{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:20:06Z","timestamp":1762100406043,"version":"3.40.4"},"reference-count":20,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T00:00:00Z","timestamp":1104537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T00:00:00Z","timestamp":1104537600000},"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":[[2005]]},"abstract":"<i>Background:<\/i> Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells (EC) in vitro and angiogenesis in vivo. Furthermore, a role of VEGF in K<sup>+<\/sup> channel, nitric oxide (NO) and Ca<sup>2+<\/sup> signaling was reported. We examined whether the K<sup>+<\/sup> channel blocker margatoxin (MTX) influences VEGF-induced signaling in human EC. <i>Methods:<\/i> Fluorescence imaging was used to analyze changes in the membrane potential (DiBAC), intracellular Ca<sup>2+<\/sup> (FURA-2) and NO (DAF) levels in cultured human EC derived from human umbilical vein EC (HUVEC). Proliferation of HUVEC was examined by cell counts (CC) and [<sup>3<\/sup>H]-thymidine incorporation (TI).<i>Results:<\/i> VEGF (5\u201350 ng\/ml) caused a dose-dependent hyperpolarization of EC, with a maximum at 30 ng\/ml (n = 30, p < 0.05). This effect was completely blocked by MTX (5 \u00b5mol\/l). VEGF caused an increase in transmembrane Ca<sup>2+<\/sup> influx (n = 30, p < 0.05) that was sensitive to MTX and the blocker of transmembrane Ca<sup>2+<\/sup> entry 2-aminoethoxydiphenyl borate (APB, 100 \u00b5mol\/l). VEGF-induced NO production was significantly reduced by MTX, APB and a reduction in extracellular Ca<sup>2+<\/sup> (n = 30, p < 0.05). HUVEC proliferation, examined by CC and TI, was significantly increased by VEGF and inhibited by MTX (CC: \u201358%, TI \u2013121%); APB (CC \u201399%, TI \u2013187%); N-monomethyl-<i>L<\/i>-arginine (300 \u00b5mol\/l: CC: \u201386%, TI \u2013164%). <i>Conclusions:<\/i> VEGF caused an MTX-sensitive hyperpolarization which results in an increased transmembrane Ca<sup>2+<\/sup> entry that is responsible for the effects on endothelial proliferation and NO production.<\/jats:p>","DOI":"10.1159\/000087159","type":"journal-article","created":{"date-parts":[[2005,7,26]],"date-time":"2005-07-26T10:27:42Z","timestamp":1122373662000},"page":"368-376","source":"Crossref","is-referenced-by-count":29,"title":["Margatoxin Inhibits VEGF-Induced Hyperpolarization, Proliferation and Nitric Oxide Production of Human Endothelial Cells"],"prefix":"10.1159","volume":"42","author":[{"given":"Ali","family":"Erdogan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian Alexander","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doerte Wiebke","family":"Luedders","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Stockhausen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaser","family":"Abdallah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrid Kerstin","family":"Most","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"Tillmanns","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans Michael","family":"Piper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph Ruediger Wolfram","family":"Kuhlmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2005,9,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1210%2Fer.18.1.4"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016%2F0006-291X%2892%2990483-2"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1126%2Fscience.1312256"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1038%2F386671a0"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038%2Fnm0195-27"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1126%2Fscience.6823562"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1006%2Fmvre.1998.2131"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1146%2Fannurev.ph.50.030188.001231"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1146%2Fannurev.physiol.59.1.145"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1159%2F000025606"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.cardiores.2003.08.010"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1161%2F01.ATV.0000130663.37663.6a"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1097%2F01.ASN.0000115782.77586.88"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016%2FS1357-2725%2801%2900021-8"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1469-7793.1997.397bk.x"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.bjp.0704465"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1172%2FJCI119868"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1172%2FJCI119451"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1007%2Fs00424-001-0741-5"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.274.21.14838"}],"container-title":["Journal of Vascular Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/87159","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/87159","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T03:19:38Z","timestamp":1745464778000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000087159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005]]},"references-count":20,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2005,10,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000087159","archive":["Portico"],"relation":{},"ISSN":["1018-1172","1423-0135"],"issn-type":[{"type":"print","value":"1018-1172"},{"type":"electronic","value":"1423-0135"}],"subject":[],"published":{"date-parts":[[2005]]}}}