Plasma lipid transfer protein as a determinant of the atherogenicity of monkey plasma lipoproteins.

Quinet, Elaine; Tall, Alan R.; Ramakrishnan, R.; Rudel, L L

doi:10.1172/jci115169

Cited by 158 publications

(77 citation statements)

References 24 publications

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“…42 Moreover, in monkeys fed high-fat, high-cholesterol diets, plasma CETP concentration had a strong inverse correlation with HDL-C concentration but was positively correlated with LDL-C concentration. 4 In fact, similar results were observed in humans.…”

Section: Effect Of Incubation Of Total Plasma On Ldl Patterns To Invsupporting

confidence: 68%

Influence of plasma cholesteryl ester transfer activity on the LDL and HDL distribution profiles in normolipidemic subjects.

Lagrost¹,

Gandjini²,

Athias³

et al. 1993

Arterioscler Thromb

114

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The relations of cholesteryl ester transfer protein (CETP) activity to the distribution of low density lipoproteins (LDLs) and high density lipoproteins (HDLs) were investigated in fasting plasma samples from 27 normolipidemic subjects. LDL and HDL subtractions were separated by electrophoresis on 20-160 g/L and 40-300 g/L polyacrylamide gradient gels, respectively. Subjects were subdivided into two groups according to their LDL pattern. Monodisperse patterns were characterized by the presence of a single LDL band, whereas polydisperse patterns were characterized by the presence of several LDL bands of different sizes. To investigate the influence of lipid transfers on LDL patterns, total plasma was incubated at 37°C in the absence of lecithin: cholesterol acyltransferase (LCAT) activity. The incubation induced a progressive transformation of polydisperse patterns into monodisperse patterns. Under the same conditions, initially monodisperse patterns remained unchanged. Measurements of the rate of radiolabeled cholesteryl esters transferred from HDL 3 s to very low density lipoproteins (VLDLs) and LDLs revealed that subjects with a monodisperse LDL pattern presented a significantly higher plasma CETP activity than subjects with a polydisperse LDL pattern (301±85%/hr per milliliter versus 216±47%/hr per milliliter, respectively; p<0.02). In addition, when total plasma was incubated for 24 hours at 37°C in the absence of LCAT activity, the relative mass of cholesteryl esters transferred from

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Section: Effect Of Incubation Of Total Plasma On Ldl Patterns To Invsupporting

confidence: 68%

Influence of plasma cholesteryl ester transfer activity on the LDL and HDL distribution profiles in normolipidemic subjects.

Lagrost¹,

Gandjini²,

Athias³

et al. 1993

Arterioscler Thromb

114

View full text Add to dashboard Cite

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“…In humans, liver, spleen, and adipose tissue are the most abundant sources of CETP mRNA (7). Studies in nonhuman primates also demonstrate that adipose tissue expresses high levels of CETP mRNA (8,9). All human tissues expressing CETP contain both a full-length form, which gives rise to plasma CETP, and a shortened mRNA, in which the exon 9-derived sequence has been deleted (10).…”

Section: Cholesteryl Ester Transfer Protein (Cetp)mentioning

confidence: 99%

Cholesteryl Ester Transfer Protein Biosynthesis and Cellular Cholesterol Homeostasis Are Tightly Interconnected

Izem

Morton

2001

Journal of Biological Chemistry

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Cholesteryl ester transfer protein (CETP) mediates triglyceride and cholesteryl ester (CE) transfer between lipoproteins, and its activity is strongly modulated by dietary cholesterol. To better understand the regulation of CETP synthesis and the relationship between CETP levels and cellular lipid metabolism, we selected the SW872 adipocytic cell line as a model. These cells secrete CETP in a time-dependent manner at levels exceeding those observed for Caco-2 or HepG2 cells. The addition of LDL, 25OH-cholesterol, oleic acid, or acetylated LDL to SW872 cells increased CETP secretion (activity and mass) up to 6-fold. In contrast, CETP production was decreased by almost 60% after treatment with lipoprotein-deficient serum or ␤-cyclodextrin. These effects, which were paralleled by changes in CETP mRNA, show that CETP biosynthesis in SW872 cells directly correlates with cellular lipid status. To investigate a possible, reciprocal relationship between CETP expression and cellular lipid homeostasis, CETP biosynthesis in SW872 cells was suppressed with CETP antisense oligonucleotides. Antisense oligonucleotides reduced CETP secretion (activity and mass) by 60% compared with sensetreated cells. When CETP synthesis was suppressed for 24 h, triglyceride synthesis was unchanged, but cholesterol biosynthesis was reduced by 20%, and acetate incorporation into CE increased 31%. After 3 days of suppressed CETP synthesis, acetate incorporation into the CE pool increased 3-fold over control. This mirrored a similar increase in CE mass. The efflux of free cholesterol to HDL was the same in sense and antisensetreated cells; however, HDL-induced CE hydrolysis in antisense-treated cells was diminished 2-fold even though neutral CE hydrolase activity was unchanged. Thus, CETP-compromised SW872 cells display a phenotype characterized by inefficient mobilization of CE stores leading to CE accumulation. These results strongly suggest that CETP expression levels contribute to normal cholesterol homeostasis in adipocytic cells.Overall, these studies demonstrate that lipid homeostasis and CETP expression are tightly coupled.

