OBJECTIVETo investigate the effects of simvastatin (Sim) and the interference by mevalonate (MVA) against its effect on DNA synthesis in rat cardiac fibroblasts (CFs).

METHODSCFs were isolated from neonatal SD rats by trypsin digestion and growth-arrested CFs were stimulated with Sim and/or MVA at varied concentrations for different time lengths, and the DNA synthesis in the cells was measured by (3)H-thymidine ((3)H-TdR) incorporation assay.

RESULTSSim decreased (3)H-TdR incorporation in the CFs in a concentration-dependent manner, and (3)H-TdR incorporation was significantly lower in cells treated with 1 x 10(-6) and 1 x 10(-5) mol/L Sim (1,175+/-202.66 and 771+/-164.86 cpm/2000 cells, respectively) than in the control cells (1,608+/-204.32 cpm/2000 cells, P<0.01). As the treatment time with 1 x 10(-5) mol/L Sim prolonged (for 6, 12, 18, 24, 36, 42, and 48 h), (3)H-TdR incorporation in CFs decreased gradually, showing an obvious inverse correlation with the treatment time (r=-919, P<0.01). (3)H-TdR incorporation in cells treated with 1 x 10(-6) to 1 x 10(-3) mol/L MVA and 1 x 10(-5) mol/L Sim rose steadily as MVA concentration increased. A significant difference in the incorporation was found between cells treated with both 1 x 10(-4)/1 x 10(-3) mol/L MVA and 1 x 10(-5) mol/L Sim (1,612+/-308.57 and 1,995+/-353.83 cpm/2000 cells, respectively) and the cells with 1 x 10(-5) mol/L Sim treatment alone (P<0.01); difference was also noted between cells treated with 1 x 10(-5) mol/L MVA and the control cells (P<0.05), but treatment with 1 x 10(-6) mol/L MVA did not produce much difference in comparison with the control cells (P>0.05) With the increase of treatment time (for 6, 12, 18, 24, 36, 42, 48 h), 1 x 10(-3) mol/L MVA caused steady increase in (3)H-TdR incorporation in the CFs, showing a significant positive correlation with the treatment time (r=0.968, P<0.01).

CONCLUSIONSim can decrease DNA synthesis in rat CFs and postpone the occurrence of myocardial fibrosis, which can be reversed by MVA.