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

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128 Scopus citations

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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ASJC Scopus subject areas

  • Immunology

Cite this

Maharaj, A. S., Walshe, T. E., Saint-Geniez, M., Venkatesha, S., Maldonado, A. E., Himes, N. C., Matharu, K. S., Ananth Karumanchi, S., & 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