针对VEGF-A/ VEGFR2 Y949信号介导的血管透性 缓解低毒性肺高血压
Weibin Zhou1,2,3, Keli Liu2, Lei Zeng2
1Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China (W.Z., J.H., M.W., D.W., J.W., Y.C.).
Circulation
|November 17, 2022
概括
肺高血压是由VEGF-A/ VEGFR2 Y949信号驱动的过度血管泄漏. 针对这种特定途径可以缓解疾病,而不是阻断所有VEGFR2信号.
科学领域:
- 心血管研究
- 肺部医学
- 分子生物学
背景情况:
- 肺高血压 (PH) 与血管内皮生长因子A (VEGF- A) 和其受体VEGFR2的增加有关.
- VEGF-A信号在PH病变中的确切作用尚不清楚.
研究的目的:
- 研究VEGF-A/VEGFR2信号传递和VEGFR2 Y949依赖性血管泄漏在PH中的作用.
- 阐明低氧PH所涉及的机械途径.
主要方法:
- 检查PH患者和暴露于低氧的小鼠的肺样本.
- 使用VEGFR2 Y949氨酸敲入和内皮特异性Vegfr2删除的突变小鼠.
- 评估了右心室缩压,高和肺血管病变.
主要成果:
- 通过过度激活的VEGF-A/ VEGFR2 Y949信号,PH会导致过度的肺血管泄漏.
- VEGFR2 Y949信号包括Yes1,c-Src和VE-cadherin酸化,导致血管透性.
- 阻断VEGFR2Y949信号改善了PH的表现,而完全删除VEGFR2则使PH恶化.
结论:
- 基于VEGF-A/VEGFR2 Y949的血管透性是PH病变的一个关键因素.
- VEGF-A/ VEGFR2 Y949轴代表了PH的潜在治疗目标.
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