Effects of simvastatin on hypertrophy and PTEN expression of rat cardiac myocytes

Objective To study the effects of simvastatin on the hypertrophy of cultured rat cardiac myocytes induced by serum and the role of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in the signal pathway. Methods Cultured neonatal SpragueDawley (SD) rat cardiac myocytes were treated with 15% fetal bovine serum, or without serum, or different consentrations of simvastatin. Image analysis system was used to measure the cardiac myocytes surface area. Protein synthesis of myocytes was measured via [3H]-leucine incorporation method. The expression level of atrial natriuretic peptide (ANP) mRNA in myocytes was determined with reverse transcription polymerase chain reaction (RT-PCR). The mRNA and protein expression levels of PTEN in cardiac myocytes were investigated with RT-PCR and Western blot respectively. Results At 24 hours, cardiac myocytes surface area was significantly higher in 15% serum group (1611.16±160.75 μm2) than in serum-free group (538.04±118.60 μm2, P<0.01). Simvastatin decreased the cell surface area in a concentration dependent manner. The cell surface area in 10-5 and 10-6 mol/L simvastatin groups were 799.84±167.70 μm2 and 1076.88±199.28 μm2 respectively, which were both significantly lower than that in 15% fetal bovine serum group (P<0.01). Incorporation rate of [3H]-leucine was significantly higher in 15% fetal bovine serum group (2360±106cpm/well) than that in serum-free group (1305±92 cpm/well, P<0.01). Incorporation rate of [3H]-leucine in 10-5 and 10-6 mol/L simvastatin groups were 1707±101 cpm /well and 1962±125 cpm/well respectively, which were both lower than that in serum group (P<0.01). With the increase of simvastatin concentration, the expression level of ANP mRNA in cardiac myocytes was decreased gradually, which were 0.29±0.03 and 0.40±0.03 respectively in 10-5 and 10-6 mol/L simvastatin groups, and significantly lower than that in serum group(0.60±0.03, P<0.01). Simvastatin increased the expressions of PTEN mRNA and protein in cardiac myocytes in a concentration dependent manner. PTEN mRNA expression level in 10-7, 10-6 and 10-5 mol/L simvastatin groups were 0.38±0.03, 0.83±0.04 and 0.85±0.05, respectively, which were all higher than that in 15% fetal bovine serum group (0.29±0.04, P<0.05). Similarly, PTEN protein level in 10-7, 10-6 and 10-5 mol/L simvastatin groups (39.25±3.41, 46.35±1.78 and 47.22±2.39 respectively) were also significantly higher than that in 15% fetal bovine serum group (32.21±4.06, P<0.05). Conclusion Simvastatin can inhibit the hypertrophy of cultured rat cardiac myocytes induced by serum, and the increase of expression level of PTEN might be involved in the mechanism (J Geriatr Cardiol 2010; 7:47-51).