| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effects of cardiac rehabilitation and exercise training on low-density lipoprotein cholesterol in patients with hypertriglyceridemia and coronary artery disease Lavie, C. J. and R. V. Milani (1994), Am J Cardiol 74(12): 1192-5. Abstract: Substantial data suggest that elevated triglycerides are associated with increased coronary risk, and may be an independent coronary risk factor. Although it is generally accepted that patients with hypertriglyceridemia can have marked improvement in lipids after vigorous nonpharmacologic therapy, data to support this belief are lacking. This study assessed 313 consecutive patients before and after outpatient phase II cardiac rehabilitation and exercise programs to compare the response of patients with elevated triglycerides (> or = 250 mg/dl; n = 39) to vigorous nonpharmacologic therapy with the response of patients with "normal" triglyceride levels (< 150 mg/dl; n = 157). The independent effects that baseline triglycerides, as well as other variables, had on improving lipids after nonpharmacologic therapy were also determined. After cardiac rehabilitation and exercise training, patients had improvement in total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol levels, low-density lipoprotein (LDL) cholesterol levels, LDL/HDL ratios, body mass index, percent body fat, and METs. Patients with hypertriglyceridemia were younger (p = 0.05) and had higher baseline body mass index (p < 0.001) and LDL/HDL ratios (p < 0.0001) but lower HDL cholesterol levels (p < 0.0001) than patients with low baseline triglycerides. Both groups had improvement in lipids, obesity indexes, and exercise capacity. However, patients with hypertriglyceridemia had significantly greater reductions in triglycerides (-31% vs +3%; p < 0.0001), but had less improvement in both LDL cholesterol levels (0% vs -4%; p < 0.01) and LDL/HDL ratios (-5% vs -9%; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) |
| Effects of casein and soy protein on accumulation of cholesterol and dolichol in rat liver Ishinaga, M., M. Hamada, et al. (1993), Proc Soc Exp Biol Med 203(1): 74-7. Abstract: A diet containing 15% (w/w) fat and 20% (w/w) of either casein (CAS) or soy protein (SOY) was fed to 4-week-old rats for a period of 18 months. The effects of these dietary proteins on the accumulation of cholesterol and dolichol in livers were studied. After 1 month, the amount of liver cholesterol was about 5 mg/g of liver. After an additional 5 months of feeding, there was a slight decrease in cholesterol per gram of liver (3.6 mg/g of liver in CAS-fed rats and 2.6 mg/g of liver in SOY-fed rats). However, after 18 months, there were a remarkable increase (7.5 mg/g of liver) in CAS-fed rats and only a slight increase in SOY-fed rats. The proportions of liver cholesterol ester in rats fed the CAS diet were 60-70% of the total cholesterol during the experimental period, but in the case of the SOY diet, only rats fed the diet for 1 month showed a high level, 70%, of cholesterol ester. The amounts of liver dolichol in rats fed the CAS and SOY diets after feeding for 18 months were 60 micrograms and 47 micrograms of liver, respectively. There was a 1.5-fold increase in both diets for a period of 18 months. The proportions of liver dolichyl fatty ester in rats fed the CAS diet were 35-40% of the total dolichol during the experimental period, but in the case of the SOY diet, only rats fed the diet for 1 month showed a high level, 36%, of dolichyl fatty ester. The proportions of dolichol ester in rats fed the SOY diet were 25-30% after 6 and 18 months of feeding. These observations indicated that the SOY diet depresses the accumulation of both liver dolichol and cholesterol. |
