{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:01:07Z","timestamp":1790485267090,"version":"4.1.0"},"reference-count":90,"publisher":"American Society for Clinical Investigation","issue":"21","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-HL121797"],"award-info":[{"award-number":["R01-HL121797"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["TL1TR001069"],"award-info":[{"award-number":["TL1TR001069"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009364","name":"Saving tiny Hearts Society","doi-asserted-by":"crossref","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}],"id":[{"id":"10.13039\/100009364","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,11,2]]},"abstract":"<jats:p>\n                    An ascending aortic aneurysm (AscAA) is a life-threatening disease whose molecular basis is poorly understood. Mutations in\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    have been linked to bicuspid aortic valve (BAV), which is associated with AscAA. Here, we describe a potentially novel role for Notch1 in AscAA. We found that\n                    <jats:italic>Notch1<\/jats:italic>\n                    haploinsufficiency exacerbated the aneurysmal aortic root dilation seen in the Marfan syndrome mouse model and that heterozygous deletion of\n                    <jats:italic>Notch1<\/jats:italic>\n                    in the second heart field (SHF) lineage recapitulated this exacerbated phenotype. Additionally,\n                    <jats:italic>\n                      Notch1\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice in a predominantly 129S6 background develop aortic root dilation, indicating that loss of Notch1 is sufficient to cause AscAA. RNA sequencing analysis of the\n                    <jats:italic>\n                      Notch1.129S6\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    aortic root demonstrated gene expression changes consistent with AscAA. These findings are the first to our knowledge to demonstrate an SHF lineage\u2013specific role for Notch1 in AscAA and suggest that genes linked to the development of BAV may also contribute to the associated aortopathy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.91353","type":"journal-article","created":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T11:00:36Z","timestamp":1509534036000},"source":"Crossref","is-referenced-by-count":58,"title":["Notch1 haploinsufficiency causes ascending aortic aneurysms in mice"],"prefix":"10.1172","volume":"2","author":[{"given":"Sara N.","family":"Koenig","sequence":"first","affiliation":[{"name":"Center for Cardiovascular Research and"},{"name":"The Heart Center, Nationwide Children\u2019s Hospital, Columbus, Ohio, USA."},{"name":"Dorothy M. Davis Heart and Lung Research Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8625-4199","authenticated-orcid":true,"given":"Stephanie","family":"LaHaye","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research and"},{"name":"The Heart Center, Nationwide Children\u2019s Hospital, Columbus, Ohio, USA."},{"name":"Department of Molecular Genetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Feller","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research and"},{"name":"The Heart Center, Nationwide Children\u2019s Hospital, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Rowland","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research and"},{"name":"The Heart Center, Nationwide Children\u2019s Hospital, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan N.","family":"Hor","sequence":"additional","affiliation":[{"name":"The Heart Center, Nationwide Children\u2019s Hospital, Columbus, Ohio, USA."},{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron J.","family":"Trask","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research and"},{"name":"The Heart Center, Nationwide Children\u2019s Hospital, Columbus, Ohio, USA."},{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.L.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freddy","family":"Radtke","sequence":"additional","affiliation":[{"name":"Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne, Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Lilly","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research and"},{"name":"The Heart Center, Nationwide Children\u2019s Hospital, Columbus, Ohio, USA."},{"name":"Department of Molecular Genetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidu","family":"Garg","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research and"},{"name":"The Heart Center, Nationwide Children\u2019s Hospital, Columbus, Ohio, USA."},{"name":"Dorothy M. 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