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Cholesteryl ester transfer protein promotes the association of HDL apolipoproteins A-I and A-II with LDL: potentiation by oleic acid

Identifieur interne : 00ED70 ( Main/Merge ); précédent : 00ED69; suivant : 00ED71

Cholesteryl ester transfer protein promotes the association of HDL apolipoproteins A-I and A-II with LDL: potentiation by oleic acid

Auteurs : Laurent Lagrost [France] ; Philip J. Barter [Australie]

Source :

RBID : ISTEX:6EF1ECBF285EF6FBC3BD60C9F0F1CA79DC6B34D0

Descripteurs français

English descriptors

Abstract

Abstract: The association of apolipoprotein (apo) A-I and apo A-II with apo-B-containing particles was measured after incubation at 37°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 γ-globulin fraction. In mixtures containing LDL and HDL3, either maintained at 4°C or incubated at 37°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°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°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. The present study has demonstrated that CETP can promote the association of apo A-I and apo A-II with apo-B-containing particles and that this process is enhanced by oleic acid.

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DOI: 10.1016/0005-2760(92)90229-O

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ISTEX:6EF1ECBF285EF6FBC3BD60C9F0F1CA79DC6B34D0

Le document en format XML

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<term>CETP</term>
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<term>Chem</term>
<term>Cholesteryl</term>
<term>Cholesteryl ester transfer protein</term>
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<term>Fatty acids</term>
<term>Final protein concentration</term>
<term>Final volume</term>
<term>HDL</term>
<term>HDL3</term>
<term>Human plasma</term>
<term>Immunoprecipitated</term>
<term>Immunoprecipitated samples</term>
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<term>LDL</term>
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<term>Lipoprotein</term>
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<term>Monoclonal</term>
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<term>Non-esterified fatty acid</term>
<term>Oleic</term>
<term>Oleic acid</term>
<term>Particle size redistribution</term>
<term>Present experiments</term>
<term>Present study</term>
<term>Protein concentration</term>
<term>Significant proportion</term>
<term>Single determination</term>
<term>Supernatant</term>
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<term>VLDL</term>
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<term>Oleic acid</term>
<term>Particle size redistribution</term>
<term>Present experiments</term>
<term>Present study</term>
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<div type="abstract" xml:lang="en">Abstract: The association of apolipoprotein (apo) A-I and apo A-II with apo-B-containing particles was measured after incubation at 37°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 γ-globulin fraction. In mixtures containing LDL and HDL3, either maintained at 4°C or incubated at 37°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°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°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. The present study has demonstrated that CETP can promote the association of apo A-I and apo A-II with apo-B-containing particles and that this process is enhanced by oleic acid.</div>
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