| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
| First Page | Previous Page | Next Page | Last Page |
| Microstructural analysis of bile: relevance to cholesterol gallstone pathogenesis Rubin, M., R. Pakula, et al. (2000), Histol Histopathol 15(3): 761-70. Abstract: The study of physical-chemical factors and pathways leading to cholesterol crystallization in bile has important clinical relevance. The major processes in cholesterol gallstone formation can be subdivided into nucleation, formation and precipitation of solid crystals (crystallization), crystal growth, crystal agglomeration and stone growth. A clear understanding of the microstructural events occurring during the earliest stages of these processes in bile is crucial for the identification of factors possibly delaying or preventing precipitation of cholesterol crystals and, therefore, gallstone formation in bile. Detection and characterization of microstructures in native and model biles can be achieved by both direct and indirect techniques. Direct imaging techniques provide more readily interpretable information, but sample preparation problems, particularly for electron microscopy, are a source of artifacts. Moreover, microscopic techniques provide only qualitative data without the possibility to quantitate or to analyse the composition of microstructures. Several indirect techniques have been used to obtain additional microstructural information about nucleating bile. These techniques have the disadvantage of often being model dependent in addition to constraints specific for each method. The systematic, judicious use of a combination of complementary direct and indirect techniques have led to a comprehensive understanding of the various microstructural processes and interactions occurring during bile secretion, flow in the biliary tract and storage in the gallbladder. This forms the basis for our current understanding of cholesterol nucleation, crystallization and gallstone formation. |
| Middle ear cholesterol granuloma Kerstetter, J. R. and K. D. Dolan (1991), Ann Otol Rhinol Laryngol 100(10): 866-8. |
| 'Might reduction of plasma cholesterol imperil cell physiology?' Oliver, M. F. (1991), J Mol Cell Cardiol 23(11): 1335-7. |
| Mild hepatic fibrosis in cholesterol and sodium cholate diet-fed rats Jeong, W. I., D. H. Jeong, et al. (2005), J Vet Med Sci 67(3): 235-42. Abstract: To date, the majority of research on hypercholesterolemia has focused on the effects of a high cholesterol diet on atherosclerosis and coronary heart disease. The toxic effects of cholesterol on the liver and the relationship between the intake of a high cholesterol diet and hepatic fibrosis, however, have not been investigated clearly or histopathologically. Male Wistar rats were fed a diet supplemented with 1.0% cholesterol and 0.3% sodium cholate for 12 weeks. Rats were sacrificed and analyzed via blood biochemistry, traditional microscopy and immunohistochemistry. Following the feeding of this diet, the rates of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and total cholesterol in the rats were elevated consistently from week 3 and throughout the remainder of the experiment. From microscopic observation, hepatic necrosis, macrophage infiltration and steatosis increased markedly throughout the experiment. Hepatic fibrosis and myofibroblast proliferation were detected at weeks 9 and 12. Mast cell appearance was proportional to the degree of hepatic damage. These findings suggest that hepatic fibrosis is inducible by a high cholesterol diet and is likely the result of the interaction between several different cell types (i.e., macrophages, myofibroblasts, and mast cells) in an inflammatory milieu. Hypercholesterolemia should be considered as a risk factor for hepatic fibrosis as well as atherosclerosis and coronary artery disease. |
| Miles run per week and high-density lipoprotein cholesterol levels in healthy, middle-aged men. A dose-response relationship Kokkinos, P. F., J. C. Holland, et al. (1995), Arch Intern Med 155(4): 415-20. Abstract: OBJECTIVE: To examine the association between miles run per week and high-density lipoprotein cholesterol levels in healthy middle-aged men. BACKGROUND: Regular exercise increases levels of high-density lipoprotein cholesterol. However, the exercise requirements for such increases are not well defined. METHODS: Healthy, nonsmoking men (n = 2906; age, 43 +/- 4 years) completed a questionnaire on health habits and physical activities and a symptom-limited exercise test. They were then stratified on the basis of the number of miles run per week. Six groups, with mileages of 0, 5, 9, 12, 17, and 31 per