| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Non-polar interactions between cholesterol and phospholipids: a molecular dynamics simulation study Rog, T. and M. Pasenkiewicz-Gierula (2004), Biophys Chem 107(2): 151-64. Abstract: A 15-ns molecular dynamics simulation of the fully hydrated dimyristoylphosphatidylcholine-cholesterol (DMPC-Chol) bilayer containing approximately 22 mol% Chol was carried out. An 8-ns trajectory was analysed to investigate the effect of Chol on the chain packing in the bilayer core. While the packing of DMPC chains on the smooth alpha-face side of the Chol ring is similar to that in the pure DMPC bilayer, the packing on the rough beta-face side is less regular and less tight. Two methyl groups located on the Chol beta-face disturb the packing; in effect, van der Waals (vdW) interactions between Chol rings and DMPC chains are weaker than the ones between sole DMPC chains. VdW interactions between an alkyl chain of DMPC and an isooctyl tail of Chol are similarly strong as those between two DMPC chains. |
| Non-raft forming sphingomyelin-cholesterol mixtures Epand, R. M. and R. F. Epand (2004), Chem Phys Lipids 132(1): 37-46. Abstract: Sphingomyelin from biological membranes forms segregated domains with cholesterol in fluid bilayers. However, a synthetic form of sphingomyelin with an oleoyl chain linked to sphingosine is not incorporated into cholesterol-rich domains. We have studied the properties of mixtures of oleoyl-sphingomyelin and cholesterol as well as mixtures of oleoyl-sphingomyelin with 1-stearoyl-2-oleoyl-phosphatidylcholine by DSC and NMR. Cholesterol has a high miscibility with oleoyl-sphingomyelin and it does not separate in crystalline form until the mol fraction of cholesterol reaches a value above 0.6. A large fraction of the cholesterol crystals that are formed are in the monohydrate form. Furthermore, these crystals rehydrate relatively rapidly compared with pure cholesterol crystals in the absence of phospholipid. The environment of the carbonyl group of the phospholipid indicates that it is similar to other forms of sphingomyelin with saturated acyl chains. Also similar to other forms of sphingomyelin, the quaternary ammonium group of oleoyl-sphingomyelin is more rigid than that of phosphatidylcholines, as indicated by the strong resonance observed with cross-polarization/magic angle spinning. Additionally, oleoyl-sphingomyelin produces a larger alteration than egg sphingomyelin of the phase transition of 1-stearoyl-2-oleoyl-phosphatidylcholine. These studies indicate that oleoyl-sphingomyelin, unlike saturated forms of sphingomyelin, does not form segregated domains with cholesterol because of its greater miscibility with phosphatidylcholine. |
| Non-significance of plasma total cholesterol in the occurrence of occupational accidents Bursey, R. G. (1992), Occup Med (Lond) 42(1): 33-5. Abstract: A recent review of cholesterol lowering intervention trials has demonstrated an increased mortality from non-illness events, including accidents. This study examines 410 middle-aged men with regards to plasma total cholesterol levels and the occurrence of minor factory accidents. There was no significant difference in mean cholesterol concentrations between those who had reported a factory accident, and those who had not, over a 2 year period; 5.7 mmol/l (SD, 0.98 mmol/l) and 5.73 mmol/l (SD, 1.06 mmol/l) respectively. The 19 men who had sustained an occupational injury of significant severity to result in absence from work did not have a mean plasma total cholesterol level which differed appreciably from any of the other subjects, their mean being 5.66 mmol/l (SD, 1:18 mmol/l). Plasma total cholesterol in itself is not participating in the occurrence of accidents in this occupational group. |
