血管内皮屏障保护通过保留心脏纳米结构来防止心房动
Louisa Mezache1, Andrew M Soltisz1, Scott R Johnstone2
1Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, Ohio, USA.
JACC. Clinical electrophysiology
|November 30, 2023
概括
保护血管屏障可以防止由炎症引起的心房动 (AF). 阻断connexin43半通道和pannexin-1通道减少了暴露于血管内皮生长因子 (VEGF) 的小鼠的AF发作.
科学领域:
- 心血管研究研究心血管研究
- 节律失常的机制 节律失常机制
- 炎症和血管生物学
背景情况:
- 心房动 (AF) 与炎症,血管功能障碍和血管内皮生长因子 (VEGF) 有关.
- 目前的AF治疗方法可以控制症状,但不能阻止疾病的进展.
- 之前的研究已经确定了被破坏的通道 (NaV1.5) 纳米域作为因炎症引起的AF启动机制.
研究的目的:
- 测试保护血管屏障是否可以预防血管泄漏引起的心房律乱.
- 确定血管屏障保护的分子标,特别是连xin43 (Cx43) 半通道和pannexin-1 (Panx1) 通道.
主要方法:
- 在小鼠体内心电图,电子显微镜和超分辨率光显微镜.
- 用血管内皮生长因子 (VEGF) 进行急性治疗.
- 对NaV1.5通道定位相对于连接43间隙连接点和机械连接点的评估.
主要成果:
- 在未接受治疗的小鼠中,VEGF增加了AF发病率和插曲持续时间.
- VEGF破坏了NaV1.5在连接43间隙连接点和机械连接点附近的定位.
- 阻断Cx43半通道或Panx1通道显著降低了AF持续时间,并保留了NaV1.5定位.
结论:
- 血管屏障保护是一种潜在的抗心律失常策略.
- 准Cx43半通道和Panx1通道可能会在炎症引起的血管泄漏后预防AF.
- 小分子抑制剂 Cx43 和 Panx1 显示出抗心律失常的疗效.
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