| Effects of cholesterol and apolipoprotein E on retinal abnormalities in ApoE-deficient mice Ong, J. M., N. C. Zorapapel, et al. (2001), Invest Ophthalmol Vis Sci 42(8): 1891-900. Abstract: PURPOSE. To examine the pathologic changes in the retina of apolipoprotein E (apoE)-deficient mice fed a high-cholesterol diet. METHODS. ApoE-deficient mice (ApoE) were maintained on either regular mouse chow (ApoE-R) or a high-cholesterol diet (ApoE-C) for 25 weeks. Age-matched control C57BL/6J mice (C57) were also maintained on either regular mouse chow (C57-R) or a cholesterol-containing diet (C57-C). Retinal function was assessed by dark-adapted electroretinography (ERG). The eyes were embedded, sectioned, and analyzed by histologic and immunohistochemical methods, as well as by light and transmission electron microscopy. RESULTS. After the 25-week feeding period, ERG tracings of ApoE-C mice revealed significant increases of a- and b-wave implicit times when compared with the C57-R group of mice. In addition, there were reductions in oscillatory potential (OP) amplitudes in the ApoE-C group. However, a- and b-wave amplitudes appeared to be unchanged among the four groups of mice. Light microscopic examination of the retinas showed that compared with control C57-R mice, ApoE-C mice had significantly lower cell numbers in the inner and outer nuclear layers (85.1% +/- 4.6%, P < 0.05 and 81.4% +/- 3.7%, P < 0.01 of C57-R controls, respectively). Transmission electron microscopy of apoE-deficient mice revealed cells of the inner nuclear layer with condensation of nuclear chromatin and perinuclear vacuolization in focal areas. Bruch's membrane was also found to be thicker, and its elastic lamina appeared disorganized and discontinuous. Immunohistochemistry demonstrated diminished or no immunoreactivity for carbonic anhydrase II and calretinin in the retinal layers of apoE-deficient mice. CONCLUSIONS. Overall, there were increasing abnormalities of retinal function and cellular morphology among the four groups of mice in the order of C57-R < C57-C < ApoE-R < ApoE-C. These findings suggest that apoE and/or cholesterol play an important role in retinal function. |
| Effects of cholesterol and cholesteryl oleate on lipolysis and liver uptake of triglyceride/phosphatidylcholine emulsions in rats Handa, T., Y. Eguchi, et al. (1994), Pharm Res 11(9): 1283-7. Abstract: Emulsions composed of soy bean triglyceride (TG), egg yolk phosphatidylcholine (PC), cholesterol (Chol) or cholesteryl-oleate (CO), labeled with a cholesteryl ether (3H-CHE) and a triglyceride (14C-TO), were injected into rats. 14C-TO was removed from plasma faster than 3H-CHE. The 14C-labeled moiety is cleaved by digestion of the TG in the emulsion in plasma and is removed to the endothelial cells (lipolysis). In contrast, the 3H-label remains stably associated and represents circulating emulsion particles. The majority (90%) of the 3H-label disappearing from the plasma accumulated in the liver for all types of emulsions. On the basis of these observations, the lipolysis and the removal of emulsion particles to organs (mainly liver) were determined: 30 mole percent of cholesterol (Chol) at the TG-PC emulsion surface markedly retarded organ uptake, but the effect on lipolysis was rather small; 20 mole percent of cholesteryl oleate (CO) in the TG-PC emulsion cores delayed both organ uptake and lipolysis, and induced a rapid increase in organ uptake rate after the initial delay accompanying the gradual progress of lipolysis. Lipolysis led to the enrichment of the cores with CO. Replacement of the core TG by CO, however, induced strong suppression of the liver uptake. These results show that the lipid composition at both surface and core of emulsion particles is a crucial factor in metabolism in the rat. |
| Effects of cholesterol and enantiomeric cholesterol on P-glycoprotein localization and function in low-density membrane domains Luker, G. D., C. M. Pica, et al. (2000), Biochemistry 39(26): 7651-61. Abstract: Multidrug resistance P-glycoprotein (Pgp) has been reported to localize in low-density, cholesterol-enriched membranes. However, effects of low-density membrane domains on function of Pgp remain unexplored in whole cell systems. In cells that express modest levels of the protein endogenously or through drug selection, Pgp predominantly localized to low-density membranes following separation on a sucrose gradient. When highly overexpressed in NIH 3T3 cells, a prominent amount of Pgp also was detected in high-density membranes. Removing cholesterol from cells with beta-methylcyclodextrin (CD), a sterol acceptor molecule, shifted fractions that contained Pgp from low toward high density, and this effect was reversed to a similar extent by restoring sterols with either cholesterol or enantiomeric cholesterol. However, function of human MDR1 Pgp as probed with Tc-Sestamibi, a transport substrate for Pgp, was not dependent on localization of Pgp in cholesterol-enriched membranes. Specific inhibition