Cholesterol Journal Articles

Record 701 to 720

An apolipoprotein AI mimetic peptide: membrane interactions and the role of cholesterol
Epand, R. M., R. F. Epand, et al. (2004), Biochemistry 43(17): 5073-83.
Abstract: The 18-amino acid amphipathic helical peptide Ac-DWFKAFYDKVAEKFKEAF-NH(2) promotes the separation of cholesterol from the phospholipid, resulting in the formation of cholesterol crystallites, even at mole fractions of cholesterol as low as 0.3. The peptide exerts a greater degree of penetration into membranes of pure phosphatidylcholine in the absence of cholesterol than into bilayers of phosphatidylcholine and cholesterol. The circular dichroism spectrum of the peptide in buffer indicates that it self-associates, leading to the formation of structures with higher helical content. However, in the presence of lipid, the peptide remains helical over a larger concentration range. The peptide undergoes a thermal transition on heating. Cholesterol has little effect on the secondary structure of the peptide; however, increased Trp emission intensity in the absence of cholesterol indicates a deeper penetration of the helix upon removal of cholesterol from the membrane. The results with these model systems demonstrate changes in peptide-lipid interactions that may be related to the observed biological properties of this peptide.

An apolipoprotein E synthetic peptide targets to lipoproteins in plasma and mediates both cellular lipoprotein interactions in vitro and acute clearance of cholesterol-rich lipoproteins in vivo
Nikoulin, I. R. and L. K. Curtiss (1998), J Clin Invest 101(1): 223-34.
Abstract: Apolipoprotein (apo) E mediates lipoprotein binding to cellular lipoprotein receptors. Previously we reported that a synthetic peptide representing a linear dimeric repeat of amino acids 141-155 binds cellular LDL receptors. To prepare an apoE peptide that bound to both cholesterol-rich lipoproteins and lipoprotein receptors, an NH2-terminal acetylated apoE dimer peptide was synthesized. This acetylated peptide preferentially associated with lipoproteins in plasma, whereas nonacylated peptides were poor lipid binders. Acetylated peptide/LDL complexes (molar ratios of 4-5:1) enhanced the interaction of LDL with cultured human fibroblasts by 7-12-fold. Participation by both receptors and cell surface heparin sulfate proteoglycans was observed. When a preformed peptide/125I-LDL complex was injected intravenously into C57BL/6J apoE-deficient mice, its rate of removal was threefold higher than that of 125I-LDL alone. The liver and the spleen were major tissue distribution sites. Intravenous administration of free acetylated peptide resulted in a 30% reduction in total plasma cholesterol within 3-30 min, which reflected a 40-50% and 20-26% reduction in very low density lipoproteins and intermediate density lipoproteins, respectively. Therefore, this peptide selectively associated with cholesterol-rich lipoproteins and mediated their acute clearance in vivo.

An apparent decrease in cholesterol biosynthesis in peroxisomal-defective Chinese hamster ovary cells is related to impaired mitochondrial oxidation
Oettl, K., G. Hofler, et al. (2003), Biochem Biophys Res Commun 305(4): 957-63.
Abstract: Recent data suggest that impaired mitochondrial activities in Zellweger fibroblasts are related to defective peroxisome biogenesis and vice versa. To investigate the contribution of functional mitochondria to cholesterol biosynthesis, radioactive precursor molecules that form acetyl-CoA via beta-oxidation-independent (pyruvate) or -dependent (palmitate and octanoate) pathways were used. Production of both 14C-labeled cholesterol and 14C-labeled CO(2) from these radioactive tracers was significantly impaired in peroxisomal-defective ZR-82 Chinese hamster ovary cells in comparison to controls. In contrast, cholesterol synthesis from acetate--a tracer directly converted to acetyl-CoA without the involvement of mitochondrial activities--was threefold higher in ZR-82 cells than in controls. Pathways further contributing to cellular cholesterol homeostasis, i.e., receptor-mediated binding of exogenous lipoprotein-associated cholesterol as well as intracellular mobilization of cholesteryl ester deposits were similar in ZR-82 and controls. From these findings, we propose that peroxisomal dysfunction in ZR-82 cells is tightly coupled to impaired mitochondrial activities, e.g., defective mitochondrial beta-oxidation and formation of acetyl-CoA from short chain fatty acids resulting in a decreased rate of CO(2) production, and an apparent decrease in cholesterol biosynthesis. Actually, cholesterol biosynthesis from acetate is increased in the peroxisomal-defective cells. This explains previous conflicting conclusions.

An assessment of the efficacy of atorvastatin in achieving LDL cholesterol target levels in patients with coronary heart disease: a general practice study
Neil, H. A., G. Fowler, et al. (1999), Int J Clin Pract 53(6): 422-6.
Abstract: Adherence to evidence-based guidelines for the secondary prevention of coronary heart disease (CHD) has been shown to be poor in a number of surveys. In this open-label, non-comparative 17-week trial, 399 patients with existing CHD and LDL cholesterol concentration > 3.4 mmol/l (130 mg/dl) were treated with atorvastatin 10 mg daily. After 5 weeks, the dose of atorvastatin was adjusted according to a patient's LDL cholesterol level. Of the 379 patients remaining in the study after five weeks of treatment, dose titration was not required for 355 patients (94%) who had reached the target LDL cholesterol of < or = 3.4 mmol/l. Of the 23 patients titrated to higher doses, 11 achieved the target LDL cholesterol after treatment for 17 weeks. Atorvastatin was well tolerated during the course of the study. Achieving LDL cholesterol targets without the need for dose titration simplifies clinical management and should encourage better adherence to evidence-based recommendations for secondary prevention of CHD.

An assessment of the efficacy of atorvastatin in treating patients with dyslipidaemia to target LDL-cholesterol goals: the atorvastatin matrix study
McVey, D., H. Patel, et al. (1999), Int J Clin Pract 53(7): 509-13.
Abstract: A total of 531 patients from 57 hospital centres across the UK, who had previously been treated with lipid-lowering agents in combination or alone, in whom the degree of cholesterol reduction was insufficient to achieve European Atherosclerosis Society target levels, were treated with atorvastatin over a 12-week period. The dose of atorvastatin (10, 20 or 80 mg/day) was determined by assignment of risk based on entry level cholesterol levels and the presence of other established CHD risk factors. Atorvastatin was successful in achieving target LDL-cholesterol levels in 86% of mild risk patients, 88% of moderate risk patients and 52% of high risk patients. Compliance with atorvastatin was 96% and treatment was well tolerated. This study demonstrates that atorvastatin is effective in achieving target lipid levels in a large proportion of patients and that the dose required can be predicted by an assessment of the patient's risk profile.

An association analysis between ApoA1 polymorphisms and the high-density lipoprotein (HDL) cholesterol level and myocardial infarction (MI) in Japanese
Shioji, K., T. Mannami, et al. (2004), J Hum Genet 49(8): 433-9.
Abstract: Association studies were performed to confirm the effect of polymorphisms in apolipoprotein A1 (ApoA1) on the high-density lipoprotein cholesterol (HDL-C) level and the incidence of myocardial infarction (MI). A sequence analysis identified nine polymorphisms in ApoA1. After considering linkage disequilibrium, four polymorphisms in ApoA1 and four polymorphisms in the 5'-flanking regions and 3'-flanking regions from the JSNP database were determined in 1,880 subjects recruited from the Suita study, which represents the general population in Japan. Of the eight polymorphisms tested, the ApoA1 T84C polymorphism had the greatest effect on the levels of HDL-C (P=0.0005, P(c)=0.0040 corrected by the Bonferroni method) and triglyceride (P<0.0001, P(c)=0.0008). The ApoA1 MspI polymorphism was not associated with HDL-C or triglyceride levels. We confirmed that the ApoA1 T84C polymorphism was associated with the HDL-C level but not the triglyceride level in patients with MI (n=637). Moreover, this polymorphism was associated with the incidence of MI in male subjects (P=0.0326). A logistic analysis indicated that the frequency of MI in the CC genotype was lower than that in the CT+TT genotype (P=0.0145, OR=0.4955, 95% CI: 0.2746-0.8525). The ApoA1 T84C polymorphism is an important marker for the HDL-C level and may be a new risk marker for MI in Japanese.

An audit of cholesterol measurement in patients with ischaemic heart disease in a district hospital
Turner, M., S. Hutchings, et al. (1997), J R Nav Med Serv 83(2): 84-6.

