EFFECT OF MARINE LIPIDS ON CHOLESTERYL ESTER TRANSFER AND LIPOPROTEIN COMPOSITION IN PATIENTS WITH HYPERCHOLESTEROLEMIA

While the effects of omega-3 (n-3) fatty acids present in marine lipids on plasma lipoprotein levels have been intensively studied, less is known about their impact on reverse cholesterol transport. For this reason, for a 3-month period we studied the effects of the administration of n-3 fatty acids (6 g/day) as a dietary supplement on cholesteryl ester transfer (CET), a key step in this process, and lipoprotein composition in 12 outpatients with genetically heterogeneous forms of hypercholesterolemia. Before treatment, CET in hypercholesterolemic patients, estimated as the mass of cholesteryl ester (CE) transferred from high density lipoprotein (HDL) to very low density lipoprotein (VLDL) plus low density lipoprotein (LDL), was markedly accelerated, peaking after only 1-2 hours of incubation of whole plasma; this response differed significantly (p < 0.001) from the initial delayed curvilinear response of control subjects. Consistent with the accelerated CET occurring in vivo, their triglyceride to esterified cholesterol core lipid ratio before treatment was reduced in the intact VLDL fraction and VLDL1 but not in VLDL2 or VLDL3 and was reciprocally increased in HDL. In addition, the free (unesterified) cholesterol to lecithin ratio of VLDL1 was abnormally increased. Recombination experiments performed with individual lipoprotein fractions revealed that accelerated CET was specifically associated with the VLDL1 subfraction and not LDL, HDL, and cholesteryl ester transfer protein (CETP), although pretreatment levels of CETP were significantly increased (p<0.01). Marine lipid treatment significantly reduced total plasma cholesterol (before, 326+/-67 versus after, 302+/-67 mg/dl; p<0.005, mean+/-SD), LDL unesterified cholesterol (before, 78.6+/-12.7 versus after, 66.9+/-9.2 mg/dl; p<0.001), and CETP levels (before, 2.28+/-0.44 versus after, 2.0+/-0.55 mug/ml; control, 1.33+/-0.25 mug/ml; p<0.05)and normalized CET. Moreover, the pretreatment compositional disturbances in the free cholesterol to lecithin ratio of VLDL, and in the triglyceride to esterified cholesterol ratios of VLDL and VLDL1 returned to normal. These data indicate that while marine lipid therapy only modestly lowers plasma cholesterol and CETP in hypercholesterolemic patients, it normalizes CET, possibly as a result of its alteration of the lipid composition of VLDL1.