顺肌细胞协调内皮细胞对流动和损伤的反应
Mercedes Balcells1, Jordi Martorell, Carla Olivé
1Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA. merche@mit.edu
Circulation
|May 12, 2010
概括
血管光滑肌细胞 (SMCs) 调节内皮细胞 (EC) mTOR信号,该信号由血液流动激活. 这种交叉影响了干预后的EC恢复,建议新的支架设计.
科学领域:
- 血管生物学 血管生物学
- 内皮和光滑肌肉细胞信号传递.
- 心血管研究的心血管研究.
背景情况:
- 拉巴胺素 (mTOR) 信号调制的血管哺乳动物点影响干预后光滑肌细胞 (SMC) 增殖,但可能导致内皮细胞 (EC) 毒性.
- 血管架构将EC和SMC定位为副沟通,SMC被屏蔽免受直接流动.
- 假设流量对EC和SMC的mTOR信号的差异影响,以及SMC在EC mTOR上的监管作用.
研究的目的:
- 研究血流对血管EC和SMC中mTOR信号传输的差异性影响.
- 确定SMC在EC中的流量诱导mTOR信号传输方面的监管作用.
- 阐明EC-SMC交叉语音在血管干预和支架设计中的含义.
主要方法:
- perfusion生物反应器中的SMCs和/或ECs暴露于冠状动脉流.
- 流细胞计,免疫光学和免疫阻塞测试以评估-S6核糖体蛋白 (p-S6RP) 的表达.
- 在体内验证使用支架的猪动脉和西罗胺支架化.
主要成果:
- 流量显著增加了EC p-S6RP (mTOR目标) 表达.
- SMC S6RP是对增长因子反应的,但不是对流量反应的.
- SMCs抑制了流量诱导的EC mTOR信号传递;西洛利取消了这些效应.
- 在支架动脉中,EC p-S6RP距离SMC的距离最高,并且在西洛利木斯化时不存在.
结论:
- 光线流激活了ECs中的mTOR路径.
- SMCs对流动诱导的内皮mTOR信号产生抑制作用.
- 确定了新的流动刺激和EC-SMC交叉通话机制.
- 研究结果为本地抗增殖药物输送和未来支架设计的策略提供了信息,考虑到流量和药物效应.
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