Plasma Cholesteryl Ester Transfer Activity Research Articles

Challenges of Existing Pediatric Dyslipidemia Guidelines

Existing guidelines for screening and managing lipoprotein abnormalities in children and adolescents are based on a consensus document published over 15 years ago by the National Cholesterol Education Program (NCEP) Expert Panel on Blood Cholesterol Levels in Children and Adolescents.1 This document was based on evidence that elevated levels of low-density lipoprotein (LDL) cholesterol are highly correlated with development of atherosclerotic cardiovascular disease (ASCVD) in adults and on pathological data suggesting that dyslipidemia in children and adolescents was associated with early arterial plaque development. The panel recommended 2 strategies to address abnormal lipoprotein levels in children: a population-based approach (dietary recommendations) and a targeted screening approach (selective screening based on family history of ASCVD and/or parental hypercholesterolemia). The guidelines recommended dietary and lifestyle interventions for children with elevated LDL cholesterol levels. They proposed that drug therapy only be considered when LDL cholesterol levels are ≥190 mg/dL or ≥160 mg/dL with concomitant ASCVD risk factors (≥2) or with a family history of ASCVD. Article p 32 Since the initial publication of the existing guidelines, many significant challenges have emerged that deserve attention. First, accumulating data suggest that the guidelines significantly underestimated the number of children who would be targeted for lipoprotein screening. Second, the guidelines do not account for variations in lipids due to race, gender, and pubertal status, all of which are known …

Plasma cholesteryl ester transfer and hepatic lipase activity are related to high-density lipoprotein cholesterol in association with insulin resistance in type 2 diabetic and non-diabetic subject

We evaluated the hypothesis that plasma cholesteryl ester transfer (CET) and lipase activities are influenced by insulin sensitivity and contribute to the low high-density lipoprotein (HDL) cholesterol observed in type 2 diabetic patients and insulin-resistant non-diabetic subjects. Sixteen type 2 diabetic and 16 nondiabetic subjects participated. Diabetic and non-diabetic subjects were divided in equal groups of eight subjects with low or high insulin sensitivity, which was documented as the glucose infusion rate (M-value) during the last hour of a 3-h euglycaemic hyperinsulinaemic clamp (150 mU kg

Plasma cholesteryl ester transfer and hepatic lipase activity are determinants of low high density lipoprotein cholesterol associated with insulin resistance in type 2 Diabetic and non-diabetic subjects

Plasma cholesteryl ester transfer and hepatic lipase activity are determinants of low high density lipoprotein cholesterol associated with insulin resistance in type 2 Diabetic and non-diabetic subjects

Differential expression of cholesteryl ester transfer protein in the liver and plasma of fasted and fed transgenic mice

Because cholesteryl ester transfer protein (CETP) is considered a potential target in the treatment of atherosclerosis, several reports have focused on the regulation of this enzyme, and there is evidence that insulin may be a regulatory factor. The present study examines the differential expression of the human CETP gene between physiologic conditions that are accompanied by low (fasted) and high (fed) insulin levels. CETP expression was examined in plasma and tissues of transgenic mice expressing the human CETP minigene after 12 hours of fasting ( n = 20) or ad libitum feeding ( n = 20) with normal mouse chow. Plasma cholesteryl ester transfer activity (CETA) was 20% higher in fed than in fasted mice, reflecting higher levels of CETP ( P < 0.05). This observation was accompanied by higher liver mRNA in fed mice (100%, P < 0.05), as determined by ribonuclease protection assays, as well as by higher CETA (23%, P < 0.05) and CETP mass (29%, P < 0.05) in the particulate fraction of liver homogenates. These parameters of liver CETP expression correlated well with each other, as well as with plasma CETA. CETP in the liver particulate fraction was found as a doublet (approximately 70 and 65 kDa), which resolved to a single band (approximately 60 kDa) upon deglycosylation. No differences in CETP expression were observed in pooled adipose tissue samples from fed and fasted mice. Insulin and glucose were not related to any plasma or tissue parameter of CETP expression. In summary, the concerted, differential expression of CETP in the liver of fed and fasted transgenic mice appears to contribute to higher plasma CETP levels in fed mice, but the precise role of insulin and glucose in regulating CETP expression under fasted and fed conditions needs to be defined.

