{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T01:32:24Z","timestamp":1790040744291,"version":"4.0.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T00:00:00Z","timestamp":1554768000000},"content-version":"am","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008473","name":"Gebauer Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008473","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wolfermann-N\u00e4geli-Stiftung"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Antihypertensive drugs are included in the medical therapy of vascular Ehlers\u2013Danlos syndrome (vEDS). The \u03b2-blocker celiprolol has been suggested to prevent arterial damage in vEDS, but the underlying mechanism remains unclear. It is also unknown whether the widely used angiotensin II receptor type 1 antagonist losartan has a therapeutic effect in vEDS. Here, we evaluated the impact of celiprolol and losartan on the biomechanical integrity of the vEDS thoracic aorta.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We established a new approach to measure the maximum tensile force at rupture of uniaxially stretched murine thoracic aortic rings. In a vEDS model, which we (re-)characterized here at molecular level, heterozygous mice showed a significant reduction in the rupture force compared to wild-type mice, reflecting the increased mortality due to aortic rupture. For the assessment of treatment effects, heterozygous mice at 4\u2009weeks of age underwent a 4-week treatment with celiprolol, losartan, and, as a proof-of-concept drug, the matrix metalloproteinase inhibitor doxycycline. Compared to age- and sex-matched untreated heterozygous mice, treatment with doxycycline or celiprolol resulted in a significant increase of rupture force, whereas no significant change was detected upon losartan treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In a vEDS model, celiprolol or doxycycline, but not losartan, can improve the biomechanical integrity of the aortic wall, thereby potentially reducing the risk of dissection and rupture. As doxycycline is a broad-spectrum antibiotic with considerable side effects, celiprolol may be more suitable for a long-term therapy and thus rather indicated for the medication of patients with vEDS.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cvr\/cvz095","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T15:11:10Z","timestamp":1554390670000},"source":"Crossref","is-referenced-by-count":11,"title":["Celiprolol but not losartan improves the biomechanical integrity of the aorta in a mouse model of vascular Ehlers\u2013Danlos syndrome"],"prefix":"10.1093","author":[{"given":"Nicolo","family":"Dubacher","sequence":"first","affiliation":[{"name":"Center for Cardiovascular Genetics and Gene Diagnostics, Foundation for People with Rare Diseases, Schlieren-Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"M\u00fcnger","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Genetics and Gene 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Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0144-4813","authenticated-orcid":false,"given":"Sylvan M","family":"Caspar","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Genetics and Gene Diagnostics, Foundation for People with Rare Diseases, Schlieren-Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik N T P","family":"Bakker","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, GG, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8654-986X","authenticated-orcid":false,"given":"Ed","family":"van Bavel","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, GG, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7860-1867","authenticated-orcid":false,"given":"Urs","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Center for Microscopy and Image Analysis, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Carrel","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, University Hospital, Berne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beat","family":"Steinmann","sequence":"additional","affiliation":[{"name":"Division of Metabolism, University Children\u2019s Hospital, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Zeisberger","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland"},{"name":"Wyss Zurich, 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