HMG-CoA Reductase Inhibitor, Pitavastatin, Prevents Migration of
Cultured Smooth Muscle Cells by Suppressing Myosin Light Chain Phosphorylation
The present study showed that statin inhibits MLC phosphorylation more effectively than ROCK inhibitor Y compound or MLCK inhibitor ML-9 and that it is as potent as a combination of these inhibitors. In addition, rescue with GGPP, a modulator that is specifically involved in the Rho or Rac pathway, only partially inhibited the effects of statins. These data suggest that statins inhibit MLC phosphorylation not only via ROCK inhibition but also via a ROCK-independent pathway. We suggest that MLCK may be involved in a ROCK-independent MLC phospholylation by statin. However, neither MLCK nor MLC phosphatase have yet been assayed due to technical difficulties.
CONCLUSION
We found that pitavastatin inhibits VSMC migration and adhesion, as well as MLC phosphorylation. It is concluded that the inhibitory mechanisms involve not only the Rho pathway but also the Rho- or Ras- independent pathway such as MLCK inhibition.