week, were established. RESULTS: A gradual increase in high-density lipoprotein cholesterol level was observed with increased miles (0.008-mmol/L 0.308-mg/dL increase in high-density lipoprotein cholesterol level per mile). Most of the changes were associated with distances of 7 to 14 miles per week. Levels of low-density lipoprotein cholesterol, triglycerides, and the ratio of total cholesterol to high-density lipoprotein cholesterol also improved with weekly mileage. The high-density lipoprotein cholesterol level correlated significantly with all exercise components, anthropometric measures, and alcohol consumption. Group comparisons disclosed significant differences (P <.05) in exercise time to exhaustion, miles run per week, body fat, body weight, and body mass index. Age and alcohol consumption were similar across groups. CONCLUSIONS: These results indicate a dose-response relationship between miles run per week, high-density lipoprotein cholesterol level, and other lipoprotein-lipid levels. Most changes were noted in those who ran 7 to 14 miles per week at mild to moderate intensities. A mile-age threshold for changes in high-density lipoprotein cholesterol level was not observed. However, when compared with those of the nonexercising group, high-density lipoprotein cholesterol levels attained statistical significance at 7 or more miles per week. |
| Milk cholesterol concentration in sows selected for three generations for high or low serum cholesterol Kandeh, M. M., Y. W. Park, et al. (1993), J Anim Sci 71(5): 1100-3. Abstract: Female crossbred swine (Chester White x Landrace x Large White x Yorkshire) selected for three generations for low (L, n = 24) or high (H, n = 26) serum cholesterol at 8 wk of age were milked at d 20 or 21 of their first lactation to measure cholesterol, fat, lactose, protein, and ash concentrations. A contemporary, unselected control (C) group from the same original population (third lactation, n = 7) was sampled concurrently. All sows were fed a standard gestation, then lactation, diet that contained no cholesterol or added fat (all plant, corn-soybean meal). Genetic selection for low or high serum cholesterol at 8 wk of age induced corresponding changes in milk cholesterol and fat concentration in the third generation of selection, but not in any other milk constituents. Milk cholesterol concentrations (milligrams/100 grams fresh weight) were L, 25.3 +/- 3.0; C, 35.7 +/- 8.0; and H, 41.4 +/- 6.9 (L < C < H, P <.01). Corresponding values for milk fat were 5.7 +/- 1.3, 7.2 +/-.8, and 7.0 +/-.8 mg (L < C = H, P <.01). Serum cholesterol concentrations at 8 wk of age were L, 66.1 +/- 8.1; C, 93.7 +/- 13.7; and H, 126.2 +/- 9.7 mg/dL (P <.01). Milk cholesterol concentration was significantly correlated with serum cholesterol (r =.782, P <.01) and milk fat (r =.36, P <.01). It seems that selecting swine for low or high serum cholesterol at 8 wk of age induced changes in lipid metabolism reflected in differences in milk cholesterol concentrations. |
| Milk sphingomyelin is more effective than egg sphingomyelin in inhibiting intestinal absorption of cholesterol and fat in rats Noh, S. K. and S. I. Koo (2004), J Nutr 134(10): 2611-6. Abstract: We reported previously that egg sphingomyelin (SM) inhibits the intestinal absorption of cholesterol and fat in rats. This study was conducted to compare the relative efficiencies of milk and egg SM in inhibiting intestinal absorption of cholesterol and other lipids. Adult male rats with lymph cannulae were infused at 3.0 mL/h for 8 h via a duodenal catheter with a lipid emulsion (451.7 micromol triolein, 20.7 micromol cholesterol, 33.3 kBq (14)C-cholesterol, 3.1 micromol alpha-tocopherol, and 396.0 micromol sodium taurocholate in 24 mL PBS, pH, 6.5), without SM (controls), or with 80.0 micromol egg SM or milk SM. The lymphatic absorptions of (14)C-cholesterol were significantly lower in rats infused with milk SM (19.5 +/- 1.4% dose) and egg SM (24.4 +/- 1.9% dose) than in those infused with no SM (37.6 +/- 1.8% dose). In addition, the lymphatic outputs of fatty acids and phospholipid were significantly lowered by milk and egg SM. Similarly, the absorption of alpha-tocopherol also was decreased by milk SM (13.6 +/- 1.7% dose) and egg SM (18.3 +/- 2.4% dose) compared with controls (27.0 +/- 1.8% dose). Total lymphatic SM output was not affected by egg SM, but markedly decreased by milk SM, relative to controls. The results indicate that both milk and egg SM markedly inhibit the absorption of cholesterol, fat, and other lipids. However, milk SM is a more potent inhibitor than egg SM. The strong inhibitory effect of milk SM may be associated with the higher degree of saturation and longer chain length of its fatty acyl groups, which may slow the rate of luminal lipolysis, micellar solubilization, and transfer of micellar lipids to the enterocyte. |
