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Barrier Maintenance in Neovessels

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Mechanical and Chemical Signaling in Angiogenesis

Part of the book series: Studies in Mechanobiology, Tissue Engineering and Biomaterials ((SMTEB,volume 12))

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Abstract

A hallmark of many pathologies is vascular leak. The extent and severity of vascular leakage is broadly mediated by the integrity of the endothelial cell (EC) monolayer, which is in turn governed by three major interactions: cell–cell and cell-substrate contacts, soluble mediators, and biomechanical forces. Despite its tremendous medical importance, no specific therapies are available directly targeting the endothelium to prevent or reduce vascular permeability. Endothelial cells constantly equilibrate contractile and adhesive forces to maintain vascular barrier integrity. Intracellular signalling, and in particular the involvement of small Rho GTPases in endothelial hyperpermeability responses to many inflammatory stimuli through actin/myosin-mediated cellular contractility, is well-understood. Surprisingly less is known about maintenance of the basal endothelial barrier integrity. Recent live cell imaging studies revealed that highly confluent endothelial monolayers actively maintain barrier integrity by a continuous remodeling of their cell–cell contacts, accompanied by a rapid opening and closure of small inter-endothelial gaps. Moreover, evidence is accumulating that mechanical cues determined by the local microenvironment of ECs are of eminent importance to the integrity of the endothelial monolayer. Here we will review chemical and mechanical signaling involved in maintenance of the integrity of the endothelial barrier.

GPvNA was supported by a grant from the Dutch Heart Foundation (2011T072)

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Authors and Affiliations

  1. Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, van der Boechorstraat 7, 1081BT, Amsterdam, The Netherlands

    Geerten P. van Nieuw Amerongen

  2. Faculty of Medicine, Laboratory of Physiology, VU University Medical Center, Room C-181, Van der Boechorstraat 7, 1081BT, Amsterdam, The Netherlands

    Geerten P. van Nieuw Amerongen

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Correspondence to Geerten P. van Nieuw Amerongen .

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  1. Department of Biomedical Engineering, Cornell Univesity, Ithaca, USA

    Cynthia A. Reinhart-King

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van Nieuw Amerongen, G.P. (2013). Barrier Maintenance in Neovessels. In: Reinhart-King, C. (eds) Mechanical and Chemical Signaling in Angiogenesis. Studies in Mechanobiology, Tissue Engineering and Biomaterials, vol 12. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30856-7_10

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  • DOI: https://doi.org/10.1007/978-3-642-30856-7_10

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