In response to uncoupled NOS and/or vascular Nox activity, arterial peroxide levels are increased in the setting of impaired peroxidase defenses that dissipate H2O2 signals. In the calcifying aortic valve, uncoupling of NOS activity prominently contributes along with reductions in valve catalase activity(10). H2O2 upregulates Msx2 (21), Runx2/Cbfa1(24), and Wnt/β-catenin cascades (23) necessary for osteogenic differentiation of multipotent vascular osteoprogenitors(3,16). GS-SG, oxidized glutathione.