title: Simvastatin reverses cardiomyocyte hypertrophy via the upregulation of phosphatase and tensin homolog expression.
abstract: The aim of the present study was to investigate the effects of simvastatin on the protein kinase B (PKB) signaling pathway and the expression of phosphatase and tensin homolog (PTEN). The effects of simvastatin were analyzed by administering the drug orally to male spontaneously hypertensive rats (SHRs) at a dose of 10 mg/kg/day, while the control animals received an equal volume of saline. The systolic pressure (mmHg) of the rat tail artery was measured prior to the initiation of the experiment, and once a week until the end of the experiment. At the end of the experiment, the animals were euthanized and the hearts were removed. The left ventricular and interventricular septum were weighed, after which the left ventricular mass/body mass ratio was calculated. In addition, cardiomyocytes isolated from Sprague Dawley rats were cultured with 15% fetal bovine serum to induce hypertrophy, following which the cells were treated with different doses of simvastatin. Thein vitroeffects were assessed by measuring the surface area of the cardiomyocytes, while the rate of protein synthesis was measured using a 3H-leucine incorporation assay and western blot analyses. Simvastatin was demonstrated to inhibit cardiomyocyte hypertrophy in thein vivoandin vitroexperiments. Notably, simvastatin increased PTEN expression and inhibited PKB expression in the SHR model, as well as in the cardiomyocytes in culture. In addition, the use of PTEN antisense oligodeoxynucleotides was revealed to inhibit the effects of simvastatin on cardiomyocytes. Therefore, these results indicated that simvastatin was able to reverse cardiomyocyte hypertrophyin vivoandin vitro, possibly by increasing the expression of PTEN.
authors.affiliation: Department of Cardiology, General Hospital of Lanzhou Military Area Command, Lanzhou, Gansu 730050, P.R. China.
authors.forename: Yong-Qing
authors.initials: YQ
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Lian-You
authors.initials: LY
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, General Hospital of Lanzhou Military Area Command, Lanzhou, Gansu 730050, P.R. China.
authors.forename: Wei-Ze
authors.initials: WZ
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, General Hospital of Lanzhou Military Area Command, Lanzhou, Gansu 730050, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
keywords: cardiomyocyte hypertrophy; phosphatase and tensin homolog; protein kinase B; simvastatin