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

Abstract

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.

• Authors: Lara Matilla, Ernesto Martín-Núñez, Mattie Garaikoetxea, Adela Navarro, Ibai Tamayo, Amaya Fernández-Celis, Alicia Gainza, Joaquín Fernández-Irigoyen, Enrique Santamaría, Pieter Muntendam, Virginia Álvarez, Rafael Sádaba, Eva Jover, Natalia López-Andrés
• Journal: Biology of sex differences (Biol Sex Differ) Vol. 14 Issue 1 Pg. 72 (10 24 2023) ISSN: 2042-6410 [Electronic] England
• PMID: 37875993 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. Society for Women's Health Research and BioMed Central Ltd.

Chemical References

• Galectin 3
• LGALS3 protein, human

Topics

• Female
• Humans
• Male
• Aortic Valve (metabolism, pathology)
• Aortic Valve Stenosis (genetics, metabolism, pathology)
• Endothelial Cells (metabolism)
• Galectin 3
• Proteomics