Plasma lipoprotein distribution and lipid transfer activities in patients with type IIb hyperlipidemia treated with simvastatin

The aim of the present study was to search in type IIb hyperlipidemic patients for putative concomitant effects of simvastatin on the physicochemical characteristics of low density lipoproteins (LDL) and high density lipoproteins (HDL), as well as on the activities of the cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) that were determined in both endogenous lipoprotein-dependent and endogenous lipoprotein-independent assays. In a double-blind, randomized trial, patients received either placebo (one tablet/day; n=12) or simvastatin (20 mg/day; n=12) for a period of 8 weeks after a 5-week run-in period. Simvastatin, unlike placebo, reduced the lipid and apolipoprotein B contents of the most abundant LDL-1, LDL-2, and LDL-3 subfractions without inducing significant changes in the overall size distribution of LDL and HDL. Whereas simvastatin significantly increased PLTP activity in an endogenous lipoprotein-dependent assay ( P<0.01), no variation was observed in a lipoprotein-independent assay. Simvastatin significantly decreased plasma CETP activity in an endogenous lipoprotein-dependent assay ( P<0.01), and the reduction in plasma cholesteryl ester transfer rates was explained by a 16% drop in CETP mass concentration ( P<0.01). In contrast, the specific activity of CETP was unaffected by the simvastatin treatment reflecting at least in part the lack of significant alteration in plasma triglyceride-rich lipoprotein acceptors. The simvastatin-induced changes in plasma CETP mass levels correlated positively with changes in plasma CETP activity ( r=0.483, P=0.0561), in total cholesterol levels ( r=0.769; P<0.01), and in LDL-cholesterol levels ( r=0.736; P<0.01). Whereas the observations suggest that simvastatin might exert concomitant beneficial effects on plasma CETP and LDL levels, neither plasma cholesteryl ester transfer activity nor plasma phospholipid transfer activity appeared as the main determinants of the LDL and HDL distribution profiles in type IIb hyperlipidemic patients.

Phospholipid and cholesteryl ester transfer activities in plasma from 14 vertebrate species. Relation to atherogenesis susceptibility

Cholesteryl ester and phospholipid transfer activities were determined in plasmas from 14 vertebrates, and lipid transfer values were analyzed in the light of the known atherogenesis susceptibility of studied species. Whereas cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) activities among vertebrate species were only measured in lipoprotein-deficient fractions in previous studies, both endogenous lipoprotein-dependent and endogenous lipoprotein-independent assays were used in the present work. In agreement with previous studies, a few species (chicken, man, rabbit and trout) displayed substantial CETP activity, whereas CETP activity was not detectable in other species (cow, dog, horse, mouse, pig, and rat). Additional species that were not studied before, i.e. cat, goat, and sheep, were shown to be deficient in plasma cholesteryl ester transfer activity, while duck was shown to constitute a new member of the high activity group. Unlike CETP activity, PLTP activity was detected in plasmas from all studied species, most of them being assayed here for the first time (cat, chicken, cow, duck, goat, horse, sheep, and trout). While dog, trout, mouse, and pig displayed the highest phospholipid transfer activity levels, the remarkable preservation of facilitated phospholipid transfers in plasma from all vertebrates might indicate an essential role of PLTP in vivo. Interestingly, animals with well-documented atherogenesis susceptibility (chicken, pig, rabbit, and man) displayed significantly higher mean CETP activity, but lower mean PLTP activity than known `resistant' animals (cat, dog, mouse, and rat). In conclusion, the present study revealed marked differences in plasma lipid transfer activities between vertebrate species, and interspecies comparisons indicated that both CETP and PLTP may constitute two determinants of the atherogenicity of the plasma lipoprotein profile.

