诺克斯激活剂1:在动脉样硬化动脉中的血管活性氧物种调节的潜在目标
Xi-Lin Niu1, Nageswara R Madamanchi, Aleksandr E Vendrov
1McAllister Heart Institute, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599-7005, USA.
Circulation
|January 20, 2010
概括
诺克斯激活剂1 (NoxA1) 被确定为血管光滑肌细胞NADPH氧化酶的关键调节剂. 降低NoxA1的调节减少了活性氧物种和扩散,为血管疾病提供了潜在的治疗点.
科学领域:
- 血管生物学 血管生物学
- 分子医学是分子医学.
- 生物化学 生物化学
背景情况:
- 血管光滑肌细胞 (VSMCs) 中NADPH氧化酶的特定子单元在很大程度上是未知的.
- 了解这些组成部分对于开发针对血管疾病的向疗法至关重要.
研究的目的:
- 调查诺克斯激活剂1 (NoxA1),p67phox同类物,在VSMCNADPH氧化酶功能中的作用.
- 评估NoxA1在动脉样硬化发展中的参与.
主要方法:
- 在小鼠VSMC中使用RT-PCR和测序确认NoxA1的存在.
- 利用免疫沉和西方分析来研究NoxA1/p47phox相互作用.
- 在VSMC和小鼠模型中,用于NoxA1过度表达的腺病毒载体和shRNA降低调节.
- 分析了反应性氧物种 (ROS) 的产生,VSMC的扩散,以及对氧化还原敏感激酶的激活.
- 在动脉样硬化 (ApoE-/-) 和人类动脉样硬化病变的小鼠模型中检查了NoxA1表达.
主要成果:
- 在依赖p47phox和Nox1.1的野生型VSMC中,NoxA1过度表达增强了由血栓激素诱导的ROS生成.
- 低调NoxA1降低了ROS的产生,VSMC的扩散和JAK2,Akt和p38MAPK的激活.
- 在受伤的动脉中NoxA1过度表达增加了超氧化物生产和新极端增生.
- 在ApoE-/-小鼠的动脉样性主动脉中,NoxA1表达升高,在人类动脉样性病变中存在.
结论:
- 在VSMC中,NoxA1作为p67phox同类体,调节氧化还原信号和VSMC表型.
- 调节NoxA1表达是一种对血管疾病有前途的治疗策略.
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