在心肌缺血后,CD95/Apo1/Fas在细胞死亡中的参与
I Jeremias1, C Kupatt, A Martin-Villalba
1German Cancer Research Center, Heidelberg, Germany.
Circulation
|August 23, 2000
概括
缺血/再输血后的心脏细胞死亡涉及亡. CD95系统,包括CD95连接体,在这个过程中扮演着直接的角色,这表明它是心脏病发作恢复的治疗目标.
科学领域:
- 心血管生物学 心血管生物学
- 细胞死亡机制 细胞死亡机制
- 分子心脏病学分子心脏病学
背景情况:
- 缺血和再注射损伤后的心脏细胞死亡是一个重要的临床问题.
- 细胞亡是一种被编程的细胞死亡途径,在急性心肌梗塞后会导致心肌损伤.
研究的目的:
- 为了研究CD95/Fas/Apo1受体系统在调解后性心脏细胞死亡中的特定作用.
- 探索CD95连接体和其他诱导死亡的连接体在心肌缺血-再输血的背景下参与.
主要方法:
- 利用一个孤立的老鼠和小鼠的心脏兰登多夫 perfusion 模型来模拟缺血-reperfusion.
- 评估了酶依赖的亡以及CD95连接体和其他死亡连接体 (TNF-alpha, TRAIL) 的释放/合成.
- 检查了初级成年大鼠肌细胞在低氧/低氧化下对CD95连接体的敏感性,并比较了CD95缺乏 (lpr) 小鼠和野生类型对照中的细胞死亡.
主要成果:
- 在隔离心脏中发生的后缺血再注射诱导了卡斯巴酶依赖的亡.
- 可溶性CD95配体被释放并由后缺血性心脏新合成,与TNF-alpha和TRAIL一起.
- 低氧/低氧化增加了肌细胞对CD95连接体的敏感性,CD95缺陷的心脏在缺血-再输液后显示细胞死亡减少.
结论:
- CD95/Apo1/Fas系统直接参与心肌缺血后的心脏细胞死亡.
- CD95信号通路为预防缺血事件后心脏细胞死亡提供了一个潜在的新型治疗点.
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