Critically, on stiff substrates and matrices, TGFβ robustly induces apoptosis and dystrophic calcific nodule formation in aortic valve interstitial cells from a variety of species, suggesting that the matrix accumulation and sclerosis occurring in early stages of valvular heart disease may shift the phenotypic consequences of increased TGF-β across the spectrum of the disease and contribute to both fibrosis and dystrophic calcification to different extents during the evolution of disease (22, 23). This evidence concerns the gene TGFB1 and heart valve disorder.