Sex-specific role of galectin-3 in aortic stenosis
Fecha
2023Autor
Versión
Acceso abierto / Sarbide irekia
Tipo
Artículo / Artikulua
Versión
Versión publicada / Argitaratu den bertsioa
Identificador del proyecto
Impacto
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10.1186/s13293-023-00556-1
Resumen
Background: 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) ...
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Background: 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. [--]
Materias
Angiogenesis,
Aortic stenosis,
Calcification,
Galectin-3,
Inflammation,
Sex differences,
Valve interstitial cell
Editor
BMC
Publicado en
Biology of Sex Diferences (2023), 14(1):72, 1-16
Departamento
Universidad Pública de Navarra. Departamento de Ciencias de la Salud /
Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila
Versión del editor
Entidades Financiadoras
Open 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).