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PubMed2005

Maintenance of the LDL cholesterol:HDL cholesterol ratio in an elderly population given a dietary cholesterol challenge.

We previously evaluated the responses to dietary cholesterol in children and young adults. In this study, the effects of dietary cholesterol on plasma lipids and LDL atherogenicity were evaluated in 42 elderly subjects (29 postmenopausal women and 13 men > 60 y old). Our exclusion criteria were diabetes, heart disease, and the use of reductase inhibitors. The study followed a randomized crossover design in which subjects were assigned to consume the equivalent of 3 large eggs (EGG) daily or the same amount of a cholesterol-free, fat-free egg substitute (SUB) for a 1-mo period. After a 3-wk washout period, subjects were assigned to the alternate treatment. The concentration of plasma cholesterol after the EGG period varied among subjects. When all subjects were evaluated, there were significant increases in LDL cholesterol (LDL-C) (P < 0.05) and HDL-C (P < 0.001) for both men and women during the EGG period, resulting in no alterations in the LDL-C:HDL-C or the total cholesterol:HDL-C ratios. In addition, the LDL peak diameter was increased during the EGG period for all subjects. In contrast, the measured parameters of LDL oxidation, conjugated diene formation, and LDL lag time did not differ between the EGG and the SUB periods. We conclude from this study that dietary cholesterol provided by eggs does not increase the risk for heart disease in a healthy elderly population.

Aged↗
PubMedDate not supplied

[Activity of cholesterol acyltransferase and cholesterol esterase in liver subcellular fractions of rabbits fed a cholesterol supplemented ration].

The paper deals with the content of free and esterified cholesterol and also with the activity of cholesterol acetyltransferase and cholesterol esterase in the fraction of plasma membranes and liver subcellular fractions of rabbits fed a ration supplemented with cholesterol and sunflower oil. Under these conditions the content of cholesterol esters in the animals increases sharply in nuclei and cytosol and to a less extent--in microsomes and mitochondria. The activity of cholesterol acetyltransferase rises in the fractions of microsomes, nuclei and mitochondria being unchanged in the fractions of the plasma membranes. The activity of cholesterol esterase remains unchanged in all the fractions, being the highest in the fraction of the plasma membranes.

Acyltransferases↗
PubMed1993

Plasma lecithin cholesterol acyl transferase activity, high density lipoprotein cholesterol and cholesterol ester in cholestasis.

Lecithin cholesterol acyl transferase activity, cholesterol ester and high density lipoprotein cholesterol concentrations were determined in Nigerian subjects suffering from cholestatic jaundice. Plasma lecithin cholesterol acyl transferase activities in all the study groups were similar. High density lipoprotein cholesterol and cholesterol ester were significantly increased in extrahepatic cholestasis while reduced levels were found in intrahepatic cholestasis. Enhanced cholesterol esterification may occur in extrahepatic cholestasis.

Adolescent↗
PubMed1982

The Muscatine Cholesterol Family Study: distribution of cholesterol levels within families of probands with high, low and middle cholesterol levels.

The Muscatine Cholesterol Family Study includes the relatives of three groups of schoolchildren: those with cholesterol levels above the 95th percentiles in two consecutive school screens, those with cholesterol levels below the 5th percentile twice, and random sample of those with cholesterol levels between the 5th and 95th percentiles twice. This paper examines the cholesterol distribution within and among these families for evidence of major gene effects. Three screening techniques are used: admixture analysis using maximum likelihood, comparison of within-sibship variances among groups, and regression of within-sibships variance on within-sibship mean. The results of the three techniques are consistent and indicate the existence of a major gene in a subset of the families with a proband above the the 95th percentile, but not in the other two groups of families. We estimate that 15% of schoolchildren with a cholesterol level above the 95th percentile twice, or 3 per thousand in the general population, have a dominant gene as a cause of the cholesterol elevation.