| Norethindrone acetate enhances the antiatherogenic effect of 17beta-estradiol: a secondary prevention study of aortic atherosclerosis in ovariectomized cholesterol-fed rabbits Alexandersen, P., J. Haarbo, et al. (1998), Arterioscler Thromb Vasc Biol 18(6): 902-7. Abstract: The influence of progestogens in combination with 17beta-estradiol (E2) on cardiovascular disease remains controversial. This study investigated the effect of norethindrone acetate (NETA) combined with E2 on aortic atherosclerosis. Eighty mature female rabbits were ovariectomized, then fed a cholesterol-rich diet (240 mg/d) for 14 weeks to induce aortic atherosclerosis. They were randomized to four equally large groups for the following 38-week intervention period. One group received placebo, another group oral E2 4 mg daily (E2), and the last two groups oral E2 4 mg daily combined with either NETA 1 mg (E2NETA1) or NETA 3 mg (E2NETA3). The cholesterol intake was reduced to a "maintenance" level of 80 mg/d during the intervention period. Total serum cholesterol and ultracentrifuged lipoproteins were analyzed enzymatically throughout the study. The cholesterol content in the aortic wall was 2.76+/-0.44 micromol/cm2 (mean+/-SEM) in the E2NETA1 group, 1.77+/-0.37 micromol/cm2 in the E2NETA3 group, 5.46+/-0.77 micromol/cm2 in the E2 group, and 7.20+/-0.94 micromol/cm2 in the placebo group (ANOVA P<0.0001). The difference (in the aortic cholesterol accumulation) between the E2 and each of the combined E2/NETA groups was statistically significant (P<0.01) but could only partly be explained by the differences in serum lipids and lipoproteins. In conclusion, NETA enhances the antiatherogenic effect of E2 in cholesterol-fed rabbits. This effect is only partially mediated through changes in serum lipids and lipoproteins. |
| Normal and inhibited cholesterol synthesis in the cultured rat embryo Llirbat, B., C. Wolf, et al. (1997), J Lipid Res 38(1): 22-34. Abstract: The Smith-Lemli-Opitz syndrome-affected fetus presents a deficiency in delta7-dehydrocholesterol reductase, the last enzymatic step in the cholesterol biosynthesis pathway. Development of the abnormal human fetus takes place in a normal environment as the heterozygous mother's cholesterolemia remains normal. An animal model for this disease has been obtained from the offspring of pregnant rats treated with "distal" inhibitors of delta7-dehydrocholesterol reductase, AY-9944 or BM15766. In the animal model, embryonic development occurs in a disturbed environment characterized by hypocholesterolemia and accumulation of delta7-dehydrocholesterol and delta8-dehydrocholesterol in the maternal serum. The purpose of the present study was to assess, in cultured rat embryos at early developmental stages, the relative contributions of exogenous and de novo synthesized cholesterol in the total embryonic cholesterol, according to the conditions of normal and altered de novo biosynthesis. Cultured rat embryos are able to synthesize cholesterol as shown by 13C-incorporation into cholesterol from 13C-labeled precursors added to the culture medium. De novo cholesterol biosynthesis is altered by addition to the culture medium of AY-9944 which inhibits the delta7-dehydrocholesterol reductase and the delta8-delta7-sterol isomerase as suggested by the emergence of characteristic aberrant sterols in the embryonic tissues. Cholesterol-rich serum used for embryo culture alters the pattern in a way that confirms that the rat embryos are able to import exogenous cholesterol which down-regulates de novo cholesterol biosynthesis. Exogenous cholesterol substitutes for the deficit in a manner efficient enough to prevent the embryonic abnormalities induced by AY-9944. |
| Normal cholesterol measurements in white collar workers still at cardiovascular risk? Berg, J. E. (1996), Occup Med (Lond) 46(2): 141-5. Abstract: Low serum total cholesterol (TC) in workers has been taken to indicate absence of cardiovascular (CV) risk. In angiographically confirmed coronary artery disease TC has been shown to be less poignant than compound indices of cardiovascular risk in separating patients from controls. The implications for prevention in an industrial medical setting of relying on TC measurements are discussed. Employees (n = 229) tested by an occupational health service in a non-manufacturing firm were dichotomized as low and high cardiovascular risk subjects either by the level of total cholesterol, or by two compound indices of blood lipid components. The compound indices were: the TC/HDLc-ratio, and an 'atherogenic index' (ATH-index) defined as (TC-HDLc x apo B) + (HDLc x apo A). (apo A = apolipoprotein A-I, apo B = apolipoprotein B). Cut-off values to separate between low- and high-risk subjects were defined as TC = 6.0 mmol/l, HDLc = 0.9 mmol/l, apo A = 1.8 milligrams and apo B = 1.3 milligrams, based on clinical guidelines