局部DIO2升高在形脑血管系统中是一种适应
Ruofei Li1, Yushan Tang1, Haiyue Wang1
1State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (R.L., Y.T., H.W., P.H., L.Y., C.L., Y.Z., Y.W.).
Circulation research
|March 25, 2025
概括
甲状腺激素信号,特别是通过DIO2,在修复脑血管形方面发挥着至关重要的作用. 针对这种途径为这些衰弱性疾病提供了潜在的新疗法.
科学领域:
- 血管生物学 血管生物学
- 内分泌学 在内分泌学.
- 神经学 神经学
背景情况:
- 大脑血管形导致严重的出血和神经缺陷.
- 目前,这些疾病缺乏有效的治疗方法.
- 甲状腺激素 (THs) 在脑血管形中的作用尚不清楚.
研究的目的:
- 研究氨酸二氧化酶2 (DIO2) 和TH信号在脑血管形的参与.
- 探索针对TH信号传导用于脑血管疾病的治疗潜力.
主要方法:
- 对人类大脑洞腔形和大脑动脉静脉形形的单细胞转录组分析.
- 在体内研究中,使用具有Pdcd10或Kras突变的内皮特异性淘汰的小鼠模型.
- 在小鼠模型中操纵Dio2表达和TH水平 (使用triiodothyronine或methimazole).
主要成果:
- 在人类和小鼠的大脑血管形中,DIO2表达和TH信号被激活.
- 在小鼠模型中,Triiodothyronine补充减少了出血,ECM重塑和血管泄漏.
- DIO2沉默或TH抑制恶化了血管异常.
- 转录因子FOXK1通过PI3K-Akt-mTOR信号调节DIO2.
- 三氨基氨酸治疗改善了线粒体功能,并以Pgc1a依赖的方式减少了氧化应激.
结论:
- 在形脑血管系统中存在一种新的DIO2介导的适应机制.
- 针对TH信号提供了一个有前途的治疗策略,用于脑血管疾病.
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