C/EBP同源蛋白-10 (CHOP-10) 通过控制内皮氧化合成酶基因表达来限制产后新血管化
Céline Loinard1, Yasmine Zouggari, Patricia Rueda
1Department of Medicine, Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK.
Circulation
|January 24, 2012
概括
C/EBP同源蛋白-10 (CHOP-10) 对产后新血管化的负面调节. 删除CHOP-10可以促进血管形成和成熟,特别是在缺血病和糖尿病患者中.
科学领域:
- 分子生物学分子生物学
- 心血管生物学 心血管生物学
- 发育生物学 发展生物学
背景情况:
- C/EBP同源蛋白-10 (CHOP-10) 是一种调节细胞分化,增殖和存活的核蛋白.
- 它在产后新血管化中的作用在很大程度上仍未被描述.
研究的目的:
- 研究CHOP-10在产后新血管化的功能.
- 阐明CHOP-10在血管形成中的作用背后的分子机制.
主要方法:
- 使用CHOP-10缺乏的小鼠模型 (CHOP-10(-/-)) 和野生类型的 littermates.
- 通过大腿动脉绑定诱导的缺血.
- 使用血管造影,毛细血管密度测量和足部 perfusion 评估新血管化.
- 研究了亡,内皮氧化合成酶 (eNOS) 表达,以及CHOP-10与eNOS促进体结合.
- 在人类内皮细胞中采用短干扰RNA (siRNA) 和过度表达研究.
主要成果:
- 在缺血症和糖尿病后,骨肌肉毛细血管中的CHOP-10表达被上调.
- 与野生类型小鼠相比,CHOP-10(-/-) 小鼠表现出增强的新血管化,增加的毛细血管密度和改善的输液.
- 在CHOP-10(-/-) 小鼠的缺血组织中观察到减少了亡和增加了eNOS水平.
- CHOP-10直接与eNOS促进体结合,抑制其转录活性.
- 在CHOP-10(-/-) 小鼠中的亲血管效应在CHOP-10/eNOS双击动物中被取消.
- 糖尿病诱导的CHOP-10高调,损害了后血性新血管化.
结论:
- CHOP-10作为产后新血管化的显著负调节剂.
- CHOP-10调节血管形成和成熟,部分是通过对eNOS的调节.
- 针对CHOP-10可能为特征是血管形成受损的疾病提供治疗潜力.
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