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Polarised VEGFA Signalling at Vascular Blood–Neural Barriers

Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK
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Int. J. Mol. Sci. 2018, 19(5), 1378; https://doi.org/10.3390/ijms19051378
Received: 18 April 2018 / Revised: 2 May 2018 / Accepted: 3 May 2018 / Published: 5 May 2018
(This article belongs to the Special Issue Vascular Endothelial Growth Factor)
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Abstract

At blood–neural barriers, endothelial VEGFA signalling is highly polarised, with entirely different responses being triggered by luminal or abluminal stimulation. These recent findings were made in a field which is still in its mechanistic infancy. For a long time, endothelial polarity has intuitively been presumed, and likened to that of epithelial cells, but rarely demonstrated. In the cerebral and the retinal microvasculature, the uneven distribution of VEGF receptors 1 and 2, with the former predominant on the luminal and the latter on the abluminal face of the endothelium, leads to a completely polarised signalling response to VEGFA. Luminal VEGFA activates VEGFR1 homodimers and AKT, leading to a cytoprotective response, whilst abluminal VEGFA induces vascular leakage via VEGFR2 homodimers and p38. Whilst these findings do not provide a complete picture of VEGFA signalling in the microvasculature—there are still unclear roles for heterodimeric receptor complexes as well as co-receptors—they provide essential insight into the adaptation of vascular systems to environmental cues that are naturally different, depending on whether they are present on the blood or tissue side. Importantly, sided responses are not only restricted to VEGFA, but exist for other important vasoactive agents. View Full-Text
Keywords: VEGF; endothelial cells; polarity VEGF; endothelial cells; polarity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Dragoni, S.; Turowski, P. Polarised VEGFA Signalling at Vascular Blood–Neural Barriers. Int. J. Mol. Sci. 2018, 19, 1378.

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