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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, Ernestoes_ES
dc.contributor.authorGaraikoetxea Zubillaga, Mattiees_ES
dc.contributor.authorNavarro, Adelaes_ES
dc.contributor.authorTamayo Rodríguez, Ibai
dc.contributor.authorFernández Celis, Amayaes_ES
dc.contributor.authorGaínza Calleja, Aliciaes_ES
dc.contributor.authorFernández Irigoyen, Joaquín
dc.contributor.authorSantamaría, Enriquees_ES
dc.contributor.authorMuntendam, Pieteres_ES
dc.contributor.authorÁlvarez, Virginiaes_ES
dc.contributor.authorSádaba Sagredo, Rafaeles_ES
dc.contributor.authorJover, Evaes_ES
dc.contributor.authorLópez Andrés, Nataliaes_ES
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.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
relation.isAuthorOfPublication803d8f90-85aa-4e9f-bfa0-30454dc4e7dd
relation.isAuthorOfPublication488f1d4a-17fc-4f8c-87c0-8939257c87d7
relation.isAuthorOfPublication86d1b76e-4790-40b1-a3ec-72331c5c6199
relation.isAuthorOfPublication.latestForDiscovery803d8f90-85aa-4e9f-bfa0-30454dc4e7dd

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