Cholesterol Journal Articles

Record 13041 to 13060

Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase
Parker, R. A., B. C. Pearce, et al. (1993), J Biol Chem 268(15): 11230-8.
Abstract: Tocotrienols are natural farnesylated analogues of tocopherols which decrease hepatic cholesterol production and reduce plasma cholesterol levels in animals. For several cultured cell types, incubation with gamma-tocotrienol inhibited the rate of 14Cacetate but not 3H mevalonate incorporation into cholesterol in a concentration- and time-dependent manner, with 50% inhibition at approximately 2 microM and maximum approximately 80% inhibition observed within 6 h in HepG2 cells. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase total activity and protein levels assayed by Western blot were reduced concomitantly with the decrease in cholesterol synthesis. In HepG2 cells, gamma-tocotrienol suppressed reductase despite strong blockade by inhibitors at several steps in the pathway, suggesting that isoprenoid flux is not required for the regulatory effect. HMG-CoA reductase protein synthesis rate was moderately diminished (57% of control), while the degradation rate was increased 2.4-fold versus control (t1/2 declined from 3.73 to 1.59 h) as judged by 35Smethionine pulse-chase/immunoprecipitation analysis of HepG2 cells treated with 10 microM gamma-tocotrienol. Under these conditions, the decrease in reductase protein levels greatly exceeded the minor decrease in mRNA (23 versus 76% of control, respectively), and the low density lipoprotein receptor protein was augmented. In contrast, 25-hydroxycholesterol strongly cosuppressed HMG-CoA reductase protein and mRNA levels and the low density lipoprotein receptor protein. Thus, tocotrienols influence the mevalonate pathway in mammalian cells by post-transcriptional suppression of HMG-CoA reductase, and appear to specifically modulate the intracellular mechanism for controlled degradation of the reductase protein, an activity that mirrors the actions of the putative non-sterol isoprenoid regulators derived from mevalonate.

Too little cholesterol reduction may be hazardous
Vine, D. L. (1991), Kans Med 92(2): 53-4.

Too low blood cholesterol?
Retterstol, K. (2005), Scand J Clin Lab Invest 65(1): 1-2.

Tophus-like cholesterol nodules in 2 patients with rheumatoid disease
Lanting, P. J., J. van Baarlen, et al. (1995), J Rheumatol 22(2): 338-41.
Abstract: We describe 2 patients, both with rheumatoid disease, with tophus-like nodules that contained cholesterol crystals. A tophus-like cholesterol nodule had developed in a tendon sheath of the left little finger of one. The other presented with multiple tophus-like nodules on his left elbow and both forefeet. We discuss the etiology and pathogenesis of crystalline deposits of cholesterol. Nodules at sites of local pressure in patients with rheumatoid arthritis may be deposits of cholesterol crystals.

Topical dissolution treatment of cholesterol gallstones with methyl tert-butyl ether
Thistle, J. L. (1990), Semin Liver Dis 10(3): 187-90.

Topical mevalonic acid stimulates de novo cholesterol synthesis and epidermal permeability barrier homeostasis in aged mice
Haratake, A., K. Ikenaga, et al. (2000), J Invest Dermatol 114(2): 247-52.
Abstract: Extracellular lipids of the stratum corneum, which are composed of cholesterol, fatty acid, and ceramides, are essential for the epidermal permeability barrier function. With damage to the barrier, a decreased capacity for epidermal lipid biosynthesis in aged epidermis results in an impaired repair response. Mevalonic acid is an intermediate after the rate-limiting step in cholesterol biosynthesis, which is catalyzed by 3-hydroxy-3-methylglutaryl coenzyme A reductase. In the present study, we investigated the effect of topical mevalonic acid on the murine epidermal permeability barrier function, comparing it with that of cholesterol. Topical treatment with acetone caused linear increases in transepidermal water loss, in proportion to the number of treatments more rapidly in aged mice than in young mice. Administration of mevalonic acid on aged murine epidermis enhanced its resistance against damage and the recovery rate of barrier function from acute barrier disruption. In contrast, although cholesterol also had the same effect, it required a much higher amount than mevalonic acid. In young mice, neither mevalonic acid nor cholesterol had any effect on resistance against acetone damage nor the recovery rate from acetone damage. In the skin of mice topically administered with mevalonic acid, stimulation of cholesterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity were both observed, whereas none was seen with stimulation by equimolar cholesterol. These data indicate that a topical application of mevalonic acid enhances barrier recovery in aged mice, which is accompanied by not only acceleration of cholesterol synthesis from mevalonic acid but also stimulation of the whole cholesterol biosynthesis.

