Cholesteryl ester transfer protein promotes the association of HDL apolipoproteins A-I and A-II with LDL: potentiation by oleic acid.
The association of apolipoprotein (apo) A-I and apo A-II with apo-B-containing particles was measured after incubation at 37 degrees C of either total plasma or low-density lipoproteins (LDL) and high-density lipoproteins-3 (HDL3) in the presence of partially purified cholesteryl ester transfer protein (CETP). At the end of the incubation, apo-B-containing lipoproteins were separated by immunoprecipitation with an anti-apo B gamma-globulin fraction. In mixtures containing LDL and HDL3, either maintained at 4 degrees C or incubated at 37 degrees C, optimal concentrations of anti-apo B antibodies induced the precipitation of more than 95% of apo B without precipitation of apo A-I and apo A-II. When total plasma was incubated at 37 degrees C for 24 h, a significant proportion of apo A-I and apo A-II became associated with apo-B-containing lipoproteins. The fraction of HDL apoproteins associated with apo-B-containing lipoproteins was significantly reduced when plasma was supplemented with TP2 anti-CETP monoclonal antibodies, which are known to inhibit CETP activity. Incubation of LDL and HDL3 for 24 h at 37 degrees C in the presence of purified CETP also induced the association of a significant proportion of apo A-I and apo A-II with apo-B-containing particles. This effect was dependent on CETP concentration in the incubation mixtures and could be suppressed by the addition of anti-CETP monoclonal antibodies. While oleic acid alone, at a final concentration of 0.2 mmol/l, did not promote any association of HDL-apolipoproteins with LDL, it was able, at this concentration, to greatly enhance the CETP-mediated association of apo A-I and apo A-II with apo-B-containing particles. In the presence of both CETP and oleic acid, the association of apo A-I and apo A-II with apo-B-containing particles was apparent within 3 h of commencing the incubation. Approximately 3 mol of apo A-I and 1 mol of apo A-II co-precipitated with each mol of apo B after a 24 h incubation of LDL, HDL3 and CETP. When oleic acid was added to the incubation mixture in addition to CETP, up to 5.5 mol of apo A-I and 2.3 mol of apo A-II were associated with each mol of apo B.(ABSTRACT TRUNCATED AT 400 WORDS)
Lagrost
L
L
Laboratoire de Biochimie des lipoprotéines, Faculté de Médecine, Dijon, France.
Barter
P J
PJ
D000911:Antibodies, Monoclonal; D016632:Apolipoprotein A-I / Q000378:metabolism*; D016633:Apolipoprotein A-II / Q000378:metabolism*; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism*; D006023:Glycoproteins; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000302:isolation & purification / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D009829:Oleic Acids; D019301:Oleic Acid