Cannavo et al. have also proven that in C57BL/6 mice with HF, ISO resulted in a S1PR1 downregulation at the level of the plasma membrane, while chronic administration of a S1PR1-selective agonist resulted in the downregulation of β1AR cardiac plasma membrane levels; both agonists significantly increased the heart-to-body weight (HW/BW) ratio (158). This evidence concerns the gene ADRB1 and hydrops fetalis.