Adolescent↗
PubMed1997

Percentile reference values of lipid risk factors of ischaemic heart disease: cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides in individuals aged 20 to 60 years in Plovdiv region.

1408 men and 1069 women aged 20 to 60 years selected at random from the Plovdiv region were studied during an epidemiological screening. Statistical analysis of the data was carried out using a SPSS/PC+ program. The percentiles (reference values and intervals) of the lipid risk factors were determined. The reference intervals and values at the 75th and 90th percentile for both sexes showed a prevalence of cholesterol, HDL-cholesterol and LDL-cholesterol for women, and of HDL-cholesterol at the 90th percentile for men below the age of 45 years. The derived percentile reference values for cholesterol, LDL-cholesterol and triglycerides are higher than the respective values for some European and American populations. A moderate and high lipid risk was identified for women over the age of 40-45 and in men in the age range 20-60 from all age groups. The established reference values for individuals of both sexes aged 20 to 60 years make it possible to diagnose and monitor dyslipidemias. They can be used for the purposes of the educational lipid program of the Plovdiv region population.

Adult↗
PubMed1992

The influence of dietary olive oil and margarine on aortic cholesterol accumulation in cholesterol-fed rabbits maintained at similar plasma cholesterol level.

The present study compares the atherogenicity of a standard diet and diets with 10% olive oil or 10% margarine added, in rabbits maintained at a mean plasma cholesterol level of about 20 mM for 13 weeks. Each group consisted of 15 animals. The distribution of cholesterol in plasma between VLDL, IDL, LDL and HDL was similar in the 3 groups. The thoracic aortic cholesterol accumulation was 16.6 +/- 1.6, 11.4 +/- 1.0 (P < 0.05) and 12.6 +/- 1.7 (P > 0.05) nmol/mg wet weight for the group receiving standard diet, diet with 10% olive oil added and diet with 10% margarine added, respectively. There was no significant difference between groups in the occurrence of the atherosclerotic changes in the proximal and distal parts of coronary arteries, abdominal aorta and renal arteries. The occurrence of atherosclerotic changes in the pulmonary arteries was equal in the groups receiving standard diet and diet with 10% margarine added while it was significantly lower (P < 0.05) in the group receiving diet with 10% olive oil added. The atherosclerotic changes at the aortic orifice of coronary arteries were quanticated morphometrically and were most severe in the group on the standard diet. The results indicate a comparable atherogenic effect of 10% olive oil or margarine addition to standard diet on development of atherosclerosis in rabbits maintained at a similar plasma cholesterol level. The study also suggests that supplementation of olive oil or margarine to standard rabbit diet leads to lower cholesterol accumulation in the thoracic aorta compared with standard diet, an effect not modulated by changes in plasma cholesterol concentrations.

Animals↗
PubMed2005

LDL-cholesterol lowering or HDL-cholesterol raising for cardiovascular prevention. A lesson from cholesterol turnover studies and others.

A number of reports have indicated that both lowering low density lipoprotein (LDL)-cholesterol and raising high density lipoprotein (HDL)-cholesterol can result in significant cardiovascular benefit, both in terms of reduction of events and also, to a variable extent, of atheromatous lesions. LDL and HDL have opposite roles in body cholesterol regulation and, in theory, both reduced deposition (LDL reduction) and increased removal (raised HDL) can improve vascular disease. A number of reports over the last 30 years have attempted to quantitate with cholesterol balance/turnover studies, the correlations between LDL and HDL levels and body cholesterol pool sizes. More recently, these studies have evaluated the effects of LDL or HDL changes on cholesterol elimination. Data have, at times, been fully consistent with theoretical expectations, whereas at others they have not. Evaluation of these, at times, historical data provides, however, an important clue to the understanding of current results with different medications for the management of lipoprotein disorders.

Anticholesteremic Agents↗
PubMed2002

Interaction of the Vibrio cholerae cytolysin (VCC) with cholesterol, some cholesterol esters, and cholesterol derivatives: a TEM study.

