由冠状动脉狭窄引起的重复性缺血导致缺血预先调节的新窗口
You-Tang Shen1, Christophe Depre, Lin Yan
1Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA.
Circulation
|October 22, 2008
概括
反复性冠状动脉狭窄 (RCS) 与传统的第二窗口缺血预调 (SWIPC) 相比,通过不同的分子途径提供强大的心脏保护. RCS激活了独特的基因表达特征,包括自和内质网膜应激,在SWIPC中没有看到.
科学领域:
- 心血管生理学心血管生理学
- 分子心脏病学分子心脏病学
- 基因组学就是基因组学.
背景情况:
- 缺血预先调节 (IPC) 是一种现象,在短暂的缺血发作中保护心脏免受随后的长期缺血的影响.
- 经典的IPC协议涉及到第一或第二窗口预条件.
- 不同IPC协议背后的分子机制尚未完全理解.
研究的目的:
- 与传统的第二窗口缺血预制 (SWIPC) 相比,研究重复性冠状动脉狭窄 (RCS) 诱导的心脏保护的分子机制.
- 为了确定RCS和SWIPC是否激活类似或不同的分子通路和基因组反应.
主要方法:
- 有意识的猪接受了RCS或SWIPC协议.
- 诱导了致死性缺血,随后进行了心脏病发作大小的评估.
- 分子分析包括西方斑点分析,微阵列分析,以及对氧化合成酶和蛋白质激酶Cepsilon活性的评估.
主要成果:
- 与SWIPC (16+/-3%) 和假装组 (42+/-4%) 相比,RCS导致心脏病发作大小显著减少 (6+/-3%).
- SWIPC显示诱导性氧化合成酶表达和蛋白质激酶Cepsilon转位的增加,这些在RCS中不存在.
- 微阵列分析揭示了不同的基因组概况,其中RCS调节了5739,SWIPC调节了2394个基因;只有31%的RCS调节基因与SWIPC重叠.
- RCS 独特地调高了参与自,内质网膜应激和线粒体氧化代谢的基因.
结论:
- 重复性冠状动脉狭窄 (RCS) 提供了强大的心脏保护,防止心肌梗塞.
- 调解RCS诱导心脏保护的分子机制与传统的第二窗口缺血性预制 (SWIPC) 根本不同.
- RCS激活了不同的基因通路,包括与自和ER压力相关的基因通路,突出了心肌保护的新治疗标.
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