PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction

Significance Heart failure is the leading global cause of death; therefore developing a greater understanding of disease etiology and identifying novel therapeutic targets is critical. Here, we describe the role of the cyclic nucleotide-degrading protein phosphodiesterase 1C (PDE1C) in the context of pathological cardiac remodeling. In cardiac myocytes, we found that PDE1C regulates both cyclic AMP- and cyclic GMP-mediated signaling pathways under different conditions. In both isolated cells and mice we found that inhibition of PDE1C could potentiate protective signaling and prevent the development of many aspects of heart failure, potentially by signaling through multiple cell types. PDE1 inhibition therefore may represent a viable therapeutic strategy for treatment of heart failure.