Topical timolol decreases plasma high-density lipoprotein cholesterol level
Coleman, A. L., D. L. Diehl, et al. (1990), Arch Ophthalmol 108(9): 1260-3.
Abstract: beta-Adrenergic antagonists taken orally adversely alter plasma lipid profiles. This study was designed to determine whether 0.5% topical timolol maleate has a similar effect. Forty volunteers who were not using medications known to alter plasma lipid levels were recruited for an unmasked study in which each subject served as his or her own control. Twelve subjects did not complete the study because of ocular and systemic side effects or extraneous factors. Twenty-eight subjects used topical timolol for an average of 76 days, with two 12-hour fasting plasma specimens obtained at the beginning and end of the period. Mean total cholesterol and low-density lipoprotein cholesterol levels did not change significantly with treatment. Triglyceride values increased 12%; high-density lipoprotein cholesterol levels decreased 9%; and the total cholesterol-high-density lipoprotein cholesterol ratio increased 8%. Higher baseline high-density lipoprotein cholesterol levels were associated with larger reductions in high-density lipoprotein cholesterol levels. Changes in high-density lipoprotein cholesterol levels of this magnitude have been estimated to increase the risk of coronary artery disease by 21%.

Topography of alphaxalone and delta 16-alphaxalone in membrane bilayers containing cholesterol
Mavromoustakos, T., D. P. Yang, et al. (1994), Biochim Biophys Acta 1194(1): 69-74.
Abstract: We have used small-angle X-ray diffraction and differential scanning calorimetry (DSC) to study the topographies of alphaxalone and its biologically inactive analog delta 16-alphaxalone in dimyristoylphosphatidylcholine (DMPC) and DMPC/cholesterol model membranes. Diffraction patterns were obtained and analyzed for preparations of bilayers without and with the steroids. Temperature dependence of the total period repeat distance (d-spacing) allowed us to identify equivalent temperatures at which the preparations had similar d-spacing and were in the same mesomorphic state. The combination of X-ray and DSC data showed that the anesthetic steroid alphaxalone broadens the membrane phase transition and increases the ratio of gauche: trans conformers in the membranes in contrast to the inactive steroid delta 16-alphaxalone which affects the membranes only marginally. In model DMPC membranes alphaxalone and delta 16-alphaxalone are located near the bilayer interface. This location is maintained by alphaxalone when cholesterol is incorporated in the bilayer as evidenced by the X-ray measurements. However, when delta 16-alphaxalone is incorporated in cholesterol containing bilayers, a decrease in the electron density profile of the preparation is observed. This can be explained by invoking the formation of a delta 16-alphaxalone-cholesterol complex. The delta 16-alphaxalone complex shows no periodicity and is therefore, not detected in the X-ray diffraction experiment. Presumably, this complex forms aggregates either on the surface or inside the bilayer. This explanation corroborates DSC results which show that delta 16-alphaxalone sharpens the phase transition of DMPC/cholesterol preparations, an indication that some cholesterol is excluded from the bilayer preparation after the addition of the biologically inactive steroid.

Topological properties of two cubic phases of a phospholipid:cholesterol:diacylglycerol aqueous system and their possible implications in the phospholipase C-induced liposome fusion
Nieva, J. L., A. Alonso, et al. (1995), FEBS Lett 368(1): 143-7.
Abstract: Water dispersions of phospholipid:cholesterol:diacylglycerol may, under certain conditions, originate either the lipid- and water-permeable Q224 cubic phase, or the lipid-permeable but water-impermeable Q227 cubic phase. These results are discussed within the framework of the phospholipase C-induced fusion of liposomes Nieva et al. (1993) Biochemistry 32, 1054. It is suggested that the cubic phases Q224 and Q227 represent two classes of lipid organization, one promoting, the other hindering the mixing of aqueous contents that is characteristic of membrane fusion. In this context, inverted micelles appear to be the end point of the fusion process, rather than fusion intermediates.

