PKA and Epac synergistically inhibit smooth muscle cell proliferation

► PKA is required but not sufficient for the anti-mitogenic effects of cAMP in VSMC. ► cAMP-induced smooth muscle cell growth arrest is Epac-dependent but Rap1-independent. ► PKA and Epac synergise to inhibit smooth muscle cell proliferation. ► cAMP inhibits ERK and JNK phosphorylation in a PKA- and Epac-dependent manner. ► cAMP-induced stellate morphology of SMC requires PKA and Epac.