Sex-specific Role of Galectin-3 in Aortic Stenosis

Overview

Journal Biol Sex Differ

Publisher Biomed Central

Specialties Biology
Physiology

Date 2023 Oct 24

PMID 37875993

Authors

Lara Matilla

Ernesto Martin-Nunez

Mattie Garaikoetxea

Adela Navarro

Ibai Tamayo

Amaya Fernandez-Celis

Alicia Gainza

Joaquin Fernandez-Irigoyen

Enrique Santamaria

Pieter Muntendam

Virginia Alvarez

Rafael Sadaba

Eva Jover

Natalia Lopez-Andres

Affiliations

Soon will be listed here.

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.

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