Total and HDL cholesterol and risk of stroke. EUROSTROKE: a collaborative study among research centres in Europe
Bots, M. L., P. C. Elwood, et al. (2002), J Epidemiol Community Health 56 Suppl 1: i19-24.
Abstract: BACKGROUND: Controversy remains on the relation between serum lipids levels and stroke risk. This paper investigated the association of total and HDL cholesterol level to fatal and non-fatal, and haemorrhagic and ischaemic stroke in four European cohorts participating in EUROSTROKE. METHODS: EUROSTROKE is a collaborative project among ongoing European cohort studies on incidence and risk factors of stroke. EUROSTROKE is designed as a nested case-control study. For each stroke case, two controls were sampled. Strokes were classified according to MONICA criteria or reviewed by a panel of four neurologists. At present, data on stroke and risk factors were available from cohorts in Cardiff (84 cases), Kuopio (74 cases), Rotterdam (157 cases), and Novosibirsk (79 cases). RESULTS: Pooled analyses showed no significant association between total cholesterol and risk of stroke (odds ratio for increase of 1 mmol/l in cholesterol of 0.98 (95% CI 0.88 to 1.09)). Analyses for haemorrhagic stroke and cerebral infarction revealed odds ratios of 0.80 (95% CI 0.61 to 1.05) and 1.06 (95% CI 0.94 to 1.19), respectively. The association of HDL cholesterol to stroke was different in men compared with women. In men, there was a general trend towards a lower risk of stroke with an increase in HDL (odds ratio per 1 mmol/l increase in HDL cholesterol 0.68 (95% CI 0.40 to 1.16)). In women, however, an increase in HDL was associated with a significant increased risk of non-fatal stroke and of cerebral infarction (odds ratios of 2.46 (95% 0.1.20 to 5.04) and 2.52 (95% CI 1.15 to 5.50), respectively. The difference between men and women in the association of HDL with stroke seemed to differ mainly in smokers and never smokers, but not among ex smokers. CONCLUSION: This analysis of the EUROSTROKE project could not disclose an association of total cholesterol with fatal, non-fatal, haemorrhagic or ischaemic stroke. HDL cholesterol however, seemed to be related to stroke differently in men than in women.

Total and HDL cholesterol and their correlates in elderly men in Finland, Italy, and The Netherlands
Kromhout, D., A. Nissinen, et al. (1990), Am J Epidemiol 131(5): 855-63.
Abstract: In 1984 and 1985, 25-year follow-up studies were carried out in the Italian, Finnish, and Dutch cohorts of men originally examined around 1960 in the Seven Countries Study. Risk factors for coronary heart disease were determined in 2,255 men aged 65-84 years. The average serum total cholesterol levels of the elderly men in Finland and the Netherlands were similar, at around 236 mg/dl (6.10 mmol/liter). The average serum total cholesterol levels of the elderly men in Italy were about 10 mg/dl (0.26 mmol/liter) lower. During 25 years of follow-up, the average serum total cholesterol level increased by 29 mg/dl (0.75 mmol/liter) among the Italian survivors, decreased by 23 mg/dl (0.59 mmol/liter) in the Finnish survivors, and did not change in the Dutch survivors. Age, Quetelet index, and coffee consumption were the most important correlates of total cholesterol in these elderly men. Quetelet index, alcohol consumption, age, and cigarette smoking were significantly associated with high density lipoprotein (HDL) cholesterol. The results of this study suggest that modifiable risk factors are related to total and HDL cholesterol in elderly men in different cultures.

Total and HDL cholesterol in human hematologic neoplasms
Dessi, S., B. Batetta, et al. (1991), Int J Hematol 54(6): 483-6.
Abstract: In this study serum cholesterol was measured in different types of human hematologic malignancies characterized by a wide range of cell proliferation. In all tumoral types a significant decrease of HDL cholesterol was observed, whereas total serum cholesterol generally remained unchanged. Another interesting observation of our study was the apparent inverse correlation between the extent of cell proliferation in these neoplastic disorders and the level of HDL cholesterol. Since a decrease of HDL cholesterol was previously observed, in our laboratory, in different experimental models of normal and neoplastic cell proliferation, we suggest that the decrease of HDL cholesterol may be a generalized phenomenon related to massive cellular growth in normal and malignant processes.

Total and HDL-cholesterol in The Netherlands: 1987-1992. Levels and changes over time in relation to age, gender and educational level
Verschuren, W. M., G. J. Boerma, et al. (1994), Int J Epidemiol 23(5): 948-56.
Abstract: BACKGROUND. To gain insight into the prevalence of and trends in plasma cholesterol levels in the general population of the Netherlands, a monitoring project was carried out from 1987 to 1992. METHODS. Each year a random sample of men and women aged 20-59 years in three towns in the Netherlands was invited to participate in the study. The overall response rate was 50% for men and 57% for women and a total of almost 42,000 men and women participated. Total (TC) and high density lipoprotein cholesterol (HDL-C) was measured and the non-HDL-C/HDL-C ratio was computed. Data were age-standardized to the Dutch population distribution aged 20-59 years. RESULTS. The prevalence of hypercholesterolaemia (TC > or = 6.5 mmol/l) in men ranged from 5% in the youngest (20-29 years) to 29% in the oldest age group (50-59 years), and from 4% to 38% in women. Low HDL-C levels (< or = 0.9 mmol/l) in men ranged from 15% in the youngest to 26% in the oldest age group, and in women from 4% in the youngest to 7% in the oldest age group. The lipid profile of those with a higher educational level was more favourable than that of the less educated. From 1987 to 1992, in men, TC decreased by 0.12 mmol/l, HDL-C decreased by 0.07 mmol/l and the non-HDL-C/HDL-C ratio increased by 0.22. In women no statistically significant changes were observed. Changes over time did not differ according to age and educational level. CONCLUSION. The prevalence of hypercholesterolaemia is still high in the Netherlands. During the period 1987-1992 the lipid profile worsened in men and remained stable in women.

