We found in the transgenic (TG) mice that augmented S1PR1 signaling in myofibroblasts led to the development of pathological cardiac hypertrophy with interstitial fibrosis, which was mediated through the paracrine actions of Ang II and interleukin-6 (IL-6) released by myofibroblasts. The gene discussed is AGT; the disease is cardiac hypertrophy.