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Biomedical subjects

P N Demacker

Publications and source records attributed to P N Demacker.

At least 109 records · Page 6Linked to original sources
PubMed1992

A study of the chylomicron metabolism in WHHL rabbits after fat loading. Discrepancy between results based on measurement of apoprotein B-48 or retinyl palmitate.

We studied the metabolism of chylomicrons in homozygous Watanabe heritable hyperlipidaemic (WHHL) rabbits and in cholesterol-fed or normally fed New Zealand White (NZW) rabbits by measuring the concentrations of apoprotein B-48 and of retinyl palmitate in their serum after feeding fat plus this vitamin according to two different protocols. Compared with NZW controls, retinyl palmitate accumulated in both hyperlipidaemic groups under study, not only in the d less than 1.019 fraction but also in the low-density lipoprotein (LDL) fraction. A strong correlation was found between the retinyl palmitate concentration in either the d less than 1.019 fraction or the LDL fraction of the WHHL rabbits and the concentrations of cholesterol and triacylglycerols in these fractions. This suggests that retinyl palmitate is exchanged rapidly between exogenous and endogenous lipoproteins. This is supported by the lack of a correlation between the retinyl palmitate concentrations and the intensity of the apoprotein B-48 band in the respective d less than 1.019 fractions or LDL fractions; in most fractions, in which large amounts of retinyl palmitate were present, the intensity of the apoprotein B-48 band was not increased compared with the fasting concentrations. Assuming that retinyl palmitate is a marker for the transfer of exogenous lipids, the results of our experiments indicate that the removal of exogenous lipids is delayed by complexing to endogenously synthesized lipoproteins. However, the clearance of apoprotein B-48 is normal and thus independent of the LDL-receptor activity.

Animals↗
PubMed1992

Failure of N-acetylcysteine to reduce low-density lipoprotein oxidizability in healthy subjects.

We have studied the effects of N-acetylcysteine, which is thought to have antioxidant properties, on the susceptibility of low-density lipoprotein to oxidation and on whole-blood glutathione concentrations in six healthy volunteers. N-acetylcysteine was given orally in a dosage of at 1.2 g per day for 4 weeks, followed by 2.4 g per day for a further two weeks. The susceptibility of low-density lipoprotein to in vitro Cu(2+)-oxidation was determined by continuously measuring the formation of conjugated dienes. Whole-blood concentrations of reduced and oxidized glutathione were also determined. N-acetylcysteine had no effect on the susceptibility of LDL to oxidation. Concentrations of vitamin E in the serum and in low-density lipoprotein were not changed. Compared with controls the concentration of glutathione in N-acetylcysteine treated subjects was reduced (-48%) and the concentration of oxidized glutathione was higher (+80%). The GSH/GSSG-ratio, a marker of oxidative stress was 83% lower. The results do not support the supposed antioxidative action of N-acetylcysteine. It seems more likely that N-acetylcysteine acts as a pro-oxidant in the dosage used.

Acetylcysteine↗
PubMed1992

Low-density lipoprotein turnover in inbred strains of rabbits hypo- or hyperresponsive to dietary cholesterol.

In two inbred strains of rabbit with high or low response of plasma cholesterol to dietary cholesterol, low density lipoprotein (LDL) apolipoprotein (apoLDL) kinetics were determined with the use of a heterologous tracer isolated from a Watanabe heritable hyperlipidemic (WHHL) rabbit. On a diet without added cholesterol, the total clearance of apoLDL (which equals apoLDL production) did not differ significantly between rabbits of both strains. After the feeding of a diet containing 0.1% cholesterol for six weeks, plasma LDL cholesterol, plasma apoLDL and liver cholesterol concentrations rose significantly in the hyperresponsive but not in the hyporesponsive rabbits. Cholesterol feeding depressed the total fractional catabolic rate (FCR) of apoLDL in the hyper- but not in the hyporesponsive rabbits; this was attributed to a decrease of receptor-dependent FCR while receptor-independent FCR was similar in the two strains. On the diet containing cholesterol, the receptor-mediated absolute catabolic rate (ACR) of apoLDL did not differ between hyper- and hyporesponsive rabbits but receptor-independent ACR of apoLDL was higher in hyperresponders. It is concluded that the higher plasma apoLDL levels in hyperresponsive rabbits fed the 0.1% cholesterol diet are caused by a higher production of apoLDL and not by a lower flux of apoLDL through the receptor-mediated pathway.

