诱导性氧化合成酶基因疗法提供的心脏保护是由循环氧化酶-2通过核因子-kappaB依赖途径介导的
Qianhong Li1, Yiru Guo, Wei Tan
1Institute of Molecular Cardiology, University of Louisville, Louisville, KY, USA.
Circulation
|September 6, 2007
概括
诱导性氧化合成酶 (iNOS) 基因疗法通过通过核因子-kappaB (NF-kappaB) 途径上调循环氧化酶-2 (COX-2) 来保护心脏. 这种遗传机制对于iNOS介导的心脏保护至关重要.
科学领域:
- 心血管研究研究心血管研究
- 分子生物学分子生物学
- 基因治疗 基因治疗
背景情况:
- 诱导性氧化合成酶 (iNOS) 基因疗法减少了心脏病发作的大小,与循环氧化酶-2 (COX-2) 相关,但机制不清楚.
- 药理学COX-2抑制剂缺乏特异性,需要进行遗传研究.
研究的目的:
- 测试iNOS基因疗法的心脏保护是否依赖于通过核因子-kappaB (NF-kappaB) 依赖途径的COX-2上调.
主要方法:
- 使用基因工程小鼠,包括COX-2淘汰和NF-kappaB通路受抑制的模型.
- 通过心脏内注射进行iNOS基因疗法.
- 诱导心肌梗塞和评估心脏病发作大小和蛋白质表达.
主要成果:
- 在野生型小鼠中,iNOS基因疗法减少了心脏病发作的大小,但在COX-2淘汰小鼠中没有.
- 在被抑制NF-kappaB信号传导的小鼠中,iNOS基因治疗未能提高COX-2的调节或提供心脏保护.
- 在没有iNOS上调的基础条件下,COX-2没有保护作用.
结论:
- 对于依赖iNOS的心脏保护,COX-2是必不可少的.
- NF-kappaB充当关键调解者,将iNOS与COX-2上调相关联.
- iNOS基因疗法通过激活NF-kappaB并随后上调COX-2来保护心脏,至少部分是如此.
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