| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Cholesteryl ester transfer protein TaqIB polymorphism in the cholesterol and recurrent events study Marian, A. J. (2005), Curr Atheroscler Rep 7(3): 178-9. |
| Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: individual patient meta-analysis of 13,677 subjects Boekholdt, S. M., F. M. Sacks, et al. (2005), Circulation 111(3): 278-87. Abstract: BACKGROUND: Several studies have reported that the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism is associated with HDL cholesterol (HDL-C) levels and the risk of coronary artery disease (CAD), but the results are inconsistent. In addition, an interaction has been implicated between this genetic variant and pravastatin treatment, but this has not been confirmed. METHODS AND RESULTS: A meta-analysis was performed on individual patient data from 7 large, population-based studies (each >500 individuals) and 3 randomized, placebo-controlled, pravastatin trials. Linear and logistic regression models were used to assess the relation between TaqIB genotype and HDL-C levels and CAD risk. After adjustment for study, age, sex, smoking, body mass index (BMI), diabetes, LDL-C, use of alcohol, and prevalence of CAD, TaqIB genotype exhibited a highly significant association with HDL-C levels, such that B2B2 individuals had 0.11 mmol/L (0.10 to 0.12, P<0.0001) higher HDL-C levels than did B1B1 individuals. Second, after adjustment for study, sex, age, smoking, BMI, diabetes, systolic blood pressure, LDL-C, and use of alcohol, TaqIB genotype was significantly associated with the risk of CAD (odds ratio=0.78 0.66 to 0.93) in B2B2 individuals compared with B1B1 individuals (P for linearity=0.008). Additional adjustment for HDL-C levels rendered a loss of statistical significance (P=0.4). Last, no pharmacogenetic interaction between TaqIB genotype and pravastatin treatment could be demonstrated. CONCLUSIONS: The CETP TaqIB variant is firmly associated with HDL-C plasma levels and as a result, with the risk of CAD. Importantly, this CETP variant does not influence the response to pravastatin therapy. |
| Cholesteryl ester transfer protein: pharmacological inhibition for the modulation of plasma cholesterol levels and promising target for the prevention of atherosclerosis Ruggeri, R. B. (2005), Curr Top Med Chem 5(3): 257-64. Abstract: Cholesteryl ester transfer protein (CETP) facilitates the exchange of neutral lipids (such as cholesteryl esters and triglycerides) between anti-atherogenic HDL particles and pro-atherogenic VLDL and LDL particles in human plasma. Individuals possessing a genetic deficiency for CETP have higher HDL cholesterol and lower LDL cholesterol and may have a reduced risk for developing cardiovascular disease. Small molecule inhibitors of CETP are being developed that would appear to provide a beneficial change in lipoprotein profile. However, randomized clinical trials are ultimately required to determine whether CETP inhibition will afford a reduction in cardiovascular events. |
| Cholesteryl ester transfer proteins, reverse cholesterol transport, and atherosclerosis Bruce, C. and A. R. Tall (1995), Curr Opin Lipidol 6(5): 306-11. Abstract: Plasma cholesteryl ester transfer protein plays a central role in lipoprotein metabolism by exchanging cholesteryl esters with triglycerides. Human genetic deficiency is associated with increased HDL-cholesterol levels, whereas cholesteryl ester transfer protein overexpression in transgenic mice results in decreased HDL-cholesterol. Thus, it has been proposed that cholesteryl ester transfer protein deficiency is an antiatherogenic state. However, recent observations in human cholesteryl ester transfer protein deficiency and cholesteryl ester transfer protein transgenic mice also suggest antiatherogenic effects of the expression of this protein, probably reflecting its role in reverse cholesterol transport. |
| Cholesteryl hemisuccinate-cholesterol interaction: miscibility properties of the sterols Bach, D., N. Borochov, et al. (1995), Chem Phys Lipids 76(1): 123-7. Abstract: Miscibility of cholesterol and cholesteryl hemisuccinate was investigated by differential scanning calorimetry and small-angle X-ray scattering. In an excess of cholesterol, above 2:1 mol ratio, phase separation takes place into a mixed phase and an almost pure cholesterol phase. |
