{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:46:55Z","timestamp":1791877615937,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ascending thoracic aortic aneurysm formation differs fundamentally between patients with bicuspid (BAV) and tricuspid (TAV) aortic valve phenotypes, yet current clinical management largely relies on shared diameter thresholds, although clinical and scientific data fail to correlate with diameter and risk of rupture. Over the past two decades, histological, biochemical and biomechanical studies have revealed unique differences between dilated tissue properties from patients with BAV\u2010 and TAV\u2010associated idiopathic degenerative ascending aortic aneurysms even at similar aortic diameters. This review focuses on histological, biochemical and biomechanical differences between BAV and TAV aortopathy with a focus on ageing. Idiopathic degenerative TAV aortopathy is characterised by medial degeneration with elastic lamellar fragmentation and loss, smooth muscle cell depletion, medial fibrosis, mucoid extracellular matrix accumulation and inflammatory features. These degenerative changes correlate with ageing and, in region\u2010specific mechanical testing, with reduced delamination resistance and age\u2010dependent biomechanical weakening. In contrast, BAV aortopathy frequently demonstrates relative preservation of medial architecture despite similar dilatation, alongside altered collagen maturation, and distinct osteogenic\/microcalcification signatures. Lifespan analyses indicate that TAV follows a maturation\u2013stabilisation\u2013degeneration trajectory, whereas BAV exhibits aberrant vascular maturation without a true stabilisation phase. Importantly, aortic diameter correlates poorly with histological severity or biomechanical vulnerability, particularly in BAV. Collectively, these data support the concept that ascending thoracic aortic aneurysms in BAV and idiopathic degenerative TAV patients represent biologically divergent aortopathies requiring phenotype\u2010informed risk stratification beyond diameter alone.<\/jats:p>","DOI":"10.1113\/ep092864","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:02:48Z","timestamp":1791874968000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From maturation to degeneration: Distinct biological trajectories in bicuspid and tricuspid aortopathy"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7963-6874","authenticated-orcid":false,"given":"Riaz","family":"Akhtar","sequence":"first","affiliation":[{"name":"Department of Materials Design and Manufacturing Engineering School of Engineering University of Liverpool  Liverpool UK"},{"name":"Department of Biochemistry, Cell and Systems Biology Institute of Systems, Molecular and Integrative Biology University of Liverpool Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Olaf","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Materials Design and Manufacturing Engineering School of Engineering University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9963-5871","authenticated-orcid":false,"given":"Jillian","family":"Madine","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology Institute of Systems, Molecular and Integrative Biology University of Liverpool Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Field","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery Liverpool Heart and Chest Hospital  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"issue":"4","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"e255","DOI":"10.1016\/j.jtcvs.2020.09.041","article-title":"When diameter is not enough: In search of the ideal patient\u2010specific size parameter for aortic risk prediction","volume":"161","author":"Acharya M.","year":"2021","journal-title":"The Journal of Thoracic and Cardiovascular Surgery"},{"issue":"4","key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/j.athoracsur.2006.11.086","article-title":"Endothelial nitric oxide synthase in bicuspid aortic valve disease","volume":"83","author":"Aicher D.","year":"2007","journal-title":"The Annals of Thoracic Surgery"},{"issue":"1","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/s41598-024-83233-6","article-title":"Fracture properties of porcine versus human thoracic aortas from tricuspid\/bicuspid aortic valve patients via symmetry\u2010constraint compact tension testing","volume":"15","author":"Alloisio M.","year":"2025","journal-title":"Scientific Reports"},{"issue":"1","key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/S0003-4975(02)03650-0","article-title":"Morphometric analysis of aortic media in patients with bicuspid and tricuspid aortic valve","volume":"74","author":"Bauer M.","year":"2002","journal-title":"The Annals of Thoracic Surgery"},{"issue":"1","key":"e_1_2_9_6_1","first-page":"54","article-title":"Histopathological grading of ascending aortic aneurysm: Comparison of patients with bicuspid versus tricuspid aortic valve","volume":"12","author":"Bechtel J. 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