AimThe effect of ezetimibe (EZE) on acetylation of sterol regulatory element binding protein-1c (SREBP-1c) in lipid-loaded cells derived from vascular smooth muscle cell (VSMC) and its mechanisms have been explored.MethodsThe cholesterol∶methyl-β-cyclodextrin (Chol∶MβCD) complexes were used to build VSMC-derived lipid-loaded cells.After treated by 30 μmol/L EZE, the level of acetylated SREBP-1c, the level of fatty acid synthase (FAS) protein expression in lipid-loaded cells were detected by western blot, and the interaction between SIRT1 and SREBP-1c were analyzed by co-immunoprecipitation, and the role of SIRT1 in deacetylation of SREBP-1c was investigated using shRNA-mediated protein knockdown.ResultsThe level of acetylated SREBP-1c, the level of FAS protein expression were increased, but the interaction between SIRT1 and SREBP-1c was significantly reduced in lipid-loaded cells.However, EZE could weaken all these effects induced by Chol∶MβCD in lipid-loaded cells.A further study reveals that effects of EZE in lipid-loaded cells could be abolished by SIRT1 shRNA transfection.ConclusionEZE inhibits hyperacetylation of SREBP-1c in lipid-loaded cells required for SIRT1.