in Norway. These individual cut-off values gave TC/HDLc and ATH-index cut-off values of 6.7 and 4.1, respectively. Assuming a more correct discrimination between persons at low- and high-risk, using compound lipid indices, both the number of persons given unnecessary advice on lifestyle changes or urged to take TC reducing medication, and the number of persons not treated on the basis of normal TC levels, would be reduced. Percentages of persons classified as TC-level-low risk, were adjusted using empirical data on sensitivity and specificity of the compound indices. Among employees with TC < 6.0mmol/l, 15% and 23% of women, and 12% and 19% of men would be classified as high-risk persons using the TC/HDLc-ratio or the ATH-index, respectively. Lack of prospective data on compound indices suggests cautious interpretation. TC values in spurious testing, as often applied in occupational health service without due regard to other lipid fractions, would increase the probability of unnecessarily treating persons not at CV risk and withholding people at probable CV risk from treatment. Although prospective studies are needed to confirm findings, the changes observed suggest avoiding measurements of some single lipid factors. |
| Normal cholesterol synthesis in human cells requires functional peroxisomes Hodge, V. J., S. J. Gould, et al. (1991), Biochem Biophys Res Commun 181(2): 537-41. Abstract: To evaluate the importance of peroxisomes in cholesterol metabolism we measured the rate of cholesterol synthesis in cultured skin fibroblasts from 16 patients in whom deficiency of peroxisomes had been established. Seven complementation groups were studied, consisting of one six member group, one three member group, three groups comprising single cases and two groups with two cases each. On the average, cholesterol synthesis was below control values in all the 16 peroxisome-deficient fibroblast cell cultures. The range of cholesterol synthesis in these cells was 2% to 84% of normal values. These data strongly suggest that peroxisomes are essential for normal cholesterol synthesis in human fibroblasts. |
| Normal cholesterol values in children Wiesmann, U. (1994), Dtsch Med Wochenschr 119(40): 1371. |
| Normal genetic variation at the low density lipoprotein receptor (LDLR) locus influences cholesterol levels in children Poledne, R., Z. Pisa, et al. (1993), Clin Genet 43(3): 122-6. Abstract: The population of Czechoslovakia is at high risk of premature atherosclerosis. Normal DNA polymorphism at the low density lipoprotein receptor (LDLR) locus detectable with the restriction enzyme PvuII was analyzed in Czech children with a high or a low concentration of total serum cholesterol. The PvuII restriction site was found significantly more often in the low cholesterol group than in the high cholesterol group. Thus, normal genetic variation at the LDLR locus contributes to the population variation in cholesterol in children in the population studied. |
| Normal intestinal dietary fat and cholesterol absorption, intestinal apolipoprotein B (ApoB) mRNA levels, and ApoB-48 synthesis in a hypobetalipoproteinemic kindred without any ApoB truncation Pulai, J. I., M. Averna, et al. (1997), Metabolism 46(9): 1095-100. Abstract: The purpose of this study was to characterize intestinal apolipoprotein B (apoB) metabolism in subjects with familial hypobetalipoproteinemia (FHBL), where segregation analysis supports linkage to the apoB gene but no apoB truncations are present. We investigated cholesterol and fat absorption, intestinal apoB mRNA synthesis and editing, as well as apoB-48 synthesis. Plasma triglycerides (TG) and retinyl palmitate in the chylomicron fractions were analyzed after 12 hours of fasting and then repeatedly for 14 hours after ingestion of a vitamin A-containing high-fat meal. Cholesterol absorption was assessed using a dual stable-isotope method. Mean peak times and concentrations and areas under the curve (AUCs) for fat absorption and mean percentages of cholesterol absorption were comparable in affected and nonaffected family members. Intestinal biopsies were extracted for total RNA and also incubated with 35S-methionine for measurements of apoB synthesis. Similar quantities of apoB mRNA were found to be expressed in the intestine in affected and control subjects by RNase protection