机械反应性ETS1会通过NOTCH4/DLL4信号传递引起内皮功能障碍和静脉静脉的动脉化
B J Sreelakshmi1, C L Karthika1, S Ahalya2
1Cardiovascular Diseases and Diabetes Biology, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, Kerala 695014, India.
European journal of cell biology
|May 17, 2024
概括
动乱的血液流动激活ETS1信号,这是静脉的发展的一个关键因素. 向ETS1可能为静脉疾病提供安全有效的治疗方法.
科学领域:
- 血管生物学 血管生物学
- 分子医学是分子医学.
- 生物医学工程 生物医学工程
背景情况:
- 静脉是常见的,与血液动力学不稳定性和不清楚的生物力学触发因素有关.
- 痕信号与静脉静脉化有关,但ETS1在静脉流量传感中的作用尚不清楚.
研究的目的:
- 研究ETS1在感知静脉流动障碍方面的作用及其在静脉变形成中的参与.
- 阐明连接机械信号与静脉重塑的信号通路.
主要方法:
- 分析人类的静脉和培养的静脉内皮细胞.
- 在体外微流体研究以模拟静脉剪切应力.
- ETS1 敲除和药理抑制 (TK216).
- 对Notch信号组件 (NOTCH4/DLL4) 和分子标记物的评估.
主要成果:
- 被扰乱的静脉剪切应力激活了人类静脉和细胞中的ETS1-NOTCH4/DLL4信号.
- ETS1和Notch成分在静脉静脉中升级,特别是在新密室中.
- ETS1的激活由MEK1/2和MEK5介导,独立于p38 MAP激酶.
- 通过ETS1淘汰和TK216治疗,可以预防流动干扰导致的NOTCH4/DLL4表达和动脉化.
结论:
- ETS1作为静脉血液流动障碍的传感器.
- ETS1信号促进静脉重塑和内皮功能障碍,有助于静脉的发展.
- 针对ETS1是一个有前途的治疗策略,用于静脉缩.
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