血管光滑肌细胞衰老促进动脉样硬化和斑块脆弱性的特征
Julie Wang1, Anna K Uryga1, Johannes Reinhold1
1From Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
Circulation
|September 30, 2015
概括
血管光滑肌细胞 (VSMC) 衰老与TRF2 (端粒重复结合因子-2) 的端粒保护降低有关. 失去了TRF2加速动脉样硬化和斑块脆弱性,建议预防衰老作为治疗目标.
科学领域:
- 心血管生物学
- 细胞衰老
- 动脉样硬化研究
背景情况:
- 血管光滑肌细胞 (VSMC) 的增殖有助于动脉形成.
- 晚期动脉样硬化斑块中的VSMC表现为衰老和DNA损伤,包括端粒缩短.
- 在动脉样硬化中VSMC衰老的具体作用和机制在很大程度上仍未被探索.
研究的目的:
- 在动脉样硬化斑块中的VSMC衰老中研究端粒保护蛋白的作用.
- 阐明VSMC中改变的端粒重复结合因子-2 (TRF2) 表达的功能后果.
- 确定TRF2对动脉样硬化和斑块稳定性的影响.
主要方法:
- 在人体斑块和正常血管中的VSMC中检查TRF2表达和端粒结合.
- 通过p53依赖的降解研究了TRF2的调节.
- 使用TRF2过度表达或主导阴性突变物 (T188A) 在阿波脂蛋白E-/ -小鼠模型中进行的体外和体内研究.
主要成果:
- 斑块VSMC显示TRF2表达和端粒结合减少,与DNA损伤增加相关.
- 过度表达TRF2减轻了衰老和DNA损伤,而TRF2 (T188A) 突变则加剧了这些影响.
- 在小鼠中,VSMC特有的TRF2 ((T188A) 表达增加了动脉样硬化和死核形成,而TRF2表达改善了斑块组成.
结论:
- 动脉硬性斑块VSMC衰老与TRF2的损失有关.
- 大脑衰老促进动脉样硬化和斑块脆弱性的特征.
- 预防VSMC衰老成为动脉样硬化的潜在治疗策略.
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