{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:12:54Z","timestamp":1789665174079,"version":"4.0.1"},"reference-count":210,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL146583"],"award-info":[{"award-number":["R01 HL146583"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL169147"],"award-info":[{"award-number":["R01 HL169147"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 HL169168"],"award-info":[{"award-number":["P01 HL169168"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Leducq Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015891","name":"AHA","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015891","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100021046","name":"John Ritter","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100021046","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010258","name":"Marfan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010258","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Remembrin\u2019 Benjamin Foundations"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder that affects cardiovascular, musculoskeletal, and ocular tissues, with premature death often resulting from dissection of the thoracic aorta. MFS results from pathogenic variants in FBN1, which encodes fibrillin-1, a glycoprotein that promotes elastic fibre organization and stability and contributes to smooth muscle cell mechano-sensing of extracellular matrix. It has been 35 years since the discovery that FBN1 variants cause MFS, yet understanding links between a variant and thoracic aortic disease remains incomplete, and definitive treatments remain wanting. We review advances in understanding disease progression in the aorta in MFS from perspectives of genetics, histology, mechanobiology, and biomechanics, with a focus on mouse models that include further genetic modifications to assess factors contributing to disease progression as well as effects of pharmacological treatments. This monogenic disease results in hundreds of differentially expressed genes in the aorta, many cell specific, that should be delineated as protective compensations, pathologic consequences, or neutral changes, and therapies should promote beneficial compensations and prevent detrimental consequences. Given the complexity of aortic disease in MFS, data-informed and data-driven computational models promise to help integrate multimodal data and increase understanding of molecular and cellular changes that drive disease progression, with a goal of improved therapies that prevent disease progression.<\/jats:p>","DOI":"10.1093\/cvr\/cvag114","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T12:05:17Z","timestamp":1778760317000},"page":"1427-1442","source":"Crossref","is-referenced-by-count":5,"title":["The aorta in Marfan syndrome: from molecular mechanisms to mechanobiological dysfunction"],"prefix":"10.1093","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1011-2025","authenticated-orcid":false,"given":"Jay D","family":"Humphrey","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Yale University , New Haven, CT, 06511 \u00a0","place":["USA"]},{"name":"Vascular Biology and Therapeutics Program, Yale School of Medicine , New Haven, CT, 06520 \u00a0","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7806-0068","authenticated-orcid":false,"given":"Dianna M","family":"Milewicz","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston , Houston, TX, 77030 \u00a0","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"2026081406120410000_cvag114-B1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1146\/annurev.med.51.1.481","article-title":"The Marfan syndrome","volume":"51","author":"Pyeritz","year":"2000","journal-title":"Annu Rev Med"},{"key":"2026081406120410000_cvag114-B2","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41572-021-00298-7","article-title":"Marfan syndrome","volume":"7","author":"Milewicz","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"2026081406120410000_cvag114-B3","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1083\/jcb.103.6.2499","article-title":"Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils","volume":"103","author":"Sakai","year":"1986","journal-title":"J Cell Biol"},{"key":"2026081406120410000_cvag114-B4","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1056\/NEJM199007193230303","article-title":"Immunohistologic abnormalities of the microfibrillar-fiber system in the Marfan syndrome","volume":"323","author":"Hollister","year":"1990","journal-title":"N Engl J Med"},{"key":"2026081406120410000_cvag114-B5","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/352330a0","article-title":"Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin 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