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首页> 外文期刊>American Journal of Physiology >A transmural pressure gradient induces mechanical and biological adaptive responses in endothelial cells.
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A transmural pressure gradient induces mechanical and biological adaptive responses in endothelial cells.

机译：透壁压力梯度诱导内皮细胞的机械和生物适应性反应。

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A sudden increase in the transmural pressure gradient across endothelial monolayers reduces hydraulic conductivity (L(p)), a phenomenon known as the sealing effect. To further characterize this endothelial adaptive response, we measured bovine aortic endothelial cell (BAEC) permeability to albumin and 70-kDa dextran, L(p), and the solvent-drag reflection coefficients (sigma) during the sealing process. The diffusional permeability coefficients for albumin (1.33 +/- 0.18 x 10(-6) cm/s) and dextran (0.60 +/- 0.16 x 10(-6) cm/s) were measured before pressure application. The effective permeabilities (measured when solvent drag contributes to solute transport) of albumin and dextran (P(ealb) and P(edex)) were measured after the application of a 10 cmH(2)O pressure gradient; during the first 2 h of pressure application, P(ealb), P(edex), and L(p) were significantly reduced by 2.0 +/- 0.3-, 2.1 +/- 0.3-, and 3.7 +/- 0.3-fold, respectively. Immunostaining of the tight junction (TJ) protein zonula occludens-1 (ZO-1) was significantly increased at cell-cell contacts after the application of transmural pressure. Cytochalasin D treatment significantly elevated transport but did not inhibit the adaptive response, whereas colchicine treatment had no effect on diffusive permeability but inhibited the adaptive response. Neither cytoskeletal inhibitor altered sigma despite significantly elevating both L(p) and effective permeability. Our data suggest that BAECs actively adapt to elevated transmural pressure by mobilizing ZO-1 to intercellular junctions via microtubules. A mechanical (passive) component of the sealing effect appears to reduce the size of a small pore system that allows the transport of water but not dextran or albumin. Furthermore, the structures of the TJ determine transport rates but do not define the selectivity of the monolayer to solutes (sigma).
机译：跨内皮单层的透壁压力梯度突然增加会降低水力传导率（L（p）），这种现象称为密封效果。为了进一步表征这种内皮适应性反应，我们在封闭过程中测量了牛主动脉内皮细胞（BAEC）对白蛋白和70 kDa右旋糖酐的渗透性L（p），以及溶剂-拖曳反射系数（sigma）。在施加压力之前，测量白蛋白（1.33 +/- 0.18 x 10（-6）cm / s）和右旋糖酐（0.60 +/- 0.16 x 10（-6）cm / s）的扩散渗透系数。在施加10 cmH（2）O压力梯度后，测量白蛋白和右旋糖酐（P（ealb）和P（edex））的有效渗透率（当溶剂阻力有助于溶质运输时测得）。在施加压力的前2小时内，P（ealb），P（edex）和L（p）分别降低了2.0 +/- 0.3-，2.1 +/- 0.3-和3.7 +/- 0.3倍， 分别。施加透壁压力后，细胞间接触时紧密连接（TJ）蛋白小带闭合蛋白（ZO-1）的免疫染色显着增加。细胞松弛素D处理显着提高了转运，但没有抑制适应性反应，而秋水仙碱处理对扩散通透性没有影响，但抑制了适应性反应。尽管显着提高L（p）和有效通透性，但两种细胞骨架抑制剂均未改变sigma。我们的数据表明，BAEC通过通过微管动员ZO-1到细胞间连接来主动适应升高的跨壁压。密封作用的机械（被动）成分似乎减小了小孔系统的大小，该小孔系统允许水而不是葡聚糖或白蛋白的运输。此外，TJ的结构决定了传输速率，但没有定义单层对溶质的选择性（西格玛）。

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