It has been shown that eNOS/NO/sGC/cGMP signalling pathway was involved in the regulation of cardiac fibroblast proliferation, migration and myofibroblasts differentiation, and therefore protected the heart from cardiac fibrosis during the pathological processes of chronic heart failure.20 As mentioned above, endothelial S1P/S1pr1 praxis activated AKT/eNOS signalling, suggesting that EC‐S1pr1 regulate cardiac fibrosis via its regulation of AKT/eNOS/NO/sGC/cGMP pathway. This evidence concerns the gene NOS3 and congestive heart failure.