Thus, the role of these interacting pathways downstream of GPCRs in myocardial physiology appears to be receptor-dependent, and further investigation of how AT1R and APJ integrate ligand and mechanical stimuli to bias G protein or β-arrestin signaling, thus controlling cardioprotective versus cardiotoxic programs is important for the discovery of new therapeutics for heart failure. The gene discussed is AGTR1; the disease is heart failure.