RAPGEF3 and cardiac hypertrophy: Indeed, both EPAC1 and EPAC2 are present in cardiomyocytes.53 Diverse physiological roles of EPAC proteins have been recently reviewed by Lezoualc'h et al.54 Activation of EPAC was linked to ventricular hypertrophy, vasorelaxation and in the regulation of Ca2+ through RyR and PLB phosphorylation,54 indicating synergism between the cAMP/PKA and cAMP/EPAC pathways.