Effects of simvastatin on proliferation of rat cardiac fibroblasts induced by arginine vasopressin in vitro

Objective To investigate the effects of simvastatin (Sim) on the proliferation of rat cardiac fibroblasts (CFs) induced by arginine vasopressin (AVP) for theoretical bases of preventing and treating cardiac myofibrosis due to hypertention. Methods CFs of neonatal Sprague Dawley (SD) rats were isolated with trypsin digestion method and those growth arrested were stimulated with 10 -7 mol/L AVP in the presence of various concentrations of Sim and mevalonate (MVA). The DNA synthesis of CFs was measured with 3H Thymidine ( 3H TdR) incorporation. MTT colorimetry was adopted to evaluate cell number. Results ①Sim decreased 3H TdR incorporation in CFs in a concentration dependent manner. 3H TdR incorporation values of 10 -6 mol/L Sim and 10 -5 mol/L Sim group (1 175±202.66 and 771±164.86 cells in every 2 000 cells, respectively) were significantly lower than those of the control (1 955±372.45 in every 2 000 cells) (both P 0.01); ② A 490 values of 10 -6 mol/L Sim and 10 -5 mol/L Sim group (0.215±0.041, 0.163±0.018, respectively) were significantly lower than those of the control (0.393± 0.048) (both P 0.01) . ③ 3H TdR incorporation in CFs and A 490 value of 10 -5 mol/L Sim+10 -3 mol/L MVA group (1 995±353.83 cells in every 2 000 cells, 0.418 ±0.045 respectively) were significantly higher in comparison with 10 -5 mol/L Sim group (both P 0.01). Conclusion The results indicate that Sim can decrease CFs number and DNA synthesis induce by AVP and MVA pathway may play an important role in the CFs proliferation.