微RNA 217通过静音信息调节器1调节内皮细胞衰老
Rossella Menghini1, Viviana Casagrande, Marina Cardellini
1Department of Internal Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
Circulation
|September 30, 2009
概括
衰老会增加miR-217,一种抑制SirT1的微RNA,促进内皮衰老和动脉样硬化. 抑制miR-217可以逆转这些影响,这表明对代谢障碍的治疗潜力.
科学领域:
- 分子生物学分子生物学
- 衰老研究研究 衰老研究
- 心血管科学 心血管科学
背景情况:
- 衰老是动脉样硬化和冠状动脉疾病的重要危险因素.
- 一个微阵列识别了microRNA-217 (miR-217),在衰老的内皮细胞中表达增加.
- miR-217调节静音信息调节器1 (SirT1),这是一个关键的长寿和代谢调节器,随着年龄的增长而下降.
研究的目的:
- 研究miR-217在内皮老化和动脉样硬化中的作用.
- 阐明miR-217和SirT1.1.之间的监管关系.
- 在代谢障碍中探索针对miR-217的治疗潜力.
主要方法:
- 微阵列分析以确定与年龄相关的微RNA.
- 使用人类内皮细胞 (脉,大动脉,冠状动脉) 的体外研究.
- 对人类动脉样硬化病变中的miR-217表达的分析.
主要成果:
- miR-217通过其3'-UTR.的结合位直接抑制SirT1的表达.
- 在年轻的内皮细胞中,miR-217通过减少SirT1和影响FoxO1/eNOS乙化,诱导衰老并损害血管生成.
- 在老化的细胞中抑制miR-217可以减少衰老,并通过增加SirT1.1,增强血管生成.
- 在动脉样硬化病变中,miR-217升高,与SirT1和FoxO1乙化相反相关.
结论:
- miR-217作为SirT1.1.的内源性抑制剂起作用.
- miR-217促进内皮衰老和功能障碍,导致动脉样硬化.
- 向miR-217为代谢障碍中的内皮功能障碍提供了潜在的治疗策略.
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