Animals↗
PubMed1992

Chronic intraperitoneal infusion of low doses of tumor necrosis factor alpha in rats induces a reduction in plasma triglyceride levels.

Single and repeated bolus injections of tumor necrosis factor alpha (TNF) in laboratory animals have been reported to result in hypertriglyceridaemia, suggesting that TNF is a mediator of hypertriglyceridaemia occurring during infection. However, as during infection production of TNF is probably chronically elevated, we determined the effects of continuous infusion of low doses of TNF on plasma levels of triglycerides and cholesterol. Male rats, bearing a venous catheter to allow repeated blood sampling, were intraperitoneally equipped with osmotic minipumps which continuously delivered TNF or saline for 7 days. Infusion of rats with doses of TNF as low as 4.0 and 8.0 micrograms/24 h resulted in significant decreases in plasma levels of triglycerides as compared with those after saline infusion. Although plasma triglyceride concentrations were persistently lower in TNF than in saline animals throughout the study period, the differences were most prominent during the first days and reached statistical significance at day 1, 3, 4 and 5 and of the 4.0 micrograms experiment and on day 1, 2 and 3 of the 8.0 micrograms experiment. This suppression of plasma triglyceride concentrations was not accompanied by changes in plasma cholesterol levels. No effects of chronic TNF treatment on food intake, body weight change and rectal temperature of the animals were observed. These findings indicate that chronic infusion of low doses of TNF induces hypotriglyceridaemia in rats. The role of TNF as a factor in mediating hypertriglyceridaemia during infectious diseases needs to be reconsidered.

Animals↗
PubMed1992

Continuous infusion of interleukin-1 beta in rats induces a profound fall in plasma levels of cholesterol and triglycerides.

During infectious diseases, striking alterations in plasma concentrations of cholesterol (hypocholesterolemia) and triglycerides (hypertriglyceridemia) may occur. It has been suggested that interleukin-1 is a mediator of these alterations. We studied the effects of continuous administration of recombinant human interleukin-1 beta (rhIL-1 beta) on plasma levels of cholesterol and triglycerides. A total of 42 rats were equipped with minipumps loaded with either rhIL-1 beta (delivery rate of 0.5, 2.0, or 4.0 micrograms/day i.p. for 1 week) or saline. After 1 day of treatment with rhIL-1 beta, plasma cholesterol levels had not changed. On day 2 a remarkable decrease of plasma cholesterol levels was observed in rats treated with 2.0 micrograms rhIL-1 beta/day (1.49 +/- 0.13 versus 2.23 +/- 0.08 mmol/l, p less than 0.005; rhIL-1 beta versus saline) or 4.0 micrograms rhIL-1 beta/day (1.46 +/- 0.04 versus 2.18 +/- 0.04 mmol/l,p less than 0.0005). This decrease persisted until the end of the experiment and occurred in all major lipoprotein fractions. Triglycerides in plasma (and in very low density lipoprotein) decreased almost concomitantly with plasma cholesterol, although to a lesser degree. Infusion of 2.0 micrograms rhIL-1 beta/day did not affect either cholesterol esterification or total postheparin lipolytic activity in plasma. Long-term infusion with 4.0 micrograms rhIL-1 beta/day induced prolonged fever, whereas at the lower doses temperatures were elevated only the first 2 days. rhIL-1 beta at a dose of 2.0 and 4.0 micrograms/day induced a transient decrease of food intake and a suppression of body weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Improved measurement of low-density-lipoprotein susceptibility to copper-induced oxidation: application of a short procedure for isolating low-density lipoprotein.

Low-density-lipoprotein (LDL) oxidation may provide the crucial link between plasma LDL and atherosclerotic-lesion formation. Oxidation can be induced in vitro by incubating LDL with cells or metal ions and can be measured by continuously monitoring conjugated-diene absorbance at 234 nm. Measurement of LDL oxidizability was improved by performing the assay with 0.05 g of LDL-protein per liter of phosphate buffer containing 1 mumol of EDTA, by initiating oxidation by adding CuCl2 (5 mumol/L) at 30 degrees C, and by using a short-run ultracentrifugation method for isolating LDL, which reduced the time needed for obtaining purified LDL and thus reduced in vitro oxidation. LDL apolipoprotein analysis and oxidizability determination showed that this method is better than the longer sequential-isolation procedure. Adding butylated hydroxytoluene (BHT) to plasma as an antioxidant unpredictably increased the LDL oxidation lag time, making BHT unsuitable as an antioxidant. Adding EDTA appeared to be sufficient to prevent in vitro oxidation. Additionally, the diene production correlated highly with the concentration of thiobarbituric acid-reactive substances (r = 0.97). No relation between the vitamin E content of LDL and the oxidation lag time was found.

