{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:27:15Z","timestamp":1791296835846,"version":"4.1.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,1,11]]},"abstract":"\n Background<\/jats:title>\n \n Marfan syndrome (\n MFS<\/jats:styled-content>\n ) is caused by mutations in the gene encoding fibrillin\u20101 (\n \n FBN<\/jats:styled-content>\n 1\n <\/jats:italic>\n ); however, the mechanisms through which fibrillin\u20101 deficiency causes\n MFS<\/jats:styled-content>\n \u2010associated aortopathy are uncertain. Recently, attention was focused on the hypothesis that\n MFS<\/jats:styled-content>\n \u2010associated aortopathy is caused by increased transforming growth factor\u2010\u03b2 (\n TGF<\/jats:styled-content>\n \u2010\u03b2) signaling in aortic medial smooth muscle cells (\n SMC<\/jats:styled-content>\n ). However, there are many reasons to doubt that\n TGF<\/jats:styled-content>\n \u2010\u03b2 signaling drives\n MFS<\/jats:styled-content>\n \u2010associated aortopathy. We used a mouse model to test whether\n SMC TGF<\/jats:styled-content>\n \u2010\u03b2 signaling is perturbed by a fibrillin\u20101 variant that causes\n MFS<\/jats:styled-content>\n and whether blockade of\n SMC TGF<\/jats:styled-content>\n \u2010\u03b2 signaling prevents\n MFS<\/jats:styled-content>\n \u2010associated aortopathy.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n MFS<\/jats:styled-content>\n mice (\n Fbn1<\/jats:italic>\n C1039G\/+<\/jats:sup>\n genotype) were genetically modified to allow postnatal\n SMC<\/jats:styled-content>\n \u2010specific deletion of the type\n II TGF<\/jats:styled-content>\n \u2010\u03b2 receptor (\n TBRII<\/jats:styled-content>\n ; essential for physiologic\n TGF<\/jats:styled-content>\n \u2010\u03b2 signaling). In young\n MFS<\/jats:styled-content>\n mice with and without superimposed deletion of\n SMC<\/jats:styled-content>\n \u2010\n TBRII<\/jats:styled-content>\n , we measured aortic dimensions, histopathology, activation of aortic\n SMC TGF<\/jats:styled-content>\n \u2010\u03b2 signaling pathways, and changes in aortic\n SMC<\/jats:styled-content>\n gene expression. Young\n Fbn1<\/jats:italic>\n C1039G\/+<\/jats:sup>\n mice had ascending aortic dilation and significant disruption of aortic medial architecture. Both aortic dilation and disrupted medial architecture were exacerbated by superimposed deletion of\n TBRII<\/jats:styled-content>\n .\n TGF<\/jats:styled-content>\n \u2010\u03b2 signaling was unaltered in aortic\n SMC<\/jats:styled-content>\n of young\n MFS<\/jats:styled-content>\n mice; however,\n SMC<\/jats:styled-content>\n \u2010specific deletion of\n TBRII<\/jats:styled-content>\n in\n Fbn1<\/jats:italic>\n C1039G\/+<\/jats:sup>\n mice significantly decreased activation of\n SMC TGF<\/jats:styled-content>\n \u2010\u03b2 signaling pathways.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n In young\n Fbn1<\/jats:italic>\n C1039G\/+<\/jats:sup>\n mice, aortopathy develops in the absence of detectable alterations in\n SMC TGF<\/jats:styled-content>\n \u2010\u03b2 signaling. Loss of physiologic\n SMC TGF<\/jats:styled-content>\n \u2010\u03b2 signaling exacerbates\n MFS<\/jats:styled-content>\n \u2010associated aortopathy. Our data support a protective role for\n SMC TGF<\/jats:styled-content>\n \u2010\u03b2 signaling during early development of\n MFS<\/jats:styled-content>\n \u2010associated aortopathy.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.116.004968","type":"journal-article","created":{"date-parts":[[2017,1,25]],"date-time":"2017-01-25T02:00:18Z","timestamp":1485309618000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":108,"title":["Aortopathy in a Mouse Model of Marfan Syndrome Is Not Mediated by Altered Transforming Growth Factor \u03b2 Signaling"],"prefix":"10.1161","volume":"6","author":[{"given":"Hao","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie Hong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stoyan N.","family":"Angelov","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Enstrom","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, 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