assay. ApoB mRNA editing assay showed that the majority of apoB-100 mRNA was edited to the apoB-48 form to a similar extent in both groups. Virtually no apoB-100 protein was synthesized by the intestine in any subject, and apoB-48 protein synthesis was not significantly different in the affected individuals. These data are consistent with in vivo metabolism data that show normal production rates for liver-derived apoB-100 but increased apoB-100 fractional catabolic rates in affected members of this family. Thus, the molecular defect probably does not affect transcription, translation, or secretion of apoB-containing lipoproteins, but may instead affect their clearance. |
| Normal perinatal rise in serum cholesterol is inhibited by hepatic delivery of adenoviral vector expressing apolipoprotein B mRNA editing enzyme (Apobec1) in rabbits Wu, Y., B. B. Teng, et al. (1999), J Surg Res 85(1): 148-57. Abstract: BACKGROUND: Prenatal or neonatal hepatic gene delivery may result in more effective therapy for inborn errors of metabolism due to the immature immune system of the perinatal animal, and the ability to intervene prior to any significant cellular damage. Newborn New Zealand White rabbits have low serum levels of cholesterol at birth, with a significant and sustained rise of cholesterol while they are nursing. We used this physiologic hypercholesterolemia model to study the effect of adenovirus-mediated hepatic gene transfer of rat apolipoprotein B mRNA editing enzyme (Apobec1) on modulation of plasma cholesterol levels. METHODS AND RESULTS: Transcutaneous injection of recombinant adenovirus expressing Apobec1 (AvApobec1) into the liver of newborn rabbits in vivo resulted in efficient Apobec1 expression until Day 50, as detected by PCR-Southern blot analysis. By in vitro editing assay, liver extracts of AvApobec1-treated rabbits were found to have apoB mRNA editing activities of approximately 12, 15, and 15%, on Days 2, 10, and 20 after AvApobec1 administration, compared with 0% editing activity in AvLacZ control vector-injected animals. This physiological level of Apobec1 expression was associated with the production of apoB-48-containing lipoprotein particles from rabbit liver, with a concomitant 30% reduction in total plasma cholesterol compared to AvLacZ-treated or untreated control animals. CONCLUSION: Neonatal intrahepatic delivery of a first-generation adenoviral vector results in efficient gene transfer with little immune response, suggesting that repeated administration may be possible in the neonatal period. |
| Normal plasma cholesterol in an 88-year-old man who eats 25 eggs a day. Mechanisms of adaptation Kern, F., Jr. (1991), N Engl J Med 324(13): 896-9. |
| Normal serum cholesterol in panic disorder Tancer, M. E., M. B. Stein, et al. (1990), Biol Psychiatry 27(1): 99-101. |
| Normal upper limit of serum cholesterol 250 mg/dl or 200 mg/dl? Kumar, H. (1995), J Indian Med Assoc 93(10): 399. |
| Normalization of high density lipoprotein cholesterol following cessation from cigarette smoking Moffatt, R. J. (1990), Adv Exp Med Biol 273: 267-72. |
| Normolipidemic subjects with low HDL cholesterol levels have altered HDL subpopulations Asztalos, B. F., M. Lefevre, et al. (1997), Arterioscler Thromb Vasc Biol 17(10): 1885-93. Abstract: Epidemiological studies have established that plasma concentration of HDL is inversely correlated with the risk of coronary heart disease, even in the absence of increased LDL cholesterol levels. We postulate that specific HDL subpopulations may be responsible for antiatherogenic properties of HDL. HDL subpopulations were quantitated by two-dimensional gel electrophoresis in 79 normolipidemic healthy male subjects. To eliminate the influence of diet, volunteers consumed an average American diet for 6 weeks. After the diet period, subjects were stratified according to their HDL cholesterol (HDL-C) levels to low HDL-C < 0.91 mmol/L (< 35 mg/dL), medium > 0.91 < 1.30 mmol/L (> 35 < 50 mg/dL), and high > or = 1.30 mmol/L (> or = 50 mg/dL) groups. Plasma triglycerides and insulin levels were in the normal range, but subjects with low HDL-C levels had higher concentrations of plasma triglycerides and insulin than subjects with medium or high HDL-C concentrations. The absolute concentration (mg/dL) of apoA-I in the largest alpha-migrating HDL