The Vibrio cholerae cytolysin (VCC) 63-kDa monomer has been shown to interact in aqueous suspension with cholesterol microcystals to produce a ring/pore-like heptameric oligomer approximately 8 nm in outer diameter. Transmission electron microscopy data were produced from cholesterol samples adsorbed to carbon support films, spread across the holes of holey carbon films, and negatively stained with ammonium molybdate. The VCC oligomers initially attach to the edge of the stacked cholesterol bilayers and with increasing time cover the two planar surfaces. VCC oligomers are also released into solution, with some tendency to cluster, possibly via the hydrophobic membrane-spanning domain. At the air/water interface, the VCC oligomers are likely to be selectively oriented with the hydrophobic domain facing the air. Despite some molecular disorder/plasticity within the oligomers, multivariate statistical analysis and rotational self-correlation using IMAGIC-5 strongly suggest the presence of sevenfold rotational symmetry. To correlate the electron microscopy data with on-going biochemical and permeability studies using liposomes of varying lipid composition, the direct interaction of VCC with several cholesterol derivatives and other steroids has been examined. 19-Hydroxycholesterol and 7 beta-hydroxycholesterol both induce VCC oligomerization. beta-Estradiol, which does not possess an aliphatic side chain, also efficiently induces VCC oligomer formation, as does cholesteryl acetate. Cholesteryl stearate and oleate and the C22 (2-trifluoroacetyl)naphthyloxy analogue of cholesterol fail to induce VCC oligomerization, but binding of the monomer to the surface of these steroids does occur. Stigmasterol has little tendency to induce oligomer formation, and oligomers are largely confined to the edge of the bilayers; ergosterol has even less oligomerization ability. Attempts to solubilize and stabilize the VCC oligomers from cholesterol suspensions have been pursued using the neutral surfactant octylglucoside. Although individual solubilized oligomers have been defined which exhibit a characteristic cytolysin channel conformation in the side-on orientation, a tendency remains for the oligomers to cluster via their hydrophobic domains.

Cholesterol↗
PubMed1995

[Levels of cholesterol, HDL-cholesterol, LDL cholesterol and triglycerides in blood serum of children from Silesia].

In order to estimate the mean and borderline total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride levels, a group of 1151 children aged 7 to 15 years was examined. They were randomly chosen from elementary schools in Katowice, the capital city of Silesia. Significantly lower total cholesterol levels were found in 14-15 year old boys and girls than in children from the younger age groups. The highest borderline total cholesterol level was found in children aged 10 years. Older children had the lowest borderline HDL-cholesterol values. As the prevention of coronary disease should already start in childhood, it is necessary to assess the mean and borderline lipoprotein levels in school children. The present work, together with the previously published papers from different parts of Poland, may contribute to establishing normal values for our country.

Adolescent↗
PubMed1992

Differential effect of subspecies of lipoprotein containing apolipoprotein A-I on cholesterol efflux from cholesterol-loaded macrophages: functional correlation with lecithin: cholesterol acyltransferase.

Two species of lipoprotein containing apoA-I, one containing only apoA-I (LpA-I), and the other containing apoA-I and apoA-II (LpA-I/A-II), were tested for their effects on macrophage foam cells. Rat macrophages were converted to foam cells by incubation with radiolabeled acetylated LDL. Incubation with LpA-I or LpA-I/A-II decreased the cellular cholesteryl esters (CE) mass. However, the free cholesterol (FC) mass was only reduced by LpA-I. All the radioactivity excreted into the medium was associated with LpA-I or LpA-I/A-II; 39% of the excreted radioactivity was esterified in LpA-I and 10% in LpA-I/A-II. Upon complete inactivation of lecithin: cholesterol acyltransferase (LCAT) activity with dithiobisnitrobenzoic acid, the cholesterol reducing capacity of LpA-I was weakened significantly. However, the CE mass reducing capacity of LpA-I/A-II was not affected. When LpA-I and LpA-I/A-II were combined, the cholesterol reducing capacity of the mixture was similar to that of LpA-I alone. However, LpA-I re-isolated from the medium showed a lower esterification rate than did the re-isolated LpA-I/A-II, thereby indicating that the cholesterol esterified in LpA-I was transferred to LpA-I/A-II. These results suggest that (i) the function of LpA-I is closely linked to the LCAT activity while that of LpA-I/A-II is not, and (ii) LpA-I in concert with LpA-I/A-II induces a series of extracellular events; LCAT-mediated esterification of excreted FC by LpA-I and a subsequent CE transfer to LpA-I/A-II. These mechanisms might be important for net cholesterol efflux from macrophage foam cells in physiological states.