Antioxidants↗
PubMed1992

Both inherited susceptibility and environmental exposure determine the low-density lipoprotein-subfraction pattern distribution in healthy Dutch families.

A lipoprotein profile characterized by a predominance of small, dense, low-density lipoprotein (LDL) particles has been associated with an increased risk of atherosclerosis. To investigate whether genetic factors are involved in determining this heavy LDL subfraction pattern, this study was undertaken with the aim of resolving the effects that major genes, multifactorial heritability, and environmental exposures have on the LDL subfraction pattern. In a random sample of 19 healthy Dutch families including 162 individuals, the distribution of the LDL subfraction pattern was determined by density gradient ultracentrifugation. For each subject a specific LDL subfraction profile was observed, characterized by the relative contribution of the three major LDL subfractions--LDL1 (d = 1.030-1.033 g/ml), LDL2 (d = 1.033-1.040 g/ml), and LDL3 (d = 1.040-1.045 g/ml)--to total LDL. A continuous variable, parameter K, was defined to characterize each individual LDL subfraction pattern. Complex segregation analysis of this quantitative trait, under a model which includes a major locus, polygenes, and both common and random environment, was applied to analyze the distribution of the LDL subfraction pattern in these families. The results indicate that the LDL subfraction pattern, described by parameter K, is controlled by a major autosomal, highly penetrant, recessive allele with a population frequency of .19 and an additional multifactorial inheritance component. The penetrance of the more dense LDL subfraction patterns, characterized by values of K < 0, was dependent on age, gender, and, in women, on oral contraceptive use and postmenopausal status. Furthermore, multiple regression analysis revealed that approximately 60% of the variation in the LDL subfraction pattern could be accounted for by alterations in age, gender, relative body weight, smoking habits, hormonal status in women, and lipid and lipoprotein levels. In conclusion, our results indicate that genetic influences as well as environmental exposure, sex, age and hormonal status in women are important in determining the distribution of the LDL subfraction patterns in this population and that these influences may contribute to the explanation of familial clustering of coronary heart disease.

Adult↗
PubMed1992

Removal of interleukin-1 beta and tumor necrosis factor from human plasma by in vitro dialysis with polyacrylonitrile membranes.

We studied the suitability of in vitro dialysis with polyacrylonitrile (PAN) membranes to remove small amounts of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) from plasma to be used as diluent for the standards in radioimmunoassays (RIA). Incubation of PAN membrane fragments with radiolabeled IL-1 beta or TNF yielded a significant binding of both cytokines to the membrane (percentage of membrane-bound cytokine after incubation in saline or plasma was 14-17% and 23-46%, respectively). Dialysis of plasma (containing radiolabeled cytokine) against plasma (initially devoid of cytokine) resulted in a binding percentage of IL-1 beta and TNF to the PAN membranes of 44 and 28%, respectively. When plasma was dialyzed against saline the percentage of membrane-bound IL-1 beta and TNF was 63 and 37%, respectively. After dialysis of plasma against either plasma or saline the percentage IL-1 beta recovered from the dialysate was approximately 16% in contrast with 1-2% TNF. The results confirm the capacity of in vitro dialysis with PAN membranes to remove IL-1 beta and to a lesser extent TNF from plasma. Removal is most marked in the first minutes of dialysis (suggesting saturation of the membrane) and less effective for TNF due to its low diffusion across the membrane.

Acrylic Resins↗
PubMed1991

Alterations in the metabolism of very-low- and low-density lipoproteins after partial ileal-bypass surgery in the Watanabe heritable hyperlipidaemic rabbit.

