Open and shut case for Rho A? The questions of when, where and how the small GTPase mediates the permeability of endothelial junctions

Abstract

This editorial refers to ‘Localized RhoA GTPase activity regulates dynamics of endothelial monolayer integrity’ by R. Szulcek et al. , pp. 471–482, this issue. It is incredible that current textbooks of Medical Physiology persist in describing the vascular endothelial lining as a passive barrier of finite permeability. Similarly, when the endothelium is observed to participate in vascular function it is treated as a homogenous population of cells possessing a limited number of signalling pathways that regulate the production of substrates that interact with neighbouring cells to regulate (or dysregulate) function. Instead, the barrier segregating flowing blood from metabolizing tissue is a complex structure composed of the endothelium with its associated basement membrane and surface glycocalyx, as well as the peripheral cells including pericytes, mast cells, and fibroblasts at the capillary level and varying coverage by smooth muscle cells in the venules and arterioles, respectively.1 This heterogeneous structure responds constantly to changing physical and chemical stimuli to regulate fluid and solute movement between compartments acutely and chronically. It is important to also recognize that the basal barrier properties, the permeability of the microvessel wall to the spectrum of solutes and fluid in vivo, support maintenance of tissue homoeostasis with appropriate solute delivery and waste removal. These properties vary by organ,2,3 vessel type,3 age,2,3 sex,4 and disease …