of MDR1 Pgp with GF120918 or LY335979 also was independent of cholesterol. Cell-type-specific effects of cholesterol content on function of human Pgp were detected by use of daunomycin, another substrate for Pgp, although efficacy of inhibitors remained independent of cholesterol. Conversely, both function and inhibition of hamster Pgp as measured with Tc-Sestamibi and daunomycin were in part dependent on normal cell content of cholesterol. These data show that Pgp preferentially localizes to low-density, cholesterol-enriched membrane domains, but acute depletion of cholesterol impacts Pgp-mediated drug transport in a substrate- and cell-type-specific manner. |
| Effects of cholesterol and fat modification of self-selected diets on serum lipids and their specific fatty acids in normocholesterolemic and hypercholesterolemic humans Flynn, M. A., G. B. Nolph, et al. (1991), J Am Coll Nutr 10(2): 93-106. Abstract: A 6-month crossover diet plan was employed to study the effects on human serum lipids of adding margarine or butter to otherwise self-selected diets that included two eggs daily. Two groups of subjects were studied: 51 free-living normocholesterolemic and 20 hypercholesterolemic (greater than 240 mg dl). Four-day diet records in each interval showed that subjects ate about 16% of total dietary fat as either butter or margarine. Blood samples taken every 6 weeks showed variable mean serum total cholesterol (SCHOL), high-density-lipoprotein cholesterol (HDL-C), and serum triglycerides (STG). The normocholesterolemic subjects who ate butter first had by 24 weeks mean SCHOL values equal to their entry values; those who ate margarine first had increased SCHOL values throughout the study. By the end of the study, the hypercholesterolemic subjects showed either no change or a slight decrease in both SCHOL and HDL-C values. Specific fatty acids were distributed differently in the serum fractions of triacylglycerol (TGFA), cholesteryl esters (CEFA), and phospholipids (PLFA). These distributions remained constant in both normocholesterolemic and hypercholesterolemic subjects regardless of the type and amount of fat consumed. |
| Effects of cholesterol and inflammation-sensitive plasma proteins on incidence of myocardial infarction and stroke in men Engstrom, G., P. Lind, et al. (2002), Circulation 105(22): 2632-7. Abstract: BACKGROUND: Although cholesterol is a major cardiovascular risk factor, its association with stroke remains controversial. This study explored whether the cholesterol-related incidence of stroke and myocardial infarction is modified by plasma markers of inflammation in a large, population-based cohort with a long follow-up. METHODS AND RESULTS: Plasma cholesterol and 5 inflammation-sensitive plasma proteins (ISP) (fibrinogen, alpha1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid) were determined in 6063 healthy men, 28 to 61 years of age. The incidence of stroke, cardiac events (fatal and nonfatal), and cardiovascular deaths was compared between groups defined by levels of cholesterol and ISP. Mean follow-up was 18.7 years. High ISP level was defined as 2 to 5 ISP in the top quartile. High cholesterol was associated with higher levels of ISP. Hypercholesterolemia (> or =6.5 mmol/L, 251 mg/dL) was associated with an increased incidence of ischemic stroke and cardiac events and with a reduced incidence of intracerebral hemorrhage. The ISP levels modified these associations. After risk factor adjustment, men with hypercholesterolemia and high ISP levels had a significantly higher risk of cardiovascular death (relative risk RR=2.4; CI, 1.8 to 3.3), cardiac events (RR=2.3; CI, 1.8 to 3.0), and ischemic stroke (RR=2.1; CI, 1.4 to 3.3) than men with normal cholesterol and low ISP levels. In the absence of high ISP levels, hypercholesterolemia was associated with a moderately higher risk of cardiovascular death (RR=1.4; CI, 1.0 to 2.0) and cardiac events (RR=1.5; CI, 1.2 to 1.9) but not significantly with ischemic stroke (RR=1.25; CI, 0.8 to 2.0). CONCLUSIONS: Hypercholesterolemia is associated with high plasma levels of ISP. These proteins increase the cholesterol-related incidence of cardiovascular diseases. In the absence of elevated ISP levels, no statistically confirmed association was found between hypercholesterolemia and ischemic stroke. |
