{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T07:09:59Z","timestamp":1772176199079,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1010059","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000}}],"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001677","name":"INSERM","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"crossref","award":["DEQ20150331716"],"award-info":[{"award-number":["DEQ20150331716"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Agence Nationale pour la Recherche","award":["ANR-14-CE15-0012-02"],"award-info":[{"award-number":["ANR-14-CE15-0012-02"]}]},{"name":"Association Fran\u00e7aise pour les Syndromes d\u2019Ehlers Danlos"},{"name":"Association David"},{"name":"R\u00e9gion Ile-de-France"},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"crossref","award":["FDT202001010883"],"award-info":[{"award-number":["FDT202001010883"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Vascular Ehlers-Danlos syndrome is a rare inherited disorder caused by genetic variants in type III collagen. Its prognosis is especially hampered by unpredictable arterial ruptures and there is no therapeutic consensus. We created a knock-in\n                    <jats:italic>Col3a1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/G182R<\/jats:italic>\n                    <\/jats:sup>\n                    mouse model and performed a complete genetic, molecular and biochemical characterization. Several therapeutic strategies were also tested.\n                    <jats:italic>Col3a1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/G182R<\/jats:italic>\n                    <\/jats:sup>\n                    mice showed a spontaneous mortality caused by thoracic aortic rupture that recapitulates the vascular Ehlers-Danlos syndrome with a lower survival rate in males, thin non-inflammatory arteries and an altered arterial collagen. Transcriptomic analysis of aortas showed upregulation of genes related to inflammation and cell stress response. Compared to water, survival rate of\n                    <jats:italic>Col3a1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/G182R<\/jats:italic>\n                    <\/jats:sup>\n                    mice was not affected by beta-blockers (propranolol or celiprolol). Two other vasodilating anti-hypertensive agents (hydralazine, amlodipine) gave opposite results on aortic rupture and mortality rate. There was a spectacular beneficial effect of losartan, reversed by the cessation of its administration, and a marked deleterious effect of exogenous angiotensin II. These results suggest that blockade of the renin angiotensin system should be tested as a first-line medical therapy in patients with vascular Ehlers-Danlos syndrome.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1010059","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T13:40:04Z","timestamp":1646401204000},"page":"e1010059","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Comparative therapeutic strategies for preventing aortic rupture in a mouse model of vascular Ehlers-Danlos syndrome"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5703-3493","authenticated-orcid":true,"given":"Anne","family":"Legrand","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charline","family":"Guery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Faugeroux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0192-5518","authenticated-orcid":true,"given":"Erika","family":"Fontaine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole","family":"Beugnon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Am\u00e9lie","family":"Gianfermi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1080-8786","authenticated-orcid":true,"given":"Irmine","family":"Loisel-Ferreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Christine","family":"Verpont","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2955-0922","authenticated-orcid":true,"given":"Salma","family":"Adham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8690-1093","authenticated-orcid":true,"given":"Tristan","family":"Mirault","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliette","family":"Hadchouel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5925-381X","authenticated-orcid":true,"given":"Xavier","family":"Jeunemaitre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"issue":"1","key":"pgen.1010059.ref001","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/(SICI)1096-8628(19980428)77:1<31::AID-AJMG8>3.0.CO;2-O","article-title":"Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK).","volume":"77","author":"P Beighton","year":"1998","journal-title":"Am J Med Genet"},{"issue":"1","key":"pgen.1010059.ref002","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/ajmg.c.31553","article-title":"Diagnosis, natural history, and management in vascular Ehlers-Danlos syndrome.","volume":"175","author":"PH Byers","year":"2017","journal-title":"Am J Med Genet C Semin Med