LDL增加了血管光滑肌肉细胞表面的非活性组织因子:过氧化激活了潜伏的细胞表面组织因子
1Departments of Cell Biology and Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Circulation
|April 6, 1999
概括
低密度脂蛋白 (LDL) 和氧化剂在光滑肌细胞中增加组织因子活性,从而导致动脉样硬化和急性冠状动脉综合征.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 动脉样硬化研究 动脉样硬化研究
背景情况:
- 组织因子 (TF) 在动脉样硬化病变和光滑肌细胞 (SMC) 中被上调.
- SMC TF表达有助于斑块生长,血栓形成和急性冠状动脉综合征.
- 了解SMC中的TF调节对于心血管疾病研究至关重要.
研究的目的:
- 阐明LDL和氧化剂调节SMC中的TF表达和活性的机制.
- 研究脂蛋白和氧化剂在TF合成和激活中的作用.
主要方法:
- 用LDL和/或过氧化 (H2O2) 处理SMC.
- 测量了TF mRNA,细胞表面蛋白水平和TF活性.
- 实验进行了野生类型和缺少细胞质尾巴的截断TF.
主要成果:
- 在SMC中,LDL增加了TF mRNA和细胞表面蛋白,但没有TF活性.
- 在没有增加TF mRNA或蛋白质的情况下,H2O2激活细胞表面TF.
- 连续的LDL和H2O2治疗协同增加了TF mRNA,蛋白质和活性.
- H2O2诱导的TF激活独立于TF细胞质尾部发生.
结论:
- 提出了一种新的两步途径,用于增加SMC表面的TF活性.
- 脂蛋白 (LDL) 调节潜伏TF的合成.
- 氧化剂 (H2O2) 激活合成的TF蛋白质复合体.
- 这一途径突出了动脉样硬化和血栓形成的新机制.
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