{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:26:29Z","timestamp":1792009589521,"version":"4.4.0"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,3,22]],"date-time":"2011-03-22T00:00:00Z","timestamp":1300752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fibrillin\u20101, the major component of extracellular microfibrils that associate with insoluble elastin in elastic fibres, is mainly synthesized during development and postnatal growth and is believed to guide elastogenesis. Mutations in the fibrillin\u20101 gene cause Marfan syndrome, a multisystem disorder characterized by aortic aneurysms and dissections. The recent finding that early deficiency of elastin modifies vascular ageing has raised the possibility that fibrillin\u20101 deficiency could also contribute to late\u2010onset pathology of vascular remodelling. To address this question, we examined cardiovascular function in 3\u2010week\u2010old, 6\u2010month\u2010old, and 24\u2010month\u2010old mice that are heterozygous for a hypomorphic structural mutation of fibrillin\u20101 (<jats:italic>Fbn1<\/jats:italic><jats:styled-content>$^{+\/{\\rm{mg}}\\Delta}$<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-ueqn-1.gif\" xlink:title=\"equation image\"\/><\/jats:styled-content> mice). Our results indicate that <jats:italic>Fbn1<\/jats:italic><jats:styled-content>$^{+\/{\\rm{mg}}\\Delta}$<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-ueqn-2.gif\" xlink:title=\"equation image\"\/><\/jats:styled-content> mice, particularly those that are 24 months old, are slightly more hypotensive than wild\u2010type littermates. Additionally, aneurysm and aortic insufficiency were more frequently observed in ageing <jats:italic>Fbn1<\/jats:italic><jats:styled-content>$^{+\/{\\rm{mg}}\\Delta}$<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-ueqn-3.gif\" xlink:title=\"equation image\"\/><\/jats:styled-content> mice than in the wild\u2010type counterparts. We also noted substantial fragmentation and decreased number of elastic lamellae in the aortic wall of <jats:italic>Fbn1<\/jats:italic><jats:styled-content>$^{+\/{\\rm{mg}}\\Delta}$<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-ueqn-4.gif\" xlink:title=\"equation image\"\/><\/jats:styled-content> mice, which were correlated with an increase in aortic stiffness, a decrease in vasoreactivity, altered expression of elastic fibre\u2010related genes, including fibrillin\u20101 and elastin, and a decrease in the relative ratio between tissue elastin and collagen. Collectively, our findings suggest that the heterozygous mg\u0394 mutation accelerates some aspects of vascular ageing and eventually leads to aortic manifestations resembling those of Marfan syndrome. Importantly, our data also indicate that vascular abnormalities in <jats:italic>Fbn1<\/jats:italic><jats:styled-content>$^{+\/{\\rm{mg}}\\Delta}$<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-ueqn-5.gif\" xlink:title=\"equation image\"\/><\/jats:styled-content> mice are opposite to those induced by elastin haploinsufficiency during ageing that affect blood pressure, vascular dimensions, and number of elastic lamellae. Copyright \u00a9 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2840","type":"journal-article","created":{"date-parts":[[2010,12,9]],"date-time":"2010-12-09T08:01:25Z","timestamp":1291881685000},"page":"33-44","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Fibrillin\u20101 genetic deficiency leads to pathological ageing of arteries in 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