Amado-Azevedo Joana, Valent Erik T, Van Nieuw Amerongen Geerten P
Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, Van den Boechorststraat 7, 1081BT, Amsterdam, The Netherlands.
Cell Tissue Res. 2014 Mar;355(3):557-76. doi: 10.1007/s00441-014-1828-6. Epub 2014 Mar 18.
Although the endothelium is an extremely thin single-cell layer, it performs exceedingly well in preventing blood fluids from leaking into the surrounding tissues. However, specific pathological conditions can affect this cell layer, compromising the integrity of the barrier. Vascular leakage is a hallmark of many cardiovascular diseases and despite its medical importance, no specialized therapies are available to prevent it or reduce it. Small guanosine triphosphatases (GTPases) of the Rho family are known to be key regulators of various aspects of cell behavior and studies have shown that they can exert both positive and negative effects on endothelial barrier integrity. Moreover, extracellular matrix stiffness has now been implicated in the regulation of Rho-GTPase signaling, which has a direct impact on the integrity of endothelial junctions. However, knowledge about both the precise mechanism of this regulation and the individual contribution of the specific regulatory proteins remains fragmentary. In this review, we discuss recent findings concerning the balanced activities of Rho-GTPases and, in particular, aspects of the regulation of the endothelial barrier. We highlight the role of Rho-GTPases in the intimate relationships between biomechanical forces, microenvironmental influences and endothelial intercellular junctions, which are all interwoven in a beautiful filigree-like fashion.
尽管内皮是一层极其薄的单细胞层，但它在防止血液渗漏到周围组织方面表现出色。然而，特定的病理状况会影响这一细胞层，损害屏障的完整性。血管渗漏是许多心血管疾病的一个标志，尽管其具有医学重要性，但尚无专门的疗法来预防或减少它。已知Rho家族的小GTP酶（GTPases）是细胞行为各个方面的关键调节因子，研究表明它们可对内皮屏障完整性产生正面和负面影响。此外，细胞外基质硬度现已被认为参与Rho-GTPase信号传导的调节，这对内皮连接的完整性有直接影响。然而，关于这种调节的精确机制以及特定调节蛋白的个体作用的知识仍然支离破碎。在这篇综述中，我们讨论了关于Rho-GTPases平衡活性的最新发现，特别是内皮屏障调节的各个方面。我们强调了Rho-GTPases在生物力学力、微环境影响和内皮细胞间连接之间密切关系中的作用，这些关系都以一种美妙的细丝状方式交织在一起。
