ApoCIII enrichment in HDL impairs HDL-mediated cholesterol efflux capacity

Apolipoprotein CIII (apoCIII) has been reported to be tightly associated with triglyceride metabolism and the susceptibility to coronary artery disease (CAD). Besides, apoCIII has also been found to affect the anti-apoptotic effects of HDL. However, the effect of apoCIII on HDL-mediated cholesterol efflux, the crucial function of HDL, has not been reported. A hospital-based case-control study was conducted to compare the apoCIII distribution in lipoproteins between CAD patients and nonCAD controls and to explore the relationship between HDL-associated apoCIII (apoCIII_HDL) and HDL-mediated cholesterol efflux. One hundred forty CAD patients and nighty nine nonCAD controls were included. Plasma apoCIII, apoCIII_HDL and cholesterol efflux capacity was measured. The apoCIII_HDL ratio (apoCIII_HDL over plasma apoCIII) was significantly higher in CAD patients than that in control group (0.52 ± 0.24 vs. 0.43 ± 0.22, P = 0.004). Both apoCIII_HDL and apoCIII_HDL ratio were inversely correlated with cholesterol efflux capacity (r = -0.241, P = 0.0002; r = -0.318, P < 0.0001, respectively). Stepwise multiple regression analysis revealed that the apoCIII_HDL ratio was an independent contributor to HDL-mediated cholesterol efflux capacity (standardized β = -0.325, P < 0.001). This study indicates that the presence of apoCIII in HDL may affect HDL-mediated cholesterol efflux capacity, implying the alternative role of apoCIII in the atherogenesis.