{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T06:44:58Z","timestamp":1781851498443,"version":"3.54.5"},"reference-count":60,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T00:00:00Z","timestamp":1548288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sanofi, Frankfurt, Germany"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Marfan syndrome (<jats:styled-content style=\"fixed-case\">MFS<\/jats:styled-content>) is an autosomal dominant genetic disorder caused by mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">FBN<\/jats:styled-content>1<\/jats:italic> gene. Although many peripheral tissues are affected, aortic complications, such as dilation, dissection and rupture, are the leading causes of <jats:styled-content style=\"fixed-case\">MFS<\/jats:styled-content>\u2010related mortality. Aberrant <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010beta signalling plays a major role in the pathophysiology of <jats:styled-content style=\"fixed-case\">MFS<\/jats:styled-content>. However, the contributing mechanisms are still poorly understood. Here, we aimed at identifying novel aorta\u2010specific pathways involved in the pathophysiology of <jats:styled-content style=\"fixed-case\">MFS<\/jats:styled-content>. For this purpose, we employed the <jats:italic>Fbn1<\/jats:italic> under\u2010expressing mgR\/mgR mouse model of <jats:styled-content style=\"fixed-case\">MFS<\/jats:styled-content>. We performed <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010sequencing of aortic tissues of 9\u2010week\u2010old mgR\/mgR mice compared with wild\u2010type (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>) mice. With a false discovery rate &lt;5%, our analysis revealed 248 genes to be differentially regulated including 20 genes previously unrelated with <jats:styled-content style=\"fixed-case\">MFS<\/jats:styled-content>\u2010related pathology. Among these, we identified <jats:italic>Igfbp2<\/jats:italic>,<jats:italic> Ccl8<\/jats:italic>,<jats:italic> Spp1<\/jats:italic>,<jats:italic> Mylk2<\/jats:italic>,<jats:italic> Mfap4<\/jats:italic>,<jats:italic> Dsp<\/jats:italic> and <jats:italic>H19<\/jats:italic>. We confirmed the expression of regulated genes by quantitative real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>. Pathway classification revealed transcript signatures involved in chemokine signalling, cardiac muscle contraction, dilated and hypertrophic cardiomyopathy. Furthermore, our immunoblot analysis of aortic tissues revealed altered regulation of <jats:styled-content style=\"fixed-case\">pS<\/jats:styled-content>mad2 signalling, Perk1\/2, Igfbp2, Mfap4, Ccl8 and Mylk2 protein levels in mgR\/mgR vs <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> mice. Together, our integrative systems approach identified several novel factors associated with <jats:styled-content style=\"fixed-case\">MFS<\/jats:styled-content>\u2010aortic\u2010specific pathophysiology that might offer potential novel therapeutic targets for <jats:styled-content style=\"fixed-case\">MFS<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/jcmm.14137","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T22:58:22Z","timestamp":1548370702000},"page":"2526-2535","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["An integrative systems approach identifies novel candidates in Marfan syndrome\u2010related pathophysiology"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6960-6025","authenticated-orcid":false,"given":"Raghu","family":"Bhushan","sequence":"first","affiliation":[{"name":"Charit\u00e9 University Hospital Berlin 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