Of note, the differences between these two predominant cardiac βARs in terms of signaling properties might take a quite different shape and have a much bigger bearing on pathophysiologic implications in the setting of heart failure (HF): for instance, β1AR is selectively down-regulated (i.e., total cellular receptor number reduced) in HF, thus shifting the above mentioned stoichiometry of β1AR:β2AR towards 50:50 in the failing heart from 75:~25 in the normal, healthy heart [3]. Here, ADRB1 is linked to heart failure.