Along with these observations, mice that were engineered to overexpress the β-adrenoreceptor or Gα protein displayed initial sustained increases in heart rate and ventricular contractile function, followed by ventricular dilation, myocardial fibrosis, and heart failure.33 In contrast, there were distinct differences in mice with cardiac-directed expression of AC6—despite 20-fold excess cardiac AC6 protein, there was no increase in heart rate or left ventricular function in unstimulated animals. Here, ADCY6 is linked to heart failure.