Matilla Cuenca, LaraMartín Núñez, ErnestoGaraikoetxea Zubillaga, MattieNavarro, AdelaTamayo Rodríguez, IbaiFernández Celis, AmayaGaínza Calleja, AliciaFernández Irigoyen, JoaquínSantamaría, EnriqueMuntendam, PieterÁlvarez, VirginiaSádaba Sagredo, RafaelJover, EvaLópez Andrés, Natalia2024-05-062024-05-062023Matilla, 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/s13293-023-00556-1.2042-641010.1186/s13293-023-00556-1https://academica-e.unavarra.es/handle/2454/48052Background: 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.application/pdfapplication/zipeng© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License.AngiogenesisAortic stenosisCalcificationGalectin-3InflammationSex differencesValve interstitial cellArtículo / Artikulua2024-05-06Acceso abierto / Sarbide irekiainfo:eu-repo/semantics/openAccess