Calcium Signaling, Calcineurin and NFAT3 Molecular Pathway in Reprogramming of Fetal Gene (BNP) Expression in Cardiac Hypertrophy and Inhibitors of Cardiac Hypertrophy-Review

G-Protein Coupled Receptor (GPCR) plays a major role in cardiac hypertrophy. Isoproterenol is an agonist which binds to GPCR. This results in the activation of GS subunit. Activated Gs subunit stimulates cAMP mediated pathway. This activates the calcium signaling and elevates the calcium level. Increased calcium activates the phosphatase activity of calcineurin. Activated calcineurin dephosphorylates NFAT in cytoplasm. Dephosphorylated NFAT translocates to nucleus and binds to target region in DNA and activates re-expression of fetal genes in synergy with GATA-4 trascription factor. Reprogramming of fetal genes by NFAT- 3 and GATA-4 results in cardiac hypertrophy. Calcineurin inhibitors and rephosphorylation of NFAT can prevent cardiac hypertrophy.