RAPGEF4 and cardiac hypertrophy: Despite the fact that cAMP-producing β-adrenergic stimulation induces cardiac hypertrophy [78], cAMP/PKA or cAMP/Epac signaling is not likely to mediate the hypertrophic effects of PGE2 in cardiomyocytes, since all the treatment like cAMP activator (forskolin), cAMP inhibitor (SQ-22536), PKA inhibitor (H89), and Epac activator (8-CPT-2Me-cAMP) at different concentrations had no effect on PGE2-induced protein synthesis in ventricular myocytes [57, 68, 79].