诱导的内皮细胞循环停止 预防遗传性出血长膜炎的动脉静脉形
Gael Genet1, Nafiisha Genet1, Umadevi Paila1
1Department of Cell Biology (G.G., N.G., U.P., S.R.C., A.C., S.P.M., D.S., M.H., E.A.N., K.K.H.), School of Medicine, University of Virginia, Charlottesville.
Circulation
|December 21, 2023
概括
内皮细胞循环的失调导致遗传性出血长管病 (HHT) 的血管形. 使用palbociclib恢复细胞循环可以预防这些动脉静脉形 (AVM).
科学领域:
- 血管生物学
- 细胞周期调节
- 遗传学
背景情况:
- 内皮细胞循环状态影响动脉静脉特异性.
- 细胞循环控制和动脉静脉认同受损与遗传性出血性长长 (HHT) 血管形有关,包括动脉静脉形 (AVM).
- 内皮细胞循环调节和与HHT相关的AVM发展之间的机制性联系尚不清楚.
研究的目的:
- 研究内皮细胞周期状态在与HHT相关的AVM病变中的作用.
- 评估使用palbociclib来预防AVM调节内皮细胞周期G1状态的治疗潜力.
主要方法:
- 在Fucci 2小鼠中使用BMP9/ 10阻断抗体和内皮特异性Alk1删除诱导HHT.
- 在AVM中评估内皮细胞周期状态.
- 评估了CDK4/ 6抑制剂palbociclib在预防AVM的疗效.
主要成果:
- 在HHT血管形中,内皮细胞循环状态和基因表达失调.
- 帕尔博西基布治疗预防了由BMP9/ 10抑制和Alk1删除引起的AVM的发展.
- 参与动脉静脉识别,迁移,新陈代谢和信号通路 (VEGF- A,BMP9) 的G1状态晚期调节基因,预防AVM.
结论:
- 由于BMP9/ 10和Alk1信号缺陷导致内皮细胞循环失调,导致HHT AVM.
- 通过CDK4/ 6抑制恢复内皮细胞循环控制显示出HHT中AVM的治疗潜力.
相关概念视频
01:24Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
01:10Mechanism of Angiogenesis
5.5K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
5.5K