{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:32:13Z","timestamp":1793046733425,"version":"4.5.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Transmural failure of the aorta is responsible for substantial morbidity and mortality; it occurs when mechanical stress exceeds strength. The aortic root and ascending aorta are susceptible to dissection and rupture in Marfan syndrome, a connective tissue disorder characterized by a progressive reduction in elastic fiber integrity. Whereas competent elastic fibers endow the aorta with compliance and resilience, cross-linked collagen fibers confer stiffness and strength. We hypothesized that postnatal reductions in matrix cross-linking increase aortopathy when turnover rates are high.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              We combined ex vivo biaxial mechanical testing with multimodality histological examinations to quantify expected age- and sex-dependent structural vulnerability of the ascending aorta in\n              <jats:italic>Fbn1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>C1041G\/+<\/jats:italic>\n              <\/jats:sup>\n              Marfan versus wild-type mice without and with 4-week exposures to \u03b2-aminopropionitrile, an inhibitor of lysyl oxidase\u2013mediated cross-linking of newly synthesized elastic and collagen fibers.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              We found a strong \u03b2-aminopropionitrile\u2013associated sexual dimorphism in aortic dilatation in Marfan mice and aortic rupture in wild-type mice, with dilatation correlating with compromised elastic fiber integrity and rupture correlating with compromised collagen fibril organization. A lower incidence of rupture of \u03b2-aminopropionitrile\u2013exposed Marfan aortas associated with increased lysyl oxidase, suggesting a compensatory remodeling of collagen that slows disease progression in the otherwise compromised\n              <jats:italic>Fbn1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>C1041G\/+<\/jats:italic>\n              <\/jats:sup>\n              aorta.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Collagen fiber structure and function in the Marfan aorta are augmented, in part, by increased lysyl oxidase in female and especially male mice, which improves structural integrity, particularly via fibrils in the adventitia. Preserving or promoting collagen cross-linking may represent a therapeutic target for an otherwise vulnerable aorta.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.123.319122","type":"journal-article","created":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T09:00:23Z","timestamp":1689843623000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Effects of Age, Sex, and Extracellular Matrix Integrity on Aortic Dilatation and Rupture in a Mouse Model of Marfan Syndrome"],"prefix":"10.1161","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6097-6038","authenticated-orcid":true,"given":"Dar","family":"Weiss","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Yale University, New Haven, CT (D.W., B.V.R., C.C., D.S.L., Y.K., N.E., J.D.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno V.","family":"Rego","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale University, New Haven, CT (D.W., B.V.R., C.C., D.S.L., Y.K., N.E., J.D.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6021-8920","authenticated-orcid":true,"given":"Cristina","family":"Cavinato","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale University, New Haven, CT (D.W., B.V.R., C.C., D.S.L., Y.K., N.E., J.D.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6489-0191","authenticated-orcid":true,"given":"David S.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale University, New Haven, CT (D.W., B.V.R., C.C., D.S.L., Y.K., N.E., J.D.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2137-6464","authenticated-orcid":true,"given":"Yuki","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale University, New Haven, CT (D.W., B.V.R., C.C., D.S.L., Y.K., N.E., J.D.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nir","family":"Emuna","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale University, New Haven, CT (D.W., B.V.R., C.C., D.S.L., Y.K., N.E., J.D.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1011-2025","authenticated-orcid":true,"given":"Jay D.","family":"Humphrey","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale University, New Haven, CT (D.W., B.V.R., C.C., D.S.L., Y.K., N.E., J.D.H.)."},{"name":"Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT (J.D.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.783753"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21189"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.7.3819"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI20641"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.800730"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00255.2021"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00205.2018"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.304936"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1008273"},{"key":"e_1_3_3_11_2","first-page":"2687","volume-title":"Through Thick and Thin Collagen Fibrils, Stress, and Aortic Rupture: Another Piece in the Jigsaw","author":"Powell JT","year":"2007","unstructured":"Powell, JT, L\u00e4nne, T. 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