在ERG-APLNR轴控制肺静脉内皮增殖在肺静脉闭塞性疾病
Christopher Lathen1, Yu Zhang1, Jennifer Chow1
1From the Division of Cardiothoracic Surgery (C.L., Y.Z, J.C., M.S., Y.A.A., P.A.T), Department of Pathology (G.L.), Division of Cardiology (V.N), University of California, San Diego; Department of Medicine, University of Illinois, Chicago (J.X.Y.); and Division of Pulmonary Medicine, Vanderbilt University School of Medicine, Nashville, TN (I.M.R.).
肺静脉封闭性疾病涉及肺静脉损伤. 研究人员发现,Erg-Aplnr通路对静脉内皮质健康至关重要,可能是这种无法治愈的疾病的治疗点.
科学领域:
- 血管生物学 血管生物学
- 分子遗传学 分子遗传学
- 心血管研究的心血管研究.
背景情况:
- 肺静脉封闭性疾病 (PVOD) 导致严重的肺高血压和由于肺静脉消灭而导致的右心力衰竭.
- PVOD的预后不佳,五年生存率低于5%,缺乏有效的治疗方法.
- 了解PVOD机制对于开发新疗法至关重要.
研究的目的:
- 调查Ets转录因子Erg及其下游标在肺静脉封闭性疾病的发病过程中的作用.
- 通过阐明潜在的分子机制来确定PVOD的潜在治疗点.
主要方法:
- 使用了具有同卵性缺失Erg和Aplnr (阿林受体) 的小鼠模型.
- 评估肺静脉封闭性疾病表型,包括死亡率,出血和内皮增殖.
- 从PVOD患者的肺组织中分析了Erg和Aplnr表达水平.
主要成果:
- 在小鼠中,ERG缺乏导致PVOD,毛细血管出血和全细胞减小.
- Erg直接激活了Aplnr表达,这种表达是特定于静脉内皮的.
- 在实验室和体内PVOD中,Erg或Aplnr诱导的肺静脉内皮增殖的淘汰.
- 在PVOD患者中观察到降低ERG和APLNR水平.
结论:
- ERG和APLNR对于维持肺静脉内皮稳定至关重要.
- 破坏ERG-APLNR信号通路是PVOD发展的一个关键因素.
- ERG-APLNR途径代表了治疗肺静脉封闭性疾病的有希望的治疗标.
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