Abstract:Aim To investigate the mechanism of ezetimibe-induced cholesterol efflux by observing the effect of ezetimibe on ATP binding cassettet transporter A1 and Liver X Receptor α in lipid-loaded cells derived from vascular smooth muscle cell(VSMC). Methods Lipid-loaded cell model was established with the mix of 20 mg/L Chol∶MβCD treating VSMC. Lipid-loaded cells were treated with different concentration of ezetimibe(3,10,30 μmol/L)for 24 hours respectively,and 30 μmol/L ezetimibe was selected for lipid-loaded cell treatment of different time respectively (0,6,12,24,48 h). ATP binding cassettet transporter-A1 mRNA was detected by reverse transcription PCR(RT-PCR) and the protein expression of Liver X Receptor α was examined by Western-blotting. Results (1) With different concentration of ezetimibe treated lipid-loaded cells,the mRNA expression of ATP binding cassettet transporter-A1 increased with concentration. Compared with the model group,the 30 μmol/L ezetimibe-treated group (24 h ) had a 3.4 folds rising. Treated with 30 μmol/L ezetimibe for different time(0,6,12,24,48 h),the mRNA expression of ATP binding cassettet transporter-A1 had a time dependant trend reaching plateau at 24 h and the best concentration was 30 μmol/L. (2) With different concentration of ezetimibe treated lipid-loaded cells,the protein expression of Liver X Receptor α increased with rising concentration. Compared with the model group,the 30 μmol/L ezetimibe-treated group(24 h) had an increase of more than 2 folds. Treated with 30 μmol/L ezetimibe for different time(0,6,12,24,48 h),the protein expression of Liver X Receptorα had a time dependant trend with 24 h reaching plateau and the best time was 24h. Conclusion Ezetimibe promotes cellular cholesterol efflux in lipid-loaded cells derived from VSMC by up-regulating Liver X Receptorα and ATP binding cassettet transporter-A1 expression.

Abstract:Cholesterol efflux from lipid-loaded cells is a key event associating with stability and subsidence of plaque. There are many proteins and factors participating in regulation of cholesterol efflux of lipid-loaded cells, which is very complex. We propose,by summarizing the recent research,a novel mode of “four systems and one center with coupling transportation and networking regulation. The novel mode consists of 1) intracellular trafficking system of caveolin-1 complex,2) transmembrane transporting system of ATP binding cassette transporter(ABC)-A1 complex,3) transmembrane transporting system of scavenger receptor (SR-) B1 complex,4) extracelluar trafficking system of high density lipoprotein/apolipoprotein (HDL/Apo)-A1 and 5) caveolae transporting center. In brief,caveolin-1 complex system transports cholesterol from intracellular compartments to caveolae; both ABC-A1 and SR-B1 complex systems transfer cholesterol from caveolae to HDL/Apo-A1. There are networking regulation among four systems. This mode provides a simple and concise way to understand the dynamic process of atherosclerosis.