Fluvastatin inhibits basal and stimulated plasminogen activator inhibitor 1, but induces tissue type plasminogen activator in cultured human endothelial cells.

摘要: The effects of fluvastatin, a synthetic hydroxymethylglutaryl coenzyme A (HMG-CoA) inhibitor, on the biosynthesis tissue plasminogen activator (t-PA) and its major physiological inhibitor (plasminogen type 1, PAI-1) were investigated in cultured human umbilical vein endothelial cells (HUVEC). Fluvastatin (0.1 to 2.5 µM), concentration-dependently reduced release PAI-1 antigen by unstimulated HUVEC, subsequent reduction steady-state mRNA levels de novo protein synthesis. In contrast, it increased t-PA secretion. drug also secreted response 10 µg/ml bacterial lipopolysaccharide (LPS), 100 U/ml tumour necrosis factor (TNFα) or 0.1 M phorbol myristate acetate (PMA). Mevalonate (100 precursor isoprenoids, added simultaneously with suppressed effect both stimulated as well antigen. Among intermediates isoprenoid pathway, all-trans-geranylgeraniol (5 µM) but not farnesol (10 prevented µM fluvastatin antigen, which suggests that former intermediate synthesis is responsible for observed effects.