| Milk--a better drink? Relationships with total serum cholesterol in a cross-sectional survey. The Nordland Health Study Jacobsen, B. K. and I. Stensvold (1992), Scand J Soc Med 20(4): 204-8. Abstract: Cross-sectional studies have not consistently shown a positive association between milk drinking and serum cholesterol. We studied this relationship in a cohort of 7506 men and women aged 40-42 years in the county of Nordland in northern Norway (72% of all subjects in the age-bracket living in the county). We found a positive relationship between the percentage of fat in the milk and total serum cholesterol, but no positive relationship between whole fat milk consumption (number of glasses per day) and serum cholesterol. The findings were, however, to some extent influenced by effects of present atherosclerotic disease, or perceived threat of this. |
| Millions of healthy people can be considered ill because of the American cholesterol policy Ravnskov, U. (2001), Lakartidningen 98(42): 4574-7. |
| Mineral-cholesterol concentrations of the aortic aneurysmatic wall Pawlikowski, M., R. Pfitzner, et al. (1996), Pol J Pathol 47(4): 225-32. Abstract: Mineralogical investigations were performed on specimens from the aneurysmatic wall of ascending and descending thoracic and abdominal aortas collected intraoperatively from 10 patients (8 male, 2 female) aged 40-80 years. Scanning electron microscopy with energy dispersive x-ray analyses (microprobe-SEM/EDXA), and atomic absorption spectroscopy (AAS) showed incipient mineral and cholesterol depositions in the tissues of the patients when compared with the normal aorta of the young individual. Grains and crystals of cholesterol, and spherulitic mineralization, probably apatitic, were detected. It is suggested that localized cations imbalance precedes mineralization and is the potential co-factor of aortic wall pathology and aneurysm formation. |
| Miscibility gap in fluid dimyristoylphosphatidylcholine:cholesterol as "seen" by x rays Richter, F., G. Rapp, et al. (2001), Phys Rev E Stat Nonlin Soft Matter Phys 63(5 Pt 1): 051914. Abstract: A binary mixture of dimyristoylphosphatidylcholine (DMPC) and cholesterol displays a fluid miscibility gap under excess water conditions. Effects due to the imperfect miscibility of the two amphiphiles are studied near to and far from thermodynamic equilibrium by time-resolved small angle x-ray diffraction. The experiment discloses that this mixture phase separates when leaving the miscibility gap upon heating, a transition that is not included in current phase diagrams. This transition appears to be reversible and shows a temperature hysteresis of only a few degrees. We suggest a model in which the transition is driven with increasing temperature by a movement of the cholesterol away from the hydrophilic-hydrophobic interface toward the hydrophobic core of the bilayer. |
| Miscibility of ternary mixtures of phospholipids and cholesterol in monolayers, and application to bilayer systems Stottrup, B. L., D. S. Stevens, et al. (2005), Biophys J 88(1): 269-76. Abstract: We investigate miscibility transitions of two different ternary lipid mixtures, DOPC/DPPC/Chol and POPC/PSM/Chol. In vesicles, both of these mixtures of an unsaturated lipid, a saturated lipid, and cholesterol form micron-scale domains of immiscible liquid phases for only a limited range of compositions. In contrast, in monolayers, both of these mixtures produce two distinct regions of immiscible liquid phases that span all compositions studied, the alpha-region at low cholesterol and the beta-region at high cholesterol. In other words, we find only limited overlap in miscibility phase behavior of monolayers and bilayers for the lipids studied. For vesicles at 25 degrees C, the miscibility phase boundary spans portions of both the monolayer alpha-region and beta-region. Within the monolayer beta-region, domains persist to high pressures, yet within the alpha-region, miscibility phase transition pressures always fall below 15 mN/m, far below the bilayer equivalent pressure of 32 mN/m. Approximately equivalent phase behavior is observed for monolayers of DOPC/DPPC/Chol and for monolayers of POPC/PSM/Chol. As expected, pressure-area isotherms of our ternary lipid mixtures yield smaller molecular area and compressibility for monolayers containing more saturated acyl chains and cholesterol. All monolayer experiments were conducted under argon. We show that exposure of unsaturated lipids to air causes monolayer surface pressures to decrease rapidly and miscibility transition pressures to increase rapidly. |
| Misconceptions about cholesterol French, J. and H. White (1990), N Z Med J 103(882): 19-20. |
| Misinterpretation of coronary cholesterol atheromata in cholesterol-fed rabbits as suitable model for conventional human coronary plaques Thimm, F., M. Frey, et al. (1994), Adv Exp Med Biol 361: 417-24. |
| Misleading cholesterol statistics Ravnskov, U. (1999), Lakartidningen 96(16): 1947, 1949. |
| Mismatch of coronary risk and treatment intensity under the National Cholesterol Education Program guidelines McIsaac, W. J., C. D. Naylor, et al. (1991), J Gen Intern Med 6(6): 518-23. Abstract: OBJECTIVE: To assess the match between multifactorial risk of coronary heart disease (CHD) and treatment intensity under the National Cholesterol Education Program (NCEP) guidelines for primary prevention of CHD. METHODS: The multiple logistic regression equation from the Framingham Study was used to derive predicted risks for development of CHD over eight years of follow-up for different age-gender groupings, with serum total cholesterol (TC) values chosen in light of the NCEP cutoff points for both TC and low-density-lipoprotein cholesterol levels. Additional risk factors--hypertension, glucose intolerance, and smoking--were considered in combination for each of these values. RESULTS: Controlling for the effects of age and gender, there is little difference in the ranges of absolute CHD risks for persons who would receive interventions of differing intensities (i.e., general dietary advice, dietary treatment, or drug therapy). Those who are candidates for drug treatment because of serum lipids alone are often at low levels of risk for the development of CHD when compared with those of the same age with lower TC values who have other risk factors. Discrepancies in CHD risk are wider still when age is also allowed to vary. Furthermore, in every age grouping, women with high TC levels (e.g., 6.9 mmol/L) and two other risk factors are eligible for drug treatment but have a CHD risk that is no higher, and often much lower, than that of males with one other risk factor and TC levels of 4.8 mmol/L or 5.7 mmol/L who are candidates for dietary advice or dietary therapy, respectively. CONCLUSIONS: Inconsistencies exist in the NCEP guidelines such that persons at low risk for the development of CHD are offered more intensive interventions than are other who actually are at much higher risks, and vice versa. Women in particular tend to be overtreated, relative to men. These findings point out the difficulties of promulgating guidelines that will appropriately match risk to preventive interventions in a complex multifactorial disease. |
| Mitochondrial and microsomal cholesterol mobilization after oxidative stress induced by adriamycin in rats fed with dietary olive and corn oil Huertas, J. R., M. Battino, et al. (1992), Life Sci 50(26): 2111-8. Abstract: The influence of three different dietary fats (8%) and of endogenous lipid peroxidation with regard to cholesterol concentrations in liver mitochondria and microsomes and in serum has been investigated in the rat. Although the different diet fat used did not produce any effect on serum cholesterol, it was possible to show that each experimental diet differently influenced the microsomal and mitochondrial levels of cholesterol. The highest mitochondrial and microsomal cholesterol content was found in case of diet supplemented with virgin olive oil and the lowest with rectified olive oil. An endogenous oxidative stress induced by adriamycin was able to produce a clear decrease in microsomal and mitochondrial cholesterol level and a sharp increase in serum concentration in all three groups. However, dietary fats and adriamycin had no effect on the microsomal and mitochondrial membrane viscosity as detected by fluorescence polarization. These results are consistent with the hypothesis that mitochondrial and microsomal cholesterol can exchange with exogenous pools when phospholipid peroxidation occurs. |
