动脉样硬化相关的内皮功能障碍是由circHIF1ɑ调节的miR-199a-5p/SIRT1轴促进的
Shan Qiao1, Xing Wang2, Haiyun Li3
1Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University, Jinan, China; Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China; Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China; Shandong Laibo Biotechnology Co., Ltd, China.
概括
微RNA-199a-5p通过破坏内皮细胞在动脉样硬化中发挥关键作用. 针对circHIF1ɑ/miR-199a-5p/SIRT1通路为动脉样硬化提供了一个新的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 在RNA生物学,RNA生物学.
背景情况:
- 动脉样硬化 (AS) 是一种由高脂血症驱动的慢性炎症性疾病,导致内皮功能障碍和增加动脉血风险.
- 异位微RNA-199a-5p (miR-199a-5p) 与内皮损伤有关,但其在AS竞争性内源性RNA (CeRNA) 网络中的功能尚不清楚.
研究的目的:
- 调查miR-199a-5p在动脉样硬化病变发生过程中的作用.
- 阐明AS中miR-199a-5p介导的内皮功能障碍背后的分子机制.
- 在已识别的监管网络中确定潜在的治疗点.
主要方法:
- 使用牛-LDL.构建高脂肪饮食 (HFD) 诱导的apoE-/-小鼠动脉样和体外内皮细胞 (EC) 损伤模型.
- 在AS患者的甲状腺组织,EC和血细胞外囊泡 (EV) 中评估miR-199a-5p表达.
- 功能增益和丧失研究,以评估miR-199a-5p对EC增殖,运动性和新血管化的影响.
- 涉及免疫组织化学,免疫光学和分析FOXO信号通路,SIRT1和circHIF1ɑ相互作用的测试的机制研究.
主要成果:
- 发现miR-199a-5p在AS小鼠模型,牛LDL治疗的EC和脑AS患者的血EV中过度表达.
- 沉默miR-199a-5p显著减轻了小鼠的动脉样硬化进展.
- miR-199a-5p过度表达加剧了ox-LDL诱导的EC功能障碍,而circHIF1ɑ通过调节SIRT1表达通过FOXO信号通路来恢复EC功能.
结论:
- 这项研究揭示了circHIF1ɑ/miR-199a-5p/SIRT1轴在AS病变发生过程中的关键作用.
- 这种调节途径代表了治疗动脉样硬化治疗的新治疗标.
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