Sex-dependent expression of galectin-1, a cardioprotective beta-galactoside- binding lectin, in human calcific aortic stenosis

EVA JOVER; ERNESTO MARTÍN-NÚÑEZ; MATTIE GARAIKOETXEA; LARA MATILLA; LUIS M BLANCO-COLIO; JUAN M. PÉREZ-SÁEZ; ADELA NAVARRO; AMAYA FERNÁNDEZ-CELIS; ALICIA GAINZA; VIRGINIA ÁLVAREZ; RAFAEL SÁDABA; IBAI TAMAYO; GABRIEL A. RABINOVICH; JOSÉ L. MARTÍN-VENTURA; NATALIA LÓPEZ-ANDRÉS

FASEB JOURNAL

FEDERATION AMER SOC EXP BIOL

Lugar: Bethesda; Año: 2024

0892-6638

We aimed to analyze sex-related differences in galectin-1 (Gal-1),a β-galactoside-binding lectin, in aortic stenosis (AS) and its association with the inflammatory andfibrocalcific progression of AS. Gal-1 was determined in serum and aortic valves(AVs) from control and AS donors by western blot and immunohistochemistry.Differences were validated by ELISA and qPCR in AS samples. In vitro experimentswere conducted in primary cultured valve interstitial cells (VICs). Serum Gal-1was not different neither between control and AS nor between men and women. Therewas no association between circulating and valvular Gal-1 levels. The expressionof Gal-1 s was higher in men than women, even after adjusting for confounding factors, and was associated with inflammation, oxidative stress, extracellular matrix remodeling, fibrosis, and osteogenesis. Gal-1 enhanced within fibrocalcific areas of stenotic AVs, especially in men. Secretion of Gal-1was up-regulated over a time course of 2, 4, and 8 days in men's calcifyingVICs, only peaking at day 4 in women's VICs. In vitro, Gal-1 was associatedwith similar mechanisms to those in our clinical cohort. β-Estradiol significantlyup-regulated the activity of an LGALS1 promoter vector and the secretion of Gal-1,only in women's VICs. Supplementation with rGal-1 prevented the effects by calcific challenge including the metabolic shift to glycolysis. In conclusion, Gal-1 is up-regulatedin stenotic AVs and VICs from men in association with inflammation, oxidative stress, matrix remodeling, and osteogenesis. Estrogens can regulate Gal-1 expression with potential implications in post-menopause women.Exogenous rGal-1 can diminish calcific phenotypes in both women and men.