Please use this identifier to cite or link to this item:
logo share SHARE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE

Selective Inhibition of Vascular Endothelial Growth Factor–mediated Angiogenesis by Cyclosporin A: Roles of the Nuclear Factor of Activated T Cells and Cyclooxygenase 2

AuthorsHernández, Gabriela L.; Volpert, Olga V.; Íñiguez, Miguel Ángel; Lorenzo, Elisa; Martínez Martínez, Sara; Grau, Raquel; Fresno, Manuel CSIC ORCID ; Redondo, Juan Miguel CSIC ORCID
Cyclosporin A
Cyclooxygenase 2
Issue Date5-Mar-2001
PublisherRockefeller University Press
CitationThe Journal of Experimental Medicine, Volume 193, Number 5, 2001, 607-620
AbstractCyclosporin A (CsA) is an immunosuppressive drug that inhibits the activity of transcription factors of the nuclear factor of activated T cells (NFAT) family, interfering with the induction of cytokines and other inducible genes required for the immune response. Here we show that CsA inhibits migration of primary endothelial cells and angiogenesis induced by vascular endothelial growth factor (VEGF); this effect appears to be mediated through the inhibition of cyclooxygenase (Cox)-2, the transcription of which is activated by VEGF in primary endothelial cells. Consistent with this, we show that the induction of Cox-2 gene expression by VEGF requires NFAT activation. Most important, the CsA-mediated inhibition of angiogenesis both in vitro and in vivo was comparable to the Cox-2 inhibitor NS-398, and reversed by prostaglandin E2. Furthermore, the in vivo corneal angiogenesis induced by VEGF, but not by basic fibroblast growth factor, was selectively inhibited in mice treated with CsA systemically. These findings involve NFAT in the regulation of Cox-2 in endothelial cells, point to a role for this transcription factor in angiogenesis, and may provide a novel mechanism underlying the beneficial effects of CsA in angiogenesis-related diseases such as rheumatoid arthritis and psoriasis.
Publisher version (URL)
Appears in Collections:(CBM) Artículos

Files in This Item:
File Description SizeFormat
JMRedondo_JExpMed_607.pdf556,79 kBAdobe PDFThumbnail
Show full item record
Review this work

Google ScholarTM


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.