An autopsy case of renal failure due to cholesterol embolism following angiography
Fukuda, H., M. Tsuji, et al. (1991), Kokyu To Junkan 39(2): 193-6.
Abstract: A 59-year-old man with a 10-year history of hypertension was admitted to the Osaka Medical College Hospital because of left shoulder pain, lower blood pressure in left arm, and nasal lower quadrant defect of the visual field of the left eye. After admission, he underwent coronary angiography and aortography. The examinations revealed that, although coronary arteries were normal, the orifice of the left subclavian artery was occluded almost completely. Two weeks after the examination, he underwent intra arterial DSA of the cerebral artery. After manipulation of the DSA, the patient complained of severe calf pain, developed blue toe and progressive renal failure with severe proteinuria. He died of uremia about three months after the DSA. Autopsy revealed multiple cholesterol emboli in small arteries in the visceral organs, urogenital organs and thyroid gland. In the kidneys, especially, damage by cholesterol emboli was large with irregular cortical necrosis. Examination of the brain was not permitted. This case shows that cholesterol embolism of the kidneys can be a lethal complication of angiography.

An easy and inexpensive way to lower cholesterol?
Gordon, J. B. (1991), West J Med 154(3): 352.

An ecological perspective of cholesterol
Cantor, C. H. (2002), Med J Aust 176(11): 564.

An ecological study of serum cholesterol and ischaemic heart disease between 1950 and 1990
Law, M. R. and N. J. Wald (1994), Eur J Clin Nutr 48(5): 305-25.
Abstract: OBJECTIVE: (i) To carry out a quantitative analysis of the average serum cholesterol levels in different countries in relationship to the ischaemic heart disease (IHD) mortality in these countries. (ii) To examine changes in serum cholesterol levels over time in different countries. DESIGN: Analysis of published surveys measuring average serum cholesterol in specified communities in different countries. SETTING: The original cholesterol surveys were mainly in occupational and residential settings. RESULTS: Survey data allowed estimation of average serum cholesterol levels during specified time periods for 17 countries; estimates in men aged 40-59 years varied from 3.8 mmol/l (rural China) to 7.0 mmol/l (Finland). Variation in serum cholesterol accounted for 80% of the tenfold range in risk of IHD across countries. A difference in total (or LDL) cholesterol of 0.6 mmol/l between countries was associated with an average difference in IHD mortality of 37% at age 55-64 years. Repeat surveys showed that serum cholesterol reductions of the order of 0.6 mmol/l have occurred in some communities over about 5-10 years. CONCLUSIONS: Variation in serum cholesterol explains four-fifths of the geographical variation in IHD mortality. Reductions in cholesterol of about 0.6 mmol/l (10%) have been achieved in some Western communities or countries over periods of a few years, a change that is associated with a decrease in IHD mortality of over one-third.

An economic analysis of the Atorvastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS)
Smith, D. G. and C. R. McBurney (2003), Pharmacoeconomics 21 Suppl 1: 13-23.
Abstract: INTRODUCTION: The objective of the Atorvastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS) was to compare the efficacy and safety of the five 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors in a randomised, controlled, yet large-scale study. ACCESS also produced data that permitted comparative analysis of the cost to achieve National Cholesterol Education Panel (NCEP) II low density lipoprotein-cholesterol (LDL-C) targets. STUDY DESIGN: A 54-week, multicentre, open-label, randomised, parallel-arm, active-control study in men and women with or without documented coronary heart disease or peripheral vascular disease. Data included medication use, clinic visits, adverse events, LDL-C and other laboratory measures. Analyses of resource use and cost are reported from a third-party payer perspective. METHODS: Patients were randomly assigned to receive one of the following treatments: atorvastatin (10-80 mg/day); fluvastatin (20-40 mg/day, or 40 mg twice daily); lovastatin (20-40 mg/day, or 40 mg twice daily); pravastatin (10-40 mg/day); or simvastatin (10-40 mg/day). Patients were started at the lowest available dose and titrated to higher doses at 6-week intervals until they achieved the NCEP II LDL-C target or reached the highest available dose of medication. PATIENTS: A total of 153 centres enrolled 3887 patients: atorvastatin (n = 1944); fluvastatin (n = 493); lovastatin (n = 494); pravastatin (n = 478); and simvastatin (n = 478). Inclusion criteria included LDL-C >or= 30 mg/dL higher than NCEP II LDL-C target (stratified by risk factors), fasting triglyceride values < 400 mg/dL, and a confirmed negative serum pregnancy test. Known hypersensitivity to statins, use of prohibited medications, uncontrolled diabetes, acute liver disease and age > 80 years or < 18 years were among the exclusion criteria. RESULTS: Mean total treatment costs to reach LDL-C targets for patients receiving atorvastatin (US dollars 683.37 in 2001) were significantly less than mean total treatment costs for patients receiving fluvastatin (difference = US dollars 211.35, p < 0.01), lovastatin (US dollars 607.96, p < 0.01), pravastatin (US dollars 424.60, p < 0.01) and simvastatin (US dollars 95.74, p < 0.01). Results were robust to sensitivity analyses using alternative definitions of the patient population (randomised, intent-to-treat, completers) and cost measures (50th percentile charges, 95th percentile charges, Medicare prices). CONCLUSIONS: Compared with the other statins studied, atorvastatin was associated with the lowest resource use and costs when used to treat patients to their NCEP II LDL-C targets. Atorvastatin was also associated with the highest percentage of patients achieving their desired clinical outcomes. Therefore, in cost-effectiveness terms, it dominated the four other statins.

