Simvastatin exerts favourable effects on neointimal formation in a mouse model of vein graft.

Abstract Background Simvastatin inhibits human saphenous vein neointima formation in human saphenous vein organ cultures. However, it is not known if simvastatin actually inhibits vein graft intima hyperplasia in vivo , and the underlying mechanisms behind that. In this study, we used a murine vein graft model to address these issues. Methods and results Vein grafting was performed among C57BL/6 J mice treated with low-dose (2 mg kg −1 ) or high-dose (20 mg kg −1 ) simvastatin or vehicle subcutaneously 72 h before and then daily after surgery. As compared to the vehicle, simvastatin dose-dependently significantly inhibited vein graft intima hyperplasia 4 weeks after surgeries. Immunohistochemistry studies suggested that vein graft neointima was mainly composed of vascular smooth muscle cells (VSMCs), and the rate of proliferating cell nuclear antigen (PCNA)-positive cells in the intima of vein grafts was significantly lower in simvastatin-treated groups than in control group. We isolated VSMC from mouse vena cava, simvastatin significantly reduced VSMC proliferation, and platelet-derived growth factor (PDGF)-induced VSMC migration in a dose-dependent manner. Conclusion Simvastatin inhibits neointima formation of mouse vein graft under normocholesterolaemic condition in vivo , the mechanisms might be associated with inhibitory effects of simvastatin on VSMC proliferation and migration.