| Cholestin inhibits cholesterol synthesis and secretion in hepatic cells (HepG2) Man, R. Y., E. G. Lynn, et al. (2002), Mol Cell Biochem 233(1-2): 153-8. Abstract: Hyperlipidemia is a well-known risk factor for atherosclerosis and statins are widely used to treat patients with elevated levels of lipids in their plasma. Notwithstanding the proven benefits of statin drugs on both primary and secondary prevention of heart disease, the high cost of statin treatment, in addition to possible side effects such as liver function abnormalities, may limit their widespread use. We conducted a study on a natural product as an alternative to statin treatment. Cholestin, a dietary supplement, is prepared from rice fermented with red yeast (Monascus purpureus), which has been shown to significantly decrease total cholesterol levels in hyperlipidemic subjects. Our objective was to determine the cellular effect of Cholestin on cholesterol synthesis in human hepatic cells (HepG2) and the mechanism by which it caused a change in lipid metabolism. Cholestin had a direct inhibitory effect on HMG-CoA reductase activity (78-69% of control). Cholesterol levels in HepG2 cells treated with Cholestin (25-100 microg/mL) were significantly reduced in a dose-dependent manner (81-45% of control, respectively). This reduction was associated with decreased synthesis and secretion of both unesterified cholesterol (54-31 and 33-14% of control, respectively) and cholesteryl ester (18-6 and 37-19% of control, respectively). These results indicate that one of the anti-hyperlipidemic actions of Cholestin is a consequence of an inhibitory effect on cholesterol biosynthesis in hepatic cells and provide the first documentation of a biomolecular action of red yeast rice. |
| Cholic acid aids absorption, biliary secretion, and phase transitions of cholesterol in murine cholelithogenesis Wang, D. Q., F. Lammert, et al. (1999), Am J Physiol 276(3 Pt 1): G751-60. Abstract: Cholic acid is a critical component of the lithogenic diet in mice. To determine its pathogenetic roles, we fed chow or 1% cholesterol with or without 0.5% cholic acid to C57L/J male mice, which because of lith genes have 100% gallstone prevalence rates. After 1 yr on the diets, we measured bile flow, biliary lipid secretion rates, hepatic cholesterol and bile salt synthesis, and intestinal cholesterol absorption. After hepatic conjugation with taurine, cholate replaced most tauro-beta-muricholate in bile. Dietary cholic acid plus cholesterol increased bile flow and biliary lipid secretion rates and reduced cholesterol 7alpha-hydroxylase activity significantly mostly via deoxycholic acid, cholate's bacterial 7alpha-dehydroxylation product but did not downregulate cholesterol biosynthesis. Intestinal cholesterol absorption doubled, and biliary cholesterol crystallized as phase boundaries shifted. Feeding mice 1% cholesterol alone produced no lithogenic or homeostatic effects. We conclude that in mice cholic acid promotes biliary cholesterol hypersecretion and cholelithogenesis by enhancing intestinal absorption, hepatic bioavailability, and phase separation of cholesterol in bile. |
| Cholic acid as key regulator of cholesterol synthesis, intestinal absorption and hepatic storage in mice Murphy, C., P. Parini, et al. (2005), Biochim Biophys Acta 1735(3): 167-75. Abstract: To study the effects of cholic acid (CA) feeding on hepatic cholesterol metabolism, male sterol 12alpha-hydroxylase (CYP8B1) knockout (-/-) mice and wildtype controls (+/+) were fed either a control diet or the same diet supplemented with CA (0.1% or 0.5% w/w) or cholesterol (1% w/w). During feeding of the control diet, cholesterol synthesis was increased in CYP8B1-/- compared to +/+ mice. Both cholesterol and CA feeding down regulated mRNA expression of cholesterogenic genes and hepatic de novo cholesterol synthesis as also reflected by a concomitant decrease in the nuclear factor SREBP-2 precursor protein and increased hepatic free cholesterol levels. Mice with an intact CYP8B1 gene (CYP8B1+/+ and C57Bl/6 mice) accumulated higher concentrations of cholesteryl esters (24- and 25-fold, respectively) in their livers compared to CYP8B1-/- mice (8-fold). Feeding of CA increased intestinal cholesterol absorption in CYP8B1+/+ mice by 23% and in CYP8B1-/- mice by 50%. While plasma cholesterol did not differ between CYP8B1+/+ and -/- mice under control conditions and cholesterol feeding a decrease was seen in CYP8B1-/- but not CYP8B1+/+ mice fed CA. This study indicates that CA is an important determinant for intestinal cholesterol absorption and that the levels of the transcription factor SREBP-2 in the liver are dependent upon the combined effect of CA on intestinal cholesterol absorption and CYP7A1. The possibility is discussed that inhibition of CYP8B1 and thus CA synthesis may be beneficial for the treatment of hyperlipidemic disorders. |
