来自IgE刺激性母细胞的外体细胞通过circRNA CDR1as-Mediated Endothelial Cell Dysfunction在小鼠中加剧喘介导的动脉样硬化
Hongqin Yang1, Junye Chen1,2, Siyang Liu1
1Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China (H.Y., J.C., S.L., Y.X., Z.L., J.W., H.Z.).
来自巨细胞的免疫球蛋白E (IgE) 通过携带圆形RNA CDR1as的外体促进了喘加重的动脉样硬化,影响内皮细胞并提供了新的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 心血管研究研究心血管研究
- 分子生物学分子生物学
背景情况:
- 免疫球蛋白E (IgE) 参与内皮功能障碍和巨细胞激活,有助于喘加重的动脉样硬化.
- 喘媒介性动脉样硬化的精确机制,特别是IgE在标准饮食和杆细胞-内皮细胞交叉作用中的作用,需要进一步阐明.
研究的目的:
- 通过使用标准实验室饮食,研究IgE-FcεR1信号在喘媒介性动脉样硬化中的作用.
- 探索涉及巨细胞分泌的外体和循环RNACDR1as在内皮细胞功能障碍中的机制.
主要方法:
- 使用了标准饮食中的喘-动脉样硬化小鼠模型和FcεR1淘汰小鼠.
- 通过Oil Red O染色和免疫组织化学评估动脉样硬化;使用纳米粒子跟踪和电子显微镜分析了外体.
- 通过免疫光和光 in situ 杂交,研究杆细胞衍生的外体对内皮细胞的影响,并在患者队伍中分析了血CDR1as.
主要成果:
- 接受标准饮食的喘小鼠表现出动脉样硬化病变和炎症的增加,这取决于IgE-FcεR1信号传递.
- FcεR1淘汰和IgE阻断 (奥马利祖马布) 显著降低了动脉样硬化和血管炎症.
- IgE刺激上调杆细胞外体CDR1as,通过CDR1as-FUS-p65通路促进内皮粘附分子 (VCAM-1,ICAM-1);动脉样硬化和过敏患者的血CDR1as升高.
结论:
- 来自IgE刺激的巨细胞的外体细胞通过CDR1as介导的内皮功能障碍加剧动脉样硬化.
- 这项研究揭示了喘媒介性动脉样硬化的一种新机制,突出了CDR1as作为潜在的诊断和治疗点.
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