Among the nucleus-annotated proteins, we selected the CtBP2, phospho-HDAC-1, and SMAD4 interaction for further analysis as these proteins form a complex that acts downstream of TGF-β (transcription growth factor beta).52–55 Notably, TGF-β is associated with cardiac hypertrophy, fibrosis, and conduction abnormalities,43,56 all features that characterize the long-term detrimental effect that PDE3 inhibitors have in patients with HF. Here, SMAD4 is linked to cardiac hypertrophy.