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Simvastatin inhibits angiotensin II‐induced cardiac cell hypertrophy: Role of Homer 1a
Author(s) -
Guo WanGang,
Su FeiFei,
Yuan LiJun,
Yang GuoDong,
Shi XiaoQin,
Li RuoYu,
Shu Qing,
Liu XiongTao,
Lu ZiFan,
Zheng QiangSun
Publication year - 2010
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2009.05221.x
Subject(s) - simvastatin , angiotensin ii , muscle hypertrophy , medicine , endocrinology , mapk/erk pathway , protein kinase a , renin–angiotensin system , chemistry , phosphorylation , biology , receptor , biochemistry , blood pressure
Summary1 The scaffolding protein Homer 1a is constitutively expressed in the myocardium, although its function in cardiomyocytes remains poorly understood. The aim of the present study was to investigate Homer 1a expression in hypertrophic cardiac cells and its role in angiotensin (Ang) II‐induced cardiac hypertrophy. 2 After serum starvation for 24 h, cells were treated with 1 μmol/L simvastatin, 100 nmol/L angiotensin (Ang) II or their combination added to Dulbecco's modified Eagle's medium containing 0.5% serum. For combination treatment with AngII plus simvastatin, cells were exposed to simvastatin 12 h before the addition of AngII to the medium and cells were then incubated in the presence of both drugs for a further 24 h. Western blotting was used to determine Homer 1a protein expression. Hypertrophy was evaluated by determining the protein content per cell. 3 Homer 1a protein levels were upregulated following AngII‐induced hypertrophy in H9C2 cells and neonatal rat cardiomyocytes, and these increases were augmented by simvastatin pretreatment. Concomitantly, simvastatin pretreatment inhibited extracellular signal‐regulated kinase (ERK) 1/2 phosphorylation and AngII‐induced hypertrophy. 4 The inhibitory effects of simvastatin against AngII‐induced hypertrophy were attenuated by Homer 1a silencing, suggesting that simvastatin suppresses cardiac hypertrophy in a Homer 1a‐dependent manner. Furthermore, AngII‐induced hypertrophy and ERK1/2 phosphorylation in neonatal rat cardiomyocytes were significantly inhibited following the overexpression of Homer 1a using an adenovirus. 5 These results suggest a possible role for Homer 1a in inhibiting cardiac hypertrophy perhaps in part through inhibition of ERK1/2 activation.