Abstract
The heart is capable of remodeling in response to hemodynamic stress. However, molecular details of mechanical responses in cardiomyocytes remain unclear. Transient receptor potential vanilloid family type 2 (TRPV2) is stretch-activated Ca^<2+> channel and localized to intercalated discs in mammalian cardiomyocytes. In this study, we show that mechanical signaling via TRPV2 in cardiomyocytes is pivotal for the maintenance of cardiac function in adult mice. Stretch-induced insulin-like growth factor (IGF-1) secretion was significantly reduced in TRPV2-deficient cardiomyocytes isolated from neonatal mice. In addition, the IGF-1 receptor/PI3K/Akt signaling pathway was significantly down-regulated in TRPV2-deficient adult hearts. Furthermore, administration of IGF-1 to TRPV2-decieinet adult hearts partially prevented impairment in cardiac pump function. These results suggest that TRPV2 regulates IGF-1/PI3K/Akt signaling pathway, which is required to maintain cardiac function in physiological hearts.
