{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:56:32Z","timestamp":1791572192455,"version":"4.3.4"},"reference-count":48,"publisher":"American Society for Clinical Investigation","issue":"11","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AR06930,HL134605,GM02853,GM0,1558"],"award-info":[{"award-number":["AR06930,HL134605,GM02853,GM0,1558"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["NONAGES14CE15-0012"],"award-info":[{"award-number":["NONAGES14CE15-0012"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"name":"F\u00e9d\u00e9ration Fran\u00e7aise de Cardiologie 2015","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Bourse de la Fondation de Cardiologie 2016","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Netherlands Organisation for Scientfic Research Rubicon Grant","award":["4521,2006"],"award-info":[{"award-number":["4521,2006"]}]},{"name":"SUNY at Buffalo Startup funds","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"National Marfan Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Elster Research Endowment","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,6,6]]},"abstract":"<jats:p>\n                    Marfan syndrome (MFS) is associated with mutations in fibrillin-1 that predispose afflicted individuals to progressive thoracic aortic aneurysm (TAA) leading to dissection and rupture of the vessel wall. Here we combined computational and experimental approaches to identify and test FDA-approved drugs that may slow or even halt aneurysm progression. Computational analyses of transcriptomic data derived from the aortas of MFS patients and MFS mice (\n                    <jats:italic>\n                      Fbn1\n                      <jats:sup>mgR\/mgR<\/jats:sup>\n                    <\/jats:italic>\n                    mice) predicted that subcellular pathways associated with reduced muscle contractility are key TAA determinants that could be targeted with the GABA\n                    <jats:sub>B<\/jats:sub>\n                    receptor agonist baclofen. Systemic administration of baclofen to\n                    <jats:italic>\n                      Fbn1\n                      <jats:sup>mgR\/mgR<\/jats:sup>\n                    <\/jats:italic>\n                    mice validated our computational prediction by mitigating arterial disease progression at the cellular and physiological levels. Interestingly, baclofen improved muscle contraction\u2013related subcellular pathways by upregulating a different set of genes than those downregulated in the aorta of vehicle-treated\n                    <jats:italic>\n                      Fbn1\n                      <jats:sup>mgR\/mgR<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Distinct transcriptomic profiles were also associated with drug-treated MFS and wild-type mice. Thus, systems pharmacology approaches that compare patient- and mouse-derived transcriptomic data for subcellular pathway\u2013based drug repurposing represent an effective strategy to identify potential new treatments of human diseases.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.127652","type":"journal-article","created":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T11:01:16Z","timestamp":1559732476000},"source":"Crossref","is-referenced-by-count":33,"title":["Systems pharmacology\u2013based integration of human and mouse data for drug repurposing to treat thoracic aneurysms"],"prefix":"10.1172","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1362-6534","authenticated-orcid":true,"given":"Jens","family":"Hansen","sequence":"first","affiliation":[{"name":"Department of Pharmacological Sciences and Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinai, New York, New York, 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Diderot, H\u00f4pital Bichat, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhodora C.","family":"Calizo","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences and Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1076-1922","authenticated-orcid":true,"given":"Bart","family":"Spronck","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6578-4585","authenticated-orcid":true,"given":"Sae-Il","family":"Murtada","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshan","family":"Borkar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6137-109X","authenticated-orcid":true,"given":"Evren U.","family":"Azeloglu","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences and Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bintanel-Morcillo","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences and Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1553-4817","authenticated-orcid":true,"given":"James M.","family":"Gallo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay D.","family":"Humphrey","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0101-2076","authenticated-orcid":true,"given":"Guillaume","family":"Jondeau","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Maladies Rares Syndrome de Marfan et Pathologies Apparent\u00e9es, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, Paris, France."},{"name":"LVTS, INSERM U1148, Universit\u00e9 Paris Diderot, H\u00f4pital Bichat, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Boileau","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Maladies Rares Syndrome de Marfan et Pathologies Apparent\u00e9es, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, Paris, France."},{"name":"LVTS, INSERM U1148, Universit\u00e9 Paris Diderot, H\u00f4pital Bichat, Paris, 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