• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

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.

DOI:10.18632/oncotarget.11180
PMID:27517153
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5302896/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5302896/7bab70adb610/oncotarget-07-56060-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5302896/9e49c77d06e6/oncotarget-07-56060-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5302896/bd2219e5b670/oncotarget-07-56060-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5302896/62af05ba6b12/oncotarget-07-56060-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5302896/f474a7e43f7b/oncotarget-07-56060-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5302896/e2f77e395e4c/oncotarget-07-56060-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5302896/7bab70adb610/oncotarget-07-56060-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5302896/9e49c77d06e6/oncotarget-07-56060-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5302896/bd2219e5b670/oncotarget-07-56060-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5302896/62af05ba6b12/oncotarget-07-56060-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5302896/f474a7e43f7b/oncotarget-07-56060-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5302896/e2f77e395e4c/oncotarget-07-56060-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5302896/7bab70adb610/oncotarget-07-56060-g006.jpg

相似文献

1
Overexpression of complement component C5a accelerates the development of atherosclerosis in ApoE-knockout mice.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。
Oncotarget. 2016 Aug 30;7(35):56060-56070. doi: 10.18632/oncotarget.11180.
2
Complement C5a inhibition reduces atherosclerosis in ApoE-/- mice.补体 C5a 抑制可减少 ApoE-/- 小鼠的动脉粥样硬化。
FASEB J. 2011 Jul;25(7):2447-55. doi: 10.1096/fj.10-174284. Epub 2011 Apr 13.
3
CCR5 facilitates endothelial progenitor cell recruitment and promotes the stabilization of atherosclerotic plaques in ApoE-/- mice.CCR5促进内皮祖细胞募集，并促进载脂蛋白E基因敲除小鼠动脉粥样硬化斑块的稳定。
Stem Cell Res Ther. 2015 Mar 19;6(1):36. doi: 10.1186/s13287-015-0026-0.
4
Immunization with a combination of 2 peptides derived from the C5a receptor significantly reduces early atherosclerotic lesion in Ldlr(tm1Her) Apob(tm2Sgy) J mice.用来源于 C5a 受体的 2 个肽的联合免疫显著减少 Ldlr(tm1Her) Apob(tm2Sgy) J 小鼠的早期动脉粥样硬化病变。
Arterioscler Thromb Vasc Biol. 2012 Oct;32(10):2358-71. doi: 10.1161/ATVBAHA.112.253179. Epub 2012 Jul 26.
5
C5a receptor targeting in neointima formation after arterial injury in atherosclerosis-prone mice.动脉损伤后动脉粥样硬化倾向小鼠内膜新生中 C5a 受体的靶向作用。
Circulation. 2010 Sep 7;122(10):1026-36. doi: 10.1161/CIRCULATIONAHA.110.954370. Epub 2010 Aug 23.
6
Endothelin-1 overexpression exacerbates atherosclerosis and induces aortic aneurysms in apolipoprotein E knockout mice.内皮素-1 过表达加剧载脂蛋白 E 基因敲除小鼠的动脉粥样硬化并诱导其发生主动脉瘤。
Arterioscler Thromb Vasc Biol. 2013 Oct;33(10):2306-15. doi: 10.1161/ATVBAHA.113.302028. Epub 2013 Jul 25.
7
Atheroprotective role of C5ar2 deficiency in apolipoprotein E-deficient mice.C5ar2缺乏在载脂蛋白E缺乏小鼠中的抗动脉粥样硬化作用。
Thromb Haemost. 2015 Oct;114(4):848-58. doi: 10.1160/TH14-12-1075. Epub 2015 Jun 18.
8
Complement 5a stimulates macrophage polarization and contributes to tumor metastases of colon cancer.补体 5a 可刺激巨噬细胞极化，并有助于结肠癌的肿瘤转移。
Exp Cell Res. 2018 May 15;366(2):127-138. doi: 10.1016/j.yexcr.2018.03.009. Epub 2018 Mar 15.
9
GM-CSF deficiency reduces macrophage PPAR-gamma expression and aggravates atherosclerosis in ApoE-deficient mice.粒细胞-巨噬细胞集落刺激因子缺乏会降低巨噬细胞中过氧化物酶体增殖物激活受体γ的表达，并加重载脂蛋白E缺乏小鼠的动脉粥样硬化。
Arterioscler Thromb Vasc Biol. 2006 Oct;26(10):2337-44. doi: 10.1161/01.ATV.0000238357.60338.90. Epub 2006 Jul 27.
10
Pivotal role of serum- and glucocorticoid-inducible kinase 1 in vascular inflammation and atherogenesis.血清和糖皮质激素诱导激酶1在血管炎症和动脉粥样硬化发生中的关键作用。
Arterioscler Thromb Vasc Biol. 2015 Mar;35(3):547-57. doi: 10.1161/ATVBAHA.114.304454. Epub 2015 Jan 22.