Total and high density lipoprotein cholesterol as risk factors for coronary heart disease in elderly men during 5 years of follow-up. The Zutphen Elderly Study
Weijenberg, M. P., E. J. Feskens, et al. (1996), Am J Epidemiol 143(2): 151-8.
Abstract: The associations of serum total and high density lipoprotein (HDL) cholesterol with coronary heart disease were investigated in men aged 64-84 years from the Dutch town of Zutphen during 5 years of follow-up. In 1985, 885 randomly selected men, 710 of whom did not have a history of clinical coronary heart disease, participated in the study. Associations were adjusted for age, body mass index, systolic blood pressure, cigarette smoking, and alcohol consumption. Total cholesterol was not significantly associated with the incidence of coronary heart disease, but for mortality the relative risk corresponding to a 1.00 mmol/liter increase was 1.40 (95 percent confidence interval (CI) 1.07-1.83). HDL cholesterol was not associated with mortality from coronary heart disease. The relative risk for the incidence of the disease, corresponding to a 0.26 mmol/liter increase, was 0.80 (95 percent CI 0.60-1.08). For the ratio of HDL cholesterol to total cholesterol, the relative risk for coronary heart disease incidence corresponding to a 0.05 increase amounted to 0.70 (95 percent CI 0.51-0.95). These results show that in elderly men followed for 5 years, both total and HDL cholesterol are important in predicting coronary heart disease. Total cholesterol seems to be a stronger risk factor for mortality from the disease, whereas HDL cholesterol is more strongly associated with the incidence of a first coronary heart disease event.

Total and low-density-lipoprotein cholesterol lipoprotein fractions and fecal fatty acid excretion of men consuming diets containing high concentrations of stearic acid
Dougherty, R. M., M. A. Allman, et al. (1994), Am J Clin Nutr 60(6 Suppl): 1043S.

Total biliary protein, mucus glycoproteins, cyclic-AMP, and apolipoproteins in the gallbladder bile of patients with cholesterol stones and stone-free controls
Swobodnik, W., H. Wenk, et al. (1991), Scand J Gastroenterol 26(7): 771-8.
Abstract: The concentrations of total protein, mucus glycoprotein, cyclic-AMP, and apolipoproteins A-I, A-II, and B were determined in the gallbladder bile of patients with cholesterol gallbladder stones and in stone-free controls. The total protein content was significantly increased in gallstone patients (2.03 +/- 0.6 versus 1.31 +/- 0.67 mg/ml; p less than 0.05), as was the mucus glycoprotein concentration (380 +/- 88.5 versus 128 +/- 57.2 micrograms/ml; p less than 0.05). The cyclic-AMP concentration in the gallbladder fluid was increased up to 91 +/- 20 pmol/100 microliters in the gallstone subjects, as compared with 46 +/- 26 pmol/100 microliters (p less than 0.01) in stone-free controls. Cyclic-AMP concentrations correlated positively with the glycoprotein content of the bile in cholesterol gallstone patients (r = 0.66; p less than 0.05). The apolipoprotein concentrations were determined by the radial immundiffusion technique. The corresponding values for patients with stones and controls were 7.5 +/- 0.8 versus 3.0 +/- 0.8 for Apo A-I (p less than 0.025), 10.4 +/- 0.6 versus 6.3 +/- 1.3 for Apo A-II (p less than 0.02), and 1.9 +/- 0.5 versus 1.6 +/- 0.2 mg/dl for Apo B (NS), respectively. Biliary proteins probably play an important role in the nucleation process during the pathogenesis of cholesterol gallbladder stones.

