Dose-dependent effect of rosuvastatin in the regulation of metalloproteinase expression.
The importance of rosuvastatin at therapeutic dosage in regulating the release, activity, protein level, and expression of matrix metalloproteinases (MMP)-2 and MMP-9 was investigated. Human umbilical artery smooth muscle cells were stimulated, in vitro, in a serum-free medium with rosuvastatin at various concentrations (2, 4, 7, and 10 ng/mL, which correspond to the maximal plasma concentration observed in healthy men after a daily oral intake of 5, 10, 20, and 40 mg, respectively). The release of MMP-2 and MMP-9 in the conditioned medium was assessed by enzyme-linked immunosorbent assay and confirmed by Western blot, the activity and expression were determined by zymography and polymerase chain reaction, respectively. Human umbilical artery smooth muscle cells stimulated with rosuvastatin at 7 and 10 ng/mL had a significant lower release, activity, protein level, and expression of MMP-2 and MMP-9, when compared with those stimulated at 2 and 4 ng/mL (MMP-2 =p < 0.0001 and p < 0.0001, respectively; MMP-9 =p < 0.0001 and p < 0.0001, respectively). The effects of rosuvastatin in reducing MMP-2 and MMP-9, which might stabilize the atherosclerotic plaques, are dose-dependent.