维生素D受体缺乏导致肺动脉Kv7通道活动升高
Miguel A Olivencia1,2,3, Marta Villegas-Esguevillas1,2,3, Maria Sancho2,3,4
1Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain.
International journal of molecular sciences
|August 12, 2023
概括
在缺乏维生素D受体的小鼠中,维生素D缺乏不会导致肺动脉高血压. 然而,它增加了肺动脉中的Kv7通道活性,这是PAH的特征.
科学领域:
- 心血管研究研究心血管研究
- 内分泌学 在内分泌学.
- 肺部医学 肺部医学
背景情况:
- 新出现的证据将维生素D与肺动脉高血压 (PAH) 的发展联系起来.
- 维生素D受体 (Vdr) 在调节肺动脉 (PA) 功能中的作用尚未完全理解.
研究的目的:
- 研究维生素D受体淘汰小鼠 (Vdr-/-) 肺动脉的电生理和收缩性质.
- 分析Vdr缺失对Kv7通道功能和肺动脉表达的影响.
主要方法:
- 肺动脉被剖析并安装在线索肌谱仪中进行收缩性研究.
- 在PA光滑肌细胞中记录了膜电流,使用补丁技术.
- 分析了Kv7通道基因和蛋白质表达中的潜在维生素D反应元素 (VDRE).
主要成果:
- Vdr-/-小鼠没有表现出肺高血压表型 (没有右心室缩或内皮功能障碍).
- 来自Vdr-/-小鼠的肺动脉对Kv7激活剂 retigabine的反应增强,对Kv7抑制剂XE991.1.的电流敏感性增加.
- 在KCNE4基因中发现了潜在的VDRE,Vdr-/-小鼠显示肺KCNE4表达增加,而Kv7.1/7.4蛋白水平没有变化.
结论:
- 缺少单独的Vdr不足以诱导小鼠的肺动脉高血压.
- 缺少Vdr导致Kv7通道对肺动脉调节电流贡献增加,模仿PAH的方面.
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