Besides the clinical application of the PDE inhibitors described above, preclinical studies support that PDE4 enzymes, which constitute the greatest PDE family with four members and multiple variants, critically control vascular and cardiac function by fine-tuning cAMP-dependent phosphorylation cascades (Table 1); thereby, these enzymes also constitute an appealing therapeutic target in cardiovascular diseases. This evidence concerns the gene PDE4A and cardiovascular disorder.