Increased plasma cholesteryl ester transfer activity in obese children

To determine whether enhanced activity of cholesteryl ester transfer protein (CETP) contributes to the development of atherogenic lipoprotein profiles in obese children, plasma CETP activity was assayed according to a micro-method, by co-incubating lipoprotein-deficient samples with exogenous donor and acceptor lipoproteins. The study subjects were 31 obese children (14 males and 17 females). Serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TC:high-density lipoprotein (HDL)-C, LDL-C:HDL-C, apolipoprotein (apo) B, and apo B:apo A1 were increased in obese children. Thus they appeared to exhibit an atherogenic lipoprotein profile, with a relative decrease in cholesterol carried by HDL compared with the cholesterol in the other lipoprotein fractions. The mean fasting plasma insulin level was also increased. CETP activity was significantly higher in the obese children than in nonobese control children, and was correlated with LDL-C, TC:HDL-C, LDL-C:HDL-C, and apo B:apo A1. These results suggest that an increase in plasma CETP activity results in atherogenic change in lipoprotein metabolism in obese children. The increase in CETP may be due to the adiposity or insulin resistance. Alternatively, dyslipidemia per se, physical inactivity or excessive fat intake, that are commonly found in obese children, may contribute to the increase in CETP activity.

Plasma cholesteryl ester transfer activity is modulated by the phase transition of the lipoprotein core

Previous studies have shown that lipid transfer protein (LTP) activity is strongly temperature dependent, demonstrating a dramatic rise in activity near 37 degrees C. We have investigated the origin of this rapid rise in LTP activity. LTP-mediated transfers of radiolabeled cholesteryl ester (CE) from LDL to HDL, HDL to LDL, LDL to biotin-LDL, HDL to biotin-HDL, and between liposomes were determined as a function of assay temperature. Only assays containing LDL demonstrated this rapid rise in CE transfer activity. In contrast, TG transfer was almost linear with assay temperature. As human LDL CE undergoes a thermal phase transition near 37 degrees C, we investigated whether the rapid rise in CE transfer was dependent on this transition. Monkey LDL were isolated from animals consuming diets containing cholesterol and enriched in saturated, monounsaturated, or polyunsaturated fatty acids. With these LDL as substrate, the CE transfer between 21 degrees and 49 degrees C could be described by two straight lines, the intersection of which defined the inflection temperature. Among eight LDL samples, the inflection temperature was highly correlated with the CE phase transition determined by differential scanning calorimetry (r2 = 0.86). Both calorimetry and CE transfer activity inflection values were correlated with the saturated + monoene/polyene ratio of the LDL cholesteryl esters (r2 = 0.733 and 0.612, respectively). For LDL with inflection temperatures below 37 degrees C, CE transfer activity at 37 degrees C increased 10-14% for each 1 degree C decrease in the inflection temperature. We conclude that LTP activity is markedly affected by the physical state of the core CE. Diets rich in saturated fatty acids may result in LDL that are poor LTP substrates, which may hinder LTP's ability to promote normal lipoprotein remodeling.

Higher level of plasma cholesteryl ester transfer activity from high-density lipoprotein to apo B-containing lipoproteins in subjects with angiographically detectable coronary artery disease.

Plasma high-density lipoprotein cholesterol (HDL-C) levels correlate inversely with the incidence of coronary artery disease. In order to ascertain whether the transfer activity is related to coronary atherosclerosis, we studied plasma cholesteryl ester transfer activity (CETA) from HDL to apo B-containing lipoproteins in a consecutive series of 64 Japanese men aged < 60 years who had undergone diagnostic coronary angiography. The subjects were divided into two groups: those who had > or = 50% luminal stenosis in one or more coronary arteries (Group 1) and those who had < 50% stenosis (Group 2). CETA was 20.8 +/- 6.0%/2 h in 38 subjects in Group 1, significantly higher than 17.4 +/- 6.9%/2 h in 26 subjects in Group 2 (p < 0.05). Plasma HDL-C levels in Group 1 were significantly lower than those in Group 2 (p < 0.05). CETA correlated inversely with HDL-C levels (r = -0.46, p < 0.001). Plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and Lp(a) levels did not differ significantly between the two groups. There was no significant correlation between CETA and either LDL-C or TG levels. Results suggest that high CETA is related to low plasma HDL-C levels and may lead to the development of coronary atherosclerosis. Also, CETA was independent of plasma LDL-C or TG levels.

Reduced cholesteryl ester transfer in plasma of patients with lipoprotein lipase deficiency.