| Cholic acid supplementation enhances cholesterol absorption in humans Woollett, L. A., D. D. Buckley, et al. (2004), Gastroenterology 126(3): 724-31. Abstract: BACKGROUND & AIMS: Qualitative and quantitative changes in intralumenal bile acid composition may alter cholesterol absorption and synthesis and low-density lipoprotein (LDL) receptor expression. The role of cholic acid (CA) in cholesterol absorption in humans remains unclear and, thus, was examined in the current study. METHODS: In a crossover design outpatient study, 12 adults aged 24-36 years took 15 mg/kg/day (CA) or no bile acid supplement (control) while being fed a controlled diet (AHA heart-healthy diet). A liquid meal of defined composition was given on day 14 of the diet, and lumenal samples were collected. Thereafter, cholesterol absorption and cholesterol fractional synthetic rate (FSR) were assessed by stable isotopic methods from days 16 to 20. RESULTS: With CA treatment, bile was enriched significantly with CA (P < 0.0004) to 60.2% +/- 2.4% (mean +/- SEM) compared with 43.3% +/- 2.4% for controls. CA plus diet treatment significantly increased (P = 0.013) cholesterol absorption (72.6% +/- 2.9%) compared with diet treatment alone (60.4% +/- 2.9%). Percentage micellar cholesterol was increased by CA plus diet treatment vs. diet alone after meal ingestion (P = 0.004). Plasma total and high-density lipoprotein (HDL) and LDL cholesterol was unchanged with CA treatment. CONCLUSIONS: Thus, enrichment in lumenal bile with CA results in an increase in cholesterol absorption, an effect potentially mediated by enhanced cholesterol solubilization in micelles. |
| Choose a diet that is low in saturated fat and cholesterol and moderate in total fat: subtle changes to a familiar message Dixon, L. B. and N. D. Ernst (2001), J Nutr 131(2S-1): 510S-526S. Abstract: "Choose a diet that is low in saturated fat and cholesterol and moderate in total fat," issued in Nutrition and Your Health: Dietary Guidelines for Americans in the year 2000, has an interesting and lengthy history. The first guideline, for which there was extensive scientific data to show that dietary excess increased chronic disease risk, prompted much scientific discussion and debate when implemented as dietary guidance. Three major changes in the guideline are noted since it was issued in 1980, i.e., numerical goals for dietary fats; the applicability of recommended fat intakes for all individuals > or =2 y old; and rewording to emphasize reducing saturated fat and cholesterol intakes. The shift in emphasis includes the terminology moderate fat, which replaces the phrasing low fat. National data about the food supply, the population's dietary intake, knowledge, attitudes and behaviors, and nutritional status indicators (e.g., serum cholesterol levels) related to dietary fats help to monitor nutrition and health in the population. Experts consider that national data, although not without limitations, are sufficient to conclude that U.S. intakes of fats, as a proportion of energy, have decreased. The lower intakes of saturated fat and cholesterol are consistent with decreases in blood cholesterol levels and lower rates of coronary mortality over the past 30 years. Strategies are needed and some are suggested, to further encourage the population to achieve a dietary pattern that is low in saturated fat and cholesterol and moderate in total fat. Other suggestions are offered to improve national nutrition monitoring and surveillance related to the guideline. |
| Choosing a cholesterol screening service vendor Lefebvre, R. C. (1990), Am Pharm NS30(8): 37-41. |
