ADCY6 and heart failure: Several earlier studies reported that overexpression of AC6 in the heart could protect animals from heart failure induced by a pace-maker, ISO, or aging via increasing the efficiency of βAR-AC6 coupling, thereby activating the downstream PKA-signaling cascade that produces a significantly positive inotropic effect to ameliorate the function of a failing heart and lower sympathetic tone via a baroreflex [12, 20, 35].