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“…The major role of CETP is a net transfer of CE from HDL to TG-rich lipoprotein (TRL) and of LDL and TG from TRL to LDL and HDL. CETP mRNA is expressed in several tissues, but the majority of circulating CETP originates from the liver (3).…”

mentioning

confidence: 99%

Apolipoprotein composition of HDL in cholesteryl ester transfer protein deficiency

Asztalos

Horvath

Kajinami

et al. 2004

Journal of Lipid Research

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Our purpose was to compare HDL subpopulations, as determined by nondenaturing two-dimensional gel electrophoresis followed by immunoblotting for apolipoprotein A-I (apoA-I), apoA-II, apoA-IV, apoCs, and apoE in heterozygous, compound heterozygous, and homozygous subjects for cholesteryl ester transfer protein (CETP) deficiency and controls. Heterozygotes, compound heterozygotes, and homozygotes had CETP masses that were 30, 63, and more than 90% lower and HDL-cholesterol values that were 64, 168, and 203% higher than those in controls, respectively. Heterozygotes had ‫ف‬ 50% lower pre ␤ -1 and more than 2-fold higher levels of ␣ -1 and pre ␣ -1 particles than controls. Three of the five heterozygotes' ␣ -1 particles also contained apoA-II, which was not seen in controls. Compound heterozygotes and homozygotes had very large particles not observed in controls and heterozygotes. These particles contained apoA-I, apoA-II, apoCs, and apoE. However, these subjects did not have decreased pre ␤ -1 levels. Our data indicate that CETP deficiency results in the formation of very large HDL particles containing all of the major HDL apolipoproteins except for apoA-IV. We hypothesize that the HDL subpopulation profile of heterozygous CETP-deficient patients, especially those with high levels of ␣ -1 containing apoA-I but no apoA-II, represent an improved antiatherogenic state, although this might not be the case for compound heterozygotes and homozygotes with very large, undifferentiated HDL particles. -Asztalos, B. F., K. V. Horvath, K. Kajinami, C. Nartsupha, C. E. Cox, M. Batista, E. J. (1, 2). The major role of CETP is a net transfer of CE from HDL to TG-rich lipoprotein (TRL) and of LDL and TG from TRL to LDL and HDL. CETP mRNA is expressed in several tissues, but the majority of circulating CETP originates from the liver (3).CETP plays a key role in HDL metabolism (4). It regulates total plasma HDL-cholesterol (HDL-C) level and also facilitates the remodeling of HDL particles (5). A high CETP concentration correlates with a low HDL-C level, a strong risk factor for coronary artery disease (6). On the other hand, Asian subjects with CETP deficiency have markedly increased HDL-C (3-to 6-fold) and apoA-I concentrations (7-9). CETP deficiency-induced increase in HDL-C level is mainly found in the large HDL2 subclass. Moreover, the average HDL size of CETP-deficient subjects is significantly increased and enriched in cholesterol (10). These large HDL particles have been reported to be less effective in promoting cholesterol efflux from lipidloaded macrophages than HDL particles of control subjects (11).Several mutations of the CETP gene have been identified as causes of CETP deficiency and increased HDL-C levels. These include a G-to-A substitution within intron 14 at the donor splice site (Int14A), a mutation that is present in up to 2% of the total Japanese population and in as many as 27% of people in the Omagari area of Japan, as well as a missense mutation in exon 15 (D422G) present in up to 7% of the Japanese...

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Plasma lipid transfer protein as a determinant of the atherogenicity of monkey plasma lipoproteins.

Cited by 158 publications

References 24 publications

Influence of plasma cholesteryl ester transfer activity on the LDL and HDL distribution profiles in normolipidemic subjects.

Influence of plasma cholesteryl ester transfer activity on the LDL and HDL distribution profiles in normolipidemic subjects.

Cholesteryl Ester Transfer Protein Biosynthesis and Cellular Cholesterol Homeostasis Are Tightly Interconnected

Apolipoprotein composition of HDL in cholesteryl ester transfer protein deficiency

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