昼夜时钟的遗传成分调节了体内血栓发生的过程
Elizabeth J Westgate1, Yan Cheng, Dermot F Reilly
1Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, USA.
Circulation
|April 17, 2008
概括
分子时钟调节血栓事件,影响心血管健康. 像BMAL1和CLOCK这样的关键时钟基因会影响血液凝固时间和血压,可能解释心脏病发作和中风的日间变化.
科学领域:
- 心血管生理学心血管生理学
- 时间生物学 时间生物学
- 分子生物学分子生物学
背景情况:
- 诸如心脏病发作和中风等心血管事件表现出日间模式.
- 循环节律会影响与血液静止和血管健康相关的基因.
- 分子时钟在血栓事件中的特定作用需要阐明.
研究的目的:
- 研究分子时钟在调节血栓事件中的作用.
- 确定核心时钟基因如何影响到血栓性血管封闭 (TTVO) 的时间.
主要方法:
- 野生类型和突变小鼠的光化学损伤模型.
- 在不同的Zeitgeber时间 (ZT) 评估TTVO.
- 在BMAL1,CLOCK和NPAS中发生突变/删除的小鼠中分析TTVO和血压2.
主要成果:
- 野生型小鼠显示TTVO的日间变化,ZT2,ZT8,ZT14和ZT20之间存在显著差异.
- CLOCK的突变取消了白天TTVO的变化;NPAS2的删除改变了模式并延长了TTVO.
- BMAL1 删除缩短了 ZT8 的 TTVO,而内皮特异性的 BMAL1 删除破坏了白天的 TTVO 变化.
结论:
- 核心分子钟组件是活体中对血栓性刺激的反应的关键调节者.
- 分子时钟,环境因素和血压调节之间的相互作用可能是人类日常心血管事件变化的基础.
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