Targeting NOS as a therapeutic approach for heart failure

Nitric oxide is a key signaling molecule in the heart and is produced endogenously by three isoforms of nitric oxide synthase, neuronal NOS (NOS1), endothelial NOS (NOS3), and inducible NOS (NOS2). Nitric oxide signals via cGMP-dependent or independent pathways to modulate downstream proteins via specific post translational modifications (i.e. cGMP-dependent protein kinase phosphorylation, S-nitrosylation, etc.). Dysfunction of NOS (i.e. altered expression, location, coupling, activity, etc.) exists in various cardiac disease conditions, such as heart failure, contributing to the contractile dysfunction, adverse remodeling, and hypertrophy. This review will focus on the signaling pathways of each NOS isoform during health and disease, and discuss current and potential therapeutic approaches targeting nitric oxide signaling to treat heart disease.