Adolescent↗
PubMed1982

Relationship between hepatic cholesterol synthesis and biliary cholesterol secretion in man: hepatic cholesterol synthesis is not a major regulator of biliary lipid secretion.

1. To examine the role of newly synthesized cholesterol as a determinant of bile lipid secretion, both hepatic cholesterol synthesis (as judged by the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, EC 1.1.1.34; HMGCoAR) and steady state biliary cholesterol output were measured in nine patients. 2. HMGCoAR levels varied four fold (9-40 pmol min-1 mg-1) and biliary cholesterol secretion 2.5-fold (0.60-1.15 mumol h-1 kg-1) but there was no correlation between these two variables (r = 0.18; P greater than 0.05) nor between biliary bile acid output and HMGCoAR activity (r = 0.34; P greater than 0.05). 3. There was, however, a linear relationship between bile acid and phospholipid secretion (r = 0.77; P less than 0.001) and between bile acid and cholesterol secretion (r = 0.69; P less than 0.05). 4. These results suggest that HMGCoAR activity is not a major determinant of cholesterol secretion nor at these secretion rates is HMGCoAR activity related to bile acid return to the liver.

Bile Acids and Salts↗
PubMed1980

Unreliability of tritiated cholesterol: studies with [1,2-3H]-cholesterol and [24,25-3H]cholesterol in humans.

Over the past 18 months different lots of [1,2-3H]cholesterol and [24,25-3H]cholesterol were found to be radiochemically acceptable by conventional chemical and other in vitro tests, yet, when co-administered with [4-14C]cholesterol to human subjects, an abrupt fall in the 3H/14C specific activity ratio in plasma cholesterol was discovered in every case. We have concluded that all batches of [3H]cholesterol should be regarded as radiochemically unreliable unless they are shown to behave identically in all respects to [4-14C]cholesterol in an appropriate in vivo assay system.

Carbon Radioisotopes↗
PubMed2000

Dual HDL/total cholesterol test: a single-tube, homogeneous assay for sequential measurement of HDL cholesterol and total cholesterol.

The quantitation of cholesterol in lipoprotein subfractions is valuable in estimating the risk for coronary artery disease, but requires multiple tests. We describe a relatively simple procedure, referred to as the dual HDL/total cholesterol (DHT) assay, which allows the sequential measurement of HDL cholesterol (HDL-C) and total cholesterol (total-C) in a single tube. HDL-C is first measured using a homogeneous assay that utilizes an anti-apolipoprotein B [apo(B)] antibody, which sterically blocks the enzymatic measurement of cholesterol on the non-HDL subfractions. Next, deoxycholate is added, which disrupts the antibody-apo(B) complex and allows the subsequent enzymatic measurement of the remaining cholesterol in the non-HDL subfractions. The DHT assay has an acceptable analytical performance and yields results similar to standard methods: for HDL-C, y(DHT) = 0.98x + 0.19, r=0.90; for total-C, y(DHT) = 1.11x - 0.09, r=0.99. In summary, the DHT assay is a homogeneous assay for both HDL-C and total-C, and provides a simple and cost-effective method for screening for hyperlipidaemia.

