{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:15:01Z","timestamp":1791774901075,"version":"4.3.4"},"reference-count":60,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2003,2,19]],"date-time":"2003-02-19T00:00:00Z","timestamp":1045612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["WE2672\/1\u20101"],"award-info":[{"award-number":["WE2672\/1\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2003,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The heterodimeric hypoxia\u2010inducible factor (HIF)\u20101 is a master regulator of oxygen homeostasis. Protein stability and transactivation function of the \u03b1 subunit are controlled by iron\u2010 and oxygen\u2010dependent hydroxylation of proline and asparagine residues. The anti\u2010mycotic ciclopirox olamine (CPX) is a lipophilic bidentate iron chelator that stabilizes HIF\u20101\u03b1 under normoxic conditions at lower concentrations than other iron chelators, probably by inhibiting HIF\u20101\u03b1 hydroxylation. As shown by the inhibition of iron\u2010dependent quenching of FITC\u2010labeled deferoxamine (DFX) fluorescence, CPX appears to have an even higher affinity for iron than DFX. Initial observations that treatment with 1% CPX, but not with placebo, occasionally caused reddening of wound margins in a mouse skin wound model prompted us to investigate the capability of CPX to induce angiogenesis. CPX\u2010induced HIF\u20101\u2010mediated reporter gene activity and endogenous HIF\u20101 target gene expression, including elevation of transcription, mRNA, and protein levels of the vascular endothelial growth factor (VEGF). In the chick chorioallantoic membrane assay, inert polymer disks containing CPX but not the solvent alone induced angiogenesis. In summary, these results suggest that CPX induces angiogenesis\n                    <jats:italic>in vivo<\/jats:italic>\n                    via HIF\u20101 and VEGF induction. Therefore, CPX might serve as an alternative to recombinant VEGF treatment or to VEGF gene therapy for therapeutic angiogenesis.\n                  <\/jats:p>","DOI":"10.1096\/fj.02-0586fje","type":"journal-article","created":{"date-parts":[[2003,3,28]],"date-time":"2003-03-28T21:03:22Z","timestamp":1048885402000},"page":"761-763","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["The antimycotic ciclopirox olamine induces HIF\u20101\u03b1 stability, VEGF expression, and angiogenesis"],"prefix":"10.1096","volume":"17","author":[{"given":"Tobias","family":"Linden","sequence":"first","affiliation":[{"name":"Institute of Physiology Medical University of L\u00fcbeck D\u201023538 L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00f6rthe M.","family":"Katschinski","sequence":"additional","affiliation":[{"name":"Institute of Physiology Medical University of L\u00fcbeck D\u201023538 L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Eckhardt","sequence":"additional","affiliation":[{"name":"Carl\u2010Ludwig\u2010Institute of Physiology University of Leipzig D\u201004103 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Scheid","sequence":"additional","affiliation":[{"name":"Department of Surgery University Children's Hospital of Z\u00fcrich and Institute of Physiology University of Z\u00fcrich\u2010Irchel CH\u20108000 Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horst","family":"Pagel","sequence":"additional","affiliation":[{"name":"Institute of Physiology Medical University of L\u00fcbeck D\u201023538 L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland H.","family":"Wenger","sequence":"additional","affiliation":[{"name":"Institute of Physiology Medical University of L\u00fcbeck D\u201023538 L\u00fcbeck Germany"},{"name":"Carl\u2010Ludwig\u2010Institute of Physiology University of Leipzig D\u201004103 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,2,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1993.01420160061009"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(01)00150-4"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/415234a"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.29308"},{"key":"e_1_2_6_6_1","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0928-4257(01)00045-6","article-title":"Gene expression and gene therapy in experimental duodenal ulceration","volume":"95","author":"Szabo S.","year":"2001","journal-title":"J. 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