influence of hydrophilic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (pravastatin) on gelatinase activity in vitro

Besides having lipid-lowering properties, statins (HMG-CoA reductase inhibitors) are known as strong anti-inflammatory agents reducing the expression of inducible matrix metalloproteinases (MMP). Our objective was to evaluate pravastatin effect (a hydrophilic statin) on serum gelatinase activities (MMP-2 and MMP-9) in vitro. Blood samples were obtained from 17 healthy individuals never treated with statins, and gelatinase activities were measured by gelatin zymography. After electrophoresis zymographic gels were incubated with or without pravastatin (5 μg/mL) for 18 h. We noticed that pravastatin enhances gelatinolytic activity at 72 kDa molecular mass (MMP-2) as well as at 130 kDa (MMP-9 heterodimer with neutrophil gelatinase-B associated lipocalin, NGAL) without significant effects on 92 kDa (MMP-9). The comparison of the above finding with previous studies suggests that statins can exert the opposite effects; the inhibition of MMP expression and the augmentation of its activity.