The reason for CaV1.2 downregulation-induced cardiac hypertrophy may be that, due to the lack of sufficient LTCC current, Ca2+ release from Ryanodine receptor 2 (RYR2) is sensitized to compensate for reduced systolic Ca2+ in order to maintain cardiac contractility, thereby resulting in hypertrophic remodeling through activating the calcineurin/Nuclear factor of activated T cells (NFAT) pathway. This evidence concerns the gene CACNA1C and cardiac hypertrophy.