INFLUENCE OF PLASMA CHOLESTERYL ESTER TRANSFER ACTIVITY ON THE LDL AND HDL DISTRIBUTION PROFILES IN NORMOLIPIDEMIC SUBJECTS

The relations of cholesteryl ester transfer protein (CETP) activity to the distribution of low density lipoproteins (LDLs) and high density lipoproteins (HDLs) were investigated in fasting plasma samples from 27 normolipidemic subjects. LDL and HDL subfractions were separated by electrophoresis on 20-160 g/L and 40-300 g/L polyacrylamide gradient gels, respectively. Subjects were subdivided into two groups according to their LDL pattern. Monodisperse patterns were characterized by the presence of a single LDL band, whereas polydisperse patterns were characterized by the presence of several LDL bands of different sizes. To investigate the influence of lipid transfers on LDL patterns, total plasma was incubated at 37-degrees-C in the absence of lecithin: cholesterol acyltransferase (LCAT) activity. The incubation induced a progressive transformation of polydisperse patterns into monodisperse patterns. Under the same conditions, initially monodisperse patterns remained unchanged. Measurements of the rate of radiolabeled cholesteryl esters transferred from HDL3s to very low density lipoproteins (VLDLs) and LDLs revealed that subjects with a monodisperse LDL pattern presented a significantly higher plasma CETP activity than subjects with a polydisperse LDL pattern (301+/-85%/hr per milliliter versus 216+/-47%/hr per milliliter, respectively; p<0.02). In addition, when total plasma was incubated for 24 hours at 37-degrees-C in the absence of LCAT activity, the relative mass of cholesteryl esters transferred from HDLs to apolipoprotein B-containing lipoproteins was greater in plasma with monodisperse LDL than in plasma with polydisperse LDL (0.23+/-0.06 versus 0.17+/-0.06, respectively; p<0.02). These results indicated that in normolipidemic plasma, CETP could play an important role in determining the size distribution of LDL particles. The analysis of lipoprotein cholesterol distribution in the two groups of subjects sustained this hypothesis. Indeed, HDL cholesterol levels, the HDL:VLDL+LDL cholesterol ratio, and the esterified cholesterol: triglyceride ratio in HDL were significantly lower in plasma with the monodisperse LDL pattern than in plasma with the polydisperse LDL pattern (p<0.01, p<0.01, and p<0.02, respectively). Plasma LCAT activity did not differ in the two groups. Plasma CETP activity correlated positively with the level of HDL3b (r=0.542, p<0.01) in the entire study population. Whereas plasma LCAT activity correlated negatively with the level of HDL2b (r=-0.455, p<0.05) and positively with the levels of HDL2a (r=0.475, p<0.05) and HDL3a (r=0.485, p<0.05), no significant relation was observed with the level of HDL3b. These results suggest that both monodisperse LDL patterns and high levels of HDL3b particles are specific markers of an elevation of CETP activity in normolipidemic plasma.