RT Journal Article
T1 Role for Galectin-3 in Calcific Aortic Valve Stenosis
A1 Sádaba JR, 
A1 Martínez Martínez, Ernesto
A1 Arrieta V, 
A1 Álvarez V, 
A1 Fernández-Celis A, 
A1 Ibarrola J, 
A1 Melero A, 
A1 Rossignol P, 
A1 Cachofeiro Ramos, María Victoria
A1 López-Andrés N., 
AB Background: Aortic stenosis (AS) is a chronic inflammatory disease, and calcification plays an important role in the progression of the disease. Galectin-3 (Gal-3) is a proinflammatory molecule involved in vascular osteogenesis in atherosclerosis. Therefore, we hypothesized that Gal-3 could mediate valve calcification in AS.Methods and results: Blood samples and aortic valves (AVs) from 77 patients undergoing AV replacement were analyzed. As controls, noncalcified human AVs were obtained at autopsy (n=11). Gal-3 was spontaneously expressed in valvular interstitial cells (VICs) from AVs and increased in AS as compared to control AVs. Positive correlations were found between circulating and valvular Gal-3 levels. Valvular Gal-3 colocalized with the VICs markers, alpha-smooth muscle actin and vimentin, and with the osteogenic markers, osteopontin, bone morphogenetic protein 2, runt-related transcription factor 2, and SRY (sex-determining region Y)-box 9. Gal-3 also colocalized with the inflammatory markers cd68, cd80 and tumor necrosis factor alpha. In vitro, in VICs isolated from AVs, Gal-3 induced expression of inflammatory, fibrotic, and osteogenic markers through the extracellular signal-regulated kinase 1 and 2 pathway. Gal-3 expression was blocked in VICs undergoing osteoblastic differentiation using its pharmacological inhibitor, modified citrus pectin, or the clustered regularly interspaced short palindromic repeats/Cas9 knockout system. Gal-3 blockade and knockdown decreased the expression of inflammatory, fibrotic, and osteogenic markers in differentiated VICs.Conclusions: Gal-3, which is overexpressed in AVs from AS patients, appears to play a central role in calcification in AS. Gal-3 could be a new therapeutic approach to delay the progression of AV calcification in AS.
PB Journal of the American Heart Association logo
SN 2047-9980
YR 2016
FD 2016-11-06
LK https://hdl.handle.net/20.500.14352/115777
UL https://hdl.handle.net/20.500.14352/115777
LA eng
NO Sádaba JR, Martínez-Martínez E, Arrieta V, Álvarez V, Fernández-Celis A, Ibarrola J, Melero A, Rossignol P, Cachofeiro V, López-Andrés N. Role for Galectin-3 in Calcific Aortic Valve Stenosis. J Am Heart Assoc. 2016 Nov 4;5(11).
DS Docta Complutense
RD 5 abr 2025