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Building Blood Vessels—One Rho GTPase at a Time

机译:建造血管-一次一个Rho GTPase

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摘要

Blood vessels are required for the survival of any organism larger than the oxygen diffusion limit. Blood vessel formation is a tightly regulated event and vessel growth or changes in permeability are linked to a number of diseases. Elucidating the cell biology of endothelial cells (ECs), which are the building blocks of blood vessels, is thus critical to our understanding of vascular biology and to the development of vascular-targeted disease treatments. Small GTPases of the Rho GTPase family are known to regulate several processes critical for EC growth and maintenance. In fact, many of the 21 Rho GTPases in mammals are known to regulate EC junctional remodeling, cell shape changes, and other processes. Rho GTPases are thus an attractive target for disease treatments, as they often have unique functions in specific vascular cell types. In fact, some Rho GTPases are even expressed with relative specificity in diseased vessels. Interestingly, many Rho GTPases are understudied in ECs, despite their known expression in either developing or mature vessels, suggesting an even greater wealth of knowledge yet to be gleaned from these complex signaling pathways. This review aims to provide an overview of Rho GTPase signaling contributions to EC vasculogenesis, angiogenesis, and mature vessel barrier function. A particular emphasis is placed on so-called “alternative” Rho GTPases, as they are largely understudied despite their likely important contributions to EC biology.
机译:任何大于氧气扩散极限的生物的生存都需要血管。血管的形成是严格控制的事件,血管的生长或通透性的变化与许多疾病有关。因此,阐明内皮细胞(EC)的细胞生物学是血管的组成部分,因此对于我们对血管生物学的理解以及对血管靶向疾病治疗的发展至关重要。众所周知,Rho GTPase家族的小型GTPases调节几种对EC生长和维持至关重要的过程。实际上,已知哺乳动物中的21种Rho GTPases中有许多可调节EC连接重塑,细胞形状变化和其他过程。因此,Rho GTPases是疾病治疗的诱人靶标,因为它们通常在特定的血管细胞类型中具有独特的功能。实际上,某些Rho GTPases甚至在患病血管中相对特异性地表达。有趣的是,尽管许多Rho GTPases在发育中或成熟的血管中都有已知表达,但在EC中却没有对其进行深入研究,这表明尚需从这些复杂的信号途径中获得更多的知识。这篇综述旨在概述Rho GTPase信号对EC血管生成,血管生成和成熟的血管屏障功能的贡献。特别强调的是所谓的“替代” Rho GTPases,因为尽管它们可能对EC生物学做出重要贡献,但对它们的研究仍很少。

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