Role for Galectin-3 in Calcific Aortic Valve Stenosis

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. © 2016 the authors.