通过氧化调节人体微血管内皮细胞中的组织因子表达
1Whitaker Cardiovascular Institute and Evans Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Circulation
|May 10, 2000
概括
由内皮衍生的氧化 (NO) 显著抑制内皮细胞中组织因子 (TF) 的表达和活性. 这一发现表明,NO在减少这些细胞的原血栓现象型中起着关键作用.
科学领域:
- 血管生物学 血管生物学
- 内皮细胞功能 内皮细胞功能
- 血栓形成和血液静止.
背景情况:
- 组织因子 (TF) 在血液静止和动脉血性疾病中对血栓生成至关重要.
- 由内皮衍生的氧化 (NO) 具有抗血栓和抗动脉样硬化性质.
- 在TF表达中NO的调节作用仍未得到研究.
研究的目的:
- 为了研究内源性内皮质衍生NO对TF表达和活性的影响.
- 为了确定NO是否通过炎症刺激调节TF诱导.
主要方法:
- 人类微血管内皮细胞用脂多糖 (LPS) 或互白素-1β (IL-1β) 进行刺激,以诱导TF.
- 测量了TF活性,蛋白质和mRNA水平.
- 添加L-氨酸 (NO前体) 来评估其抑制作用;D-氨酸和NO合成酶抑制被用作对照.
主要成果:
- 根据剂量和时间,LPS和IL-1β增加了TF活性和表达.
- 在24小时内,L-氨酸显著抑制了TF活动诱导 (66%的LPS,59%的IL-1β).
- 抑制TF活性与降低TF蛋白和mRNA水平相关;D-氨酸和NO合成酶抑制没有影响.
结论:
- 增强内皮衍生的NO的产生减少了内毒素和细胞因子诱导的TF表达.
- NO减少了内皮细胞的原血栓现象型.
- 这些发现突出了NO介导血管保护的新机制.
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