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CD137 (4-1BB) 缺乏在高脂血症小鼠中减少动脉样硬化
Hyung Jun Jeon1, Jae-Hoon Choi, In-Hyuk Jung
1Division of Life and Pharmaceutical Science, Ewha Womans University, Seoul, Korea.
Circulation
|February 24, 2010
概括
阻止CD137 (4-1BB) 信号传输可以减少动脉样硬化的进展. 这一途径促进炎症分子和细胞因子,有助于斑块形成. 向CD137为动脉样硬化提供了一个有前途的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
背景情况:
- 瘤亡因子受体超级家族与动脉样硬化有关.
- CD137 (4-1BB) 在动脉样硬化病变中存在,但其具体作用尚不清楚.
- 了解CD137的功能对于开发动脉样硬化疗法至关重要.
研究的目的:
- 研究CD137在动脉样硬化发展中的作用.
- 为了确定阻断CD137/CD137连接体信号传递对病变形成的影响.
主要方法:
- 生成的CD137缺乏的阿波利波蛋白E-淘汰赛 (ApoE(-/-) CD137(-/-)) 和LDL受体淘汰赛 (Ldlr(-/-) CD137(-/-)) 的小鼠.
- 分析了动脉样硬化斑块的大小和炎症标志物.
主要成果:
- 在两种小鼠模型中,CD137缺乏减少了动脉样硬化斑块病变.
- 减少的病变与干扰素-,单细胞化疗吸引蛋白-1和瘤缩因子-α水平的降低相关.
- 在内皮细胞和激活的单细胞/巨细胞中,CD137信号上调的炎症分子 (MCP-1,IL-6,VCAM-1,ICAM-1).
结论:
- CD137/CD137连接体信号传递在动脉样硬化进展中起着重要作用.
- 阻断CD137通路是治疗动脉样硬化的潜在治疗标.
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