由流动干扰诱导的内皮CCRL2通过单细胞中依赖于化学素的β2整体激活促进动脉样硬化
Chaojun Tang1,2,3,4,5, Guona Chen1, Fan Wu1,6
1Cyrus Tang Medical Institute, Soochow University, Rm 509, Bldg 703, 199 Ren'ai Road, Suzhou 215123, China.
Cardiovascular research
|June 6, 2023
概括
扰乱血液流动可以调节非典型的化学激素受体5 (CCRL2),从而促进动脉样硬化. 这种新的途径涉及化学素和β-2整合素,为预防斑块形成提供了新的治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 分子医学是分子医学.
背景情况:
- 动脉样硬化是由白细胞向动脉壁招募的驱动,特别是在流动受损的区域 (d-流).
- 非典型的化学因受体 (ACKRs),包括ACKR5 (CCRL2),都与炎症过程有关.
- 在动脉样硬化条件下和d流下,CCRL2在内皮细胞中被上调.
研究的目的:
- 为了研究CCRL2及其配体化学素在动脉样硬化中的作用.
- 阐明在d流区域中CCRL2介导的白细胞招募的潜在分子机制.
主要方法:
- 在d-flow下分析从小鼠动脉中单细胞RNA测序数据的分析.
- 使用CCRL2-/-ApoE-/-小鼠食高脂肪饮食以评估斑块形成.
- 通过生物化学试验和近距离结合试验,研究了基梅林与β-2整合素的相互作用.
主要成果:
- 在d流和动脉样硬化条件下,内皮细胞中CCRL2的表达增加.
- 在ApoE-/-小鼠中,CCRL2缺乏减少了动脉样硬化斑块的形成,特别是在d流区域.
- 化学素通过其类似蛋白质二硫化异构酶的活性激活β-2整合素,增强单细胞粘附和ERK1/2酸化.
- 在急性动脉血栓性中风患者中观察到血清海默林水平升高.
结论:
- 由流动干扰诱导的CCRL2通过新型CCRL2-chemerin-beta-2整合因子轴促进动脉样斑块的形成.
- 这一途径代表了动脉样硬化预防和治疗的潜在治疗标.
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