CHOLESTERYL ESTER TRANSFER ACTIVITY IN LIPOPROTEIN-LIPASE DEFICIENCY AND OTHER PRIMARY HYPERTRIGLYCERIDEMIAS

Cholesteryl ester transfer protein (CETP) activity was measured in d > 1.21 g/ml plasma from hypertriglyceridemic patients and compared with normolipidemic subjects. The assay consisted in measuring the specifi c transfer of [H-3]cholesteryl oleate from a prelabelled, apo E-poor H DL fraction to VLDL after incubation at 37 degrees C in the presence o f the d > 1.21 g/ml plasma sample: the lipoproteins were then separate d by precipitation with dextran sulfate/Mg2+ solution. Increasing the volume of d > 1.21 g/ml plasma or purified human CETP in the assay pro duced linear responses in measured activity, whereas, either during in cubation at 4 degrees C or in the presence of rat plasma instead of hu man plasma, the transfer of [3H]cholesteryl oleate to VLDL was not sti mulated. Thus, the assay reflects changes in CETP in the sample and ap pears to be suitable for measuring CETP activity in d > 1.21 g/ml plas ma. CETP activity was very similar in the two groups of normolipidemic subjects considered: adolescents (203 +/- 11 nmol esterified choleste rol transferred per 8 h/ml plasma) and adults (215 +/- 5). Patients we re grouped into lipoprotein-lipase (LPL)-deficient and non-LPL-deficie nt according to their enzyme activity in postheparin plasma. CETP acti vity was highly increased in LPL-deficient, severe hyperchylomicronemi c patients (430 +/- 42) and was directly correlated with VLDL levels i n the non-LPL-deficient individuals. Marked differences were observed in the lipid composition of HDL and apolipoprotein A-I levels among pa tients and controls. In the control group, CETP activity was correlate d only with HDL-triglyceride and HDL-triglyceride/apo A-I mass ratio, which is compatible with the physiological role of CETP in transferrin g triglyceride to HDL from other lipoprotein particles. When all hyper triglyceridemic patients were considered together, CETP activity was i nversely correlated with apo A-I and HDL-cholesterol, whereas it was d irectly correlated with HDL-triglyceride/HDL-cholesterol and HDL-trigl yceride/apo A-I mass ratios. The results indicate that the enhanced CE TP activity associated with hypertriglyceridemia contributes to the co mpositional change of HDL, which in turn may be responsible for the re duction of HDL levels in this condition.