Factors Regulating the Distribution of Cholesterol Between LDL and HDL

Abstract

The importance of understanding factors which influence the partitioning of cholesterol between different plasma lipoprotein fractions is highlighted by the observation that the risk of developing coronary heart disease correlates positively with the concentration of cholesterol in low density lipoproteins (LDL)¹ and negatively with that in high density lipoproteins (HDL)². Most of the cholesterol in plasma exists as cholesteryl esters which reside with triacylglycerol in the hydrophobic core of lipoproteins. In human plasma, cholesteryl esters exchange between all lipoprotein fractions in a process of equilibration catalysed by the cholesteryl ester transfer protein (CETP)^3,4. Since the rate of the CETP-mediated exchange between LDL and HDL in human plasma is rapid relative to the rate of catabolism of each lipoprotein fraction⁵ (Fig.l), the cholesteryl esters in these two lipoproteins must be close to equilibrium in vivo. Thus, in terms of regulating the partitioning of cholesteryl esters between LDL and HDL, it is probable that the level of activity of CETP is not normally rate limiting. We have recently reported, however, that the CETP-mediated equilibrium between LDL and HDL can be disrupted by Na oleate which, as a consequence, promotes a shift in the partitioning of cholesteryl esters from the non-atherogenic HDL to the atherogenic LDL⁶.