| Chromatographic behavior of oxygenated derivatives of cholesterol Shan, H., J. Pang, et al. (2003), Steroids 68(3): 221-33. Abstract: Oxygenated derivatives of cholesterol have important functions in many biochemical processes. These oxysterols are difficult to study because of their low physiological concentrations, the facile formation of cholesterol autoxidation artifacts, and lack of information on their chromatographic behavior. Focusing on metabolites and autoxidation products of cholesterol, we have documented the chromatographic mobilities of 35 oxysterols under a variety of conditions: eight solvent systems for thin-layer chromatography on silica gel, several mobile phases for reversed-phase high-performance liquid chromatography (HPLC), and two types of stationary phase for capillary gas chromatography (GC) using trimethylsilyl derivatives. Notable differences in selectivity could be obtained by modifying the stationary or mobile phases. Separations of oxysterol pairs isomeric at side-chain carbons or C-7 were achieved on normal-phase, reversed-phase, chiral, or silver-ion HPLC columns. Chromatographic behavior is also described for side-chain hexadeuterated and heptafluorinated oxysterols, which are useful as standards in isotope dilution analyses and autoxidation studies, respectively. The overall results are relevant to many problems of oxysterol analysis, including the initial separation of oxysterols from cholesterol, determination of highly polar and nonpolar oxysterols, separation of isomeric pairs, selection of derivatization conditions for GC analysis, and quantitation of the extent of cholesterol autoxidation. |
| Chromatographic characteristics of cholesterol-imprinted polymers prepared by covalent and non-covalent imprinting methods Hwang, C. C. and W. C. Lee (2002), J Chromatogr A 962(1-2): 69-78. Abstract: Cholesterol-imprinted polymers were prepared in bulk polymerization by the methods of covalent and non-covalent imprinting. The former involved the use of a template-containing monomer, cholesteryl (4-vinyl)phenyl carbonate, while the latter used the complexes of template and functional monomer, methacrylic acid or 4-vinylpyridine prior to polymerization. Columns packed with these molecularly imprinted polymers (MIPs) were all able to separate cholesterol from other steroids. For different combinations of cholesterol and beta-estradiol concentrations in a total of 1 g/l, the peak retention times for both compounds were nearly constant. The adsorption capacity for cholesterol onto the MIPs was found to significantly depend on the use of functional monomers, but the selectivity factors were only slightly different from each other at 2.9 to 3.2 since the separation was all based on the specific binding of cholesterol to recognition sites formed on the imprinted polymers. The capacity factors for cholesterol were determined to be 3.5, 4.0 and 3.1, respectively, for covalently imprinted, 4-vinylpyridine-based, and methacrylic acid-based non-covalently imprinted polymers. However, the covalently imprinted polymer was found to have a higher adsorption capacity for cholesterol and about fivefold higher chromatographic efficiency for cholesterol separation, in comparison with non-covalently imprinted polymers. The use of covalent imprinting significantly reduced the peak broadening and tailing. This advantage along with constant retention suggests that the covalently imprinted polymer has potential for quantitative analysis. |
| Chromatographic methods in the analysis of cholesterol and related lipids Hoving, E. B. (1995), J Chromatogr B Biomed Appl 671(1-2): 341-62. Abstract: Methods using thin-layer chromatography, solid-phase extraction, gas chromatography, high-performance liquid chromatography and supercritical fluid chromatography are described for the analysis of single cholesterol, esterified and sulfated cholesterol, and for cholesterol in the context of other lipid components, like other sterols and lipid classes. In connection with these techniques several clinical applications are mentioned. |
