{"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":1793138954221,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T00:00:00Z","timestamp":1692489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NHLBI","award":["R01HL142685"],"award-info":[{"award-number":["R01HL142685"]}]},{"name":"NIH\/NHLBI","award":["S10 OD026816"],"award-info":[{"award-number":["S10 OD026816"]}]},{"name":"NIH\/NHLBI","award":["5520519"],"award-info":[{"award-number":["5520519"]}]},{"name":"Advancing a Healthier Wisconsin","award":["R01HL142685"],"award-info":[{"award-number":["R01HL142685"]}]},{"name":"Advancing a Healthier Wisconsin","award":["S10 OD026816"],"award-info":[{"award-number":["S10 OD026816"]}]},{"name":"Advancing a Healthier Wisconsin","award":["5520519"],"award-info":[{"award-number":["5520519"]}]},{"name":"Peter Sommerhauser Endowment Fund for Quality, Outcomes and Research","award":["R01HL142685"],"award-info":[{"award-number":["R01HL142685"]}]},{"name":"Peter Sommerhauser Endowment Fund for Quality, Outcomes and Research","award":["S10 OD026816"],"award-info":[{"award-number":["S10 OD026816"]}]},{"name":"Peter Sommerhauser Endowment Fund for Quality, Outcomes and Research","award":["5520519"],"award-info":[{"award-number":["5520519"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Organization of extracellular matrix (ECM) components, including collagens, proteoglycans, and elastin, is essential for maintaining the structure and function of heart valves throughout life. Mutations in ECM genes cause connective tissue disorders, including Osteogenesis Imperfecta (OI), and progressive debilitating heart valve dysfunction is common in these patients. Despite this, effective treatment options are limited to end-stage interventions. Mice with a homozygous frameshift mutation in col1a2 serve as a murine model of OI (oim\/oim), and therefore, they were used in this study to examine the pathobiology of aortic valve (AoV) disease in this patient population at structural, functional, and molecular levels. Temporal echocardiography of oim\/oim mice revealed AoV dysfunction by the late stages of disease in 12-month-old mice. However, structural and proteomic changes were apparent much earlier, at 3 months of age, and were associated with disturbances in ECM homeostasis primarily related to collagen and proteoglycan abnormalities and disorganization. Together, findings from this study provide insights into the underpinnings of late onset AoV dysfunction in connective tissue disease patients that can be used for the development of mechanistic-based therapies administered early to halt progression, thereby avoiding late-stage surgical intervention.<\/jats:p>","DOI":"10.3390\/jcdd10080355","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T01:46:56Z","timestamp":1692582416000},"page":"355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Temporal Progression of Aortic Valve Pathogenesis in a Mouse Model of Osteogenesis Imperfecta"],"prefix":"10.3390","volume":"10","author":[{"given":"Kaitlyn","family":"Thatcher","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Herma Heart Institute, Children\u2019s Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol R.","family":"Mattern","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Herma Heart Institute, Children\u2019s Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Chaparro","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Florida International University, Miami, FL 33174, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Goveas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Herma Heart Institute, Children\u2019s Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"McDermott","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, The Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Fulton","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, The Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Hutcheson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Florida International University, Miami, FL 33174, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Mass Spectrometry and Protein Chemistry, Protein Sciences, The Jackson Laboratory, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1517-6888","authenticated-orcid":false,"given":"Joy","family":"Lincoln","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Herma Heart Institute, Children\u2019s Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1161\/01.RES.0000224114.65109.4e","article-title":"Extracellular matrix remodeling and organization in developing and diseased aortic valves","volume":"98","author":"Hinton","year":"2006","journal-title":"Circ. 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