{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T23:42:46Z","timestamp":1771890166795,"version":"3.50.1"},"reference-count":27,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:00:00Z","timestamp":1705536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health funds","doi-asserted-by":"publisher","award":["GR-2019-12370560"],"award-info":[{"award-number":["GR-2019-12370560"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health funds","doi-asserted-by":"publisher","award":["FPF-14"],"award-info":[{"award-number":["FPF-14"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondazione Gigi e Pupa Ferrari ONLUS","award":["GR-2019-12370560"],"award-info":[{"award-number":["GR-2019-12370560"]}]},{"name":"Fondazione Gigi e Pupa Ferrari ONLUS","award":["FPF-14"],"award-info":[{"award-number":["FPF-14"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyloid deposition within stenotic aortic valves (AVs) also appears frequent in the absence of cardiac amyloidosis, but its clinical and pathophysiological relevance has not been investigated. We will elucidate the rate of isolated AV amyloid deposition and its potential clinical and pathophysiological significance in aortic stenosis (AS). In 130 patients without systemic and\/or cardiac amyloidosis, we collected the explanted AVs during cardiac surgery: 57 patients with calcific AS and 73 patients with AV insufficiency (41 with AV sclerosis and 32 without, who were used as controls). Amyloid deposition was found in 21 AS valves (37%), 4 sclerotic AVs (10%), and none of the controls. Patients with and without isolated AV amyloid deposition had similar clinical and echocardiographic characteristics and survival rates. Isolated AV amyloid deposition was associated with higher degrees of AV fibrosis (p = 0.0082) and calcification (p &lt; 0.0001). Immunohistochemistry analysis suggested serum amyloid A1 (SAA1), in addition to transthyretin (TTR), as the protein possibly involved in AV amyloid deposition. Circulating SAA1 levels were within the normal range in all groups, and no difference was observed in AS patients with and without AV amyloid deposition. In vitro, AV interstitial cells (VICs) were stimulated with interleukin (IL)-1\u03b2 which induced increased SAA1-mRNA both in the control VICs (+6.4 \u00b1 0.5, p = 0.02) and the AS VICs (+7.6 \u00b1 0.5, p = 0.008). In conclusion, isolated AV amyloid deposition is frequent in the context of AS, but it does not appear to have potential clinical relevance. Conversely, amyloid deposition within AV leaflets, probably promoted by local inflammation, could play a role in AS pathophysiology.<\/jats:p>","DOI":"10.3390\/ijms25021171","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T03:50:56Z","timestamp":1705549856000},"page":"1171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Isolated Valve Amyloid Deposition in Aortic Stenosis: Potential Clinical and Pathophysiological Relevance"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6840-8593","authenticated-orcid":false,"given":"Maddalena","family":"Conte","sequence":"first","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131 Naples, Italy"},{"name":"Casa di Cura San Michele, 81024 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Poggio","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7775-7154","authenticated-orcid":false,"given":"Maria","family":"Monti","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, University of Naples Federico II, 5, 80131 Naples, Italy"},{"name":"CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Petraglia","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Cabaro","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9911-4646","authenticated-orcid":false,"given":"Dario","family":"Bruzzese","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3176-5391","authenticated-orcid":false,"given":"Giuseppe","family":"Comentale","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Science, University of Naples Federico II, 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aurelio","family":"Caruso","sequence":"additional","affiliation":[{"name":"Casa di Cura San Michele, 81024 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariagabriella","family":"Grimaldi","sequence":"additional","affiliation":[{"name":"Casa di Cura San Michele, 81024 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8787-731X","authenticated-orcid":false,"given":"Emilia","family":"Zampella","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Science, University of Naples Federico II, 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annarita","family":"Gencarelli","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Science, University of Naples Federico II, 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Rosaria","family":"Cervasio","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Science, University of Naples Federico II, 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4648-8107","authenticated-orcid":false,"given":"Flora","family":"Cozzolino","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, University of Naples Federico II, 5, 80131 Naples, Italy"},{"name":"CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7459-8733","authenticated-orcid":false,"given":"Vittoria","family":"Monaco","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, University of Naples Federico II, 5, 80131 Naples, Italy"},{"name":"CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8414-5300","authenticated-orcid":false,"given":"Veronika","family":"Myasoedova","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenza","family":"Valerio","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adele","family":"Ferro","sequence":"additional","affiliation":[{"name":"Institute of Biostructure and Bioimaging, CNR, 80145 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0006-4410","authenticated-orcid":false,"given":"Luigi","family":"Insabato","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Science, University of Naples Federico II, 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Bellino","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7265-7613","authenticated-orcid":false,"given":"Gennaro","family":"Galasso","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Graziani","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"Pucci","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, University of Naples Federico II, 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7020-6870","authenticated-orcid":false,"given":"Pietro","family":"Formisano","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, Via S. 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Pansini, 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Parisi","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jacc.2003.08.036","article-title":"Adverse outcome in aortic sclerosis is associated with coronary artery disease and inflammation","volume":"43","author":"Chandra","year":"2004","journal-title":"J. Am. Coll. 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