CETP overexpression in transgenic mice does not impair macrophage reverse cholesterol transport or HDL's LDL-antioxidant activity (Atherosclerosis 2007)

CETP inhibition increases HDL cholesterol levels and presumably could contribute to human atheroprotection via increasing macrophage-specific reverse cholesterol transport (RCT) and antioxidant properties of HDL. However, the impact of CETP activity variation on these two antiatherogenic functions of HDL remain unknown. In this study, we assessed the effects of overexpressing CETP in transgenic (Tg) mice on macrophage-specific RCT and HDL ability to protect against LDL oxidative modification. [(3)H]cholesterol-labeled macrophages were injected intraperitoneally into mice maintained on a chow diet or an atherogenic diet, after which the appearance of [(3)H]cholesterol in plasma, liver and feces over 48 h was determined. The degree of protection of oxidative modification of LDL coincubated with HDL was evaluated by measuring relative electrophoretic mobility and dichlorofluorescein fluorescence. CETP-Tg mice presented decreased radiolabeled HDL-bound [(3)H]cholesterol 24 and 48 h after the label injection. However, the magnitude of macrophage-derived [(3)H]cholesterol in liver and feces did not differ between CETP-Tg and control mice on either diet. Similar results were found when [(3)H]cholesterol-labeled endogenous peritoneal macrophages were injected into the CETP-Tg and control mice. Further, the injection of endogenous macrophages from CETP-Tg mice did not alter macrophage RCT in control mice. HDL from CETP-Tg and control mice protected LDL from oxidative modification similarly, and paraoxonase 1, platelet activated factor acetyl-hydrolase and lecithin-cholesterol acyl transferase activities of transgenic mice did not differ from those of control mice. In conclusion, CETP overexpression in transgenic mice does not affect RCT from macrophages to feces in vivo or the protection conferred by HDL against LDL oxidative modification.