Fluvastatin inhibits matrix metalloproteinase-1 expression in human vascular endothelial cells.
Matrix metalloproteinase-1 (MMP-1), also called interstitial collagenase, may play an important role in the pathogenesis of atherosclerosis and atherosclerotic plaque rupture. We investigated the effects of fluvastatin on MMP-1 expression in human vascular endothelial cells (ECs). The addition of fluvastatin 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 fluvastatin on MMP-1 expression was completely reversed in the presence of mevalonate or geranylgeranyl-pyrophosphate, but not in the presence of squalene. Inhibition of Rho by C3 exoenzyme also significantly decreased MMP-1 expression in ECs. Our findings revealed that fluvastatin decreases MMP-1 expression in human vascular ECs through inhibition of Rho.
Ikeda
U
U
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Shimpo
M
M
Ohki
R
R
Inaba
H
H
Takahashi
M
M
Yamamoto
K
K
Shimada
K
K
D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000187:drug effects* / Q000378:metabolism; D008798:Mevalonic Acid / Q000494:pharmacology; D011106:Polyisoprenyl Phosphates / Q000494:pharmacology; D017035:Pravastatin / Q000494:pharmacology; D012717:Sesquiterpenes; D013185:Squalene / Q000494:pharmacology; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; D019715:Tissue Inhibitor of Metalloproteinase-1; D000077340:Fluvastatin; C004808:farnesyl pyrophosphate; D013185:Squalene; D008148:Lovastatin; D020781:Matrix Metalloproteinase 1; D017035:Pravastatin; C002963:geranylgeranyl pyrophosphate; D008798:Mevalonic Acid