Antibodies↗
PubMed1998

[Mechanism of cellular cholesterol removal: a communication system between extracellular cholesterol transport and intracellular cholesterol homeostasis].

Cholesterol efflux is one of the essential events in cellular cholesterol homeostasis since peripheral cells do not catabolize the cholesterol molecule. There are two distinct mechanisms for the efflux. One is the non-specific classical pathway mediated by physicochemical diffusion of cholesterol through the aqueous phase and its esterification on high density lipoprotein (HDL) by lecithin: cholesterol acyltransferase (LCAT). The other is the specific and biological pathway in which new HDL particles are generated from cellular lipid by the direct interaction of cell membrane and amphiphilic apolipoproteins that have dissociated from HDL. The latter reaction consists of binding of apolipoprotein to the specific binding site of the cellular surface and subsequent mobilization of intracellular cholesterol for the HDL generation mediated by intracellular signal transduction. This reaction seems to be a major source of plasma HDL.

Animals↗
PubMed2006

AMP-kinase alpha2 subunit gene PRKAA2 variants are associated with total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol in normal women.

BACKGROUND: 5'-AMP-activated protein kinase (AMPK) inactivates critial ensymes in fatty acid and cholesterol synthesis. We hypothesised that the serum lipid profile may be influenced by genetic variation in the AMPK catalytic alpha2 subunit. METHOD: We examined association of 5 tagging SNPs (tSNPs) in the PRKAA2 gene with serum lipids in 2777 normal Caucasian females (mean age 47.4+/-12.5 years). RESULTS: All tSNPs were associated with total- and LDL-cholesterol, (p<0.001 to 0.034), explaining variances of 0.13-0.59% and 0.11-0.55% respectively. One haplotype (frequency 34.7%) showed lower total- and LDL-cholesterol compared with the most common haplotype (frequency 45.7%) (p< or =0.001), explaining 0.78% of total- and 0.75% of LDL-cholesterol. Another haplotype (frequency 10.5%) was significantly associated with lower HDL-cholesterol (p = 0.005), explaining 0.59% of variance. CONCLUSIONS: PRKAA2 gene variants are significantly associated with serum lipoproteins in a large sample of normal female Caucasians.

AMP-Activated Protein Kinases↗
PubMed1999

Effects of NTE-122, a novel acyl-CoA:cholesterol acyltransferase inhibitor, on cholesterol esterification and high-density lipoprotein-induced cholesterol efflux in macrophages.

We investigated the effects of a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylamino phenyl)ureido]methyl]cyclohexane), on ACAT activities in macrophages originating from several species and high-density lipoprotein (HDL)-induced cholesterol efflux in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells. NTE-122 inhibited cell-free ACAT activities in human PMA-treated THP-1 cells and mouse J774.1 cells with IC50 values of 0.88 and 360 nM, respectively. NTE-122 competively inhibited the ACAT activity in PMA-treated THP-1 cells. NTE-122 also inhibited cellular ACAT activities in PMA-treated THP-1 cells, rat peritoneal macrophages and J774.1 cells with IC50 values of 3.5, 84 and 6800 nM, respectively. Furthermore, NTE-122 prevented cholesterol accumulation in PMA-treated THP-1 cells incubated with acetylated low density lipoprotein, simultaneously with HDL, while it caused accumulation of a significant amount of free cholesterol in the absence and even in the presence of HDL. NTE-122 also enhanced HDL-induced cholesterol efflux from established foam cells converted from PMA-treated THP-1 cells. These results suggest that NTE-122, capable of inhibiting macrophage ACAT activity in humans more strongly than those in the other species, exhibits anti-atherogenic effects by preventing the foam cell formation and enhancing the foam cell regression in humans.

Aniline Compounds↗
PubMed2003

Comparison of biosensors based on entrapment of cholesterol oxidase and cholesterol esterase in electropolymerized films of polypyrrole and diaminonaphthalene derivatives for amperometric determination of cholesterol.