| Chromatographic separation and electrochemical determination of cholesterol hydroperoxides generated by photodynamic action Korytowski, W., G. J. Bachowski, et al. (1991), Anal Biochem 197(1): 149-56. Abstract: Reverse-phase HPLC with electrochemical detection (HPLC-EC) was used to separate and quantitate photochemically generated cholesterol hydroperoxides. The EC measurements were performed in the reduction mode under anaerobic conditions. When cholesterol-containing liposomes were irradiated in the presence of a phthalocyanine dye, at least four major oxidation products of cholesterol were detected by HPLC-EC:5 alpha-hydroperoxide (5 alpha-OOH), 6 beta-hydroperoxide (6 beta-OOH), 7 alpha-hydroperoxide (7 alpha-OOH), and 7 beta-hydroperoxide (7 beta-OOH). The detection limit for each compound was found to be approximately 25 pmol. Product identification was based on matching HPLC and TLC behavior of standards and on physical indicators (melting points and NMR chemical shifts). The cholesterol hydroperoxides were barely separated from EC-silent diol derivatives, which could be detected by 210 nm absorbance after reduction of the hydroperoxides with triphenylphosphine. Irradiation of a dye-sensitized natural membrane, the human erythrocyte ghost, also resulted in formation of 5 alpha-OOH, 6-OOH, and 7-OOH, as evidenced by HPLC-EC. Under the chromatographic conditions used, these species were well separated not only from one another but also from a family of at least six phospholipid hydroperoxides. These results illustrate the strengths of HPLC-EC as a relatively convenient, sensitive, and selective means of analyzing cholesterol hydroperoxides in biological samples. |
| Chromatographic separation of cholesterol in foods Fenton, M. (1992), J Chromatogr 624(1-2): 369-88. Abstract: Based on the current literature and on experience gained in the laboratory, a simplified procedure using direct saponification (0.4 M potassium hydroxide in ethanol and heating at 60 degrees C for 1 h) is the most appropriate method for the determination of total cholesterol in foods. Extraction of the unsaponifiable matter with hexane is efficient and no extra clean-up is required before quantification. An internal standard, 5 alpha-cholestane or epicoprostanol, should be added to the sample prior to saponification and, together with reference standards, carried through the entire procedure to ensure accurate results. A significant improvement in cholesterol methodology has been achieved by decreasing the sample size and performing all the sample preparation steps in a single tube. The method has the advantages of elimination of an initial solvent extraction for total lipids and errors resulting from multiple extractions, transfers, filtration and wash steps after saponification. The resulting hexane extract, which contains a variety of sterols and fat soluble vitamins, requires an efficient capillary column for complete resolution of cholesterol from the other compounds present. The development of fused-silica capillary columns using cross-linked and bonded liquid phases has provided high thermal stability, inertness and separation efficiency and, together with automated cold on-column gas chromatographic injection systems, has resulted in reproducible cholesterol determinations in either underivatized or derivatized form. If free cholesterol and its esters need to be determined separately, they are initially extracted with other lipids with chloroform-methanol followed by their separation by column or thin-layer chromatography and subsequently analysed by gas or liquid chromatography. Although capillary gas chromatography offers superior efficiency in separation, the inherent benefits of liquid chromatography makes it a potential alternative. Isotope dilution mass spectrometry has been widely accepted as a reliable analytical method for highly accurate determination of cholesterol in serum and several definitive methods have been reported. The combination of capillary gas chromatography with mass spectrometry has become an excellent approach for the determination of cholesterol in complex mixtures of sterols and tocopherols, providing high resolution with positive identification. When used to determine cholesterol in multi-component foods, spectrophotometric methods have been documented to overestimate significantly the amount of cholesterol owing to the presence of other interfering substances. A re-evaluation of food products should be undertaken using the more specific chromatographic methods to accumulate data that will more accurately reflect the true cholesterol content. |
