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

Arindel S Maharaj, Tony E. Walshe, Magali Saint-Geniez, Shivalingappa Venkatesha, Angel E. Maldonado, Nathan C. Himes, Kabir S. Matharu, S. Ananth Karumanchi, Patricia A. D'Amore

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

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 VEGFneutralizing 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. JEM

Original languageEnglish (US)
Pages (from-to)491-501
Number of pages11
JournalJournal of Experimental Medicine
Volume205
Issue number2
DOIs
StatePublished - Feb 18 2008
Externally publishedYes

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Ependyma
Choroid Plexus
Transforming Growth Factors
Vascular Endothelial Growth Factor A
Maintenance
Vascular Endothelial Growth Factor Receptor-1
Endothelial Cells
Pathologic Neovascularization
Vascular Endothelial Growth Factor Receptor
Vascular Endothelium
Receptor Protein-Tyrosine Kinases
Microvilli
Pre-Eclampsia
Fibrin
Blood Vessels
Permeability
Edema
Perfusion

ASJC Scopus subject areas

  • Immunology

Cite this

Maharaj, A. S., Walshe, T. E., Saint-Geniez, M., Venkatesha, S., Maldonado, A. E., Himes, N. C., ... D'Amore, P. A. (2008). VEGF and TGF-β are required for the maintenance of the choroid plexus and ependyma. Journal of Experimental Medicine, 205(2), 491-501. https://doi.org/10.1084/jem.20072041

VEGF and TGF-β are required for the maintenance of the choroid plexus and ependyma. / Maharaj, Arindel S; Walshe, Tony E.; Saint-Geniez, Magali; Venkatesha, Shivalingappa; Maldonado, Angel E.; Himes, Nathan C.; Matharu, Kabir S.; Ananth Karumanchi, S.; D'Amore, Patricia A.

In: Journal of Experimental Medicine, Vol. 205, No. 2, 18.02.2008, p. 491-501.

Research output: Contribution to journalArticle

Maharaj, AS, Walshe, TE, Saint-Geniez, M, Venkatesha, S, Maldonado, AE, Himes, NC, Matharu, KS, Ananth Karumanchi, S & D'Amore, PA 2008, 'VEGF and TGF-β are required for the maintenance of the choroid plexus and ependyma', Journal of Experimental Medicine, vol. 205, no. 2, pp. 491-501. https://doi.org/10.1084/jem.20072041
Maharaj, Arindel S ; Walshe, Tony E. ; Saint-Geniez, Magali ; Venkatesha, Shivalingappa ; Maldonado, Angel E. ; Himes, Nathan C. ; Matharu, Kabir S. ; Ananth Karumanchi, S. ; D'Amore, Patricia A. / VEGF and TGF-β are required for the maintenance of the choroid plexus and ependyma. In: Journal of Experimental Medicine. 2008 ; Vol. 205, No. 2. pp. 491-501.
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