Statins Intervene The Expression Of Matrix Metalloproteinase -1 In Cultured Vascular Endothelial Cells

Objective: To investigate the expression of matrix metalloproteinase -1(MMP-1) by interaction between monocytes and vascular endothelial cells and the intervention action of atorvastatin, which provide the experimental evidence of prevention and treatment on atherosclerosis. Methods: The level of MMP-1 in 1.2×106 cultured human umbilical vein endothelial cells (HUVECs) strain(ECV-304)exposed to(0,6×104, 1.2×105,6×105,1.2×106,6×106)freshly isolated normal human monocytes for 24h,or incubated with 1.2×106 monocytes for 6h,12h, 24h and 48h, or incubated with (0.01,0.05,0.1,0.5,1μmol/L)atorvastatin and 1.2×106 monocytes for 24h was measured by cell enzyme linked immunosorbent assay(ELISA). And proliferation rates of HUVECs in the coculcure 1.2×106 monocytes and 1.2×106 HUVECs treated with (0.05,0.1,0.5,1μmol/L)atorvastatin for 24h was counted by cell counting. Results: Monocytes didn't secrete MMP-1.The expression of MMP-1 in cocultured HUVECs remarkably increased (P<0.05) in time-dependent manner. The productions of MMP-1 in HUVECs increased up to the peak in 1:1 coculcure(P<0.001). Atorvastatin (0.05,0.1,0.5,1μmol/L)could inhibit the expression of matrix metalloproteinase -1 in HUVECs(P<0.05), but not in 0.01μmol/L. The inhibitory effect was dose-dependent.Monocytes could inhibit proliferation of HUVECs. Atorvastatin could significantly enhanced proliferation rates of HUVECs in a dose-dependent manner.Conclusion: It is suggested that enhanced MMP-1 expression induced by monocytes-endothelial cell interaction may play an important role in the pathogenesis of atherosclerosis and plaque rupture. Monocytes-endothelial cell coculture not only leads to changes of endothelial cell shape,but also to decreasing the number of endothelial cells.Atorvastatin can inhibit the expression of MMP-1 ,improve the inpaired endothelial cell.The inhibitory effect of atorvastatin may be non-lipid regulation function.