{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T17:03:19Z","timestamp":1773421399495,"version":"3.50.1"},"reference-count":32,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[2008,1,1]],"date-time":"2008-01-01T00:00:00Z","timestamp":1199145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2008,1,1]],"date-time":"2008-01-01T00:00:00Z","timestamp":1199145600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Vasc Res"],"published-print":{"date-parts":[[2008]]},"abstract":"<jats:p>The vascular endothelial growth factor\/vascular endothelial growth factor receptor 2 (VEGF\/VEGFR-2) signal transduction system plays a key role during embryonic vascular development and adult neovascularization. In contrast to many endothelial genes, &lt;i&gt;VEGFR-2&lt;\/i&gt; is expressed at low levels in most adult vessels but is strongly upregulated during neovascularization, leading to a pro-angiogenic response. Here, we analyzed the activity of regulatory sequences of the murine &lt;i&gt;Vegfr2&lt;\/i&gt; gene during neovessel formation in vivo under ischemic and inflammatory conditions. Hindlimb ischemia was induced in transgenic mice, expressing the &lt;i&gt;LacZ&lt;\/i&gt; reporter gene under the control of &lt;i&gt;Vegfr2&lt;\/i&gt; promoter\/enhancer elements. Most vessels in the ischemic muscle tissue showed strong endothelium-specific reporter gene expression, whereas nearly no &lt;i&gt;LacZ&lt;\/i&gt;-expressing capillaries were observed in untreated control tissue. Cutaneous punch wounds were created to induce angiogenesis under inflammatory conditions, leading to robust &lt;i&gt;LacZ&lt;\/i&gt; expression in the majority of the blood vessels in the wound tissue. Since the cornea is physiologically avascular, the functionality of these promoter\/enhancer elements exclusively in newly formed vessels was confirmed using the cornea micropocket assay. Taken together, our results show that these &lt;i&gt;Vegfr2&lt;\/i&gt; regulatory elements are active during adult neovessel formation in general. Therefore, these sequences may prove to be valuable targets for novel endothelium-specific anti-angiogenic as well as pro-angiogenic treatment strategies. They may especially allow directing therapeutic gene expression to sites of adult neovascularization. Moreover, the Vegfr2\/LacZ reporter mice represent a powerful model to generally analyze the transcriptional control mechanisms involved in the induction of &lt;i&gt;Vegfr2&lt;\/i&gt; expression during adult neovascularization.<\/jats:p>","DOI":"10.1159\/000126106","type":"journal-article","created":{"date-parts":[[2008,4,17]],"date-time":"2008-04-17T09:12:51Z","timestamp":1208423571000},"page":"437-444","source":"Crossref","is-referenced-by-count":9,"title":["Tracking Adult Neovascularization during Ischemia and Inflammation Using Vegfr2-LacZ Reporter Mice"],"prefix":"10.1159","volume":"45","author":[{"given":"Regina","family":"Heidenreich","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshinori","family":"Murayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcy","family":"Silver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Essl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Asahara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"R\u00f6cken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Breier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2008,4,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038%2Fnm0195-27"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1056%2FNEJM197108122850711"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016%2FS0092-8674%2800%2980108-7"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1182%2Fblood.V99.2.538"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1365-2230.1995.tb01274.x"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038%2Fnm0603-653"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1159%2F000090949"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038%2Fnm0603-669"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038%2F367576a0"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1002%2Fijc.20260"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1182%2Fblood-2002-12-3793"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016%2F0092-8674%2894%2990200-3"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1038%2Fnature04478"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1159%2F000088479"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016%2FS0140-6736%2896%2903361-2"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016%2FS0002-9343%2802%2901392-X"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1006%2Fmthe.2002.0638"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1161%2F01.CIR.0000061911.47710.8A"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvoice.2012.06.001"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1159\/000093180"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvoice.2006.08.001"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvoice.2007.03.010"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1080\/14015430050175932"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1016\/S0892-1997(00)80080-6"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/S0892-1997(02)00106-6"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1097\/01.psy.0000126207.43307.c0"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1177\/0891988709351834"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291702005974"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.161.2.286"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.12.2437"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2002.1227"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1207\/s15326942dn3002_3"}],"container-title":["Journal 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