Overexpression of PEP-19 Suppresses Angiotensin II–Induced Cardiomyocyte Hypertrophy

抄録

The precise molecular mechanisms leading to disturbance of Ca²⁺/calmodulin-dependent intracellular signalling in cardiac hypertrophy remains unclear. As an endogenous calmodulin regulator protein, the pathophysiology role of PEP-19 during cardiac hypertrophy was investigated in the present study. We here demonstrated that PEP-19 protein levels are significantly elevated in the aortic banding model in vivo and angiotensin II–induced cardiomyocyte hypertrophy in vitro. Consistent with inhibitory actions of PEP-19 on cardiomyocyte hypertrophy, induction of CaMKII and calcineurin activation as well as hypertrophy-related genes including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was significantly inhibited by PEP-19 transfection. Moreover, PEP-19 partially ameliorates angiotensin II–induced elevation of phospho-phospholamban (Thr-17) and sarcoplasmic reticulum Ca²⁺ release in cardiomyocytes. Together, our results suggest that PEP-19 attenuates angiotensin II–induced cardiomyocyte hypertrophy via suppressing the disturbance of CaMKII and calcineurin signaling.