Cholesterol amperometric biosensors constructed with enzymes entrapped in electropolymerized layers of polypyrrole and poly-naphthalene derivative polymers are compared. The biosensors are based on entrapment of cholesterol oxidase and/or cholesterol esterase in monolayer or multilayer films electrochemically synthesised from pyrrole, 1,8-diaminonaphthalene (1,8-DAN), and 1,5-diaminonaphthalene (1,5-DAN) monomers. Seven configurations were assayed and compared, and different analytical properties were obtained depending on the kind of polymer and the arrangement of the layers. The selectivity properties were evaluated for the different monolayer and bilayer configurations proposed as a function of the film permeation factor. All the steps involved in the preparation of the biosensors and determination of cholesterol were carried out in a flow system. Sensitivity and selectivity depend greatly on hydrophobicity, permeability, compactness, thickness, and the kind of the polymer used. In some cases a protective outer layer of non-conducting poly( o-phenylenediamine) polymer improves the analytical characteristics of the biosensor. A comparative study was made of the analytical performance of each of the configurations developed. The biosensors were also applied to the flow-injection determination of cholesterol in a synthetic serum.

Biosensing Techniques↗
PubMed1996

27-hydroxylated low density lipoprotein (LDL) cholesterol can be converted to 7alpha,27-dihydroxy-4-cholesten-3-one (cytosterone) before suppressing cholesterol production in normal human fibroblasts. Evidence that an altered metabolism of ldl cholesterol can underlie a defective feedback control in malignant cells.

The formation of oxysterols in cultured human fibroblasts and their physiological roles as intracellular regulators of cholesterol production have been investigated. In the presence of low density lipoproteins (LDL), normal fibroblasts converted LDL cholesterol to 27hydroxycholesterol, which was further metabolized to 7alpha, 27-dihydroxycholesterol, 7alpha,27-dihydroxy-4-cholesten-3-one, and 7alpha-hydroxy-3-oxo-4-cholestenoic acid. Autooxidation products of cholesterol contaminating the lipoproteins were also metabolized in the cells. 7alpha-Hydroxycholesterol was converted to 7alpha-hydroxy-4-cholesten-3-one prior to 27-hydroxylation and further oxidation to 7alpha-hydroxy-3-oxo-4-cholestenoic acid. 7beta-Hydroxycholesterol and 7-oxocholesterol were 27-hydroxylated and then oxidized to C27-acids. Oxidation of the 7beta-hydroxy group also occurred. 25-Hydroxycholesterol was 7alpha-hydroxylated and further oxidized to 7alpha,25-dihydroxy-4-cholesten-3-one. 25-Hydroxylation of sterols was observed only under specific conditions. In contrast, only small amounts of oxysterols were formed in virus-transformed human fibroblasts when incubated with lipoproteins. This was due to very low activities of the 27- and 7alpha-hydroxylating enzymes. The rate of oxidation at C-3 was also decreased moderately. A defective suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase by LDL and autooxidation products of cholesterol observed in the transformed fibroblasts could be caused by the deficiencies of the sterol-metabolizing enzymes, since these cells responded normally to the sterol metabolites 7alpha,27-dihydroxy-4-cholesten-3-one, 7alpha, 25-dihydroxy-4-cholesten-3-one, and 27-hydroxy-7-oxo-cholesterol. These metabolites, which all possessed an oxo group with a conjugated double bond in the steroid nucleus and a hydroxyl group in the side chain, did not seem to require further metabolism in order to be active. An impaired response to LDL was also seen in other human tumor cells, including breast carcinoma, colonic carcinoma, and malignant melanoma cells. Common to all the malignant cells was an intracellular shortage of 7alpha, 27-dihydroxy-4-cholesten-3-one caused by a decreased formation or an increased metabolism.

Cell Line, Transformed↗