Genet"},{"issue":"12","key":"pgen.1010059.ref003","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/gim.2014.53","article-title":"Pregnancy-related deaths and complications in women with vascular Ehlers-Danlos syndrome","volume":"16","author":"ML Murray","year":"2014","journal-title":"Genet Med. d\u00e9c"},{"issue":"12","key":"pgen.1010059.ref004","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/gim.2014.72","article-title":"Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV).","volume":"16","author":"MG Pepin","year":"2014","journal-title":"Genet Med. d\u00e9c"},{"issue":"12","key":"pgen.1010059.ref005","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1038\/ejhg.2015.32","article-title":"The type of variants at the COL3A1 gene associates with the phenotype and severity of vascular Ehlers-Danlos syndrome","volume":"23","author":"M Frank","year":"2015","journal-title":"Eur J Hum Genet. d\u00e9c"},{"issue":"8","key":"pgen.1010059.ref006","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1097\/GIM.0b013e3182180c89","article-title":"COL3A1 haploinsufficiency results in a variety of Ehlers-Danlos syndrome type IV with delayed onset of complications and longer life expectancy","volume":"13","author":"DF Leistritz","year":"2011","journal-title":"Genet Med. ao\u00fbt"},{"key":"pgen.1010059.ref007","article-title":"Review of the Techniques Used for Investigating the Role Elastin and Collagen Play in Arterial Wall Mechanics","author":"A Giudici","year":"2020","journal-title":"IEEE Rev Biomed Eng"},{"issue":"12","key":"pgen.1010059.ref008","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1161\/01.CIR.0000121741.50315.C2","article-title":"Increased carotid wall stress in vascular Ehlers-Danlos syndrome","volume":"109","author":"P Boutouyrie","year":"2004","journal-title":"Circulation. 30 mars"},{"issue":"9","key":"pgen.1010059.ref009","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1097\/HJH.0000000000000617","article-title":"Carotid stiffness change over the cardiac cycle by ultrafast ultrasound imaging in healthy volunteers and vascular Ehlers-Danlos syndrome","volume":"33","author":"T Mirault","year":"2015","journal-title":"J Hypertens. sept"},{"issue":"9751","key":"pgen.1010059.ref010","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/S0140-6736(10)60960-9","article-title":"Effect of celiprolol on prevention of cardiovascular events in vascular 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a Long Road","volume":"73","author":"J De Backer","year":"2019","journal-title":"J Am Coll Cardiol"},{"issue":"9","key":"pgen.1010059.ref029","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1002\/ajmg.a.38345","article-title":"Biallelic COL3A1 mutations result in a clinical spectrum of specific structural brain anomalies and connective tissue abnormalities","volume":"173","author":"D Horn","year":"2017","journal-title":"Am J Med Genet A"},{"key":"pgen.1010059.ref030","volume-title":"GeneReviews\u00ae [Internet].","author":"H. Dietz","year":"1993"},{"issue":"4","key":"pgen.1010059.ref031","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1001\/archsurg.1984.01390160041009","article-title":"Elastolytic and collagenolytic studies of arteries. Implications for the mechanical properties of aneurysms","volume":"119","author":"PB Dobrin","year":"1984","journal-title":"Arch Surg. avr"},{"issue":"6","key":"pgen.1010059.ref032","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1055\/a-0599-0841","article-title":"Arterial Stiffening with Ultrafast Ultrasound Imaging Gives New Insight into Arterial Phenotype of Vascular Ehlers-Danlos Mouse Models.","volume":"40","author":"G Goudot","year":"2019","journal-title":"Ultraschall Med. d\u00e9c"},{"issue":"1","key":"pgen.1010059.ref033","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/j.1476-5381.1995.tb14931.x","article-title":"Inhibition of calcium release from the sarcoplasmic reticulum of rabbit aorta by hydralazine","volume":"114","author":"AM Gurney","year":"1995","journal-title":"Br J Pharmacol. janv"},{"issue":"10","key":"pgen.1010059.ref034","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/sj.jhh.1002067","article-title":"Effects of amlodipine and valsartan on vascular damage and ambulatory blood pressure in untreated hypertensive patients","volume":"20","author":"A Ichihara","year":"2006","journal-title":"J Hum Hypertens. oct"},{"key":"pgen.1010059.ref035","first-page":"4","article-title":"A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome.","author":"JJ Doyle","year":"2015","journal-title":"Elife."},{"key":"pgen.1010059.ref036","first-page":"CD011103","article-title":"Beta-blockers for preventing aortic dissection in Marfan syndrome","volume":"11","author":"H-K Koo","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"issue":"2","key":"pgen.1010059.ref037","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.therap.2020.02.009","article-title":"An old drug for a rare disease: The example of celiprolol for vascular Ehlers-Danlos syndrome.","volume":"75","author":"P. 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