The net mass transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to the apolipoprotein (apo) B-containing lipoproteins, very low density lipoprotein (VLDL) and low density lipoprotein (LDL) in plasma (cholesteryl ester transfer (CET)) from three patients lacking lipoprotein lipase (LpL) activity was significantly lower (P < 0.001) than in plasma from fasting control subjects with comparable triglyceride levels. Chylomicrons isolated from LpL-deficient fasting plasma showed the same low level of CET activity as observed in the intact plasma when combined with HDL and cholesteryl ester transfer protein (CETP)-containing d 1.063 g/ml bottom fractions from control subjects. Preincubation of chylomicrons and large triglyceride-rich lipoproteins (Sf > 400) from LpL-deficient plasma with milk LpL, however, stimulated the capacity to engage in CET 4- to 5-fold to the same level as chylomicrons and VLDL from control subjects after a fat load. Consistent with these measurements of CET activity in plasma, chylomicrons obtained from the LpL-deficient subjects after a 14-h fast had higher TG/CE ratios than chylomicrons from controls 3 h after ingesting a fat load (LpL-deficient 26.3 +/- 9.0 vs. controls 6.9 +/- 2.1; mean +/- SD). The mass of CETP did not differ in LpL-deficient and control subjects (LpL-deficient 1.03 +/- 0.22 micrograms/ml vs. controls 1.58 +/- 0.58 micrograms/ml). These studies are consistent with earlier in vitro studies showing that the actions of lipoprotein lipase and its lipolytic products are essential, for maximal cholesteryl ester transfer protein activity.

Effect of treatment with a hydroxymethylglutaryl coenzyme A reductase inhibitor on fasting and postprandial plasma lipoproteins and cholesteryl ester transfer activity in patients with NIDDM

Effect of treatment with a hydroxymethylglutaryl coenzyme A reductase inhibitor on fasting and postprandial plasma lipoproteins and cholesteryl ester transfer activity in patients with NIDDM

Radiolabeled cholesteryl ethers trace LDL cholesteryl esters but not HDL cholesteryl esters in the rat

The intravascular metabolism of cholesteryl [1- 14C]oleoyl ester and [1,2- 3H(N)]cholesteryl palmityl ether was compared in the rat, an animal species without plasma cholesteryl ester transfer activity (CETA). The tracers had identical plasma disappearance rates when they were incorporated into human or rat low density lipoproteins (LDL). Fractional catabolic rates (FCR) were 0.081 ± 0.014 h −1 and 0.080 ± 0.013 h −1 for human LDL ester and ether and 0.098 ± 0.007 h −1 and 0.101 ± 0.007 h −1 for rat LDL ester and ether, respectively. In contrast, the ether had plasma disappearance rates that were 24%–25% lower than the ester when they were incorporated into human or rat high density lipoproteins (HDL). FCR were 0.230 ± 0.020 and 0.173 ± 0.030 h −1 for human HDL ester and ether and 0.131 ± 0.020 h −1 and 0.100 ± 0.017 h −1 for rat HDL ester and ether respectively. Biological screening of the rat HDL preparations did not affect these differences. The results of these studies indicate that in the absence of plasma CETA, cholesteryl ethers can be used to trace LDL cholesteryl esters but not to trace HDL cholesteryl esters.

Plasma cholesteryl ester transfer activity and lipoproteins in Japanese male patients with and without angiographically established coronary artery disease

Plasma cholesteryl ester transfer activity and lipoproteins in Japanese male patients with and without angiographically established coronary artery disease

Comparison of the metabolism of [1,2,6,7- 3H(N)]cholesteryl oleate, cholesteryl [9,10- 3H]oleate, and cholesteryl [1- 14C]oleate labeled lipoproteins in the rat

The intravascular metabolism of sterol labeled [1,2,6,7- 3H(N)]cholesteryl oleate and acyl labeled cholesteryl [9,10- 3H]oleate and cholesteryl [1- 14C]oleate was compared in the rat, an animal species without plasma cholesteryl ester transfer activity (CETA). In a first series of studies, the metabolism of sterol labeled [1,2,6,7- 3H(N)]cholesteryl oleate and acyl labeled cholesteryl [1- 14C]oleate was compared, and the two tracers had identical plasma clearance rates when incorporated into human low density lipoproteins (LDL). The 3H sterol labeled cholesteryl ester (CE), however, had a plasma clearance rate lower than the 14C acyl labeled CE when incorporated into rat a- and β-β-migrating LDL and human or rat high density lipoproteins (HDL). Unesterifed 3H cholesterol reappeared in the plasma whereas the 14C radioactivity in the plasma remained associated with the CE. In a second set of studies, LDL and HDL were radiolabeled with cholesteryl [9,10- 3H]oleate and cholesteryl [1- 14C]oleate Large amounts of 3H radioactivity that were dialyzable and not associated with the lipoprotein CE reappeared in the plasma during the kinetic studies. The two tracers had identical plasma disappearance rates when the plasma samples were dialyzed. The results of these studies indicate that the nature of the tracer used to trace lipoprotein CE can affect the estimated kinetic parameters of plasma CE.