The influence of interruption of bile-acid enterohepatic circulation by partial ileal bypass (PIB) surgery on serum lipids, lipoproteins and the turnover of very-low- (VLDL) and low-density (LDL) lipoproteins was investigated in Watanabe heritable hyperlipidaemic (WHHL) rabbits. Compared with controls, total serum cholesterol was 48% lower after PIB (16.88 +/- 1.57 versus 8.79 +/- 1.66 mmol/l; P less than 0.01), owing to lower levels of cholesterol in VLDL (-23%), intermediate-density lipoprotein (IDL; -39%) and LDL (-72%); serum triacylglycerols were 32% higher (3.86 +/- 1.35 versus 5.11 +/- 0.82 mmol/l). The ratio of the percentages of mass of cholesteryl esters to triacylglycerols was 71% lower in VLDL and LDL and 67% lower in IDL (P less than 0.01). Compared with controls, the secretion rate of LDL was 33% lower (31.1 +/- 7.2 versus 20.7 +/- 6.9 mg/day per kg; P less than 0.05) and the fractional catabolic rate (FCR) of LDL was 33% higher (0.46 +/- 0.06 versus 0.61 +/- 0.12 pool/day; P less than 0.02). The VLDL turnover showed that after PIB there was a higher secretion rate of VLDL apolipoprotein B (63.9 versus 167.4 mg/day per kg), a higher FCR (3.84 versus 8.61 pools/day), a higher direct uptake (38.8 versus 146.4 mg/day per kg) and a higher conversion of VLDL into LDL (4.8 versus 9.0 mg/day per kg). Some 82% of LDL originated from direct synthesis in controls, and after PIB this was 59%. In both controls and treated rabbits there was a direct LDL synthesis, which was 52% lower after PIB (26.3 versus 12.6 mg/day per kg). It is concluded that LDL-cholesterol lowering by PIB is due to an increased uptake of LDL, a decreased synthesis of LDL, and cholesterol depletion of the LDL particles; the decreased LDL synthesis is due to a decreased direct production of LDL, which exceeds the increased conversion of VLDL into LDL.

Animals↗
PubMed1991

Increased removal of remnants of triglyceride-rich lipoproteins on a diet rich in polyunsaturated fatty acids.

We studied the effect of two diets, one rich in polyunsaturated and the other in saturated fatty acids, on the postprandial processing of exogenous and endogenous triglyceride-rich lipoproteins (chylomicrons, very-low-density lipoproteins, and their remnants). For this purpose, 12 normolipidaemic young volunteers were fed, in a cross-over design of 9 days on each diet, either a diet rich in saturated fat (21% of their daily energy intake from saturated fat, 12% from monounsaturated fat, and 3% from polyunsaturated fat) or a diet rich in polyunsaturated fat (10% saturated fat, 9% monounsaturated fat, and 18% polyunsaturated fat) (P/S ratios 0.14 and 1.8, respectively). On the last day of each dietary period blood samples were drawn six times over a 24-h period for determination, by densitometric scanning of SDS gels, of the diurnal pattern of apoprotein B-48 and B-100 in the d less than 1.019 g ml-1 fractions, as estimates for the processing of chylomicrons and very-low-density lipoproteins. In addition to the usual decrease in the fasting and diurnal concentrations of total serum cholesterol and of cholesterol in the low-density lipoprotein fractions (between 15 and 21%), the diet rich in polyunsaturated fat resulted in 43% lower daily concentrations of chylomicrons and their remnants. This was due to differences in the clearance rate of chylomicrons and their remnants, rather than to differences in the absorption rate of exogenous fat. In addition, the concentrations of very low density lipoproteins and their remnants during the day were 20% lower on the diet rich in polyunsaturated fat.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

N-acetylcysteine and serum concentrations of lipoprotein(a).

A high plasma concentration of lipoprotein(a) [Lp(a)], a complex of low-density lipoprotein linked by disulphide bridges to apoprotein(a), is correlated with premature atherosclerosis. We determined whether the serum Lp(a) concentration could be decreased in vitro and in vivo by the reducing agent N-acetylcysteine (NAC), a drug used as a mucolytic agent, which acts by cleaving disulphide bonds. High concentrations of NAC (greater than or equal to 8 mg ml-1) resulted in dissociation of the Lp(a) antigen in vitro. However, the plasma level of Lp(a) was not changed by administration of NAC 1.2 g d-1 for 4 weeks in 7 subjects with a median Lp(a) concentration of 14.3 mg dl-1 (range 2.1-21.0 mg dl-1) or by doubling the dose to 2.4 g d-1 for a further 2 weeks. In 12 subjects with a high plasma level of Lp(a), median 87.0 mg dl-1 (range 42.0-201.6 mg dl-1), a small but significant decrease in Lp(a) concentration of 7% (P = 0.02) was observed after administration of NAC in a dose of 1.2 g d-1 for 6 weeks. These results indicate that NAC has only a limited capacity to reduce the concentration of Lp(a), which is not clinically significant.

