TREM2调节巨细胞的热和炎症反应,以改善大动脉的化
Jin-Hui Bian1, Chun-Ze Yuan1, Jia-Xi Gu1
1Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 Jiangsu, China.
在骨髓细胞2 (TREM2) 上表达的触发受体调节了动脉疾病 (CAVD) 中的巨细胞功能. 抑制TREM2会恶化大动脉的化,突出显示TREM2是CAVD的治疗标.
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
- 细胞的新陈代谢
背景情况:
- 动脉疾病 (CAVD) 涉及门的加厚和化,门间歇细胞 (VICs) 分化为骨质细胞样细胞.
- 巨细胞影响VIC分化,在CAVD中触发受体表达在骨髓细胞2 (TREM2) 的作用尚不清楚.
研究的目的:
- 在CAVD的背景下,研究巨细胞中TREM2的表达和功能.
- 阐明巨细胞TREM2影响VIC骨质分化和大动脉结石化的机制.
主要方法:
- 在公共数据集和临床CAVD样本中分析TREM2表达.
- 使用高脂肪饮食诱导的ApoE淘汰赛小鼠模型和THP-1-VIC共同培养系统来研究TREM2对VICs的影响.
主要成果:
- 在CAVD患者的巨细胞中,TREM2显著升高.
- 在小鼠中,TREM2的抑制加剧了大动脉的化,激活了NLRP3炎症酶和热.
- 通过PI3K/AKT通路,TREM2的下调会影响氧化酸化 (OXPHOS),减少ATP的产生,并增加活性氧物种 (ROS).
结论:
- TREM2在调节巨细胞氧化酸化,NLRP3炎症酶激活,热和CAVD炎症方面发挥着至关重要的作用.
- 针对TREM2提供了一种潜在的治疗策略,以缓解大动脉结石化和减缓CAVD进展.
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