NADPH氧化酶4通过内皮氧化合成酶激活促进内皮血管生成
Siobhan M Craige1, Kai Chen, Yongmei Pei
1University of Massachusetts Medical School, Department of Medicine/Division of Cardiovascular Medicine, Worcester, MA 01605, USA. Siobhan.Craige@umassmed.edu
Circulation
|July 27, 2011
概括
增加内皮NADPH氧化酶4 (Nox4) 表达促进血管生长 (血管生成) 并通过增加内皮氧化物合成酶 (eNOS) 活性从低氧条件 (低氧) 恢复.
科学领域:
- 血管生物学 血管生物学
- 细胞信号传递 细胞信号传递
- 缺氧的研究研究缺氧.
背景情况:
- 反应性氧物种 (ROS) 在血管系统中发挥信号作用.
- 缺氧与ROS产量的增加有关.
- 在缺氧反应中,NADPH氧化酶4 (Nox4) 在内皮高度表达的作用尚不清楚.
研究的目的:
- 在低氧条件下研究内皮细胞中Nox4的功能.
- 为了确定Nox4是否影响血管生成和血管修复.
主要方法:
- 在Nox4操纵的内皮细胞的体外研究.
- 产生具有内皮特异性的Nox4过度表达的转基因小鼠 (VECad-Nox4小鼠).
- 在体内评估后肢缺血恢复和大动脉毛细血管发芽的情况.
- 检查内皮氧化合成酶 (eNOS) 的表达和活性.
- 将VECad-Nox4小鼠与ENOS缺乏的小鼠交叉繁殖.
主要成果:
- 低氧在体外和体内上调Nox4表达.
- 诺克斯4过度表达增强了内皮细胞的增殖,迁移和管形成.
- 在VECad-Nox4小鼠中,后肢缺血的恢复加速,大动脉毛细血管的生长增加.
- 过度表达Nox4增加了eNOS蛋白的表达和活性.
- 在ENOS缺乏的小鼠中,Nox4的益血管效应被废除了.
结论:
- 内皮Nox4升高调节可以增强血管生成.
- 诺克斯4通过依赖eNOS的途径促进过氧的恢复.
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