HMG-CoA Reductase Inhibitor, Pitavastatin, Prevents Migration of Cultured Smooth Muscle Cells by Suppressing Myosin Light Chain Phosphorylation

Objective: To clarify the mechanism underlying the protective effect of statins against vascular events, we investigated whether pitavastatin affects the migration, adhesion and myosin light chain (MLC) phosphorylation of pig vascular smooth muscle cells (VSMCs) from the coronary artery. Methods: Migration was assayed by the modified Boyden’s chamber method and MLC phosphorylation was determined with the use of glycerol-PAGE. Results: Pitavastatin strongly inhibited cell migration and cell adhesion. Pretreatment of mevalonate (MVA) prior to the pitavastatin administration totally reversed these inhibitory effects of pitavastatin on VSMCs, whereas pretreatment of geranylgeranylpyrophosphate (GGPP) only partially reversed these inhibitory effects. Morphologically, MVA completely reversed, whereas GGPP partially reversed pitavastatin-inhibited cell spreading. Pitavastatin also inhibited MLC phosphorylation, and MVA completely reversed, whereas GGPP partially inhibited this effect. Y-27632 (a Rho-kinase inhibitor) suppressed VSMC migration and MLC phosphorylation more effectively than ML-9 (a MLC-kinase inhibitor). The inhibitory effects upon VSMC migration and MLC phosphorylation were maximal after incubation with both Y-27632 and ML-9. Conclusions: Pitavastatin inhibited VSMC migration by inhibiting cell adhesion, spreading and MLC phosphorylation. Another pathway in addition to the Rho pathway might be involved in these effects.