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).(ABSTRACT TRUNCATED AT 250 WORDS)
Bagdade
J D
JD
Rush Medical College, Chicago, Ill.
Ritter
M C
MC
Davidson
M
M
Subbaiah
P V
PV
D000328:Adult; D001692:Biological Transport; D002352:Carrier Proteins / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000097:blood*; D015525:Fatty Acids, Omega-3 / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006023:Glycoproteins; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood*; D008297:Male; D008875:Middle Aged
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D015525:Fatty Acids, Omega-3; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL