| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| A review of cholesterol crystals embolism. Moll Camps, J. J., M. Castro Forns, et al. (2004), Rev Clin Esp 204(6): 320-2. |
| A review of observational studies on the relationship between cholesterol and coronary heart disease Calvert, G. D. (1994), Aust N Z J Med 24(1): 89-91. Abstract: The likelihood that an association observed in epidemiological studies is one of cause and effect is often evaluated using criteria first put forward by Bradford Hill. The evidence on whether abnormal concentrations of cholesterol and lipoproteins in the blood plasma cause coronary heart disease (CHD) is considered using Bradford Hill's criteria. Evidence from observational studies, backed by evidence from clinical, animal and laboratory studies, leaves no doubt that a high plasma cholesterol concentration is a cause of CHD. |
| A review of recent dietary intervention trials in the United Kingdom to reduce blood cholesterol levels Yasmin, P. Croft, et al. (1999), Ann Hum Biol 26(5): 427-42. Abstract: A review of 14 UK studies conducted between 1980 and January 1997 showed that blood cholesterol levels can be reduced through screening followed by dietary and behavioural intervention in both general population and high risk individuals (hyperlipidaemic and angina patients). In most studies cholesterol levels were lowered moderately while changes in other risk factors were also in a positive direction. However, it is unclear whether the cholesterol reductions are sufficiently large to have a significant impact in lowering the risk of heart disease in the whole population. |
| A review of the analytic performance of the Reflotron System for cholesterol testing Statland, B. E. (1990), Clin Ther 12(3): 281-6. Abstract: The analytic performance of the Reflotron System for cholesterol testing has been assessed in 17 studies since 1987. The precision of the test (total coefficient of variation) ranged from 0.8% to 9.9% and was between 1% and 5% in 23 of the 27 specimen types tested. The correlation coefficient of the Reflotron with that of a reference methods was over.9 in 15 specimen types tested and over.95 in ten of 15. The type of specimen tested and the training of the test personnel affected both precision and accuracy. It is concluded that the Reflotron analyzer provides reliable and accurate cholesterol measurements. |
| A review of the treatment guidelines on the management of low levels of high-density lipoprotein cholesterol Devroey, D., K. Vantomme, et al. (2004), Cardiology 102(2): 61-6. Abstract: This paper aims to review the guidelines on the importance given to high-density lipoprotein cholesterol (HDL-C) as a risk factor or as threshold and target level in the treatment of dyslipidemia. We developed a strategy with cholesterol-related key words to search for guidelines in the major databases. The Appraisal of Guidelines Research Evaluation (AGREE) instrument was used for the evaluation and inclusion of the guidelines. In total nine guidelines were selected. Almost all selected guidelines consider low HDL-C as a marker of an increased risk for coronary heart disease. However, only few guidelines use the level of HDL-C as a threshold or target level for the treatment of dyslipidemia. The guidelines provide only little information on the management of patients with treatment-induced low HDL-C. Instead of using total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C) we consider the use of the ratios of TC to HDL-C or LDL-C to HDL-C as a threshold as well as a target for treatment. |
| A review on ethnic differences in plasma triglycerides and high-density-lipoprotein cholesterol: is the lipid pattern the key factor for the low coronary heart disease rate in people of African origin? Zoratti, R. (1998), Eur J Epidemiol 14(1): 9-21. Abstract: Black people in the UK, in the Caribbean, and to a lesser extent in the USA, experience coronary heart disease events at different rates than white people. Despite having higher prevalence of hypertension, cigarette smoking and diabetes, black males have significantly lower coronary heart disease rates than white males, whereas no significant differences have been detected in females. The only known risk factor differences that could account for the difference in CHD rates are higher HDL cholesterol and lower triglycerides that are seen in blacks compared with whites. Obesity and, in particular abdominal obesity, seems to determine TG and HDL cholesterol levels: black males are less centrally obese than whites, while total adiposity and central distribution of fat is more predominant in black females compared with white females. We propose that the less degree of abdominal adiposity observed in black males is related with an increased anti-lipolytic effect of insulin, which could account for low triglycerides and high HDL cholesterol levels, and consequently explain the higher protection from coronary heart disease experienced by black males compared with whites and black females. |
| A rising StAR: an essential role in cholesterol transport Waterman, M. R. (1995), Science 267(5205): 1780-1. |
| A role for caveolin in transport of cholesterol from endoplasmic reticulum to plasma membrane Smart, E. J., Y. Ying, et al. (1996), J Biol Chem 271(46): 29427-35. Abstract: Caveolin is a 22-kDa membrane protein found associated with a coat material decorating the inner membrane surface of caveolae. A remarkable feature of this protein is its ability to migrate from caveolae directly to the endoplasmic reticulum (ER) when membrane cholesterol is oxidized. We now present evidence caveolin is involved in transporting newly synthesized cholesterol from the ER directly to caveolae. MA104 cells and normal human fibroblasts transported new cholesterol to caveolae with a half-time of approximately 10 min. The cholesterol then rapidly flowed from caveolae to non-caveolae membrane. Cholesterol moved out of caveolae even when the supply of fresh cholesterol from the ER was interrupted. Treatment of cells with 10 microg/ml progesterone blocked cholesterol movement from ER to caveolae. Simultaneously, caveolin accumulated in the lumen of the ER, suggesting cholesterol transport is linked to caveolin movement. Caveolae fractions from cells expressing caveolin were enriched in cholesterol 3-4-fold, while the same fractions from cells lacking caveolin were not enriched. Cholesterol transport to the cell surface was nearly 4 times more rapid in cells expressing caveolin than in matched cells lacking caveolin. |
| A role for cholesterol as a structural effector of the nicotinic acetylcholine receptor Fernandez-Ballester, G., J. Castresana, et al. (1994), Biochemistry 33(13): 4065-71. Abstract: The effects of cholesterol on the protein structure and on the ionic channel activity of purified acetylcholine receptor (AcChR) reconstituted into lipid vesicles have been studied, respectively, by Fourier-transform infrared spectroscopy and by rapid kinetics of cation influx. Reconstitution of the AcChR in asolectin phospholipid vesicles in the absence of either cholesterol or the nonpolar lipids present in crude asolectin extracts results in a considerable loss of the ability of the AcChR to support cation channel function. This functional loss is accompanied by spectral changes in the conformationally-sensitive amide I band of the protein infrared spectrum which are indicative of alteration in the protein secondary structure. Quantitative estimation of such alteration by band-fitting analysis reveals a marked decrease in ordered protein structures such as the alpha-helix and beta-pleated sheet, concomitant with an increase in less ordered structures appearing at 1644 cm-1 in the infrared spectrum. Furthermore, the addition of increasing amounts of cholesterol to the reconstituted bilayer produces a progressive, complete recovery both in the control of cation channel function and in the infrared spectrum. This restoration of AcChR structure and function by cholesterol, however, does not occur when the AcChR is reconstituted in vesicles made from purified egg phosphatidylcholine, thus suggesting that the presence in the reconstituted bilayer of phospholipids other than phosphatidylcholine may be required for cholesterol to exert its modulatory effects.(ABSTRACT TRUNCATED AT 250 WORDS) |
| A role for retrosomes in intracellular cholesterol transport from endosomes to the plasma membrane Hornick, C. A., D. Y. Hui, et al. (1997), Am J Physiol 273(3 Pt 1): C1075-81. Abstract: The recycling component (retrosome) of the endocytic pathway was evaluated as a potential vehicle for the recycling of lipoprotein-derived cholesterol and the maintenance of a high concentration of free cholesterol in plasma membranes. Receptor-to-ligand ratios were established in three distinct endosomal compartments using a recycling receptor (apolipoprotein B/E) to confirm isolated retrosomes as recycling vesicles. Compositional studies showed that retrosomes have twice the free cholesterol in their limiting membranes as do the endosomal compartments from which they derive. Furthermore, of the three isolated endosomal fractions, retrosomes showed the highest ratio of free to esterified cholesterol derived from injected very low density lipoprotein as well as the highest free-to-esterified cholesterol mass ratio overall, confirming endosomal cholesteryl ester hydrolysis and sorting. Endosomal neutral cholesterol esterase was identified by immunoblot, whereas electron microscopy employing membrane cholesterol-specific filipin revealed a high concentration of cholesterol in appendages that appear to be the formative stage of retrosomal biogenesis. |
| A role for smooth endoplasmic reticulum membrane cholesterol ester in determining the intracellular location and regulation of sterol-regulatory-element-binding protein-2 Iddon, C. R., J. Wilkinson, et al. (2001), Biochem J 358(Pt 2): 415-22. Abstract: Cellular cholesterol homoeostasis is regulated through proteolysis of the membrane-bound precursor sterol-regulatory-element-binding protein (SREBP) that releases the mature transcription factor form, which regulates gene expression. Our aim was to identify the nature and intracellular site of the putative sterol-regulatory pool which regulates SREBP proteolysis in hamster liver. Cholesterol metabolism was modulated by feeding hamsters control chow, or a cholesterol-enriched diet, or by treatment with simvastatin or with the oral acyl-CoA:cholesterol acyltransferase inhibitor C1-1011 plus cholesterol. The effects of the different treatments on SREBP activation were confirmed by determination of the mRNAs for the low-density lipoprotein receptor and hydroxymethylglutaryl-CoA (HMG-CoA) reductase and by measurement of HMG-CoA reductase activity. The endoplasmic reticulum was isolated from livers and separated into subfractions by centrifugation in self-generating iodixanol gradients. Immunodetectable SREBP-2 accumulated in the smooth endoplasmic reticulum of cholesterol-fed animals. Cholesterol ester levels of the smooth endoplasmic reticulum membrane (but not the cholesterol levels) increased after cholesterol feeding and fell after treatment with simvastatin or C1-1011. The results suggest that an increased cellular cholesterol load causes accumulation of SREBP-2 in the smooth endoplasmic reticulum and, therefore, that membrane cholesterol ester may be one signal allowing exit of the SREBP-2/SREBP-cleavage-regulating protein complex to the Golgi. |
| A second complementation class of cholesterol transport mutants with a variant Niemann-Pick type C phenotype Dahl, N. K., M. A. Daunais, et al. (1994), J Lipid Res 35(10): 1839-49. Abstract: We previously isolated Chinese Hamster ovary cell mutants that were defective in the intracellular transport of low density lipoprotein (LDL)-derived cholesterol (Dahl, N.K., K.L. Reed, M.A. Daunais, J.R. Faust, and L. Liscum. 1992 J. Biol. Chem. 267: 4889-4896). Several of the mutants exhibited the same biochemical phenotype as classical Niemann-Pick type C (NPC) fibroblasts. Complementation analysis between these mutants and other cholesterol transport mutants with a variant biochemical phenotype has defined two complementation classes. One class is characterized by expression of the classical NPC phenotype and may represent a true cholesterol transport mutant, while the second is characterized by expression of a variant NPC phenotype and may represent a signaling defect in LDL-sensitive homeostatic responses. |
| A selective inhibitor of intestinal ACAT, EAB309 suppresses both intestinal and hepatic cholesterol output and stimulates chylomicron removal Umeda, Y., T. Hirano, et al. (1998), Life Sci 63(13): PL187-95. Abstract: The effect of a novel inhibitor of acylcoenzyme A:cholesterol acyltransferase (EC 2.3.1.26, ACAT), EAB309 (EAB) on plasma lipid metabolism was studied in cholesterol-fed rats. Orally administered EAB was not detected in the portal vein or the liver but distributed exclusively in the intestine, suggesting that this agent selectively inhibits intestinal ACAT. The rats were fed with either a cholesterol-diet or a cholesterol-diet containing 0.005% EAB (w/w) ad. libium for three weeks. ACAT activity in intestinal microsomes was significantly inhibited in EAB-treated rats. Hepatic ACAT activity was also decreased in EAB-treated rats, however, this was attenuated by the addition of excess cholesterol to the liver microsome, indicating that substrate availability is tightly associated with this enzyme's activity and the inhibition of hepatic ACAT by EAB is not direct. Incorporation of 3H-cholesterol to cholesteryl ester (CE) in mesenteric lymph were markedly suppressed by EAB treatment. Chylomicrons (CMs) were doubly labeled with 3H-vitamin A and 14C-triglyceride (TG) in EAB-treated or non-treated rats and injected into normal chow-fed rats. The CMs from EAB-treated rats were cleared faster from the plasma and taken up more by the liver compared with the CMs from non-treated rats. The content of CE in newly secreted VLDL was remarkably decreased by EAB treatment without affecting TG output. These results demonstrate that EAB, a novel inhibitor of intestinal ACAT, significantly suppresses both intestinal and hepatic CE output and stimulates CM removal. This suggests that the inhibition of intestinal ACAT can subsequently suppress hepatic ACAT by decreased CE delivery from the intestine to the liver. |
