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长非编码RNA lncAPAT通过向核糖体蛋白L2222来促进动脉样硬化斑块的不稳定性
Rongxia Li1, Qiyue Zhang2, Yu Chen1
1State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Clinical and translational medicine
|January 13, 2026
概括
一种新的长非编码RNA (lncRNA),IncAPAT,在冠状动脉疾病 (CAD) 患者中表达高. 通过抑制RPL22,LncAPAT促进巨细胞炎症和斑块不稳定,从而有助于心血管疾病的进展.
科学领域:
- 心血管生物学 心血管生物学
- 在RNA生物学,RNA生物学.
- 分子医学是分子医学.
背景情况:
- 长非编码RNAs (lncRNAs) 在调节巨细胞炎症和动脉样硬化斑块稳定性方面发挥着至关重要的作用.
- 需要对lncRNA参与动脉样硬化的精确机制进行全面的调查.
研究的目的:
- 为了识别和表征一种新型的人类特异性lncRNA,IncAPAT (动脉硬性斑块不稳定性相关的转录).
- 阐明IncAPAT在巨细胞炎症和动脉样硬化斑块不稳定中的作用.
主要方法:
- 全转录组测序用于在冠状动脉疾病 (CAD) 患者中识别lncAPAT.
- 定量实时聚合酶连锁反应 (qRT-PCR) 用于IncAPAT表达的验证.
- 产生髓状细胞特异性的IncAPAT敲进小鼠,以在体内研究动脉样硬化.
- 在体外巨细胞培养以评估IncAPAT功能.
- 通过RNA净化和测序 (ChIRP-seq) 和RNA免疫沉 (RIP) 的染色质分离试验来确定lncAPAT的点.
主要成果:
- 在CAD和ST段升高心肌梗塞 (STEMI) 患者的外周血液中,LncAPAT表达显著升高.
- 在小鼠中,骨髓细胞特异性的IncAPAT过度表达导致斑块负担增加,巨细胞透和矩阵金属蛋白酶 (MMP) 表达.
- 在体外,IncAPAT促进了巨细胞的炎症反应,胆固醇的积累,并减少了胆固醇的流失.
- 发现LncAPAT与核糖体蛋白L22 (RPL22) 的促进体相互作用,抑制其转录.
- 抑制RPL22导致炎症性细胞因子的表达增加,并通过与MCP-1mRNA的直接相互作用减少单细胞化学吸引蛋白-1 (MCP-1) 的表达.
结论:
- LncAPAT是一种新的生物标志物和冠状动脉疾病的致病因子.
- 通过通过RPL22/MCP-1通路增强巨细胞炎症,LncAPAT促进动脉样硬化斑块的不稳定.
- 针对IncAPAT可能为心血管疾病提供治疗策略.
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