| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Characterization of the mevalonate kinase 5'-untranslated region provides evidence for coordinate regulation of cholesterol biosynthesis Bishop, R. W., K. L. Chambliss, et al. (1998), Biochem Biophys Res Commun 242(3): 518-24. Abstract: Using a probe derived from the 5'-untranslated region of the human mevalonate kinase (MK) cDNA, we screened a lambda gt 11 genomic library and obtained a single clone containing the 5' untranslated region of the gene. Nucleotide sequencing identified several putative regulatory elements, including two Sp1 (GC box) elements and a CCAAT box. A canonical TATA box was not detected. Directly adjacent to one Sp1 element was a sterol regulatory element (SRE), 5'-CACCCCAG-3', which was a 7/8 base pair match to the consensus sequences identified in the genes encoding 3-hydroxy-3-methyl-glutaryl-coenzyme A synthase and reductase, and the LDL receptor. There was no Sp1 element upstream of the SRE. Northern blot analysis in human CRL1508T cells revealed that quantities of MK poly A+ RNA increased for cells grown in the presence of lipid-deficient calf serum, and further increased upon addition of 1 microM lovastatin. Primer extension analysis with human poly A+ RNA suggested at least 4 transcription initiation sites downstream from the CCAAT box. To assess sterol responsiveness of transcription initiation, a 1.4 kb genomic fragment upstream of the translational start site was fused to the pSV2cat vector for transient expression in COS-7 cells, with chloramphenicol acetyltransferase (CAT) as the reporter gene. This construct demonstrated modest levels of CAT expression which was induced > 2-fold when cells were grown in lipoprotein-deficient calf serum. Our data provide further evidence for coordinate regulation of cholesterol biosynthesis in response to sterol. |
| Characterization of the ovariectomized rat model for the evaluation of estrogen effects on plasma cholesterol levels Lundeen, S. G., J. M. Carver, et al. (1997), Endocrinology 138(4): 1552-8. Abstract: Estrogens protect against cardiovascular disease in women through effects on the vascular wall and liver. Here we further characterize the rat as a model for the evaluation of estrogenic effects on plasma lipid levels vs. uterine wet weight. In adult ovariectomized female rats treated for 4 days s.c., 17alpha-ethinyl estradiol (EE) was the most potent agent to lower plasma total and high density lipoprotein cholesterol levels, followed by 17beta-estradiol and 17alpha-estradiol. However, 17alpha-estradiol had the greatest separation of uterotropic vs. cholesterol-lowering effects. EE had the same lipid-lowering potency whether administered s.c. or orally to adult rats. It had no effect on cholesterol levels in immature rats, even though the uterotropic response was dramatic. Testosterone propionate, dexamethasone, and progesterone did not significantly lower cholesterol levels. The antiestrogens tamoxifen and raloxifene lowered cholesterol levels, but with less efficacy and potency than the estrogens. ICI 182780 had no effect on cholesterol levels. When coadministered with EE, ICI 182780 inhibited the cholesterol-lowering and uterotropic activities of EE, suggesting that the estrogen receptor pathway is involved. In conclusion, although the information from the rat is limited as a model of the low density lipoprotein-lowering effects of estrogens in humans, it can be used to study the effects and mechanism of action of estrogen and antiestrogens on plasma cholesterol levels. |
| Characterization of the response of growth and differentiation to lipoproteins and agents affecting cholesterol metabolism in murine neuroblastoma cells Castellano, F., G. Bruscalupi, et al. (1994), Int J Dev Neurosci 12(1): 77-84. Abstract: Treatment with mevinolin, a competitive inhibitor of HMGCoAR, the key enzyme of isoprenoid metabolism, causes the arrest of proliferation and the differentiation of a neuroblastoma cell line (N18TG2). Mevalonate and high density lipoproteins partially restore growth. Cholesterol synthesis in the presence of mevinolin remains active, because in these cells the key enzyme HMG-CoA reductase is not completely inhibited by this drug. The fact that cell growth is reduced, while cholesterogenesis remains active, suggests that mevinolin acts by interfering with the synthesis of some unknown compound, other than cholesterol, which is necessary for proliferation. |
| Characterization of triglyceride rich lipoproteins with very light density by ultracentrifugation and agarose gel electrophoresis using triglyceride- and cholesterol-staining Hidaka, H., M. Tozuka, et al. (2003), Ann Clin Lab Sci 33(2): 167-78. Abstract: Hypertriglyceridemia is an independent risk factor for atherosclerosis. This risk is most likely due to accumulation of circulating triglyceride rich lipoproteins with heterogeneous particles. The identification and characterization of these triglyceride rich lipoproteins is important to detect abnormality of triglyceride metabolism. In the present study, we developed a new method that combines ultracentrifugation and agarose gel electrophoresis with triglyceride- and cholesterol-staining. We investigated 40 subjects with hypertriglyceridemia. Triglyceride rich lipoproteins with very light density were recovered in the aqueous fraction after ultracentrifugation (17,000 x g, 15 min). The lipoproteins recovered in the aqueous fraction contained chylomicrons, if present, their remnants, and light-VLDL (d <1.000 g/ml) containing apoB-100, but not normal VLDL (d <1.006 g/ml) and IDL. Triglyceride rich lipoproteins in the aqueous fraction were characterized by electrophoresis patterns of triglyceride- and cholesterol-staining. Forty patients with hypertriglyceridemia were separated into 8 groups according to their electrophoretic patterns. In lipoproteins recovered in the aqueous fraction from each group, the triglyceride level was correlated with the respective cholesterol level. In summary, a system using ultracentrifugation and agarose gel electrophoresis with triglyceride- and cholesterol-staining is useful for characterization of triglyceride rich lipoproteins and their remnants. |
| Characterization of two unique cholesterol-rich lipid particles isolated from human atherosclerotic lesions Chao, F. F., E. J. Blanchette-Mackie, et al. (1990), Am J Pathol 136(1): 169-79. Abstract: The authors' laboratory, using histochemical methods, previously identified two types of cholesterol-containing lipid particles in the extracellular spaces of human atherosclerotic lesions, one particle enriched in esterified cholesterol and the other particle enriched in unesterified cholesterol. The authors isolated and characterized these lipid particles. The esterified cholesterol-rich lipid particle was a small lipid droplet and differed from intracellular lipid droplets found in foam cells with respect to size and chemical composition. It had an esterified cholesterol core surrounded by a phospholipid-unesterified cholesterol monolayer. Some aqueous spaces were seen within the particle core. Unesterified cholesterol-rich lipid particles were multilamellated, solid structures and vesicles comprised of single or multiple lamellas. The esterified cholesterol-rich particle had a density less than 1.01 g/ml, whereas the unesterified cholesterol-rich particle had a density between 1.03 and 1.05 g/ml. Both particles were similar in size (90% of both particles ranged in size between 40 to 200 nm in diameter) and had an unesterified cholesterol-to-phospholipid molar ratio of 2.5:1. The predominant phospholipid in both particles was sphingomyelin. The fatty acyl compositions of cholesteryl ester and phospholipid also were similar in both particles. Palmitate, oleate, and linoleate were the major fatty acids in the cholesteryl ester fraction, whereas palmitate, stearate, oleate, and linoleate were predominant in the phospholipid fraction. The origins and the role of these two unusual lipid particles in vessel wall cholesterol metabolism remain to be determined. |
| Charting the fate of the "good cholesterol": identification and characterization of the high-density lipoprotein receptor SR-BI Krieger, M. (1999), Annu Rev Biochem 68: 523-58. Abstract: Risk for cardiovascular disease due to atherosclerosis increases with increasing concentrations of low-density lipoprotein (LDL) cholesterol and is inversely proportional to the levels of high-density lipoprotein (HDL) cholesterol. The receptor-mediated control of plasma LDL levels has been well understood for over two decades and has been a focus for the pharmacologic treatment of hypercholesterolemia. In contrast, the first identification and characterization of a receptor that mediates cellular metabolism of HDL was only recently reported. This receptor, called scavenger receptor class B type I (SR-BI), is a fatty acylated glycoprotein that can cluster in caveolae-like domains on the surfaces of cultured cells. SR-BI mediates selective lipid uptake from HDL to cells. The mechanism of selective lipid uptake is fundamentally different from that of classic receptor-mediated endocytic uptake via coated pits and vesicles (e.g. the LDL receptor pathway) in that it involves efficient receptor-mediated transfer of the lipids, but not the outer shell proteins, from HDL to cells. In mice, SR-BI plays a key role in determining the levels of plasma HDL cholesterol and in mediating the regulated, selective delivery of HDL-cholesterol to steroidogenic tissues and the liver. Significant alterations in SR-BI expression can result in cardiovascular and reproductive disorders. SR-BI may play a similar role in humans; thus, modulation of its activity may provide the basis of future approaches to the treatment and prevention of atherosclerotic disease. |
| Checking your kid's cholesterol. A researcher calls the current standard flawed Comarow, A. (1999), US News World Rep 126(13): 66. |
| Chemical activity of cholesterol in membranes Radhakrishnan, A. and H. M. McConnell (2000), Biochemistry 39(28): 8119-24. Abstract: Measurements are reported for the rate constants for the release of cholesterol (and dihydrocholesterol) to beta-cyclodextrin from mixtures with phospholipids in homogeneous monolayers at constant pressure at the air-water interface. In each mixture, it is found that the release rate shows a sharp decrease as the cholesterol concentration in the monolayer decreases through a composition corresponding to the stoichiometry of a cholesterol-phospholipid complex. The stoichiometry of the complex was established previously by the position of a sharp cusp in the thermodynamic phase diagram of each mixture and also by a minimum in average molecular area versus composition measurements. A theoretical model used earlier to account for the phase diagrams predicts the chemical potential and chemical activity of cholesterol in these mixtures. The calculated chemical activity also shows a sharp change at the complex stoichiometry in homogeneous monolayers. The similarities in change of observed release rate and calculated chemical activity are expected from reaction rate theory where the release rate is proportional to the cholesterol chemical activity. The chemical activity of cholesterol as determined by complex formation between some phospholipids and cholesterol in the plasma membrane of cells may serve a regulatory function with respect to intracellular cholesterol transport and biosynthesis. |
| Chemical and physiochemical comparison of advanced atherosclerotic lesions of similar size and cholesterol content in cholesterol-fed New Zealand White and Watanabe Heritable Hyperlipidemic rabbits Nolte, C. J., A. M. Tercyak, et al. (1990), Lab Invest 62(2): 213-22. Abstract: Watanabe Heritable Hyperlipidemic (WHHL) and cholesterol-fed New Zealand White (CH-FED NZW) rabbits were sacrificed at 15 months of age or after 16 weeks of cholesterol feeding, respectively. During the experimental period, the arterial walls of both the CH-FED NZW and WHHL rabbits were exposed to similar amounts of cholesterol and the lesions which developed at the aortic arch had similar intimal thicknesses, total lipid and cholesterol content. However, the lesions of the WHHL rabbits morphologically resembled human plaques, and contained lipid in the form of smectic liquid crystalline droplets and cholesterol monohydrate crystals. The CH-FED NZW rabbits had lesions which were fatty streak-like, containing liquid crystalline cholesteryl ester droplets but few crystals. The aortic arch intimas of the CH-FED NZW rabbits contained significantly more cholesteryl ester, and less unesterified cholesterol and triglyceride, than those of the WHHL rabbits. The intimal compositions of the two rabbit models did not overlap. Analysis of the compositions predicted precipitation of cholesterol monohydrate crystals in the WHHL but not the CH-FED NZW. The physical state of the deposited cholesterol esters was similar in both with about half being in smectic liquid crystalline form at body temperature. Since the size and total lipid content of the lesions of the CH-FED NZW and WHHL rabbits were similar, we suggest that the greater time of exposure to hypercholesterolemia was important in the formation of cholesterol monohydrate crystal-containing plaques in the aortic arch of the WHHL rabbits. |
| Chemical characteristics, fatty acid compositions, conjugated linoleic acid contents and cholesterol levels of some traditional Turkish cheeses Donmez, M., A. Kemal Seckin, et al. (2005), Int J Food Sci Nutr 56(3): 157-63. Abstract: The chemical characteristics, fatty acid and conjugated linoleic acid (CLA) contents and cholesterol levels of some traditional Turkish cheeses that are consumed mostly in Turkey were determined in this study. The fatty acid and cholesterol contents and CLA amount of cheeses were analysed as methyl esters by gas chromatography. The aim of this study was to determine the nutritional profile of some Turkish cheeses produced by traditional methods. The major fatty acids of the cheeses were palmitic acid (C(16:0)) and oleic acid (C(18:1)). The saturated fatty acid content of samples changed between 60.80% and 76.57%, while the monounsaturated fatty acid content ranged from 21.42% to 34.05% and the polyunsaturated fatty acid content was between 1.47% and 3.59%. The CLA contents of the cheeses ranged from 0.44 to 1.04 g/100 g in fat. The cholesterol levels of the samples were determined as 44.6-147.69 mg/100 g in cheese. |
| Chemiluminescent determination of cholesterol hydroperoxides in human erythrocyte membrane Adachi, J., M. Asano, et al. (1998), Lipids 33(12): 1235-40. Abstract: A method for separating, detecting, and quantifying cholesterol hydroperoxide (Ch-OOH) based on extraction, purification by solid-phase extraction cartridge, high-performance liquid chromatography with chemiluminescent detection (HPLC-CL), and liquid chromatography-mass spectrometry has been developed for human erythrocyte membrane. We prepared standard compounds of the cholesterol 5alpha-, 7alpha-, and 7beta-hydroperoxides (Ch 5alpha-OOH, Ch 7alpha-OOH, and Ch 7beta-OOH). An octyl silica column with methanol/water/acetonitrile 89:9:2 (by vol) as eluent was used to determine Ch-OOH. HPLC-CL that incorporated cytochrome c and luminol as the post-column luminescent reagent was used. We also investigated the optimal assay conditions and how to prevent formation of artifact Ch-OOH. Analysis of erythrocyte membranes from seven healthy volunteers identified Ch 7alpha-OOH and Ch 7beta-OOH, but not Ch 5alpha-OOH, as commonly occurring components. The respective mean concentrations of Ch 7alpha-OOH and Ch 7beta-OOH were 2.5+/-1.6 and 5.4+/-3.5 pmol/mL blood. |
| Chemokine stimulation of lymphocyte alpha 4 integrin avidity but not of leukocyte function-associated antigen-1 avidity to endothelial ligands under shear flow requires cholesterol membrane rafts Shamri, R., V. Grabovsky, et al. (2002), J Biol Chem 277(42): 40027-35. Abstract: VLA-4 and LFA-1 are the major vascular integrins expressed on circulating lymphocytes. Previous studies suggested that intact cholesterol rafts are required for integrin adhesiveness in different leukocytes. We found the alpha(4) integrins VLA-4 and alpha(4)beta(7) as well as the LFA-1 integrin to be excluded from rafts of human peripheral blood lymphocytes. Disruption of cholesterol rafts with the chelator methyl-beta-cyclodextrin did not affect the ability of these lymphocyte integrins to generate high avidity to their respective endothelial ligands and to promote lymphocyte rolling and arrest on inflamed endothelium under shear flow. In contrast, cholesterol extraction abrogated rapid chemokine triggering of alpha(4)-integrin-dependent peripheral blood lymphocytes adhesion, a process tightly regulated by G(i)-protein activation of G protein-coupled chemokine receptors (GPCR). Strikingly, stimulation of LFA-1 avidity to intercellular adhesion molecule 1 (ICAM-1) by the same chemokines, although G(i)-dependent, was insensitive to raft disruption. Our results suggest that alpha(4) but not LFA-1 integrin avidity stimulation by chemokines involves rapid chemokine-induced GPCR rearrangement that takes place at cholesterol raft platforms upstream to G(i) signaling. Our results provide the first evidence that a particular chemokine/GPCR pair can activate different integrins on the same cell using distinct G(i) protein-associated machineries segregated within defined membrane compartments. |
| Chemometric study and analytical enzymatic methods for diagnosis of cholesterol gallstones Campanella, L., M. Tomassetti, et al. (1990), J Pharm Biomed Anal 8(3): 229-34. Abstract: The lithogenic index (IL) provides an estimate of cholesterol saturation in gallbladder bile and is of possible value for prediction of gallstone formation. A package for pattern recognition of analytical chemical data, known as "Parvus", was used to study the different values of IL obtained experimentally using common enzymic methods for cholesterol and bile salts and other analytical techniques for phospholipids. Ten patients were investigated and some interesting conclusions were drawn, both on the equivalence of various analytical methods for the determination of phospholipids and on the contribution of pattern recognition analysis to the diagnosis of gallstones. |
| Chemotaxis of the monocyte cell line U937: dependence on cholesterol and early mevalonate pathway products Kreuzer, J., J. Bader, et al. (1991), Atherosclerosis 90(2-3): 203-9. Abstract: In the present study we investigated the influence of cholesterol depletion and hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase) inhibition on chemotaxis of the human monocytic cell line U937. Chemotaxis was nearly completely depressed after incubation for 24 h in the absence of lipoproteins. This was accompanied by a significant decrease in cellular cholesterol. Addition of 10 micrograms/ml low density lipoprotein (LDL) for 2 h to the cholesterol-depleted cells restored chemotaxis. Free cholesterol had no effect under these conditions. Inhibition of HMG-CoA reductase by pravastatin (0.01-1.0 mM) for 20 or 72 h also reduced chemotaxis. However, this effect was not accompanied by a decrease in cellular cholesterol when cells were grown in the presence of lipoproteins. The effect of pravastatin could be reversed by the addition of mevalonate. Addition of LDL did not change the response to pravastatin. We propose that the availability of cholesterol plays an important role in cellular chemotaxis. Furthermore, it can be suggested that other products of the mevalonate pathway apart from cholesterol may contribute to the regulation of chemotaxis. |
| Chia seed (Salvia hispanica L.) as an omega-3 fatty acid source for broilers: influence on fatty acid composition, cholesterol and fat content of white and dark meats, growth performance, and sensory characteristics Ayerza, R., W. Coates, et al. (2002), Poult Sci 81(6): 826-37. Abstract: Five thousand four hundred, 1-d-old, male, Ross 308, broiler chicks were fed for 49 d to compare diets containing 10 and 20% chia (Salvia hispanica L.) seed to a control diet. Cholesterol content, total fat content, and fatty acid composition of white and dark meats were determined at the end of the trial. A taste panel assessed meat flavor and preference. Cholesterol content was not significantly different among treatments; however, the 10% chia diet produced a lower fat content in the dark meat than did the control diet. Palmitic fatty acid content was less in both meat types when chia was fed, with differences being significant (P < 0.05), except for the white meat and the 20% chia diet. alpha-Linolenic fatty acid was significantly higher (P < 0.05) in the white and dark meats with the chia diets. Chia significantly lowered the saturated fatty acid content as well as the saturated:polyunsaturated fatty acid and omega-6:omega-3 ratios of the white and dark meats compared to the control diet. No significant differences in flavor or preference ratings were detected among diets. Body weight and feed conversion were significantly lower with the chia diets than with the control, with weight reductions up to 6.2% recorded with the 20% chia diet. |
| Child health and nutrition: obesity and high blood cholesterol Ernst, N. D. and E. Obarzanek (1994), Prev Med 23(4): 427-36. Abstract: BACKGROUND. The epidemiology of obesity and high blood cholesterol in children is discussed, along with strategies for the prevention of these two disorders and mention of some nutrition and child health research and education programs supported by the National Heart, Lung, and Blood Institute (NHLBI). CONCLUSIONS. Available data confirm that both obesity and high blood cholesterol levels in U.S. children are higher than optimal and that the benefit of reducing the prevalence of these conditions in childhood will be realized in adulthood. Current NHLBI-supported research and education activities focus on unanswered questions about the childhood predictors of transition to the obese state, the feasibility, efficacy, and safety of long-term dietary intervention in children, and the effects of school-based intervention that include classroom curriculum and school environmental changes related to food intake, physical activity, and tobacco use and dissemination of materials that promote nutrition and cardiovascular health in children and adolescents. |
| Childhood cholesterol screening: an alternative view Schoen, E. J. (1992), Am Fam Physician 45(5): 2179-82. Abstract: Controversy exists regarding universal cholesterol screening in children. No long-term evidence has proved that lowering childhood cholesterol levels prevents the development of coronary heart disease in adulthood. Furthermore, questions remain as to the effectiveness and safety of lipid-lowering diets in children. Even if future research shows that lipid-lowering diets are beneficial, children and their families may not be willing to comply with the prescribed regimen. A more sensible way to prevent coronary heart disease in adults may be by promoting a healthy lifestyle beginning in early childhood and including a balanced diet, weight control and exercise. |
| Childhood cholesterol screening: contraindicated Newman, T. B., W. S. Browner, et al. (1992), Jama 267(1): 100-1; discussion 101-2. |
| Childhood obesity elevates blood pressure and total cholesterol independent of physical activity McMurray, R. G., J. S. Harrel, et al. (1995), Int J Obes Relat Metab Disord 19(12): 881-6. Abstract: OBJECTIVE: To compare the habitual physical activity, blood pressure, total cholesterol levels of obese and non-obese matched children. SUBJECTS: 546 obese children (BMI and sum of skinfolds > or = 90% tile) were matched for gender, race, age, and height (within 2 cm) with non-obese controls for a total sample of 1092 children. MEASUREMENTS: Systolic (BPsys) and diastolic (BPdia) blood pressure by mercury sphygmomanometer, total cholesterol by reflectance photometry, and physical activity by questionnaire. RESULTS: Mean comparisons indicated the obese children, regardless of gender, had higher BPsys (108 +/- 11 vs 104 +/- 10 mm Hg, P = 0.0001), BPdia (70 +/- 9 vs 68 +/- 8 mm Hg, P = 0.002), and greater total cholesterol levels (4.47 +/- 0.80 vs 4.11 +/- 0.75 mmol/L, P = 0.0001) than the non-obese subjects. Self-reported physical activity scores were not significantly different when comparing the obese and non-obese children. Correlations between self-reported activity and cholesterol or blood pressure were all very low and not significant (r < or = 0.06). CONCLUSION: These results suggest that childhood obesity is associated with higher blood pressures and greater circulating cholesterol levels independent of physical activity levels. |
| Childhood precursors of high blood pressure and elevated cholesterol Labarthe, D. R., M. Eissa, et al. (1991), Annu Rev Public Health 12: 519-41. |