{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:09:14Z","timestamp":1793138954201,"version":"4.5.0"},"reference-count":45,"publisher":"American Society for Clinical Investigation","issue":"5","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL107147"],"award-info":[{"award-number":["HL107147"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AR069307"],"award-info":[{"award-number":["AR069307"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Sabrina\u2019s Foundation","award":["None"],"award-info":[{"award-number":["None"]}]},{"DOI":"10.13039\/100007312","name":"Cleveland Clinic Foundation","doi-asserted-by":"crossref","award":["High Risk Cardiovascular Research Fund"],"award-info":[{"award-number":["High Risk Cardiovascular Research Fund"]}],"id":[{"id":"10.13039\/100007312","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007311","name":"Cleveland Clinic","doi-asserted-by":"crossref","award":["Research Program Committee"],"award-info":[{"award-number":["Research Program Committee"]}],"id":[{"id":"10.13039\/100007311","id-type":"DOI","asserted-by":"crossref"}]},{"name":"WL Gore, Inc.","award":["None"],"award-info":[{"award-number":["None"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["Paul G Allen Frontiers Group Distinguished Investigator Award"],"award-info":[{"award-number":["Paul G Allen Frontiers Group Distinguished Investigator Award"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,3,8]]},"abstract":"<jats:p>\n                    Proteoglycan accumulation is a hallmark of medial degeneration in thoracic aortic aneurysm and dissection (TAAD). Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome. The aortic proteoglycanome comprises 20 proteoglycans including aggrecan and versican. Antibodies against these proteoglycans intensely stained medial degeneration lesions in TAAD, contrasting with modest intralamellar staining in controls. Aggrecan, but not versican, was increased in longitudinal analysis of\n                    <jats:italic>Fbn1<\/jats:italic>\n                    <jats:sup>mgR\/mgR<\/jats:sup>\n                    aortas. TAAD and\n                    <jats:italic>Fbn1<\/jats:italic>\n                    <jats:sup>mgR\/mgR<\/jats:sup>\n                    aortas had increased aggrecan and versican mRNAs, and reduced expression of a key proteoglycanase gene,\n                    <jats:italic>ADAMTS5<\/jats:italic>\n                    , was seen in TAAD.\n                    <jats:italic>Fbn1<\/jats:italic>\n                    <jats:sup>mgR\/mgR<\/jats:sup>\n                    mice with ascending aortic dissection and\/or rupture had dramatically increased aggrecan staining compared with mice without these complications. Thus, aggrecan and versican accumulation in ascending TAAD occurs via increased synthesis and\/or reduced proteolytic turnover, and correlates with aortic dissection\/rupture in\n                    <jats:italic>Fbn1<\/jats:italic>\n                    <jats:sup>mgR\/mgR<\/jats:sup>\n                    mice. Tissue swelling imposed by aggrecan and versican is proposed to be profoundly deleterious to aortic wall mechanics and smooth muscle cell homeostasis, predisposing to type-A dissections. These proteoglycans provide potential biomarkers for refined risk stratification and timing of elective aortic aneurysm repair.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.97167","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T11:02:53Z","timestamp":1520420573000},"source":"Crossref","is-referenced-by-count":165,"title":["Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection"],"prefix":"10.1172","volume":"3","author":[{"given":"Frank S.","family":"Cikach","sequence":"first","affiliation":[{"name":"Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA."},{"name":"Department of Chemistry, Cleveland State University, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Mead","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Galatioto","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda B.","family":"Willard","sequence":"additional","affiliation":[{"name":"Proteomics and Metabolomics Core, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly B.","family":"Emerton","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Innovations,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Eagleton","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene H.","family":"Blackstone","sequence":"additional","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric E.","family":"Roselli","sequence":"additional","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery, and"},{"name":"Aorta Center, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suneel S.","family":"Apte","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2018,3,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1253026"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.304936"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nature10145"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.303229"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2016.03.002"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1159\/000342436"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01027.2007"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.19.4.1004"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s10237-013-0482-3"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2014.0397"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000126921.29919.51"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1115\/1.3118773"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2011.08.011"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.88.1.37"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2001.2507"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M110.001693"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.7.3819"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.305150"},{"issue":"1","key":"B19","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ydbio.2011.06.041","article-title":"Altered versican cleavage in ADAMTS5 deficient mice; 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