{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:30:32Z","timestamp":1792031432919,"version":"4.4.0"},"reference-count":65,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T00:00:00Z","timestamp":1751155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Histomorphometric differences in cell\u2010matrix properties were analysed between ascending thoracic aortic aneurysm (ATAA), dissection (ATAAD) and non\u2010aneurysmal patients, as well as across the circumference of the aneurysms in ATAA cases. Fresh anterior aortic wall samples were collected during surgery. A significant radius\u2010to\u2010intima\u2010media thickness (IMT) ratio variation was observed among ATAA patients, indicating patient\u2010specific adaptive responses. The radius\u2010IMT ratio was significantly lower in ATAAD patients. The quantity and quality of elastin and the quantity of collagen were particularly reduced in ATAAD compared to ATAA and non\u2010aneurysmal aortas. Matrix degradation was accompanied by an increase in the density of vascular smooth muscle cells (VSMCs), albeit with reduced expression of VSMC contractile markers (calponin and \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA)). Concomitantly ATAA and ATAAD samples exhibited increased markers (matrix metalloproteinase (MMP)\u20102\/9) of proteolysis. Based on radius\u2010IMT ratios we roughly identified \u2018thickening\u2019 and \u2018thinning\u2019 (i.e. hypertrophic and hypotrophic) aneurysm variants to capture the substantial variation in the loss of mechanical homeostasis in ATAA. Interestingly we did not find conspicuous differences along the circumference of excised aneurysms in ATAA, except for an increased IMT heterogeneity in \u2018thinning\u2019 aneurysms. We conclude that during aneurysm formation wall stress homeostasis may remain partially intact, particularly in \u2018thickening\u2019 ATAA. Our study underscores the current critique that aneurysm dimensions are poor risk predictors; therefore there is a crucial need for better\u2010informed preventive intervention in ATAAD.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16836-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Ascending thoracic aortic aneurysm (ATAA) variants can be categorised as aortic medial thickening (hypertrophic) or aortic medial thinning (hypotrophic) based on the radius\u2010to\u2010intima\u2010media thickness (IMT) ratio, reflecting distinct disruptions in mechanical homeostasis.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Morphological patterns arise from dynamic interactions in the aortic medial layer between vascular smooth muscle cells (VSMCs) and the extracellular matrix (ECM).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Increased number of synthetic VSMCs in the medial layer of ATAA patients is a compensatory response to maintain vessel elasticity and structural integrity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In acute type A aortic dissection (ATAAD) aortas with medial thinning are characterised by ECM breakdown and maladaptive remodelling.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ATAA development is circumferentially homogeneous, despite the occurrence of inter\u2010 and intrapatient variability in vascular architecture, composition and VSMC characteristics.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp288734","type":"journal-article","created":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T13:58:19Z","timestamp":1751205499000},"page":"3899-3922","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Loss of wall stress homeostasis in ascending thoracic aortic aneurysm: histomorphometric insights into patient variants"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4614-2146","authenticated-orcid":false,"given":"Berta H.","family":"Ganizada","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery Maastricht University Medical Centre Maastricht The Netherlands"},{"name":"Department of Biochemistry Maastricht University  Maastricht The Netherlands"},{"name":"Heart &amp; Vascular Center (HVC), Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen D.","family":"Reesink","sequence":"additional","affiliation":[{"name":"Heart &amp; Vascular Center (HVC), Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Center  Maastricht The Netherlands"},{"name":"Department of Biomedical Engineering Maastricht University Medical Centre Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaiv","family":"Parikh","sequence":"additional","affiliation":[{"name":"Heart &amp; Vascular Center (HVC), Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Center  Maastricht The Netherlands"},{"name":"Department of Biomedical Engineering Maastricht University Medical Centre Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pepijn J. 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