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

Journal of Pharmacological Sciences

Yang-yang Xie¹  Chen Zhang⁴  Bo-ya Zhang²  Meng-meng Sun¹  Ying-mei Lu³  Xue-fang Lou³  Feng Han⁴  Ping Wang¹ 

[1] College of Pharmaceutical Sciences, Zhejiang University of Technology, China;School of Medicine, Ningbo University, China;School of Medicine, Zhejiang University City College, China;College of Pharmaceutical Sciences, Zhejiang University, China

关键词: angiotensin II;    calmodulin kinase II;    calcineurin;    PEP-19;    cardiomyocyte hypertrophy;   

DOI  :  10.1254/jphs.13208FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(42)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.

【 授权许可】

Unknown