Our specific hypotheses were 2-fold: (1) Genetic inactivation of one copy of MnSOD will accelerate progression of aortic valve stenosis through augmented osteogenic signaling, increased valvular calcification, and increased tissue remodeling and fibrosis, and (2) genetic overexpression of MnSOD will attenuate osteogenic signaling and valve calcification, reduce tissue remodeling and fibrosis, and slow progression of aortic valve stenosis. The gene discussed is SOD2; the disease is aortic valve stenosis.