The presence of adipose tissue in aortic valves influences inflammation and extracellular matrix composition in chronic aortic regurgitation

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dc.contributor.authorSádaba, Alba
dc.contributor.authorGaraikoetxea Zubillaga, Mattie
dc.contributor.authorTiraplegui, Carolina
dc.contributor.authorSan Ildefonso-García, Susana
dc.contributor.authorGoñi Olóriz, Miriam
dc.contributor.authorFernández Celis, Amaya
dc.contributor.authorMartín Núñez, Ernesto
dc.contributor.authorCastillo, Paula
dc.contributor.authorÁlvarez, Virginia
dc.contributor.authorSádaba Sagredo, Rafael
dc.contributor.authorJover, Eva
dc.contributor.authorNavarro, Adela
dc.contributor.authorLópez Andrés, Natalia
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.date.accessioned2025-07-18T17:37:27Z
dc.date.available2025-07-18T17:37:27Z
dc.date.issued2025-03-28
dc.date.updated2025-07-18T17:26:36Z
dc.description.abstractAdipose 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® 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.en
dc.description.sponsorshipThis work was supported by Fondo de Investigaciones Sanitarias [PI18/01875; PI21/00280] from Instituto de Salud Carlos III-FEDER. M.G. is supported by a Miguel Servet Foundation PhD studentship, and E.M.-N. is supported by a Margarita Salas.
dc.format.mimetypeapplication/pdf
dc.identifier.citationSádaba, A., Garaikoetxea, M., Tiraplegui, C., San-Ildefonso-García, S., Goñi-Olóriz, M., Fernández-Celis, A., Martín-Núñez, E., Castillo, P., Álvarez, V., Sádaba, R., Jover, E., Navarro, A., López-Andrés, N. (2025) The presence of adipose tissue in aortic valves influences inflammation and extracellular matrix composition in chronic aortic regurgitation. International Journal of Molecular Sciences, 26(7), 1-22. https://doi.org/10.3390/ijms26073128.
dc.identifier.doi10.3390/ijms26073128
dc.identifier.issn1661-6596
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/54421
dc.language.isoeng
dc.publisherMDPI
dc.relation.ispartofInternational Journal of Molecular Sciences 2025, 26(7), 3128
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F01875/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI21%2F00280/ES/
dc.relation.publisherversionhttps://doi.org/10.3390/ijms26073128
dc.rights© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectExtracellular matrixen
dc.subjectInflammationen
dc.subjectAdipocytesen
dc.subjectValve interstitial cellsen
dc.titleThe presence of adipose tissue in aortic valves influences inflammation and extracellular matrix composition in chronic aortic regurgitationen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublication919e6260-466a-40a4-aded-bfbf1549d7b8
relation.isAuthorOfPublication23d03177-1c69-4293-bfd4-1de28bf3c05b
relation.isAuthorOfPublication.latestForDiscovery919e6260-466a-40a4-aded-bfbf1549d7b8

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