We found that down-regulated PTEN was reversed by orexin B, and the enhanced type I and type III collagen, TGF-β, IL6, p-STAT3, STAT3 were also reversed by orexin B, suggesting PTEN was involved in the overexpression of miR-320-induced cardiac hypertrophy and fibrosis in vitro. Here, HCRT is linked to cardiac hypertrophy.