| Chromatomass-spectrometric determination of oxidized cholesterol derivatives in blood serum Rezvukhin, A. I., E. V. Berezovskaia, et al. (1994), Vopr Med Khim 40(1): 56-8. Abstract: Content of several oxidized forms of cholesterol was studied in blood serum of patients with hypercholesterolemia using chromato-mass-spectrometry. The hydroxycholesterols detected were identified as 7-beta-hydroxycholesterol, 25-hydroxycholesterol, 7-ketocholesterol in the presence of standard substances added. Main patterns of gas chromatographic and mass spectrometric analyses of these substances are described. |
| Chromium and cholesterol-induced atherosclerosis in rabbits Abraham, A. S., B. A. Brooks, et al. (1991), Ann Nutr Metab 35(4): 203-7. Abstract: Thirty-three rabbits on a cholesterol-enriched diet were randomized into 6 groups and treated with daily injections of either water, 20 micrograms of potassium chromate or 1, 5, 10 or 20 micrograms of chromium chloride, respectively, for 135 days with a 2- to 10-fold increase in serum chromium. There was a marked reduction in the percentage of aortic intimal surface covered by plaque, in aortic weight and cholesterol content in the treated animals. Rabbits treated with 20 micrograms of chromium chloride showed a better response than those treated with either 10 or 20 micrograms of potassium chromate. |
| Chromogenic substrate assay of extrinsic pathway inhibitor (EPI): levels in the normal population and relation to cholesterol Sandset, P. M., M. L. Larsen, et al. (1991), Blood Coagul Fibrinolysis 2(3): 425-33. Abstract: A two-stage chromogenic substrate assay was standardized to measure extrinsic pathway inhibitor (EPI) activity in plasma and serum samples. In the first stage, diluted plasma or serum (0-0.8%) was incubated with factor VIIa (25 pM), tissue thromboplastin (tissue factor, TF, 1% v/v) with excess binding sites for factor VIIa, and factor Xa (0.8 nM). In the second stage, excess factor X and chromogenic substrate were added as substrate for residual TF/factor VIIa catalytic activity. Heating the samples at 56 degrees C for 15 min before assay removed greater than 95% of the factor VII amidolytic activity of the samples, defibrinated the plasma, and produced only slight reduction of EPI activity. The coefficient of variation for the same sample assayed on different days was 8.7-10.6% and the intra-assay coefficient of variation was 5.0%. Addition of anti-EPI immunoglobulin to normal plasma completely abolished the EPI activity of the sample. EPI activity was stable in plasma samples stored at -20 degrees C, but in serum, some samples lost greater than 50% activity after 3 months at -70 degrees C. Median EPI activity of umbilical cord blood was 45% (range 33-93%). In a cohort of healthy blood donors (n = 176) EPI activity was significantly correlated with age; the regression line was y = 68% + 0.60x (r = 0.39). The approximated standard deviation for the regression line was 17.9% and the age-adjusted reference limits were determined. Equal levels were seen in males and females.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Chromosomal localization of genes involved in biosynthesis, metabolism or transport of cholesterol in the rat Bonne, A. C., M. G. den Bieman, et al. (2002), Cytogenet Genome Res 97(3-4): 183-6. Abstract: Several genes involved in biosynthesis, transport or metabolism of cholesterol have been localized on rat chromosomes by using a radiation hybrid (RH) panel. The genes, coding for squalene epoxidase (Sqle), mevalonate kinase (Mvk), and farnesyl diphosphate farnesyl transferase 1 (Fdft1) which are involved in cholesterol biosynthesis, have been mapped on chromosome 7, 12, and 15, respectively. The genes coding for phospholipid transfer protein (Pltp), sterol carrier protein-2 (Scp2), ATP binding cassette reporter A7 (Abca7), scavenger receptor class B, type 1 (Cd36l1), steroidogenic acute regulatory protein (Star), and lecithin:cholesterol acyl transferase (Lcat), which are involved in the transfer and/or metabolism of cholesterol, have been mapped on chromosome 3, 5, 7, 12, 16, and 19, respectively. Each of the genes Scp2, Sqle and Fdft1 maps close to a QTL for serum total cholesterol in rat, suggesting that these three genes might represent candidate genes for the previously mapped QTLs. |