{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:32:02Z","timestamp":1791664322339,"version":"4.3.4"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"15","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010447","name":"German Center for Cardiovascular Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cardio Pulmonary Institute Excellence Cluster"},{"DOI":"10.13039\/501100022604","name":"Johanna Quandt Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022604","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Giuliani Foundation"},{"name":"Italian Ministry of Health to Centro Cardiologico Monzino IRCCS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study investigated whether TBX18, a transcription factor known for its critical roles in cardiovascular and urogenital development, but never previously studied in the context of the aorta, contributes to the normal development and homeostasis of this major artery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Histological analyses revealed Tbx18 expression in smooth muscle cells (SMCs) of the adult and embryonic aorta. Following this observation, transgenic mouse models were used to promote ablation of Tbx18 in SMCs from early embryogenesis or in adulthood. Phenotypes were assessed by quantitative imaging and histological analyses. Embryonic conditional ablation of Tbx18 resulted in severe aortic malformations and lethality, whereas adult ablation resulted in milder phenotypes. However, when adult Tbx18 ablation was combined with a Marfan-causing mutation, it promoted degradation of aortic ultrastructure, aortic root dilation, and lethality. Multiomics analyses at the transcriptomic and translatomic levels revealed up-regulation of immediate early genes encoding critical transcription factors such as EGR1, FOS, and JUNB in SMCs from Marfan aortae, a response further exacerbated by concomitant ablation of Tbx18. ChIP-seq in primary human aortic SMCs revealed that TBX18 directly binds to several of the genes that were misexpressed in mutant aortae, suggesting direct regulation. Finally, transcriptomic and histological analyses of human patient samples revealed that TBX18 expression was down-regulated in aneurysms, with the extent of down-regulation correlating with lesion severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results demonstrate that TBX18 in SMCs is essential not only for normal aortic development, but also for preventing gene expression programmes linked to adverse remodelling in adulthood. These findings enhance our understanding of the function of this transcription factor and of molecular mechanisms underlying aneurysm formation, a pathology responsible for a significant number of fatalities in developed countries.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvaf201","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T12:23:38Z","timestamp":1763641418000},"page":"2419-2431","source":"Crossref","is-referenced-by-count":1,"title":["Transcription regulation by TBX18 in smooth muscle cells is essential for normal aortic development and homeostasis"],"prefix":"10.1093","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0788-6460","authenticated-orcid":false,"given":"Debanjan","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular Regeneration, Goethe University , Frankfurt am Main 60590 ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Rhein Main , Frankfurt am Main 60590 ,","place":["Germany"]},{"name":"Cardiopulmonary Institute, Goethe University , Frankfurt am Main 60590 ,","place":["Germany"]},{"name":"Faculty of Medicine, Goethe University , Frankfurt am Main 60590 ,","place":["Germany"]},{"name":"International Max Planck Research School for Molecular Organ Biology , Bad Nauheim 61231 ,","place":["Germany"]},{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, Albert-Ludwigs-University of Freiburg , Freiburg im Breisgau 79104 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Larcher","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Regeneration, Goethe University , Frankfurt am Main 60590 ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Rhein Main , Frankfurt am Main 60590 ,","place":["Germany"]},{"name":"Cardiopulmonary Institute, Goethe University , Frankfurt am Main 60590 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Winter","sequence":"additional","affiliation":[{"name":"Institute of Molecular Vascular Medicine, TUM University Hospital Rechts der Isar, Technical University Munich , Munich 81675 ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance , Munich 80336 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Sachs","sequence":"additional","affiliation":[{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance , Munich 80336 ,","place":["Germany"]},{"name":"Department of Vascular and Endovascular Surgery, TUM University Hospital Rechts der Isar, Technical University Munich , Munich 81675 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Andriani","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS , Milan 20138 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Chiesa","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS , Milan 20138 ,","place":["Italy"]},{"name":"Department of Electronics, Information and Biomedical Engineering, Politecnico di Milano , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca L","family":"Perrucci","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS , Milan 20138 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Rega","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS , Milan 20138 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5594-4549","authenticated-orcid":false,"given":"Stefan","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Heart and Lung Research , Bad Nauheim 61231 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Kuenne","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Heart and Lung Research , Bad Nauheim 61231 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jody C","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of California, San Diego , La Jolla, CA 92093 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusu","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego , La Jolla, CA 92093 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslav","family":"Pelisek","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, University Hospital Zurich , Zurich 8091 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Regeneration, Goethe University , Frankfurt am Main 60590 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Peruzzo","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Regeneration, Goethe University , Frankfurt am Main 60590 ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Rhein Main , Frankfurt am Main 60590 ,","place":["Germany"]},{"name":"Cardiopulmonary Institute, Goethe University , Frankfurt am Main 60590 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Pizzo","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS , Milan 20138 ,","place":["Italy"]},{"name":"Institute of Genetic and Biomedical Research (IRGB), Milan Unit, National Research Council of Italy , Milan 20138 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk L","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego , La Jolla, CA 92093 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1045-2436","authenticated-orcid":false,"given":"Stefanie","family":"Dimmeler","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Regeneration, Goethe University , Frankfurt am Main 60590 ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Rhein Main , Frankfurt am Main 60590 ,","place":["Germany"]},{"name":"Cardiopulmonary Institute, Goethe University , Frankfurt am Main 60590 ,","place":["Germany"]},{"name":"Faculty of Medicine, Goethe University , Frankfurt am Main 60590 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5228-2634","authenticated-orcid":false,"given":"Lars","family":"Maegdefessel","sequence":"additional","affiliation":[{"name":"Institute of Molecular Vascular Medicine, TUM University Hospital Rechts der Isar, Technical University Munich , Munich 81675 ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance , Munich 80336 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9987-5285","authenticated-orcid":false,"given":"Paola","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Regeneration, Goethe University , Frankfurt am Main 60590 ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Rhein Main , Frankfurt am Main 60590 ,","place":["Germany"]},{"name":"Cardiopulmonary Institute, Goethe University , Frankfurt am Main 60590 ,","place":["Germany"]},{"name":"Centro Cardiologico Monzino IRCCS , Milan 20138 ,","place":["Italy"]},{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan , Milan 20133 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5035-3697","authenticated-orcid":false,"given":"Sylvia 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