A recombinant adenovirus expressing mouse C5a (Ad-C5a) was constructed and injected intravenously into ApoE-/- mice. After 12 weeks of a high-fat diet, Ad-C5a injection produced more extensive lesions than control adenovirus, and its proathrosclerotic role was significantly blocked by C5a receptor antagonist. Immunohistochemical analysis showed enhanced macrophage infiltration in atherosclerotic regions with C5a overexpression. Trans-well assay revealed C5a receptor-dependent chemotaxis of C5a to macrophages. Furthermore, Ad-C5a overexpression promoted foam cell formation and lipid deposition but reduced collagen content. In addition, with Ad-C5a overexpression, the serum levels of interleukin 6 and tumor necrosis factor α were upregulated.
CONCLUSIONS
C5a overexpression could accelerate the development of atherosclerosis in ApoE-/- mice by promoting macrophage recruitment, foam cell formation and inflammatory activation. Furthermore, its proatherogetic role is mediated by the C5a receptor.
背景
在本研究中，我们调查了C5a过表达对动脉粥样硬化的直接影响。
方法与结果
构建了表达小鼠C5a的重组腺病毒（Ad-C5a），并将其静脉注射到载脂蛋白E基因敲除（ApoE-/-）小鼠体内。高脂饮食12周后，注射Ad-C5a比注射对照腺病毒产生了更广泛的病变，并且C5a受体拮抗剂显著阻断了其促动脉粥样硬化作用。免疫组织化学分析显示，C5a过表达时动脉粥样硬化区域巨噬细胞浸润增强。Trans-well实验揭示了C5a对巨噬细胞的C5a受体依赖性趋化作用。此外，Ad-C5a过表达促进了泡沫细胞形成和脂质沉积，但降低了胶原蛋白含量。另外，随着Ad-C5a过表达，白细胞介素6和肿瘤坏死因子α的血清水平上调。
结论
C5a过表达可通过促进巨噬细胞募集、泡沫细胞形成和炎症激活来加速ApoE-/-小鼠动脉粥样硬化的发展。此外，其促动脉粥样硬化作用由C5a受体介导。
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