类药物对血管新生有双相作用
Michael Weis1, Christopher Heeschen, Alec J Glassford
1Stanford University School of Medicine, Division of Cardiovascular Medicine, Stanford, Calif 94305, USA.
Circulation
|February 13, 2002
概括
类药物对血管形成 (血管生成) 具有双重作用. 低剂量促进它,而高剂量通过影响内皮细胞和血管生长因子来抑制它,独立于胆固醇水平.
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 类药物是HMG-CoA减少酶抑制剂,影响胆固醇和异oprenoid合成.
- 异oprenoids 调节各种细胞功能,包括血管生成.
- 研究了塞里瓦斯塔丁和阿托瓦斯塔丁对血管生成的影响.
研究的目的:
- 调查他类药物对血管生成的剂量依赖作用.
- 为了确定这些影响是否依赖脂质.
- 为了探索杰拉尼尔 (geranylgeranyl pyrophosphate) 在他类药物介导的血管生成中的作用.
主要方法:
- 使用内皮细胞 (增殖,迁移,分化) 的体外研究.
- 在活体研究中,在炎症诱导血管生成的小鼠模型中.
- 在易斯肺癌模型中评估瘤生长和血管化.
主要成果:
- 低度的他类药物 (0.005-0.01μmol/L) 增强了内皮细胞功能.
- 高度的他类药物 (0.05-1μmol/L) 抑制了血管生成,降低了血管内皮生长因子 (VEGF),并增加了内皮亡.
- 高剂量的他类药物抑制了小鼠的炎症诱导血管生成和瘤生长,其效果被geranylgeranyl pyrophosphate逆转.
结论:
- 抑制HMG-CoA减少酶对血管生成具有双相,剂量依赖的作用.
- 斯坦丁对血管生成的影响是脂质独立的,与内皮细胞亡和VEGF信号传递有关.
- 较低的治疗性他类药物剂量可能是益血管性,而高剂量则是血管静止性,影响结核蛋白质.
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