Fluvastatin inhibits matrix metalloproteinase-1 expression in human vascular endothelial cells

Matrix metalloproteinase-1 (MMP-1), also called interstitial collagenase, m ay play an important role in the pathogenesis of atherosclerosis and athero sclerotic plaque rupture. We investigated the effects of fluvastatin on MMP -1 expression in human vascular endothelial cells (ECs). The addition of fl uvastatin decreased the basal MMP-1 levels in the culture media of ECs in a time-dependent (0 to 48 hours) and dose-dependent (10(-8) to 10(-5) mol/L) manner. On the other hand, fluvastatin did not affect tissue inhibitor of metalloproteinase-1 levels. Collagenolytic activity in conditioned media of ECs was also dose-dependently reduced by fluvastatin. The effect of fluvas tatin on MMP-1 expression was completely reversed in the presence of mevalo nate or geranylgeranyl-pyrophosphate, but not in the presence of squalene. Inhibition of Rho by C3 exoenzyme also significantly decreased MMP-1 expres sion in ECs. Our findings revealed that fluvastatin decreases MMP-1 express ion in human vascular ECs through inhibition of Rho.