An economic evaluation of lovastatin for cholesterol lowering and coronary artery disease reduction
Hay, J. W., E. H. Wittels, et al. (1991), Am J Cardiol 67(9): 789-96.
Abstract: The costs and benefits of cholesterol lowering in the primary prevention of coronary artery disease (CAD) were considered using lifetime lovastatin therapy as the intervention model for adults between 35 and 55 years of age. The analysis projected the benefits of CAD risk reduction using estimates from the Framingham Heart Study. The chosen analytic perspective was that of the patient. For average-risk men with total serum cholesterol levels between 5.69 and 9.83 mmol/liter (220 and 380 mg/dl), the cost per life-year saved ranged from $9,000 to $106,000, whereas for average-risk women, the cost ranged from $35,000 to $297,000 (1989 U.S. dollars). In high-risk men (with smoking habit and hypertension), the cost per life-year saved values ranged from 6,000 to $53,000, whereas in high-risk women the cost per life-year saved values ranged from $19,000 to $160,000. The results were more favorable than those found in previous studies of alternate medication therapies for hypercholesterolemia. Even using conservative parameter assumptions, at least 800,000 Americans aged 35 to 55 years are at sufficiently high risk for CAD, so that the net cost of lovastatin therapy can be favorably compared with other widely used medical interventions.

An electrochemical multienzymatic biosensor for determination of cholesterol
Bongiovanni, C., T. Ferri, et al. (2001), Bioelectrochemistry 54(1): 17-22.
Abstract: This paper describes an electrochemical biosensor for free cholesterol monitoring. The sensor is a multienzymatic electrodic system in which horseradish peroxidase and cholesterol oxidase are simultaneously immobilized within a polymeric film, on the surface of a pyrolitic graphite electrode. From voltammetric and amperometric (flow-injection) data obtained, the efficiency, reproducibility and stability of the system are discussed. Results obtained, of interest for basic and applied biochemistry, represent a first step for construction of a mediator-free biosensor with potentialities for a successful application in the biosensor area.

An elevated serum cholesterol level is secondary, not causal, in coronary heart disease
Ravnskov, U. (1991), Med Hypotheses 36(3): 238-41.

An enterosorbent with trimethylaminoethanol chloride. 2. Hypolipidemic action and effect on cholesterol absorption in the intestine (experimental data)
Ryshenkov, V. E., N. A. Samoilova, et al. (1995), Vopr Med Khim 41(1): 34-5.
Abstract: Enterosorbent containing trimethyl aminoethanol chloride administered per os into rabbits accelerated the rate of experimental hypercholesterolemia regression. Moreover, this substance decreased 4-14C-cholesterol absorption in the rat intestine.