subpopulation (alpha 1) was (P <.01) lower in the low HDL-C subjects compared with the medium and high HDL-C groups. The relative concentration (percent distribution) of apoA-I was decreased (P <.01) in alpha 1 and increased (P <.01) in alpha 3 subpopulations. A positive correlation between HDL-C and alpha 1 (P <.001) and a negative correlation between HDL-C and alpha 3 were observed. The inverse correlation of apoA-I distribution (relative concentration) between alpha 1 and alpha 3 suggests an interconversion of alpha 1 and alpha 3 subpopulations, possibly by cholesteryl ester transfer protein. Pre-beta subpopulations showed an inverse trend with HDL-C, while the pre-alpha subpopulation behaved similarly to the alpha-migrating subpopulation. Colocalization of apoA-I and apoA-II particles in the different HDL subpopulations demonstrated that alpha 1, pre-beta 1, and pre-beta 2 subpopulations are apoA-I-only particles rather than apoA-I:A-II particles. |
| Normolipidemic xanthelasma palpebrarum: lipid composition, cholesterol metabolism in monocyte-derived macrophages, and plasma lipid peroxidation Bergman, R., Y. Kasif, et al. (1996), Acta Derm Venereol 76(2): 107-10. Abstract: The lipid compositions of 8 normolipidemic xanthelasma palpebrarum (XP) lesions were analyzed using thin-layer chromatography, with the adjacent uninvolved skin used as control. The lesions were found to be composed predominantly of cholesterol, mostly cholesteryl ester, whereas in the control specimens phospholipids predominated. The degradation rates of 125I-low-density lipoprotein (LDL), oxidized LDL, and acetyl LDL, and the rates of intracellular cholesterol synthesis from 1,2-(14)C-acetate, in blood monocyte-derived macrophages (MDM) from 3 normolipidemic patients, were similar to those of MDM from 3 normal control subjects. The mean levels of lipid peroxides and conjugated dienes under basal conditions, as well as following the addition of a free radical-generating compound (2,2-azobis-2-amidinopropane hydrochloride) to the plasma of 14 normolipidemic XP patients were significantly higher than those of 14 age- and sex-matched normal controls. We conclude that the predominant lipid accumulated in normolipidemic XP lesions is cholesteryl ester, but there is no evidence for intrinsic cellular cholesterol metabolism derangement in blood MDM from patients which could account for this. Since macrophage cholesterol accumulation can also result from enhanced uptake of increased levels of oxidized LDL, the increased plasma lipid peroxidation (derived from oxidized LDL) might lead to accumulation of cholesterol in macrophages and formation of foam cells via this mechanism. |
| North Coast cholesterol check campaign Gliksman, M. D., R. Lazarus, et al. (1991), Med J Aust 155(2): 133. |
| North Coast Cholesterol Check Campaign Hocking, B. (1991), Med J Aust 154(11): 779-80. |
| Novel ABCA1 compound variant associated with HDL cholesterol deficiency Ho Hong, S., J. Rhyne, et al. (2002), Biochim Biophys Acta 1587(1): 60-4. Abstract: The recent discovery of an ATP-binding cassette transporter, ABCA1, as an important regulator of high density lipoprotein (HDL) metabolism and reverse cholesterol transport has facilitated the identification of novel variants associated with HDL cholesterol deficiency states. We identified a subject with HDL cholesterol deficiency (4 mg/dl) who developed and died of complications related to cerebral amyloid angiopathy (CAA). The proband had a compound heterozygous mutation. One mutation was a G3295T substitution with conversion of asparagine to tyrosine (D1099Y) in ABCA1. The single-base substitution at codon 1099 resulted in the abolition of an RsaI cleavage site. The proband and affected individuals having another mutation were heterozygotes for T5966C with phenylalanine converted to serine (F2009S). The presence of the T5966C mutation was detected by restriction digestion with HinfI. These variants were not identified in over 400 chromosomes of healthy subjects. In the kindred, family members heterozygous for the ABCA1 variant exhibited low levels of HDL cholesterol. Direct sequencing of all coding regions and splice site junctions of other HDL candidate genes revealed no additional mutations, indicating that combined defective ABCA1 alleles may result in familial HDL deficiency. |