| Mitochondrial permeability transition induced by reactive oxygen species is independent of cholesterol-regulated membrane fluidity Colell, A., C. Garcia-Ruiz, et al. (2004), FEBS Lett 560(1-3): 63-8. Abstract: Cholesterol enrichment of rat liver mitochondria (CHM) impairs atractyloside-induced mitochondrial permeability transition (MPT) due to decreased membrane fluidity. In this study we addressed the effect of cholesterol enrichment on MPT induced by reactive oxygen species (ROS). Superoxide anion generated by xanthine plus xanthine oxidase triggered mitochondrial swelling and cytochrome c release in CHM, which was prevented by butylated hydroxytoluene, an anti-voltage-dependent anion channel antibody, or cyclosporin A. Furthermore, hydrogen peroxide generated by the combination of ganglioside GD3 and mitochondrial GSH depletion elicited mitochondrial swelling and release of cytochrome c, Smac/Diablo and apoptosis-inducing factor in control mitochondria and CHM. Thus, ROS induce MPT and apoptosome activation regardless of decreased mitochondrial membrane dynamics due to cholesterol enrichment. |
| Mitochondrial processing of newly synthesized steroidogenic acute regulatory protein (StAR), but not total StAR, mediates cholesterol transfer to cytochrome P450 side chain cleavage enzyme in adrenal cells Artemenko, I. P., D. Zhao, et al. (2001), J Biol Chem 276(49): 46583-96. Abstract: The metabolism of cholesterol by cytochrome P450 side chain cleavage enzyme is hormonally regulated in steroidogenic tissues via intramitochondrial cholesterol transport. The mediating steroidogenic acute regulatory protein (StAR) is synthesized as a 37-kDa (p37) precursor that is phosphorylated by protein kinase A and cleaved within the mitochondria to generate 30-kDa forms (p30, pp30). The effectiveness of modified recombinant StAR forms in COS-1 cells without mitochondrial import has led to a prevailing view that cholesterol transport is mediated by p37 StAR via activity on the outer mitochondrial membrane. The present study of the activation of cholesterol metabolism by bromo-cAMP in adrenal cells in relation to (35)S-StAR turnover indicates that targeting of pp30 to the inner membrane provides the dominant cholesterol transport mechanism. We show that 1) only newly synthesized StAR is functional, 2) phosphorylation and processing of p37 to pp30 occurs rapidly and stoichiometrically, 3) both steps are necessary for optimum transport, and 4) newly synthesized pp30 exhibits very high activity (400 molecules of cholesterol/StAR/min). Segregation of cAMP activation and synthesis of StAR from cholesterol metabolism showed that very low levels of newly synthesized StAR (1 fmol/min/10(6) cells) sustained activated cholesterol metabolism (0.4 pmol/min/10(6) cells, t(1/2) = 70 min) long after complete removal of p37 (t(1/2) = 5 min). This activity was highly sensitive to inhibition of processing by CCCP only until sufficient pp30 was formed. Maximum activation preceded bromo-cAMP-induced StAR expression, indicating other limiting steps in cholesterol metabolism. |
| Mitogenic effect of lithium in FRTL-5 cells can be reversed by blocking de novo cholesterol synthesis and subsequent signal transduction Tasevski, V., D. Benn, et al. (2000), Thyroid 10(4): 305-11. Abstract: Lithium therapy is the therapeutic mainstay for bipolar disorder and has been associated in the thyroid with euthymic goiter, hyper and hypothyroidism as well as thyroid autoimmune disease. The FRTL-5 cell line is a well known model of thyroid cell physiology, where lithium has been shown to increase 3H-thymidine uptake at concentrations of 2 mM. This mitogenic effect was not associated with adenylate cyclase as measured by cyclic adenosine monophosphate (cAMP) production. The de novo synthesis of cholesterol is an important signal transduction pathway in FRTL-5 cells, where newly synthesized Rho GTPase is geranylgeranylated, enabling membrane localization of the G-protein and subsequent G1 to S-phase transition, resulting from extracellular stimulation. Here we confirm lithium mitogenicity at therapeutically relevant concentrations (1 mM) and demonstrate a lithium-associated accumulation of FRTL-5 cells in S-phase of the cell cycle. These effects could be abolished by Pravastatin, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), the rate-limiting enzyme in the formation of intermediates (de novo cholesterol synthesis) required for G-protein prenylation. Pravastatin, similar to lithium, showed no effect on cAMP production either under basal or thyroid stimulating hormone (TSH)-stimulated conditions indicating that de novo cholesterol synthesis is not involved with adenylate cyclase. The inhibitory effect of pravastatin could be overcome by reinitiating de novo cholesterol synthesis. This was achieved by the addition of the cell permeable, first metabolite (mevalonate) after HMG-CoA, which allowed the cycle to continue, leading eventually to protein prenylation, despite the presence of Pravastatin. These novel findings demonstrate lithium involvement in de novo cholesterol synthesis and G-protein prenylation, an important signal transduction pathway in FRTL-5 cells. |