Sex-specific role of galectin-3 in aortic stenosis

Aortic stenosis (AS) is a degenerative valve disease characterized by active remodelling of valve leaflets. The main hallmarks of stenotic aortic valves (AVs) include fibrosis, inflammation, osteogenesis and angiogenesis. Men and women develop these mechanisms differently. Galectin-3 (Gal-3) is a pro-inflammatory and pro-osteogenic lectin with a prominent role in the progression of AS. In this work, we aim to analyze potential sex-differences in the impact of Gal-3 in AS. 226 patients (61.50% men) with severe AS undergoing surgical valve replacement were recruited. In AVs, Gal-3 expression and its relationship with inflammatory, osteogenic and angiogenic markers was assessed. Valve interstitial cells (VIC) derived from AV tissue were primary cultured to perform in vitro experiments. Proteomic analysis revealed that Gal-3 is over-expressed in VICs of male AS patients. Gal-3 secretion also showed to be higher in men’s VICs as compared to women. In human AV tissue, 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’s AV, and with angiogenic molecules only in this sex.