Review weighs whether cholesterol redistribution by CETP is proatherogenic or a step in protective reverse cholesterol transport (Horm Res 1996)

The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from high-density lipoproteins (HDL) into very-low-density lipoproteins (VLDL) with a reciprocal exchange of triglycerides. Plasma CETP is mainly bound to HDL and is involved in the interconversion of these lipoproteins. In experimental models such as transgenic mice, CETP activity decreases HDL cholesterol and increases the cholesteryl ester content of apo B-containing lipoproteins. In humans, CETP activity and concentration are positively correlated with VLDL-LDL cholesterol. Clinical studies suggest that the effect of CETP on HDL cholesterol depends on the amount of acceptor lipoproteins. CETP activity is negatively correlated with HDL cholesterol only in hypertriglyceridemic states. Various CETP gene mutations have been reported, they induce hyper-alpha-lipoproteinemia. On the other hand, the impact of the variability of CETP gene on HDL cholesterol variations in Caucasians is controversial. CETP is often involved in secondary dyslipidemia and is susceptible to modify the composition of plasma lipoproteins in an atherogenic way. The real impact of CETP activity on atherosclerosis is still unknown. CETP is susceptible to play a proatherogenic role since it mediates a redistribution of plasma cholesterol from lipoproteins associated with a protection against atherosclerosis into the proatherogenic apo B-containing lipoproteins. However, CETP mediates one of the steps of the reverse cholesterol transport, an antiatherogenic process that channels cholesterol from peripheral tissues back to the liver.