{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:49:31Z","timestamp":1790779771159,"version":"4.1.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>Investigate the requirement of Aggrecan (Acan) cleavage during aortic wall development in a murine model with ADAMTS (a disintegrin-like and metalloprotease domain with thrombospondin-type motifs) 5 deficiency and bicuspid aortic valves.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach:<\/jats:title>\n            <jats:p>Mice with altered extracellular matrix remodeling of proteoglycans will be examined for anomalies in ascending aortic wall development. Neo-epitope antibodies that recognize ADAMTS cleaved Acan fragments will be used to investigate the mechanistic requirement of Acan turnover, in aortic wall development.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              <jats:italic>Adamts5<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <jats:italic>;Smad2<\/jats:italic>\n              <jats:sup>+\/\u2212<\/jats:sup>\n              mice exhibited a high penetrance of aortic anomalies (n=17\/17);\n              <jats:italic>Adamts5<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <jats:italic>;Smad2<\/jats:italic>\n              <jats:sup>+\/\u2212<\/jats:sup>\n              mice with bicuspid aortic valves (7\/17) showed a higher number of anomalies than\n              <jats:italic>Adamts5<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <jats:italic>;Smad2<\/jats:italic>\n              <jats:sup>+\/\u2212<\/jats:sup>\n              mice with tricuspid aortic valves. Single mutant\n              <jats:italic>Adamts5<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice also displayed a high penetrance of aortic anomalies (n=19\/19) compared with wild type (n=1\/11). Aortic anomalies correlated with Acan accumulation that was apparent at the onset of elastogenesis in\n              <jats:italic>Adamts5<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. Neo-epitope antibodies that recognize the initial amino acids in the Acan cleaved fragments neo-FREEE, neo-GLGS, and neo-SSELE were increased in the\n              <jats:italic>Adamts5<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              aortas compared with WT. Conversely, neo-TEGE, which recognizes highly digested Acan core fragments, was reduced in\n              <jats:italic>Adamts5<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. However, mice containing a mutation in the TEGE\n              <jats:sub>373<\/jats:sub>\n              \u2193\n              <jats:sub>374<\/jats:sub>\n              ALGSV site, rendering it noncleavable, had low penetrance of aortic anomalies (n=2\/4). Acan neo-DIPEN and neo-FFGVG fragments were observed in the aortic adventitia; Acan neo-FFGVG was increased abnormally in the medial layer and overlapped with smooth muscle cell loss in\n              <jats:italic>Adamts5<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              aortas.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Disruption of ADAMTS5 Acan cleavage during development correlates with ascending aortic anomalies. These data indicate that the mechanism of ADAMTS5 Acan cleavage may be critical for normal aortic wall development.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.119.313077","type":"journal-article","created":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T09:00:18Z","timestamp":1564650018000},"page":"2067-2081","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":50,"title":["<i>Adamts5<\/i>\n            <sup>\u2212\/\u2212<\/sup>\n            Mice Exhibit Altered Aggrecan Proteolytic Profiles That Correlate With Ascending Aortic Anomalies"],"prefix":"10.1161","volume":"39","author":[{"given":"Loren E.","family":"Dupuis","sequence":"first","affiliation":[{"name":"From the Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston (L.E.D., E.L.N., B.H., S.C.P., A.R.-D., C.B.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Lockett","family":"Nelson","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston (L.E.D., E.L.N., B.H., S.C.P., A.R.-D., C.B.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Hozik","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston (L.E.D., E.L.N., B.H., S.C.P., A.R.-D., C.B.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C.","family":"Porto","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston (L.E.D., E.L.N., B.H., S.C.P., A.R.-D., C.B.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Rogers-DeCotes","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston (L.E.D., E.L.N., B.H., S.C.P., A.R.-D., C.B.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Fosang","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Melbourne, Murdoch Children\u2019s Research Institute, Royal Children\u2019s Hospital, Parkville, Australia (A.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine B.","family":"Kern","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston (L.E.D., E.L.N., B.H., S.C.P., A.R.-D., 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