Sex-specific role of galectin-3 in aortic stenosis.

Autor: Matilla L; Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, C/Irunlarrea 3., 31008, Pamplona, Spain., Martín-Núñez E; Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, C/Irunlarrea 3., 31008, Pamplona, Spain., Garaikoetxea M; Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, C/Irunlarrea 3., 31008, Pamplona, Spain., Navarro A; Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, C/Irunlarrea 3., 31008, Pamplona, Spain., Tamayo I; Research Methodology Unit, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain., Fernández-Celis A; Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, C/Irunlarrea 3., 31008, Pamplona, Spain., Gainza A; Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, C/Irunlarrea 3., 31008, Pamplona, Spain., Fernández-Irigoyen J; Clinical Neuroproteomics Unit, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain., Santamaría E; Clinical Neuroproteomics Unit, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain., Muntendam P; G3 Pharmaceuticals, Burlington, MA, USA., Álvarez V; Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, C/Irunlarrea 3., 31008, Pamplona, Spain., Sádaba R; Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, C/Irunlarrea 3., 31008, Pamplona, Spain., Jover E; Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, C/Irunlarrea 3., 31008, Pamplona, Spain. eva.jover.garcia@navarra.es., López-Andrés N; Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, C/Irunlarrea 3., 31008, Pamplona, Spain. natalia.lopez.andres@navarra.es.
Jazyk: angličtina
Zdroj: Biology of sex differences [Biol Sex Differ] 2023 Oct 24; Vol. 14 (1), pp. 72. Date of Electronic Publication: 2023 Oct 24.
DOI: 10.1186/s13293-023-00556-1
Abstrakt: Background: Aortic stenosis (AS) is characterized by inflammation, fibrosis, osteogenesis and angiogenesis. Men and women develop these mechanisms differently. Galectin-3 (Gal-3) is a pro-inflammatory and pro-osteogenic lectin in AS. In this work, we aim to analyse a potential sex-differential 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 inflammatory, 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 significantly higher in men, with stronger immunostaining in VICs with myofibroblastic phenotype and valve endothelial cells. Gal-3 levels in AVs were positively correlated with inflammatory markers in both sexes. Gal-3 expression was also positively correlated with osteogenic markers mainly in men AVs, and with angiogenic molecules only in this sex. In vitro, Gal-3 treatment induced expression of inflammatory, osteogenic and angiogenic markers in male's VICs, while it only upregulated inflammatory and osteogenic molecules in women-derived cells. Gal-3 blockade with pharmacological inhibitors (modified citrus pectin and G3P-01) prevented the upregulation of inflammatory, osteogenic and angiogenic molecules.
Conclusions: Gal-3 plays a sex-differential role in the setting of AS, and it could be a new sex-specific therapeutic target controlling pathological features of AS in VICs.
(© 2023. Society for Women's Health Research and BioMed Central Ltd.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje