Trem2促进泡性巨细胞的脂质吸收和动脉样硬化中的生存
Michael T Patterson1,2,3, Maria M Firulyova4,5,3, Yingzheng Xu1,2
1Center for Immunology, University of Minnesota, Minneapolis, MN, USA.
Nature cardiovascular research
|April 22, 2024
概括
在骨髓细胞2 (Trem2) 上表达的触发受体对于动脉样硬化中泡性巨细胞的功能至关重要. 失去Trem2会影响胆固醇的吸收和斑块的生长,将其确定为潜在的治疗点.
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
- 细胞生物学 细胞生物学
背景情况:
- 动脉样硬化涉及胆固醇载荷的泡性巨细胞在动脉斑块.
- 控制泡性巨细胞分化和生存的机制尚未完全理解.
研究的目的:
- 为了研究在发泡性巨细胞生物学和动脉样硬化中表达在髓状细胞2 (Trem2) 上的触发受体的作用.
- 确定Trem2作为动脉样硬化的潜在治疗标.
主要方法:
- 综合单细胞RNA测序数据分析与轨迹分析.
- 全基因组的CRISPR查以确定关键的调节者.
- 在动脉样硬化的小鼠模型中,特异于髓的Trem2删除.
- 评估泡性巨细胞的胆固醇吸收,增殖和生存.
主要成果:
- Trem2与泡性巨细胞的特征有关.
- 丢失的Trem2减少氧化低密度脂蛋白 (oxLDL) 的吸收由泡状巨细胞.
- 骨髓细胞特异性Trem2删除减轻了动脉样硬化斑块的进展,独立于系统因素.
- Trem2 缺乏会影响胆固醇排放,导致巨细胞的增殖和存活率降低.
结论:
- Trem2是泡性巨细胞分化和生存的关键调节者.
- 在动脉样硬化斑块的发展中,Trem2起着至关重要的作用.
- 向Trem2可能为动脉样硬化提供一种新的治疗策略.
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