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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.<\/jats:p>","DOI":"10.1084\/jem.193.5.607","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"607-620","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":362,"title":["Selective Inhibition of Vascular Endothelial Growth Factor\u2013Mediated Angiogenesis by Cyclosporin a"],"prefix":"10.1084","volume":"193","author":[{"given":"Gabriela L.","family":"Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"aCentro de Biolog\u00eda Molecular \u201cSevero Ochoa, \u201d Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, Facultad de Ciencias, E-28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga V.","family":"Volpert","sequence":"additional","affiliation":[{"name":"bDepartment of Urology, Robert H. Lurie C. Cancer Center, Chicago, Illinois 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"\u00cd\u00f1iguez","sequence":"additional","affiliation":[{"name":"aCentro de Biolog\u00eda Molecular \u201cSevero Ochoa, \u201d Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, Facultad de Ciencias, E-28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Lorenzo","sequence":"additional","affiliation":[{"name":"aCentro de Biolog\u00eda Molecular \u201cSevero Ochoa, \u201d Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, Facultad de Ciencias, E-28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Mart\u00ednez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"aCentro de Biolog\u00eda Molecular \u201cSevero Ochoa, \u201d Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, Facultad de Ciencias, E-28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Grau","sequence":"additional","affiliation":[{"name":"aCentro de Biolog\u00eda Molecular \u201cSevero Ochoa, \u201d Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, Facultad de Ciencias, E-28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Fresno","sequence":"additional","affiliation":[{"name":"aCentro de Biolog\u00eda Molecular \u201cSevero Ochoa, \u201d Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, Facultad de Ciencias, E-28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Miguel","family":"Redondo","sequence":"additional","affiliation":[{"name":"aCentro de Biolog\u00eda Molecular \u201cSevero Ochoa, \u201d Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, Facultad de Ciencias, E-28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2001,3,5]]},"reference":[{"key":"2023072509421050800_R1","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/380439a0","article-title":"Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene","volume":"380","author":"Ferrara","year":"1996","journal-title":"Nature."},{"key":"2023072509421050800_R2","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s001099900019","article-title":"Molecular and biological properties of vascular endothelial growth factor","volume":"77","author":"Ferrara","year":"1999","journal-title":"J. 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