Sex-specific role of galectin-3 in aortic stenosis

Biology of Sex Differences

Research

Virginia Álvarez¹  Lara Matilla¹  Adela Navarro¹  Eva Jover¹  Mattie Garaikoetxea¹  Alicia Gainza¹  Amaya Fernández-Celis¹  Rafael Sádaba¹  Ernesto Martín-Núñez¹  Natalia López-Andrés¹  Joaquín Fernández-Irigoyen²  Enrique Santamaría²  Pieter Muntendam³  Ibai Tamayo⁴ 

[1] Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, C/Irunlarrea 3., 31008, Pamplona, Spain;Clinical Neuroproteomics Unit, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain;G3 Pharmaceuticals, Burlington, MA, USA;Research Methodology Unit, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain;

关键词: Galectin-3;    Aortic stenosis;    Sex differences;    Valve interstitial cell;    Inflammation;    Calcification;    Angiogenesis;   

DOI  :  10.1186/s13293-023-00556-1

 received in 2023-07-20, accepted in 2023-10-10,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAortic 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.Methods226 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.ResultsProteomic 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.ConclusionsGal-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.Graphical Abstract

【 授权许可】

CC BY   
© Society for Women's Health Research and BioMed Central Ltd. 2023

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