NADPH氧化酶通过人体血管光滑肌肉细胞中的血栓激素调节组织因子依赖的表面凝血活性
Olaf Herkert1, Isabel Diebold, Ralf P Brandes
1Institut für Kardiovaskuläre Physiologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Circulation
|May 1, 2002
概括
热血素通过NADPH氧化酶和活性氧物种 (ROS) 在血管细胞中调节组织因子 (TF). 这一途径涉及p38 MAP 激酶和PI 3-激酶/Akt,在血管损伤后延续凝血.
科学领域:
- 血管生物学 血管生物学
- 凝固级联是凝固级联的一个过程.
- 细胞信号传递 细胞信号传递
背景情况:
- 组织因子 (TF) 启动凝血,而血栓在血管光滑肌细胞 (VSMC) 中放大其表达.
- 这种积极的反循环有助于延长血管损伤部位的前凝剂活性和血栓性.
- 这一循环的基础是精确的信号机制,特别是反应性氧物种 (ROS) 的作用,仍然不完全理解.
研究的目的:
- 调查NADPH氧化酶的作用,这是VSMC中ROS的主要来源,在调解血栓诱导的TF表达中发挥作用.
- 阐明参与TF的这种氧化还原敏感上调的信号通路.
主要方法:
- 培养的人类VSMCs被用血栓激素治疗.
- 评估了TF mRNA表达和表面前凝剂活性.
- 评估了抗氧化剂,NADPH氧化酶抑制剂 (二烯-,p22phox反感,RacT17N) 和途径抑制剂 (p38 MAP激酶,PI 3-激酶) 的作用.
- 分析了蛋白质酸化 (Akt).
主要成果:
- 氨酸显著增加了VSMC中的TF mRNA和前凝剂活性.
- 这些反应被抗氧化剂和NADPH氧化酶抑制剂显著降低.
- 抑制p38 MAP 激酶和PI 3 激酶也减弱了血栓诱导的TF mRNA表达.
- 热血素刺激了Akt的酸化,以一种对氧化还原酶敏感和依赖NADPH氧化酶的方式.
结论:
- 在VSMC中,NADPH氧化酶对于TF mRNA的氧化回归敏感诱导和由血栓激素引起的血栓凝固活性至关重要.
- 这个过程是由p38 MAP 激酶和PI 3-激酶/Akt 途径的激活介导的.
- NADPH氧化酶可能是维持受伤血管内血栓生成周期的关键因素.
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