In contrast, in both the critical and severe AS cases, a subset of endothelial cells showed intense expression of nuclear pSmad2 and the nucleus of part of the cells in the endocardial fibro-elastosis also stained mildly positive (Figure 5g,h,l,m), indicative of activated TGF-β signaling. This evidence concerns the gene TGFB1 and aortic stenosis.