剪切敏感的circRNA-LONP2通过准NRF2/HO1信号传输来促进内皮炎症和动脉样硬化
Ruoyu Wang1,2, Yue Zeng1,2, Ziqi Chen1,2
1Department of Cardiology, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, People's Republic of China.
层状剪切应力 (LSS) 通过减少炎症来保护动脉. 然而,circRNA-LONP2通过抑制保护信号通路来促进内皮炎症和动脉样硬化,这表明它是治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
背景情况:
- 血动力学剪切应力对于内皮平衡至关重要.
- 生理层切割应力 (LSS) 通过抑制炎症来保护动脉免受动脉样硬化.
- 循环RNAs (circRNAs) 与细胞对剪切应激反应有关.
研究的目的:
- 在内皮细胞中识别由LSS改变的circRNAs.
- 研究circRNA-LONP2在内皮炎症和动脉样硬化中的作用.
- 阐明 circRNA-LONP2 的功能背后的分子机制.
主要方法:
- 在LSS刺激的内皮细胞中选差异表达的circRNAs.
- 在体外和体内实验中评估circRNA-LONP2过度表达的影响.
- 涉及微RNA海绵和途径分析的机制研究.
主要成果:
- 鉴定出 circRNA-LONP2 被 LSS. 显著改变.
- 内皮环RNA-LONP2过度表达促进了炎症和动脉样硬化.
- circRNA-LONP2海绵miR-200a-3p,导致YAP/YRT介导通路的激活和抑制Nrf2/HO-1信号,促进氧化应激和炎症.
结论:
- 通过 miR-200a-3p/Nrf2/HO-1 途径抑制内皮内膜炎症.LSS诱导的 circRNA-LONP2 的下调抑制内皮炎症.
- circRNA-LONP2促进了内皮炎症和动脉样硬化.
- circRNA-LONP2代表了动脉样硬化的潜在治疗标.
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