血管损伤涉及过氧化二型氧化素,并通过模仿氧化素活性恢复,从而诱导重新内皮质化
Dong Hoon Kang1, Doo Jae Lee, Jiran Kim
1Division of Life and Pharmaceutical Science and Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul, Korea.
Circulation
|July 4, 2013
概括
过度氧化2-Cys过氧化素 (Prx) 与血管疾病有关. 模仿Prx活性的真菌代谢物通过调节细胞信号和促进愈合,有效地治疗血管损伤.
科学领域:
- 生物化学 生物化学
- 血管生物学 血管生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 典型的2-CysPeroxiredoxin (Prx) 在氧化应激下通过过度氧化而失活.
- 在血管疾病中Prx过氧化的作用仍然在很大程度上是未知的.
研究的目的:
- 为了研究2-Cys Prx过氧化在血管损伤中的重要性.
- 探索Prx活动模拟器在血管疾病中的治疗潜力.
主要方法:
- 在受伤的血管和动脉样硬化病变中对Prx过氧化进行免疫组织化学分析.
- 对 Prx II 枯竭对新极度增生症的影响的评估.
- 在体外和体内对聚二二皮佩拉作为Prx模仿剂的评估.
- 通过epipolythiodioxopiperazines进行信号通路调节的分析.
主要成果:
- 发现2-Cys Prxs,特别是 Prx II,在受伤的动脉血管和人类动脉样硬化病变中过度氧化.
- 在受伤的血管中,Prx II 耗尽加剧了新极端增生症.
- 聚二氧化皮佩拉模仿了2-Cys Prx活性,减少了细胞内H2O2,并调节了生长因子受体信号传递.
- 聚二氧皮氨酸抑制了光滑肌肉细胞的增殖/迁移,但促进了内皮细胞的活动.
- 在体内给药的epipolythiodioxopiperazines抑制了新极度增生症,并促进了受伤的动脉血管的再内化,而没有细胞毒性.
结论:
- 这项研究表明,2-Cys Prx过氧化在血管损伤中的参与.
- 作为2-Cys Prx的功能模仿剂,Epipolythiodioxopiperazines为血管损伤提供了潜在的治疗策略,包括与支架相关的治疗策略.
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