We therefore treated cardiomyocyte with AngII in vitro to induce cell hypertrophy and examined whether EC‐S1pr1 influenced CM hypertrophy in a paracrine manner.15 In vitro co‐culture experiments showed that the conditioned medium obtained from S1PR1‐overexpressing ECs reduced cardiomyocyte hypertrophy, while the blockade of AKT/eNOS signalling diminished this inhibitory effect of EC‐S1pr1 on cardiac hypertrophy (Figure 4A). This evidence concerns the gene NOS3 and cardiac hypertrophy.