Comparison of the intravascular metabolism of cholesteryl esters and apoproteins of plasma low- and high-density lipoproteins in the rat ( Rattus norvegicus), an animal species without plasma cholesteryl ester transfer activity

1. 1. The intravascular metabolism of the cholesteryl esters (CE) and apoproteins of low density lipoproteins (LDL) and high density lipoproteins (HDL) was compared in the rat, an animal species without plasma cholesteryl ester transfer activity (CETA). 2. 2. The apoproteins and the CE of LDL had identical catabolic rates, and there was no transfer of LDL CE to other lipoprotein classes. 3. 3. The CE of the HDL, however, had higher catabolic rates than the apoproteins, and there was transfer of HDL CE to LDL but not to very low density lipoproteins.

Unidirectional transfer in vivo of high-density lipoprotein cholesteryl esters to lower-density lipoproteins in the pig, an animal species without plasma cholesteryl ester transfer activity

The metabolism of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesteryl esters (CE) was studied in the pig, an animal species without plasma cholesteryl ester transfer activity (CETA). In the first series of experiments, LDL and HDL from normocholesterolemic pigs were radiolabeled with cholesteryl (1- 14C)oleate and intravenously administered to two groups of four normocholesterolemic pigs. Radioactive tracer in LDL remained associated with the LDL fraction, and there was no transfer of LDL-CE to HDL. The transport rate (which represents the production and disposal rate) of LDL-CE in normocholesterolemic pigs was 39 μmol CE/h/L. However, radiolabeled HDL-CE were transferred to LDL (25%), and 36% of the LDL-CE mass was derived from the HDL. The transport rate of HDL-CE was 54 μmol CE/h/L, and the flux of HDL-CE to LDL was 14 μmol CE/h/L. There was no accumulation of radiolabeled HDL-CE in very-low-density lipoprotein (VLDL), which suggests that there was no transfer to VLDL. However, this does not rule out the possibility that either the very low levels of VLDL-CE (<0.09 mmol/L) or the rapid turnover rate of the VLDL pool might have prevented the accumulation of substantial amounts of tracer in VLDL. Therefore, in a second set of experiments, the kinetics of HDL-CE were studied in high-fat- and high-cholesterol-fed pigs with elevated VLDL-CE concentrations (1.92 mmol/L). Hypercholesterolemia was associated with increased transport rates of LDL-CE (165 μmol/h/L) and HDL-CE (78 μmol/h/L) and with an increased flux of HDL-CE to LDL (78 μmol/h/L). Despite the increase of the VLDL-CE pool, there was still no accumulation of radiolabeled HDL-CE in VLDL, which suggests that there was indeed no transfer of HDL-CE to VLDL. The results of these kinetic studies indicate that in the pig unidirectional transfer of HDL-CE to LDL occurs despite the absence of CETA.

Elevated high density lipoprotein concentrations in heart transplant recipients are related to impaired plasma cholesteryl ester transfer and hepatic lipase activity

Accelerated atherosclerosis is a major complication of heart transplantation, and is frequently associated with a dyslipoproteinemia characterized by a paradoxical increase in HDL-cholesterol concentration. To define this abnormality, the lipoprotein profiles of 25 heart transplant recipients (HTR) were analyzed and compared with those of 26 control subjects. HDL, as separated on the basis of density in 3 subfractions, were increased in concentration: HDLz: +51%, HDL 3a: +29%, HDL 3b: +32%. HDL 2 and HDL 3a displayed an enrichment in surface components, phospholipids, unesterified cholesterol and apo E, leading to an increased size compared with subfractions of similar density in the controls. The major steps of plasma HDL metabolism were investigated: cholesterol esterification (LCAT activity), cholesteryl ester transfer to apo B-containing lipoproteins (CETP) and the hepatic hydrolysis of HDL components (HL activity). We demonstrated a partial deficiency in CETP (-28%) and hepatic lipase (-36%) activities with normal LCAT activity. Correlations in total study population (HTR plus controls) evidenced negative associations between CETP activity and HDL 3a concentrations and between HL activity and HDL 2-cholesterol as a percent of total HDL-cholesterol. Therapeutic agents used in post transplantation treatment such as glucocorticoids and/or cyclosporine may be speculated thus to affect both CETP and HL activities and, by arresting the HDL cycle in a CE-saturated state, to decrease the efficiency of reverse cholesterol extraction at the site of the graft.

