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Sex-specific role of galectin-3 in aortic stenosis

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dc.contributor.authorMatilla Cuenca, Lara
dc.contributor.authorMartín Núñez, Ernesto
dc.contributor.authorGaraikoetxea Zubillaga, Mattie
dc.contributor.authorNavarro, Adela
dc.contributor.authorTamayo Rodríguez, Ibai
dc.contributor.authorFernández Celis, Amaya
dc.contributor.authorGaínza Calleja, Alicia
dc.contributor.authorFernández Irigoyen, Joaquín
dc.contributor.authorSantamaría Martínez, Enrique
dc.contributor.authorMuntendam, Pieter
dc.contributor.authorÁlvarez, Virginia
dc.contributor.authorSádaba Sagredo, Rafael
dc.contributor.authorJover, Eva
dc.contributor.authorLópez Andrés, Natalia
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.contributor.funderUniversidad Pública de Navarra / Nafarroako Unibertsitate Publikoaes
dc.date.accessioned2024-05-06T14:51:11Z
dc.date.available2024-05-06T14:51:11Z
dc.date.issued2023
dc.date.updated2024-05-06T13:56:15Z
dc.description.abstractBackground: Aortic stenosis (AS) is characterized by infammation, fbrosis, osteogenesis and angiogenesis. Men and women develop these mechanisms diferently. Galectin-3 (Gal-3) is a pro-infammatory and pro-osteogenic lectin in AS. In this work, we aim to analyse a potential sex-diferential role of Gal-3 in AS. Methods: 226 patients (61.50% men) with severe AS undergoing surgical aortic valve (AV) replacement were recruited. In AVs, Gal-3 expression and its relationship with infammatory, osteogenic and angiogenic markers was assessed. Valve interstitial cells (VICs) were primary cultured to perform in vitro experiments. Results: Proteomic analysis revealed that intracellular Gal-3 was over-expressed in VICs of male AS patients. Gal-3 secretion was also higher in men’s VICs as compared to women’s. In human AVs, Gal-3 protein levels were signifcantly higher in men, with stronger immunostaining in VICs with myofbroblastic phenotype and valve endothelial cells. Gal-3 levels in AVs were positively correlated with infammatory markers in both sexes. Gal-3 expression was also posi tively correlated with osteogenic markers mainly in men AVs, and with angiogenic molecules only in this sex. In vitro, Gal-3 treatment induced expression of infammatory, osteogenic and angiogenic markers in male’s VICs, while it only upregulated infammatory and osteogenic molecules in women-derived cells. Gal-3 blockade with pharma cological inhibitors (modifed citrus pectin and G3P-01) prevented the upregulation of infammatory, osteogenic and angiogenic molecules. Conclusions: Gal-3 plays a sex-diferential role in the setting of AS, and it could be a new sex-specifc therapeutic target controlling pathological features of AS in VICs.en
dc.description.sponsorshipOpen Access funding provided by Universidad Pública de Navarra. This work was supported by a Miguel Servet contract (CP13/00221) and by Fondo de Investigaciones Sanitarias (PI18/01875; PI21/00280) from the Instituto de Salud Carlos III—FEDER, and by Departamento de Salud del Gobierno de Navarra (GºNa 01/21). LM was supported by a PFIS Ph.D. studentship (FI19/00302), EM-N was supported by a Margarita Salas postdoctoral fellowship (ULL-MS-P14, granted by Universidad de La Laguna and Ministerio de Universidades, Gobierno de España—Orden UNI/551/2021 de 26 de Mayo and Fondos Next Generation EU), MG was supported by a Miguel Servet Foundation Ph.D. studentship and EJ was supported by a Sara Borrell postdoctoral fellowship (CD19/00251).en
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dc.format.mimetypeapplication/zipen
dc.identifier.citationMatilla, L., Martín-Núñez, E., Garaikoetxea, M., Navarro, A., Tamayo, I., Fernández-Celis, A., Gainza, A., Fernández-Irigoyen, J., Santamaría, E., Muntendam, P., Álvarez, V., Sádaba, R., Jover, E., López-Andrés, N. (2023) Sex-specific role of galectin-3 in aortic stenosis. Biology of Sex Differences, 14(1), 1-16. https://doi.org/10.1186/s13293-023-00556-1.en
dc.identifier.doi10.1186/s13293-023-00556-1
dc.identifier.issn2042-6410
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/48052
dc.language.isoengen
dc.publisherBMCen
dc.relation.ispartofBiology of Sex Diferences (2023), 14(1):72, 1-16en
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//CP13%2F00221/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F01875/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI21%2F00280/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gobierno de Navarra//01%2F21en
dc.relation.publisherversionhttps://doi.org/10.1186/s13293-023-00556-1
dc.rights© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License.en
dc.rights.accessRightsAcceso abierto / Sarbide irekiaes
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAngiogenesisen
dc.subjectAortic stenosisen
dc.subjectCalcificationen
dc.subjectGalectin-3en
dc.subjectInflammationen
dc.subjectSex differencesen
dc.subjectValve interstitial cellen
dc.titleSex-specific role of galectin-3 in aortic stenosisen
dc.typeArtículo / Artikuluaes
dc.typeinfo:eu-repo/semantics/articleen
dc.type.versionVersión publicada / Argitaratu den bertsioaes
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dspace.entity.typePublication
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relation.isAuthorOfPublicationabacfd17-2b93-4d99-bae2-52053d57401e
relation.isAuthorOfPublication23d03177-1c69-4293-bfd4-1de28bf3c05b
relation.isAuthorOfPublication.latestForDiscovery803d8f90-85aa-4e9f-bfa0-30454dc4e7dd

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