{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:58:30Z","timestamp":1780322310586,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2013,5,31]],"date-time":"2013-05-31T00:00:00Z","timestamp":1369958400000},"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":["GR 3415\u20101\u20102"],"award-info":[{"award-number":["GR 3415\u20101\u20102"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GE 905\/14\u20101"],"award-info":[{"award-number":["GE 905\/14\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KU 1496\/7\u20101"],"award-info":[{"award-number":["KU 1496\/7\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":[[2013,9]]},"abstract":"<jats:p>\n                    Aldosterone triggers the stiff endothelial cell syndrome (SECS), characterized by an up\u2010regulation of epithelial sodium channels (ENaCs) and mechanical stiffening of the endothelial cell cortex accompanied by endothelial dysfunction.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , aldosterone antagonism exerts sustained protection on the cardiovascular system. To illuminate the molecular mechanisms of this time\u2010dependent effect, a study on endothelial cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>ex vivo<\/jats:italic>\n                    was designed to investigate SECS over time. Endothelia (from human umbilical veins, bovine aortae, and explants of human arteries) were cultured in aldosterone\u2010supplemented medium with or without the mineralocorticoid receptor (MR) antagonist spironolactone. MR expression, ENaC expression, cortical stiffness, and shear\u2010mediated nitric oxide (NO) release were determined after 3 d (short term) and up to 24 d (long term). Over time, MR expression increased by 129%. ENaC expression and surface abundance increased by 32% and 42% (13.8 to 19.6 molecules per cell surface), paralleled by a 49% rise in stiffness. Spironolactone prevented this development and, after 3 wk of treatment, increased NO release by 50%. Thus, spironolactone improves endothelial function long\u2010lastingly by preventing a time\u2010dependent manifestation of SECS. This emphasizes the key role of vascular endothelium as a therapeutical target in cardiovascular disorders and might explain blood pressure independent actions of MR antagonism.\u2014Dr\u00fcppel, V., Kusche\u2010Vihrog, K., Grossmann, C., Gekle, M., Kasprzak, B., Brand, E., Pavenst\u00e4dt, H., Oberleithner, H., Kliche, K., Long\u2010term application of the aldosterone antagonist spironolactone prevents stiff endothelial cell syndrome. FASEB J. 27, 3652\u20133659 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-228312","type":"journal-article","created":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T02:49:27Z","timestamp":1370054967000},"page":"3652-3659","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Long\u2010term application of the aldosterone antagonist spironolactone prevents stiff endothelial cell syndrome"],"prefix":"10.1096","volume":"27","author":[{"given":"Verena","family":"Dr\u00fcppel","sequence":"first","affiliation":[{"name":"Institute of Physiology II University of M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Kusche\u2010Vihrog","sequence":"additional","affiliation":[{"name":"Institute of Physiology II University of M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Grossmann","sequence":"additional","affiliation":[{"name":"Julius\u2010Bernstein\u2010Institute of Physiology University of Halle\u2010Wittenberg Halle Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gekle","sequence":"additional","affiliation":[{"name":"Julius\u2010Bernstein\u2010Institute of Physiology University of Halle\u2010Wittenberg Halle Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Kasprzak","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery University of M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Brand","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine D University of M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Pavenst\u00e4dt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine D University of M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Oberleithner","sequence":"additional","affiliation":[{"name":"Institute of Physiology II University of M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Kliche","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery University of M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,5,31]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1993.1066"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4642fje"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.17.6.1152"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.192064"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs257"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.6.594"},{"key":"e_1_2_7_9_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1159\/000345243","article-title":"Vascular actions of aldosterone","volume":"50","author":"Briet M.","year":"2012","journal-title":"J. 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