An enzymatic synthesis of glucuronides of azetidinone-based cholesterol absorption inhibitors
Reiss, P., D. A. Burnett, et al. (1999), Bioorg Med Chem 7(10): 2199-202.
Abstract: Two derivatives, 1 and 3, of a novel cholesterol absorption inhibitor, Sch 58235, were glucuronidated with the help of glucuronyl transferases derived from bovine and dog liver microsomes. An efficient procedure for the iodination of 4 was developed on an analytical scale to be used for the preparation of a 125I-labeled radioactive glucuronide 5.

An enzyme thermistor-based assay for total and free cholesterol
Raghavan, V., K. Ramanathan, et al. (1999), Clin Chim Acta 289(1-2): 145-58.
Abstract: A method to evaluate the free (FC) and total cholesterol (TC) in human serum, bile and gallstone extract using an enzyme thermistor (ET)-based flow injection analysis (FIA) is presented. The cholesterol in high-density (HDL-C) and low density lipoprotein (LDL-C) have also been evaluated. A heparin functionalized Sepharose column was employed for the isolation of HDL and LDL fractions from serum. The estimation of cholesterol and its esters was based on their reaction with cholesterol oxidase (CO), cholesterol esterase (CE) and catalase (CAT). Three different enzyme columns, i.e. co-immobilized CO/CAT (column A), only CE (column B) and co-immobilized CO/CE/CAT (column C) were prepared by cross-linking the enzymes on glass beads using glutaraldehyde. Column A was used for estimating FC and column C was used for estimating total cholesterol (cholesterol plus esterified cholesterol). Column B was used as a pre-column which could be switched 'in' or 'out' in conjunction with column A for the estimation of TC or FC, respectively. A calibration between 1.0 and 8.0 mmol/l for FC and 0. 25 and 4.0 mmol/l for TC was obtained. For more than 2000 assays with the ET device a C.V. of less than 4% was obtained. The assay time was approximately 4 min per assay. The cholesterol estimations on the ET correlated well with similar estimations using a commercially available cholesterol diagnostic kit.

An epidemiologic study of cholesterol in the population of Acapulco, Mexico
Salgado-Sales, P. (1992), Salud Publica Mex 34(6): 653-9.
Abstract: An epidemiologic study of cholesterol and other risk factors was carried out, which included 1,011 women and 1,001 men older than 20 years, in Acapulco, Guerrero, Mexico. The aim of this study was to determine the prevalence of hypercholesterolemia, as well as to establish the relation of cholesterol levels and the following variables: Age, obesity, hypertension, tobacco smoking and cardiovascular disease in relatives. This study was done in the months of March-August 1991. The prevalence of high cholesterol was 36 percent in women with an average of 189 mg/dl, and 30 percent for men with an average of 183 mg/dl. The difference between levels of cholesterol of men and women reached statistical significance. The average levels of serum cholesterol were higher in older, overweight, hypertensive individuals and the differences were statistically significative. Although the average serum cholesterol level was higher in individuals with history of cardiovascular problems, the differences were not significative. There were no differences in cholesterol levels in individuals with tobacco smoking habits. The prevalence of high cholesterol found means that is an important risk factor for this population, which, added to the other identified factors and its statistical relation, define them as a population with high cardiovascular risk.

An estimation of human bile metastability: clinical application of a sensitive cholesterol crystal growth assay
Ohya, T., S. Tazuma, et al. (1994), J Gastroenterol Hepatol 9(3): 223-7.
Abstract: The formation of cholesterol monohydrate crystal initiates cholesterol gallstone formation. The nucleation time (NT), a light microscopy method, is used currently to estimate human bile metastability. Recently, a cholesterol crystal growth (CCG) assay utilizing photometric turbidity to quantitate cholesterol crystallization was developed using model bile systems. The object of this study was to determine whether this novel CCG assay was applicable to the quantitative assessment of native human bile metastability. Human gall-bladder bile samples were collected from patients undergoing cholecystectomy. There were five patients with cholesterol gallstone and five stone-free patients. A significant correlation between the onset time measured by the CCG assay and the NT observed by light microscopy was found in our modified assay condition where interference by bilirubin was negligible (P < 0.01). Also, the growth rate measured by the CCG assay significantly correlated with the NT (P < 0.05). These results indicate that the CCG assay is applicable to quantitative assessment of human bile metastability reflected by cholesterol crystal nucleation and that the cholesterol crystal growth is also conveniently estimated by this method.

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