分支链α-基酸以有氧方式激活血管细胞中的HIF1α信号
Wusheng Xiao1,2,3,4, Nishith Shrimali1, Niv Vigder1,5
1Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Nature metabolism
|October 30, 2024
概括
分支链α-酸 (BCKA) 激活正常细胞中的缺氧诱导因子1α (HIF1α) 信号. 这一途径影响血管光滑肌肉细胞功能,可能与肺动脉高血压有关.
科学领域:
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
- 血管生物学 血管生物学
背景情况:
- 缺氧诱导因子1α (HIF1α) 是缺氧条件的关键调节者.
- 在正常细胞中有氧HIF1α激活的机制尚不清楚.
研究的目的:
- 研究人类初级血管细胞中有氧HIF1α激活的机制和后果.
- 为了确定介导HIF1α信号在normoxia的内在因素.
主要方法:
- 在normoxia下对人类初级血管细胞中HIF1α信号的分析.
- 研究了分支链α-酸 (BCKA) 在HIF1α激活中的作用.
- 评估了BCKA介导的HIF1α信号对血管光滑肌肉细胞表型和糖解活性的影响.
- 与患者数据和肺动脉高血压的动物模型相关的发现.
主要成果:
- 在normoxia下,HIF1α信号在人类初级血管细胞中被激活.
- BCKA的副分泌通过抑制PHD2和促进L-2-基酸盐生成来调解有氧HIF1α激活.
- 由BCKA诱导的HIF1α激活刺激糖解并改变肺动脉光滑肌细胞表型.
- 在肺动脉高血压中观察到BCKA代谢失调和病原型变化.
结论:
- BCKA 是新型信号代谢物,在有氧条件下激活HIF1α.
- 该BCKA-HIF1α通路影响血管光滑肌肉细胞功能.
- 这种途径可能在肺血管疾病的病理生物学中发挥作用,例如肺动脉高血压.
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