Total blood cholesterol and contributory risk factors in an adolescent population
Berg, C. L., D. J. Swanson, et al. (1992), J Sch Health 62(2): 64-6.
Abstract: Total blood cholesterol (TBC) levels and contributory risk factors in an adolescent population were investigated. Existing TBC screening records were reviewed on 452 10th grade students in two schools. The sample consisted of 52% males and 48% females whose mean age was 15.47 years. Blood samples were analyzed by the Reflotron. Risk factors investigated included age, gender, ethnicity, individual and family history of high cholesterol, history of high blood pressure, smoking tobacco products, and oral contraceptive use. The sample mean for TBC was 150.61. The only significant factors identified by ANOVA were gender and use of oral contraceptives. Females had higher TBC levels than males, and females who used oral contraceptives had higher TBC levels than nonusers.

Total blood cholesterol in a volunteer population
Simmers, D. G. (1990), N Z Med J 103(894): 337-9.
Abstract: An analysis of the total blood cholesterol values obtained in a self selected sample of the Wakatipu basin community is presented. From this analysis it can be drawn that blood cholesterol level varies with age and weight but not with sex and smoking status. The overall mean of the sample was 5.54 mmol/L, with volunteers over age 50 having a mean of 6.44 mmol/L, those aged 25-50 having a mean of 5.37 mmol/L, and those below age 25 having a mean of 4.78 mmol/L. Obese volunteers had an average total blood cholesterol of 6.22 mmol/L, while volunteers of normal weight had an average value of 5.38 mmol/L. This analysis forms the basis of a discussion which emphasises the difficulties in interpreting and thus manipulating an individual's blood cholesterol.

Total but not high-density lipoprotein cholesterol is consistently associated with coronary heart disease mortality in elderly men in Finland, Italy, and The Netherlands
Houterman, S., W. M. Verschuren, et al. (2000), Epidemiology 11(3): 327-32.
Abstract: We studied the relation between serum total and high-density lipoprotein (HDL) cholesterol and 10-year coronary heart disease mortality in elderly men in different European countries. The Finland, Italy and the Netherlands Elderly (FINE) Study is a prospective follow-up study in 2,132 elderly men ages 65-84 years in Finland, the Netherlands, and Italy. We estimated relative risks using Cox proportional hazard analysis with time-dependent covariates. Total cholesterol was positively related to coronary heart disease mortality in all three countries. The combined relative risk for the total population of the FINE Study was 1.17 (95% confidence interval = 1.06-1.29) for each 1.00 mmol/liter increase in total cholesterol. HDL cholesterol was inversely related to coronary heart disease mortality in Finland, but not in the Netherlands and Italy. In Italy we noted an interaction among HDL cholesterol, body mass index, and alcohol intake, with an inverse association for HDL cholesterol in lean men who drank <40 gm of alcohol daily and a positive association for HDL cholesterol among overweight men who drank > or =40 gm of alcohol per day. Serum total cholesterol remains an important predictor of coronary heart disease mortality in elderly men in different European countries. The effect of HDL cholesterol differed among the three countries.

Total cholesterol and body mass index in relation to 40-year cancer mortality (the Corfu cohort of the seven countries study)
Panagiotakos, D. B., C. Pitsavos, et al. (2005), Cancer Epidemiol Biomarkers Prev 14(7): 1797-801.
Abstract: PURPOSE: We evaluated risk factors of cancer mortality based on a 40-year follow-up of the Corfu cohort (Seven Countries Study). MATERIAL AND METHODS: The population studied in this analysis consisted of 529 rural men (49 +/- 6 years old) enrolled in 1961. Since then, periodic visits every 5 years were made to define the causes of death of the participants. Cox proportional hazards models evaluated various risk factors in relation to cancer mortality. RESULTS: The death rate at the end of the follow-up was 87.1% (i.e., 461 deaths in 529 participants). Of those deaths, 118 (25.6%) were because of cancer (30 deaths were due to cancer of trachea, bronchus, and lung, and the rest were due to other malignant neoplasms). Cancer was the second cause of death in this cohort, after coronary heart disease. Age (hazard ratio, 1.05 per year; P < 0.05), smoking (hazard ratio, 1.97; P < 0.01), total serum cholesterol levels (hazard ratio, 0.95 per 10 mg/dL; P < 0.05), and body mass index (hazard ratio, 0.93 per 1 kg/m2; P < 0.05) showed a significant association with cancer deaths after controlling for physical activity status and anthropometric indices. It should be noted that the protective effect of total cholesterol on cancer mortality was observed only between 183 and 218 mg/dL baseline levels. CONCLUSION: Cancer was one of the leading causes of death in this cohort. Smoking was associated with increased risk of cancer, whereas moderate total serum cholesterol and increased body and mass index seemed to have a protective effect on 40-year cancer mortality.

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Cholesterol Journal Articles