{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:49:07Z","timestamp":1787870947241,"version":"build-2784847793"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,10,2]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Dilated cardiomyopathy (DCM) is a common cause of heart failure in adult and pediatric patients, but the underlying mechanism may vary in adults and children, with few studies conducted to date. The objective of the present study was to determine whether differential remodeling of the extracellular matrix contributes to the differences between pediatric and adult DCM hearts.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Explanted hearts were procured from adult (age, 46\u201361\u00a0years) and pediatric (age, 2\u20138) patients with DCM\u2010related heart failure and nonfailing control hearts. Fibrillar and nonfibrillar extracellular matrix (proteoglycans, glycosaminoglycans, glycoprotein), their regulatory enzymes (matrix metalloproteinases, disintegrin and metalloproteinases, and disintegrin and metalloproteinases with a thrombospondin domain), and their inhibitors (tissue inhibitor of metalloproteinases) were assessed. Pediatric DCM hearts exhibited less fibrosis compared with adult DCMs. Total glycosaminoglycans increased similarly in both DCM groups but exhibited a significantly lower affinity for transforming growth factor\u2010\u03b2 in adult DCMs versus pediatric DCMs, resulting in increased bioavailability of transforming growth factor\u2010\u03b21 and a significantly higher activity of the Smad2\/3 pathway in adult DCMs. Glycosylated biglycan and versican, and cleaved thrombospondin\u20101 increased in both DCMs. Protein expression of disintegrin and metalloproteinases with thrombospondin domains (\u20101, \u20102, \u20104, \u20107) and disintegrin and metalloproteinases (\u201012, \u201015, \u201017, \u201019) were altered differently in pediatric and adult control and failing hearts. Total matrix metalloproteinase activity increased in both DCMs. Tissue inhibitor of metalloproteinase levels were altered similarly with heart failure in both age groups, and only tissue inhibitor of metalloproteinase 3 decreased in both DCM groups.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Differential remodeling of glycosaminoglycans in pediatric DCMs versus adult DCMs could underlie the enhanced activation of the transforming growth factor\u2010\u03b2 pathway, leading to more fibrosis in adult DCM hearts. The distinct remodeling of the fibrillar and nonfibrillar extracellular matrix between pediatric and adult DCM hearts highlights a distinct pathophysiological basis for these cohorts.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.118.010427","type":"journal-article","created":{"date-parts":[[2018,9,30]],"date-time":"2018-09-30T08:43:10Z","timestamp":1538296990000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Disparate Remodeling of the Extracellular Matrix and Proteoglycans in Failing Pediatric Versus Adult Hearts"],"prefix":"10.1161","volume":"7","author":[{"given":"Sayantan","family":"Jana","sequence":"first","affiliation":[{"name":"Department of Physiology Faculty of Medicine and Dentistry University of Alberta Edmonton AB"},{"name":"Cardiovascular Research Centre Mazankowski Alberta Heart Institute Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine Faculty of Medicine and Dentistry University of Alberta Edmonton AB"},{"name":"Cardiovascular Research Centre Mazankowski Alberta Heart Institute Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary D.","family":"Lopaschuk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine and Dentistry University of Alberta Edmonton AB"},{"name":"Cardiovascular Research Centre Mazankowski Alberta Heart Institute Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren H.","family":"Freed","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medicine and Dentistry University of Alberta Edmonton AB"},{"name":"Division of Cardiac Surgery Faculty of Medicine and Dentistry University of Alberta Edmonton AB"},{"name":"Cardiovascular Research Centre Mazankowski Alberta Heart Institute Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Consolato","family":"Sergi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Faculty of Medicine and Dentistry University of Alberta Edmonton AB"},{"name":"Cardiovascular Research Centre Mazankowski Alberta Heart Institute Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F.","family":"Kantor","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine and Dentistry University of Alberta Edmonton AB"},{"name":"Cardiovascular Research Centre Mazankowski Alberta Heart Institute Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin Y.","family":"Oudit","sequence":"additional","affiliation":[{"name":"Department of Medicine Faculty of Medicine and Dentistry University of Alberta Edmonton AB"},{"name":"Cardiovascular Research Centre Mazankowski Alberta Heart Institute Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zamaneh","family":"Kassiri","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medicine and Dentistry University of Alberta Edmonton AB"},{"name":"Cardiovascular Research Centre Mazankowski Alberta Heart Institute Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.296.15.1867"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2010.08.009"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2014.06.002"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.11.059"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.10.1171"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2014.04.055"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.302335"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-011-9266-y"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c140045"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00108.2017"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.09.013"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2016.02.006"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.335901"},{"key":"e_1_3_1_15_2","first-page":"1021","volume":"118","author":"Travers JG","year":"2016","unstructured":"Travers JG, Kamal FA, Robbins J, Yutzey KE, Blaxall BC. 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