Differential action of steroid hormones on human endothelium
Differential action of steroid hormones on human endothelium
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DOI：
10.1242/jcs.02886
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发表时间：
2006-05-01
影响因子：
4
通讯作者：
Schillers, Hermann
中科院分区：
文献类型：
--
作者：
Oberleithner, Hans;Riethmueller, Christoph;Schillers, Hermann
糖皮质激素对血管通透性的作用已得到充分证实。然而，盐皮质激素对血管结构和功能的作用知之甚少。由于内皮细胞是糖皮质激素和盐皮质激素的靶细胞，我们将人脐静脉内皮细胞暴露于两种类型的类固醇。醛固酮（盐皮质激素）和地塞米松（糖皮质激素）在培养中应用3天，然后测量跨内皮离子和大分子渗透性，顶端细胞表面和细胞刚度。用电阻抗传感技术测量跨上皮离子渗透性，用荧光标记葡聚糖测量大分子渗透性，用三维原子力显微镜成像测量顶端细胞膜表面。使用AFM扫描尖端作为机械纳米传感器测量细胞刚度。我们发现，醛固酮增加顶端细胞表面和顶端细胞刚度显着，而跨内皮通透性保持不受影响。与此相反，地塞米松显着降低离子和大分子的渗透性，而顶端细胞表面和细胞刚度没有改变。特异性受体拮抗剂地塞米松（RU486）和醛固酮（螺内酯）阻止观察到的反应。我们的结论是，糖皮质激素加强细胞与细胞的接触（“外周作用”），而盐皮质激素扩大和破坏细胞（“中枢作用”）。这可以解释地塞米松介导的血管系统液体潴留和醛固酮增多症状态下的内皮功能障碍。
The action of glucocorticoids on vascular permeability is well established. However, little is known about the action of mineralocorticoids on the structure and function of blood vessels. As endothelial cells are targets for both glucocorticoids and mineralocorticoids, we exposed human umbilical vein endothelial cells to both types of steroids. Aldosterone (mineralocorticoid) and dexamethasone (glucocorticoid) were applied for 3 days in culture before measurements of transendothelial ion and macromolecule permeability, apical cell surface and cell stiffness were taken. Transendothelial ion permeability was measured with electrical cell impedance sensing, macromolecule permeability with fluorescence-labeled dextran and apical cell membrane surface by three-dimensional AFM imaging. Cell stiffness was measured using the AFM scanning tip as a mechanical nanosensor. We found that aldosterone increased both apical cell surface and apical cell stiffness significantly, while transendothelial permeability remained unaffected. By contrast, dexamethasone significantly decreased ion and macromolecule permeability, while apical cell surface and cell stiffness did not change. Specific receptor antagonists for dexamethasone (RU486) and aldosterone (spironolactone) prevented the observed responses. We conclude that glucocorticoids strengthen cell-to-cell contacts ('peripheral action'), whereas mineralocorticoids enlarge and stiffen cells ('central action'). This could explain the dexamethasone-mediated retention of fluid in the vascular system, and endothelial dysfunction in states of hyperaldosteronism.