| A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport Oliver, W. R., Jr., J. L. Shenk, et al. (2001), Proc Natl Acad Sci U S A 98(9): 5306-11. Abstract: The peroxisome proliferator-activated receptors (PPARs) are dietary lipid sensors that regulate fatty acid and carbohydrate metabolism. The hypolipidemic effects of the fibrate drugs and the antidiabetic effects of the glitazone drugs in humans are due to activation of the alpha (NR1C1) and gamma (NR1C3) subtypes, respectively. By contrast, the therapeutic potential of the delta (NR1C2) subtype is unknown, due in part to the lack of selective ligands. We have used combinatorial chemistry and structure-based drug design to develop a potent and subtype-selective PPARdelta agonist, GW501516. In macrophages, fibroblasts, and intestinal cells, GW501516 increases expression of the reverse cholesterol transporter ATP-binding cassette A1 and induces apolipoprotein A1-specific cholesterol efflux. When dosed to insulin-resistant middle-aged obese rhesus monkeys, GW501516 causes a dramatic dose-dependent rise in serum high density lipoprotein cholesterol while lowering the levels of small-dense low density lipoprotein, fasting triglycerides, and fasting insulin. Our results suggest that PPARdelta agonists may be effective drugs to increase reverse cholesterol transport and decrease cardiovascular disease associated with the metabolic syndrome X. |
| A sensitive method for determination of cholesterol growth using model solutions of supersaturated bile Busch, N., H. Tokumo, et al. (1990), J Lipid Res 31(10): 1903-9. Abstract: We describe a novel, facile, and highly reproducible spectrophotometric technique to measure a cholesterol crystal growth curve. This method permits a quantitative estimate of the potency or comparative abundance of a given kinetic effector substance. In addition to several internal validation procedures, data are provided that support the usefulness of the technique in the assay of substances with either known promoting activity, i.e., human mucin glycoprotein, or those with known inhibitory activity, i.e., human apolipoprotein A-I. |
| A serum cholesterol study in a consulting population and its implications in clinical practice Jimeno Aranda, A., S. Lou Arnal, et al. (1993), Aten Primaria 11(9): 476-8. Abstract: OBJECTIVE. To investigate serious cholesterol levels in the population seeking medical attention, utilising HOTH (How Often That High) graphs, and to look at implications these results have for recording of cholesterol incidence. DESIGN. This was a non-longitudinal, retrospective, observational study. SETTING. Carried out at the general practice level, in the Valdefierro Basic Health Area (Zaragoza Province). PATIENTS. 742 subjects aged between 18 and 65 years with no previous history of dyslipemia. MEASUREMENTS AND MAIN RESULTS. After obtaining the figures on cholesterolemia, the HOTH graph was drawn from which, for a given cholesterol value, the percentage of the population with a given value can be seen. The mean cholesterol value was 201 mg/dl. A total of 54% of male subjects and 40% of female subjects were situated above the threshold figure of 200 mg/dl. Furthermore, 15% of male subjects and 10% of female subjects were situated above 250 mg/dl. CONCLUSIONS. The application of recording procedures for cholesterol, based on a globally discriminatory score, reveals a startling number of patients who need tests and treatment. We suggest a strategy based on the different levels according to age, sex, bloodstream cholesterol level, and the existence or otherwise of other cardiovascular risk factors. Lastly, we would mention the usefulness of the HOTH graphs in improving our knowledge of the cholesterol levels in a population. |
| A shot of good cholesterol: synthetic HDL, a new intervention for atherosclerosis Dudley-Brown, S. (2004), J Cardiovasc Nurs 19(6): 421-4. Abstract: One of the American Heart Association's Top 10 Research Advances for the Treatment of Heart Disease is the use of a synthetic form of high-density lipoprotein (HDL) to reduce coronary atherosclerosis (JAMA. 2003;290:2292-2300). While HDL has not been a target for therapy for dyslipidemias, new insight into the major protein component of HDL, apolipoprotein A-I, may lead to new therapies. Apolipoprotein A-I was recently found to be a better predictor of cardiovascular events than is low-density lipoprotein (Am Heart J. 2003;146:227-233; J Intern Med. 2004;255:188-205). This article reviews the recent study by Nissen and colleagues describing the finding of a genetic mutation in HDL in some persons in Italy and the subsequent development of a synthetic form of HDL to be used as an infusion to successfully target atherosclerotic lesions (JAMA. 2003;290:2292-2300). In addition, controversies related to HDL cholesterol as a target for therapy are reviewed. Implications for nursing research, education, and practice are also described. |
