{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:08:57Z","timestamp":1760234937883,"version":"build-2065373602"},"reference-count":75,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL085122","HL117851","IUL1RR026314"],"award-info":[{"award-number":["HL085122","HL117851","IUL1RR026314"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Elastic fiber fragmentation (EFF) is a hallmark of aortic valve disease (AVD), and neovascularization has been identified as a late finding related to inflammation. We sought to characterize the relationship between early EFF and aberrant angiogenesis. To examine disease progression, regional anatomy and pathology of aortic valve tissue were assessed using histochemistry, immunohistochemistry, and electron microscopy from early-onset (&lt;40 yo) and late-onset (\u226540 yo) non-syndromic AVD specimens. To assess the effects of EFF on early AVD processes, valve tissue from Williams and Marfan syndrome patients was also analyzed. Bicuspid aortic valve was more common in early-onset AVD, and cardiovascular comorbidities were more common in late-onset AVD. Early-onset AVD specimens demonstrated angiogenesis without inflammation or atherosclerosis. A distinct pattern of elastic fiber components surrounded early-onset AVD neovessels, including increased emilin-1 and decreased fibulin-5. Different types of EFF were present in Williams syndrome (WS) and Marfan syndrome (MFS) aortic valves; WS but not MFS aortic valves demonstrated angiogenesis. Aberrant angiogenesis occurs in early-onset AVD in the absence of inflammation, implicating EFF. Elucidation of underlying mechanisms may inform the development of new pharmacologic treatments.<\/jats:p>","DOI":"10.3390\/jcdd8070075","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T11:07:40Z","timestamp":1624619260000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Early Aberrant Angiogenesis Due to Elastic Fiber Fragmentation in Aortic Valve Disease"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7771-9510","authenticated-orcid":false,"given":"Robert B.","family":"Hinton","sequence":"first","affiliation":[{"name":"Divisions of Cardiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy L.","family":"Juraszek","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Wolfson Children\u2019s Hospital, Jacksonville, FL 32207, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4759-008X","authenticated-orcid":false,"given":"Amy M.","family":"Opoka","sequence":"additional","affiliation":[{"name":"Divisions of Cardiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin J.","family":"Landis","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Indiana University School of Medicine, Indianapolis, IN 46204, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Michael","family":"Smith","sequence":"additional","affiliation":[{"name":"The Christ Hospital Heart Network, Cincinnati, OH 45219, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert P.","family":"Mecham","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University, St. Louis, MO 63130, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin E.","family":"Bove","sequence":"additional","affiliation":[{"name":"Division of Pathology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/S0140-6736(06)69208-8","article-title":"Burden of valvular heart diseases: A population-based study","volume":"368","author":"Nkomo","year":"2006","journal-title":"Lancet"},{"key":"ref_2","first-page":"e28","article-title":"Heart Disease and Stroke Statistics\u20142014 Update: A Report From the American Heart Association","volume":"129","author":"Go","year":"2013","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.jacc.2008.05.007","article-title":"2008 Focused Update Incorporated Into the ACC\/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease) Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons","volume":"52","author":"Bonow","year":"2008","journal-title":"J. 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