{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:04:21Z","timestamp":1760058261937,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III-FEDER","award":["PI18\/01875","PI21\/00280"],"award-info":[{"award-number":["PI18\/01875","PI21\/00280"]}]},{"name":"Miguel Servet Foundation PhD studentship","award":["PI18\/01875","PI21\/00280"],"award-info":[{"award-number":["PI18\/01875","PI21\/00280"]}]},{"name":"Margarita Salas","award":["PI18\/01875","PI21\/00280"],"award-info":[{"award-number":["PI18\/01875","PI21\/00280"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Adipose tissue is present in aortic valves (AVs). Valve interstitial cells (VICs) could differentiate into adipogenic lineages. We here characterize whether the presence of adipose tissue in the AV influences inflammation and extracellular matrix (ECM) composition in patients with aortic regurgitation (AR). A total of 144 AVs were analyzed by histological and molecular techniques. We performed discovery studies using Olink Proteomics\u00ae technology in 40 AVs (N = 16 without and N = 24 with adipose tissue). In vitro, human white adipocytes (HWAs) or VICs were cultured with adipogenic media and co-cultured with control VICs. Of Avs, 67% presented white-like adipocytes within the spongiosa. Discovery studies revealed increased levels of inflammatory and ECM molecules in AVs containing adipocytes. Interestingly, the presence of adipocytes was associated with greater AV thickness, higher inflammation, and ECM remodeling, which was characterized by increased proinflammatory molecules, collagen, fibronectin, proteoglycans, and metalloproteinases. AV thickness positively correlated with markers of adipose tissue, inflammation, and ECM. In vitro, adipocyte-like VICs expressed higher levels of adipocyte markers, increased cytokines, fibronectin, decorin, and MMP-13. Analyses of supernatants from co-cultured control VICs with HWA or adipocyte-like VICs showed higher expression of inflammatory mediators, collagen type I, proteoglycans, and metalloproteinases. AVs presenting adipocytes were thicker and exhibited changes characterized by increased inflammation accompanied by aberrant expression of collagen, proteoglycans, and metalloproteinases. VICs could differentiate into adipogenic pathway, affect neighbor VICs, and contribute to inflammation, collagen and proteoglycan accumulation, as well as to metalloproteinases secretion. In summary, the presence of adipose tissue in AV could modify its composition, favoring inflammation and remodeling with an impact on AV thickness.<\/jats:p>","DOI":"10.3390\/ijms26073128","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T13:36:49Z","timestamp":1743169009000},"page":"3128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Presence of Adipose Tissue in Aortic Valves Influences Inflammation and Extracellular Matrix Composition in Chronic Aortic Regurgitation"],"prefix":"10.3390","volume":"26","author":[{"given":"Alba","family":"S\u00e1daba","sequence":"first","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Fundaci\u00f3n Miguel Servet), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7656-4046","authenticated-orcid":false,"given":"Mattie","family":"Garaikoetxea","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Fundaci\u00f3n Miguel Servet), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Tiraplegui","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Fundaci\u00f3n Miguel Servet), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"San-Ildefonso-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Fundaci\u00f3n Miguel Servet), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9950-1513","authenticated-orcid":false,"given":"Miriam","family":"Go\u00f1i-Ol\u00f3riz","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Fundaci\u00f3n Miguel Servet), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amaya","family":"Fern\u00e1ndez-Celis","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Fundaci\u00f3n Miguel Servet), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0341-0956","authenticated-orcid":false,"given":"Ernesto","family":"Mart\u00edn-N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Fundaci\u00f3n Miguel Servet), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Castillo","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Fundaci\u00f3n Miguel Servet), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Fundaci\u00f3n Miguel Servet), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3776-4744","authenticated-orcid":false,"given":"Rafael","family":"S\u00e1daba","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Fundaci\u00f3n Miguel Servet), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0628-9944","authenticated-orcid":false,"given":"Eva","family":"Jover","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Fundaci\u00f3n Miguel Servet), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adela","family":"Navarro","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Fundaci\u00f3n Miguel Servet), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3728-2606","authenticated-orcid":false,"given":"Natalia","family":"L\u00f3pez-Andr\u00e9s","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Fundaci\u00f3n Miguel Servet), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), 31008 Pamplona, Spain"},{"name":"French-Clinical Research Infrastructure Network (F-CRIN) Cardiovascular and Renal Clinical Trialists (INI-CRCT), 54500 Nancy, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1161\/CIRCULATIONAHA.104.488825","article-title":"Valvular heart disease: Aortic regurgitation","volume":"112","author":"Bekeredjian","year":"2005","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/S0002-9149(98)01064-9","article-title":"Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation (the Framingham Heart Study)","volume":"83","author":"Singh","year":"1999","journal-title":"Am. 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