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机械敏感的snoRNA类圆形RNA sno-circCNOT1驱动内皮功能障碍和动脉样硬化

Lianru Bi^1,2, Yihao Zhu^3,2, Ziqi Chen^1,2

¹Department of Cardiology, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518033, Guangdong, People's Republic of China.

|January 9, 2026

概括

机械敏感的圆形RNA sno-circCNOT1通过增加内皮质炎症和炎症来促进动脉样硬化. 针对层层A/C,METTL14-N和NLRP3通路,为动脉样硬化提供了一个新的治疗策略.

科学领域:

分子生物学分子生物学
心血管研究研究心血管研究
在RNA生物学,RNA生物学.

背景情况:

血动力学剪切应激在动脉样硬化中至关重要,但与内皮激活的分子联系尚不清楚.
循环RNAs (circRNAs) 参与内皮机械传导.
在动脉样硬化中机械敏感小核RNA (snoRNA) 类circRNAs的作用尚不清楚.

研究的目的:

研究snoRNA类circRNAs,特别是sno-circCNOT1在内皮功能和动脉样硬化中的作用.
阐明 sno-circCNOT1 调节内皮质炎症和在剪切应力下炎症的分子机制.
根据发现的途径,确定动脉样硬化的潜在治疗点.

主要方法:

使用RNA测序,RNA干扰,免疫光和共免疫沉来表征sno-circCNOT1.
在内皮细胞和ApoE-/-小鼠中进行功能性研究,以评估热和动脉生成.
机械研究包括RNA拉下,质谱和功能增益/损失测定.

主要成果:

识别了sno-circCNOT1,通过亲动脉刺激上调和通过层切割应力下调.
sno-circCNOT1调解剪切压力依赖的内皮质炎症和炎症,在小鼠中加剧动脉样硬化.
发现LMNA/METTL14/NLRP3轴受 sno-circCNOT1 的调节,促进内皮炎症.

结论:

sno-circCNOT1是一种机械敏感的snoRNA类circRNA,通过LMNA/METTL14/NLRP3通路促进内皮质热致死和动脉生成.
这个轴的METTL14-N组件是动脉样硬化的潜在基于蛋白质的治疗标.
这种调节通路是治疗动脉样硬化的可用药物标.

关键词:

动脉样硬化动脉样硬化环绕RNAss 的时间.这是一种炎症炎症炎症炎症.热致灭症是什么?剪切压力的压力.

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