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VEGF and TGF-β are required for the maintenance of the choroid plexus and ependyma

Although the role of vascular endothelial growth factor (VEGF) in developmental and pathological angiogenesis is well established, its function in the adult is less clear. Similarly, although transforming growth factor (TGF) β is involved in angiogenesis, presumably by mediating capillary (endotheli...

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Autores principales: Maharaj, Arindel S.R., Walshe, Tony E., Saint-Geniez, Magali, Venkatesha, Shivalingappa, Maldonado, Angel E., Himes, Nathan C., Matharu, Kabir S., Karumanchi, S. Ananth, D'Amore, Patricia A.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2271023/
https://www.ncbi.nlm.nih.gov/pubmed/18268040
http://dx.doi.org/10.1084/jem.20072041
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author Maharaj, Arindel S.R.
Walshe, Tony E.
Saint-Geniez, Magali
Venkatesha, Shivalingappa
Maldonado, Angel E.
Himes, Nathan C.
Matharu, Kabir S.
Karumanchi, S. Ananth
D'Amore, Patricia A.
author_facet Maharaj, Arindel S.R.
Walshe, Tony E.
Saint-Geniez, Magali
Venkatesha, Shivalingappa
Maldonado, Angel E.
Himes, Nathan C.
Matharu, Kabir S.
Karumanchi, S. Ananth
D'Amore, Patricia A.
author_sort Maharaj, Arindel S.R.
collection PubMed
description Although the role of vascular endothelial growth factor (VEGF) in developmental and pathological angiogenesis is well established, its function in the adult is less clear. Similarly, although transforming growth factor (TGF) β is involved in angiogenesis, presumably by mediating capillary (endothelial cell [EC]) stability, its involvement in quiescent vasculature is virtually uninvestigated. Given the neurological findings in patients treated with VEGF-neutralizing therapy (bevacizumab) and in patients with severe preeclampsia, which is mediated by soluble VEGF receptor 1/soluble Fms-like tyrosine kinase receptor 1 and soluble endoglin, a TGF-β signaling inhibitor, we investigated the roles of VEGF and TGF-β in choroid plexus (CP) integrity and function in adult mice. Receptors for VEGF and TGF-β were detected in adult CP, as well as on ependymal cells. Inhibition of VEGF led to decreased CP vascular perfusion, which was associated with fibrin deposition. Simultaneous blockade of VEGF and TGF-β resulted in the loss of fenestrae on CP vasculature and thickening of the otherwise attenuated capillary endothelium, as well as the disappearance of ependymal cell microvilli and the development of periventricular edema. These results provide compelling evidence that both VEGF and TGF-β are involved in the regulation of EC stability, ependymal cell function, and periventricular permeability.
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spelling pubmed-22710232008-08-18 VEGF and TGF-β are required for the maintenance of the choroid plexus and ependyma Maharaj, Arindel S.R. Walshe, Tony E. Saint-Geniez, Magali Venkatesha, Shivalingappa Maldonado, Angel E. Himes, Nathan C. Matharu, Kabir S. Karumanchi, S. Ananth D'Amore, Patricia A. J Exp Med Articles Although the role of vascular endothelial growth factor (VEGF) in developmental and pathological angiogenesis is well established, its function in the adult is less clear. Similarly, although transforming growth factor (TGF) β is involved in angiogenesis, presumably by mediating capillary (endothelial cell [EC]) stability, its involvement in quiescent vasculature is virtually uninvestigated. Given the neurological findings in patients treated with VEGF-neutralizing therapy (bevacizumab) and in patients with severe preeclampsia, which is mediated by soluble VEGF receptor 1/soluble Fms-like tyrosine kinase receptor 1 and soluble endoglin, a TGF-β signaling inhibitor, we investigated the roles of VEGF and TGF-β in choroid plexus (CP) integrity and function in adult mice. Receptors for VEGF and TGF-β were detected in adult CP, as well as on ependymal cells. Inhibition of VEGF led to decreased CP vascular perfusion, which was associated with fibrin deposition. Simultaneous blockade of VEGF and TGF-β resulted in the loss of fenestrae on CP vasculature and thickening of the otherwise attenuated capillary endothelium, as well as the disappearance of ependymal cell microvilli and the development of periventricular edema. These results provide compelling evidence that both VEGF and TGF-β are involved in the regulation of EC stability, ependymal cell function, and periventricular permeability. The Rockefeller University Press 2008-02-18 /pmc/articles/PMC2271023/ /pubmed/18268040 http://dx.doi.org/10.1084/jem.20072041 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Maharaj, Arindel S.R.
Walshe, Tony E.
Saint-Geniez, Magali
Venkatesha, Shivalingappa
Maldonado, Angel E.
Himes, Nathan C.
Matharu, Kabir S.
Karumanchi, S. Ananth
D'Amore, Patricia A.
VEGF and TGF-β are required for the maintenance of the choroid plexus and ependyma
title VEGF and TGF-β are required for the maintenance of the choroid plexus and ependyma
title_full VEGF and TGF-β are required for the maintenance of the choroid plexus and ependyma
title_fullStr VEGF and TGF-β are required for the maintenance of the choroid plexus and ependyma
title_full_unstemmed VEGF and TGF-β are required for the maintenance of the choroid plexus and ependyma
title_short VEGF and TGF-β are required for the maintenance of the choroid plexus and ependyma
title_sort vegf and tgf-β are required for the maintenance of the choroid plexus and ependyma
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2271023/
https://www.ncbi.nlm.nih.gov/pubmed/18268040
http://dx.doi.org/10.1084/jem.20072041
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