Effects of Atorvastatin on the Proliferation and Cell Cycle of Human Umbilical Vein Endothelial Cells in a Hypoxic Environment

Objective To probe into the effects of atorvastatin on the proliferation and cell cycle of cultured human umbilical vein endothelial cells(HUVECs) in a hypoxic environment. Methods HUVECs were cultured in a DMEM medium with 10% fetal calf serum in 24 well plates with a concentration of 1×10~(5) cells per well.The cells were then randomly divided into 5 groups,with 8 wells of cells per group.Cells of the normal control group were further incubated in a serum-free DMEM medium for 12 h under normoxic condition.Cells of the hypoxia model group were further incubated in a serum-free DMEM medium for 12 h in a hypoxia device(PO_(2)1.0 kPa).Cells of the low,medium and high dose trial groups were further incubated in a serum-free DMEM mediumn containing 0.05,0.10 and 0.20 mmol·L~(-1) of atorvastatin,respectively,for 12 h in the hypoxia device.The proliferation of the cells was assayed with the MTT method while the preparations of cells in their different cycles were analyzed with flow cytomelry. Results Proliferation of the cells was strikingly depressed in the hypoxic environment.Atorvastatin in different concentrations was shown to significantly promote the proliferation of the endothelial cells subjected to hypoxia(P0.05 or P0.01 as compared with cells of the hypoxia model group).The dose-effect relationship,however,was not linear.Atorvastatin at the medium dose was shown to have the strongest effect in promoting the cell proliferationa.The drug at the high dose had a much weaker effects on the promotion of cell proliferation.Atorvastatin in different doses was also shown to result in significant increase in the proportion of the cells in S phase and reduce that of the cells in G_0/G_1 phase. Conclusion Atorvastatin in appropriate concentrations was shown to promote the proliferation and DNA synthesis of HUVECs in a hypoxic environment.It seems possible that atorvastatin may play a certain role in the neogenesis of blood vessels in the ischemic myocardium.