引用本文的文献

1
Exploring the intersection of atherosclerosis and Alzheimer's disease: the role of inflammation and complement activation.探索动脉粥样硬化与阿尔茨海默病的交叉点：炎症和补体激活的作用。
Inflamm Res. 2025 Jul 10;74(1):102. doi: 10.1007/s00011-025-02069-6.
2
Action of the Terminal Complement Pathway on Cell Membranes.补体终末途径对细胞膜的作用。
J Membr Biol. 2025 Mar 23. doi: 10.1007/s00232-025-00343-6.
3
Macrophages Unmasked: Their Pivotal Role in Driving Atherosclerosis in Systemic Lupus Erythematosus.巨噬细胞被揭开面纱：它们在系统性红斑狼疮引发动脉粥样硬化中的关键作用。

本文引用的文献

1
Immunization with a combination of 2 peptides derived from the C5a receptor significantly reduces early atherosclerotic lesion in Ldlr(tm1Her) Apob(tm2Sgy) J mice.用来源于 C5a 受体的 2 个肽的联合免疫显著减少 Ldlr(tm1Her) Apob(tm2Sgy) J 小鼠的早期动脉粥样硬化病变。
Arterioscler Thromb Vasc Biol. 2012 Oct;32(10):2358-71. doi: 10.1161/ATVBAHA.112.253179. Epub 2012 Jul 26.
2
Real-time imaging reveals that P2Y2 and P2Y12 receptor agonists are not chemoattractants and macrophage chemotaxis to complement C5a is phosphatidylinositol 3-kinase (PI3K)- and p38 mitogen-activated protein kinase (MAPK)-independent.实时成像显示，P2Y2 和 P2Y12 受体激动剂不是趋化因子，而补体 C5a 诱导的巨噬细胞趋化作用与磷脂酰肌醇 3-激酶（PI3K）和 p38 丝裂原活化蛋白激酶（MAPK）无关。
J Biol Chem. 2011 Dec 30;286(52):44776-87. doi: 10.1074/jbc.M111.289793. Epub 2011 Nov 4.
3
Clin Rev Allergy Immunol. 2025 Feb 7;68(1):10. doi: 10.1007/s12016-025-09025-6.
4
Canonical and non-canonical roles of complement in atherosclerosis.补体在动脉粥样硬化中的经典和非经典作用。
Nat Rev Cardiol. 2024 Nov;21(11):743-761. doi: 10.1038/s41569-024-01016-y. Epub 2024 Apr 10.
5
Significance of neutrophil extracellular traps-related gene in the diagnosis and classification of atherosclerosis.中性粒细胞胞外诱捕网相关基因在动脉粥样硬化诊断和分类中的意义。
Apoptosis. 2024 Jun;29(5-6):605-619. doi: 10.1007/s10495-023-01923-4. Epub 2024 Feb 17.
6
regulates atherosclerosis through an immune pathway.通过免疫途径调节动脉粥样硬化。
Front Immunol. 2023 Mar 14;14:1103592. doi: 10.3389/fimmu.2023.1103592. eCollection 2023.
7
Therapeutic Intervention with Anti-Complement Component 5 Antibody Does Not Reduce NASH but Does Attenuate Atherosclerosis and MIF Concentrations in Ldlr-/-.Leiden Mice.抗补体成分 5 抗体治疗干预不会减少 NASH，但会减轻 LDLR-/-.Leiden 小鼠的动脉粥样硬化和 MIF 浓度。
Int J Mol Sci. 2022 Sep 14;23(18):10736. doi: 10.3390/ijms231810736.
8
Inflammation in Metabolic and Cardiovascular Disorders-Role of Oxidative Stress.代谢与心血管疾病中的炎症——氧化应激的作用
Life (Basel). 2021 Jul 9;11(7):672. doi: 10.3390/life11070672.
9
Guanxinshutong Alleviates Atherosclerosis by Suppressing Oxidative Stress and Proinflammation in ApoE Mice.冠心舒通通过抑制载脂蛋白E基因敲除小鼠的氧化应激和促炎反应减轻动脉粥样硬化
Evid Based Complement Alternat Med. 2020 Sep 16;2020:1219371. doi: 10.1155/2020/1219371. eCollection 2020.
Complement C5a inhibition reduces atherosclerosis in ApoE-/- mice.补体 C5a 抑制可减少 ApoE-/- 小鼠的动脉粥样硬化。
FASEB J. 2011 Jul;25(7):2447-55. doi: 10.1096/fj.10-174284. Epub 2011 Apr 13.
4
C5a receptor targeting in neointima formation after arterial injury in atherosclerosis-prone mice.动脉损伤后动脉粥样硬化倾向小鼠内膜新生中 C5a 受体的靶向作用。
Circulation. 2010 Sep 7;122(10):1026-36. doi: 10.1161/CIRCULATIONAHA.110.954370. Epub 2010 Aug 23.
5
Chemokines in the vascular inflammatory response of atherosclerosis.趋化因子在动脉粥样硬化血管炎症反应中的作用。
Cardiovasc Res. 2010 May 1;86(2):192-201. doi: 10.1093/cvr/cvp391. Epub 2009 Dec 9.
6
The role of the anaphylatoxins in health and disease.过敏毒素在健康与疾病中的作用。
Mol Immunol. 2009 Sep;46(14):2753-66. doi: 10.1016/j.molimm.2009.04.027. Epub 2009 May 28.
7
Complement component 5a (C5a).补体成分 5a（C5a）。
Int J Biochem Cell Biol. 2009 Nov;41(11):2114-7. doi: 10.1016/j.biocel.2009.04.005. Epub 2009 Apr 11.
8
CD59 but not DAF deficiency accelerates atherosclerosis in female ApoE knockout mice.CD59而非衰变加速因子（DAF）的缺乏会加速雌性载脂蛋白E基因敲除小鼠的动脉粥样硬化进程。
Mol Immunol. 2009 May;46(8-9):1702-9. doi: 10.1016/j.molimm.2009.02.009. Epub 2009 Mar 17.
9
The role of complement in atherosclerosis.补体在动脉粥样硬化中的作用。
Curr Opin Lipidol. 2008 Oct;19(5):478-82. doi: 10.1097/MOL.0b013e32830f4a06.
10
Role of the calpain system in pulmonary vein connexin remodeling in dogs with atrial fibrillation.钙蛋白酶系统在心房颤动犬肺静脉连接蛋白重塑中的作用
Cardiology. 2009;112(1):22-30. doi: 10.1159/000137694. Epub 2008 Jun 25.