| A simple and rapid method to measure cholesterol binding to P450s and other proteins Mast, N. and I. A. Pikuleva (2005), J Lipid Res 46(7): 1561-8. Abstract: Cholesterol plays an important role in cellular function and membrane compartmentalization and is involved in the interaction with more than a dozen of different proteins. Using three cholesterol-metabolizing cytochrome P450s (P450s 7A1, 46A1, and 11A1), we have developed a rapid and simple assay for measurements of nanomolar to micromolar cholesterol affinities. In this assay, the P450 is incubated with a fixed amount of radiolabeled cholesterol and varying concentrations of cold cholesterol followed by separation of free and protein-bound cholesterol via filtration through a membrane. Free cholesterol is found in the flow-through fraction, whereas P450 binds to the membrane. The radioactivity of the membranes is then measured, and a saturation curve is generated after correction for nonspecific binding of cholesterol to the filter. The validity of the filter assay was confirmed by spectral assay, a traditional method to evaluate the interaction of the P450 enzymes with their substrates. Two types of membranes, one binding positively charged proteins and another binding negatively charged proteins, were identified. These membranes were also found to hold proteins through hydrophobic interactions. Thus, the cholesterol binding properties of a wide variety of proteins could be characterized using this filter assay. |
| A simplified alternative to the AOAC official method for cholesterol in multicomponent foods Thompson, R. H. and G. V. Merola (1993), J AOAC Int 76(5): 1057-68. Abstract: An AOAC official method for quantitating cholesterol in multicomponent foods, which was first published in the 13th edition of the Official Methods of Analysis, is rarely used. The method includes so many operations and manipulations--all described in excruciating detail--that most laboratories shun it altogether. Intent on finding an alternative, laboratories have developed their own methods for specific foods. As a result, new methods have proliferated, but still no practical method has been developed for the broader categories of multicomponent foods. The aim of AOAC, which is to promote greater accuracy and uniformity of analytical results primarily through collaborative testing, has not been well served under these circumstances. A different approach guided the work reported in the present paper. This approach was directed toward updating and dramatically simplifying the existing AOAC official method. The method's chloroform-methanol-water mixed-solvent extraction is preserved; however, all the remaining steps have been streamlined, updated, or eliminated by using newer technology. Cholesterol is quantitated with highly specific capillary gas-liquid chromatography using the internal standardization technique. The lipid extract is prepared for the chromatography step by a brief saponification carried out in a culture tube. The resulting method has been validated by using Standard Reference Materials and the standard addition method. Because a simplified method is now available for quantitating cholesterol in the lipid extracts, the expectation is that more attention can be given to the development of improved and efficient extraction methods. This step remains as the central difficulty in any number of methods of analysis for lipid analytes. |
| A single cholesterol measurement underestimates the risk of coronary heart disease. An empirical example from the Lipid Research Clinics Mortality Follow-up Study Davis, C. E., B. M. Rifkind, et al. (1990), Jama 264(23): 3044-6. Abstract: In prospective epidemiologic studies of coronary heart disease, a single measurement of cholesterol is made to assess its relationship to the risk of coronary disease. Statistical theory states that if this measurement is subject to within-individual variability, the strength of the relationship will be underestimated. This is empirically shown for the example of plasma cholesterol. For the Lipid Research Clinics Follow-up Study population (comprising 2170 white men over 30 years of age), the age-adjusted coronary heart disease mortality regression coefficient increases from.453 to.496 if the average of two cholesterol measurements is used instead of a single measurement. Since the correlation between the two repeated cholesterol measurements is.815, an increase in the regression coefficient up to.556 would be expected if the true cholesterol values were available. Thus, epidemiologic studies have substantially underestimated the strength of the relationship between cholesterol levels and the risk of coronary disease by calculating the relationship on the basis of a single cholesterol determination. |