Acetylcysteine↗
PubMed1991

Familial dysbetalipoproteinemia associated with apolipoprotein E3-Leiden in an extended multigeneration pedigree.

By the careful screening of familial dysbetalipoproteinemic (FD) patients, five probands showing heterozygosity for the APOE*3-Leiden allele were found. Genealogical studies revealed that these probands share common ancestry in the 17th century. In a group of 128 family members, spanning three generations, 37 additional heterozygous APOE*3-Leiden gene carriers were detected. Although with a variable degree of severity, all carriers exhibited characteristics of FD such as (a) elevated levels of cholesterol in the very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) fractions, (b) elevated ratios of cholesterol levels in these density fractions over total plasma levels of triglycerides, and (c) strongly increased plasma levels of apolipoprotein E (apoE). Multiple linear regression analysis revealed that most of the variability in expression of FD in APOE*3-Leiden allele carriers can be explained by age. Body mass index showed a less significant influence on the expression of FD. Gender had no effect on the expression in E*3-Leiden allele carriers, nor did it influence the age of onset of FD. In the group of APOE*3-Leiden allele carriers, we found that the E*2 allele enhances the expression of FD, whereas the E*4 allele had the opposite effect. Isoelectric focusing of plasma and of isolated VLDL, IDL, and high density lipoprotein density fractions showed that in E*3-Leiden allele carriers the apoE3-Leiden variant largely predominates over its normal apoE counterpart, especially in the VLDL and IDL density fractions. We conclude that in APOE*3-Leiden allele carriers FD is dominantly inherited with a high rate of penetrance, i.e., the presence of normally functioning apoE molecules in the plasma does not prevent the age-related expression of this disease.

Adolescent↗
PubMed1991

Apolipoprotein E phenotypes, serum lipoproteins and apolipoproteins in angiographically assessed coronary heart disease.

To determine the influence of the apolipoprotein E polymorphism on the occurrence of coronary artery disease (CAD) and on serum lipids, lipoproteins and apolipoproteins we studied 145 patients with angiographically defined CAD and compared them with 153 control subjects without history or complaints of vascular disease and with 35 subjects without significant stenosis on coronary arteriography. Subjects with hypertension, diabetes mellitus and endocrine or metabolic disorders were excluded. Covariance analysis and logistic regression analysis were performed with adjustment for age, sex, smoking habits and relative body weight. There were no significant differences for the apoE phenotypes on risk of cardiovascular disease. The CAD group had significantly higher mean values of serum cholesterol and triglycerides, very-low-density lipoprotein (VLDL)-cholesterol and VLDL-triglycerides, low-density lipoprotein (LDL)-cholesterol and apoprotein B; they had lower high-density lipoprotein (HDL)-cholesterol and apo A-I. The combination of LDL-cholesterol, apoA-I and VLDL-cholesterol was the best model in predicting cardiovascular disease. ApoE phenotype group E3/E2 had significantly lower values for serum cholesterol, LDL-cholesterol, and apoB and higher levels of apoE in comparison with the phenotype groups E3/E3 and E4/E3. The combination of LDL-cholesterol, cholesterol, apoE and VLDL-triglycerides was the best model in predicting the apoE phenotype. Thus, taking other risk factors into account, the apoE phenotype is not an independent risk factor for CAD; the apoE polymorphism influences lipoprotein levels and possibly, in that way, indirectly also the risk for CAD.

Aged↗
PubMed1991

Single-spin density-gradient ultracentrifugation vs gradient gel electrophoresis: two methods for detecting low-density-lipoprotein heterogeneity compared.

Single-spin density-gradient ultracentrifugation (DUC) has proven to be a reproducible method for detection of low-density-lipoprotein (LDL) heterogeneity. Recently another method has been described for this: gradient gel electrophoresis (GGE) of serum, a method that might be more suitable for screening. To gain insight into the relationship of GGE to DUC and into their reproducibility, we determined LDL heterogeneity by DUC and GGE in 41 healthy individuals. In 90.2% (n = 37) of the subjects, the number of LDL subfractions found by both methods agreed. In addition, the density and the relative migration distance of the predominant LDL subfraction observed with the respective methods showed a strong correlation (Pearson correlation, r = 0.85, P less than 0.0001). Although it was not possible to compare for all aspects of LDL heterogeneity, these data suggest that GGE is a valid method of analysis for LDL heterogeneity. In screening programs, it may be necessary to store samples. Therefore, we studied in 24 sera the influence of storage at -80 degrees C for one, four, and 12 weeks on the LDL subfraction distribution detected by each method. LDL heterogeneity was maintained during storage under these conditions.

