内皮细胞选择性粘附分子缺陷表现出肺血管阻力增加,这是由于内皮氧化信号受损
Vadym Buncha1, Liwei Lang1, Katie Anne Fopiano1
1Department of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, United States.
American journal of physiology. Heart and circulatory physiology
|December 31, 2024
概括
内皮细胞选择性粘附分子 (ESAM) 缺陷通过损害氧化介导功能来提高肺血管阻力 (PVR). 这项研究强调了ESAM在维持健康的肺血管系统中的关键作用.
科学领域:
- 心血管生物学 心血管生物学
- 肺血管生理学 肺血管生理学
背景情况:
- 内皮细胞选择性粘附分子 (ESAM) 是对内皮细胞功能至关重要的紧密结合分子.
- 以前的研究将ESAM缺乏与心脏功能障碍联系起来;它在肺血管系统中的作用尚不清楚.
研究的目的:
- 研究ESAM在调节小鼠肺血管抵抗 (PVR) 的作用.
- 为了确定ESAM缺乏是否影响肺动脉功能和氧化 (NO) 信号传递.
主要方法:
- 使用了ESAM缺陷 (ESAM-/-) 和野生型 (WT) 老鼠的隔离, perfused 全肺制剂.
- 在不同流速下和对布拉迪基宁,U46619和酸 (SNP) 的反应下评估PVR.
- 在肺动脉中检查了NO合成酶抑制和分析了蛋白质水平 (p-Akt,p-eNOS);在体外评估了内皮细胞对齐.
主要成果:
- 与WT小鼠相比,ESAM-/-小鼠在所有流速上表现出显著增加的PVR.
- 在ESAM-/-小鼠中,对布拉迪基宁和U46619的反应减少,表明内皮依赖和独立血管活性受损.
- 由SNP诱导的血管扩张类似,但NO合成酶抑制对PVR的影响不同,这表明ESAM-/-.中NO介导调节受损.
- 在ESAM-/-肺动脉中观察到减少的-Akt和-eNOS水平.
- 在人类肺部微血管内皮细胞中,siRNA介导的ESAM敲除损害了剪切应激诱导的细胞对齐.
结论:
- 在小鼠中,ESAM对于维持正常的肺血管阻力至关重要.
- 缺少ESAM会损害肺动脉功能,特别是氧化介导的血管扩张和剪切应激反应.
- 在肺血管系统中,ESAM在内皮细胞适应流动和血管活性刺激方面发挥着重要作用.
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