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

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 subfractions 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 degrees 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 HDL3s 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 degrees C in the absence of LCAT activity, the relative mass of cholesteryl esters transferred from HDLs to apolipoprotein B-containing lipoproteins was greater in plasma with monodisperse LDL than in plasma with polydisperse LDL (0.23 +/- 0.06 versus 0.17 +/- 0.06, respectively; p < 0.02). These results indicated that in normolipidemic plasma, CETP could play an important role in determining the size distribution of LDL particles. The analysis of lipoprotein cholesterol distribution in the two groups of subjects sustained this hypothesis. Indeed, HDL cholesterol levels, the HDL:VLDL+LDL cholesterol ratio, and the esterified cholesterol:triglyceride ratio in HDL were significantly lower in plasma with the monodisperse LDL pattern than in plasma with the polydisperse LDL pattern (p < 0.01, p < 0.01, and p < 0.02, respectively). Plasma LCAT activity did not differ in the two groups. Plasma CETP activity correlated positively with the level of HDL3b (r = 0.542, p < 0.01) in the entire study population. Whereas plasma LCAT activity correlated negatively with the level of HDL2b (r = -0.455, p < 0.05) and positively with the levels of HDL2a (r = 0.475, p < 0.05) and HDL3a (r = 0.485, p < 0.05), no significant relation was observed with the level of HDL3b.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of probucol on plasma lipids, lipoproteins and parameters of high density lipoprotein metabolism.

Eight patients with primary hypercholesterolemia were treated with probucol for 17 weeks. Plasma total cholesterol, low density lipoprotein (LDL)-cholesterol, and high density lipoprotein (HDL)-cholesterol decreased by 16.6, 15.0 and 25.7%, respectively, in response to probucol treatment. Plasma levels of apolipoprotein B and apolipoprotein A-I also decreased, while apolipoprotein A-II concentrations were unchanged. The decrease in HDL-cholesterol levels was associated with a reduction in HDL particle size. No changes in the plasma lecithin:cholesterol acyltransferase activity or mass occurred in response to probucol treatment. In contrast, a significant 25% increase in plasma cholesteryl ester and triglyceride transfer activity occurred following probucol treatment. There was a positive correlation (R = 0.94) between cholesterol ester and triglyceride transfer. We propose that the increase in lipid transfer activity may in part explain the changes in HDL concentration and size, as well as the previously reported effect probucol has on reducing atherosclerosis in animal models.

Estimation of HDL cholesteryl ester kinetic parameters in the cebus monkey, an animal species with high plasma cholesteryl ester transfer activity

We studied the kinetic parameters of high density lipoprotein (HDL) cholesteryl esters in the cebus monkey, an animal species with high plasma cholesteryl ester transfer activity. HDL were radiolabeled with cholesteryl [1- 14C]oleate and intravenously administered to 4 cebus monkeys. The calculated fractional catabolic rate (FCR) of the HDL cholesteryl esters was 0.081 ± 0.002 (mean ± SD) h −1 and the calculated residence time was 12.3 ± 0.3 h. The production or disposal rate of plasma HDL cholesteryl esters was 34.3 ± 4.5 μmol/h. The radiolabeled cholesteryl esters were rapidly transferred from the HDL to the very low and low density lipoproteins (VLDL + LDL) and the amount of tracer in the VLDL + LDL had already reached a maximum at 3.5 ± 0.7 h after tracer administration. The estimated fraction of VLDL + LDL cholesteryl esters derived from the HDL was 0.77 ± 0.06. We also used radiolabeled [1,2- 3H(N))cholesteryl palmityl ether to trace HDL cholesteryl esters, but the ether tracer was more slowly cleared from the plasma and less readily transferred between plasma lipoproteins than the ester tracer.