Adult↗
PubMed1990

Increased hepatic lipase activity and increased direct removal of very-low-density lipoprotein remnants in Watanabe heritable hyperlipidaemic (WHHL) rabbits treated with ethinyl oestradiol.

We studied the effects of ethinyl oestradiol on the serum concentrations and metabolism of very-low- and low-density lipoproteins (VLDL and LDL) in Watanabe heritable hyperlipidaemic (WHHL) homozygous rabbits, an animal model for familial hypercholesterolaemia. The results were compared with those in untreated homozygotes as well as in heterozygotes treated or not with ethinyl oestradiol. The gain in body weight was similar in all groups. Treatment with ethinyl oestradiol resulted in the homozygotes in an approx. 80% decrease in the concentrations of lipids and apoprotein B in the d less than 1.019 lipoprotein fraction; those in the LDL fraction did not change. In the heterozygotes, basal serum lipids and apoprotein B levels in the d less than 1.019 fraction were low; ethinyl oestradiol treatment especially affected the LDL fraction (cholesterol -84%, apoprotein B -64%). Turnover experiments with 125I-labelled VLDL revealed that, on treatment with ethinyl oestradiol, the fractional catabolic rate in homozygous rabbits increased 2-fold. The secretion rates of lipids and protein in the d less than 1.019 fraction as estimated after injection of Triton WR-1339 was not decreased. In homozygotes and heterozygotes increases in post-heparin hepatic lipase activity of 62 and 80% respectively were observed, with no changes in lipoprotein lipase activity. We conclude that ethinyl oestradiol induces in homozygous WHHL rabbits a direct removal of VLDL and VLDL remnants from the plasma, apparently due to an increase in hepatic lipase activity.

Animals↗
PubMed1990

Differences in metabolism of three low density lipoprotein subfractions in Hep G2 cells.

The metabolism of low density lipoprotein (LDL) subfractions was investigated in the human hepatoma cell line Hep G2. By means of a density gradient ultracentrifugation method three LDL subfractions were isolated from pooled serum of normolipidemic subjects: very light LDL-1A, light LDL-1B and heavy LDL-2, differing in size, relative lipid and protein content. Cell specific association, stimulation of cholesterol esterification and inhibition of sterol synthesis were determined in parallel after incubation of Hep G2 cells with increasing amounts of LDL-protein of the three LDL subfractions. These parallel experiments were repeated four times with freshly prepared LDL subfractions. Response curves were parametrized with the function y = a square root of x, depicting the relation between the cellular metabolic event (y) and the LDL-protein (x) or LDL-cholesterol (x) levels. An analysis of covariance model was used to test differences between parameters of the three LDL subfractions. When the results of all four experiments were taken into account, the cell specific association increased more with increasing LDL-protein concentration for LDL-1A than for LDL-2 (P less than 0.05). At the LDL-protein level of 80 micrograms/ml the cell specific association for LDL-2 amounted to 85.5% of that for LDL-1A. Results for LDL-1B were intermediate between those for LDL-1A and LDL-2. The corresponding cholesteryl ester formation increased more with increasing LDL-protein concentration for LDL-1A than for LDL-1B (P less than 0.001), and for LDL-1B more than for LDL-2 (P less than 0.001). At the LDL-protein level of 70 micrograms/ml the cholesterol ester accumulation for LDL-2 and LDL-1B was 48.4% and 70.3%, respectively, of that for LDL-1A. These differences between LDL subfractions in cholesteryl esterification were independent of the cholesterol content of the subfractions. Consistent with these findings, the [14C]acetate incorporation to sterols decreased more with increasing LDL-protein concentration for LDL-1A and LDL-1B than for LDL-2 (P less than 0.05). At the LDL-protein concentration of 70 micrograms/ml the decrease in sterol synthesis after incubation with LDL-2 and LDL-1B was 79.2% and 98.0%, respectively, relative to that for LDL-1A. When adjusted for differences in cholesterol content of the LDL subfractions these differences with regard to the 14C-acetate incorporation were not significant. The metabolic differences between LDL subfractions in vitro may have implications for the metabolism and atherogenic potential of the distinct LDL subfractions in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetates↗