HF is characterized by a desensitization and down-regulation of the β-adrenergic receptor (β-AR).4 We therefore examined β-AR sensitivity on peripheral blood mononuclear cells (PBMCs).23 The often-attributed mechanism of this phenomenon is elevated catecholamine levels, however, this does not fully account for the observation.19 In other cardiovascular diseases, including hypertension, unchecked protease activity in the peripheral circulation has been shown to cause proteolytic cleavage of the extracellular domain of the β-AR in arteries and arterioles.22 This evidence concerns the gene ADRB2 and hydrops fetalis.