| Effects of cholesterol and model transmembrane proteins on drug partitioning into lipid bilayers as analysed by immobilized-liposome chromatography Lagerquist, C., F. Beigi, et al. (2001), J Pharm Pharmacol 53(11): 1477-87. Abstract: We have analysed how cholesterol and transmembrane proteins in phospholipid bilayers modulate drug partitioning into the bilayers. For this purpose we determined the chromatographic retention of drugs on liposomes or proteoliposomes entrapped in gel beads. The drug retention per phospholipid amount (the capacity factor Ks) reflects the drug partitioning. Cholesterol in the bilayers decreased the Ks value and hence the partitioning into the membrane in proportion to the cholesterol fraction. On average this cholesterol effect decreased with increasing temperature. Model transmembrane proteins, the glucose transporter GLUT1 and bacteriorhodopsin, interacted electrostatically with charged drugs to increase or decrease the drug partitioning into the bilayers. Bacteriorhodopsin proteoliposomes containing cholesterol combined the effects of the protein and the cholesterol and approached the partitioning properties of red blood cell membranes. For positively charged drugs the correlation between calculated intestinal permeability and log Ks was fair for both liposomes and bacteriorhodopsin-cholesterol proteoliposomes. Detailed modeling of solute partitioning into biological membranes may require an extensive knowledge of their structures. |
| Effects of cholesterol and oxysterols on gap junctional communication between human smooth muscle cells Zwijsen, R. M., I. M. Oudenhoven, et al. (1992), Eur J Pharmacol 228(2-3): 115-20. Abstract: Intercellular communication is considered to play an essential role in maintaining and controlling cell growth, cell differentiation and homeostasis. Cell-cell communication can be regulated by factors that influence gap junctional function. In this study it was demonstrated that cholesterol and oxidized cholesterol have the potential to modulate gap junctional communication between human smooth muscle cells in an opposite way. Cholesterol supplementation to human smooth muscle cells resulted in an increase of gap junctional communication up to 130% with regard to the control values. However, autooxidized cholesterol inhibited gap junctional communication more than 40%. Testing of several pure cholesterol oxidation derivates on gap junctional communication demonstrated that all of them were capable to inhibit intercellular communication in the order 25-hydroxycholesterol greater than cholestan-3 beta,5 alpha,6 beta-triol greater than 7-ketocholesterol greater than cholesterol 5,6 alpha-epoxide. The cell-cell communication-inhibiting potency of these oxysterols is in accordance with their atherogenic potency. This implies that cholesterol oxidation products, instead of pure cholesterol, can be promoting factors in the atherogenesis by influencing gap junctional communication between arterial smooth muscle cells, the target cells of atherosclerotic lesions. |
| Effects of cholesterol and temperature on the permeability of dimyristoylphosphatidylcholine bilayers near the chain melting phase transition Kraske, W. V. and D. B. Mountcastle (2001), Biochim Biophys Acta 1514(2): 159-64. Abstract: The passive leakage of glucose across bilayers of dimyristoylphosphatidylcholine (DMPC), cholesterol (variable), and dicetyl phosphate (constant 5.9 mol%) has been measured as efflux over 30 min from multilamellar vesicles. Bilayer cholesterol was varied from 20 mol% to 40 mol%. Glucose permeation rates were measured from 10 degrees C to 36 degrees C, and showed a maximum in permeability at 24 degrees C, the DMPC phase transition temperature. Increasing the bilayer cholesterol content above 20 mol% reduced that permeability peak. These results are quite consistent with a large number of similar bilayer permeability studies over the past 25 years. However, they are not consistent with a previous study of these same systems, which reported increased glucose permeability with temperature, without any maximum at or near the lipid chain melting temperature (K. Inoue, Biochim. Biophys. Acta 339 (1974) 390-402). |
| Effects of cholesterol depletion and increased lipid unsaturation on the properties of endocytic membranes Hao, M., S. Mukherjee, et al. (2004), J Biol Chem 279(14): 14171-8. Abstract: Lipid analogs with dialkylindocarbocyanine (DiI) head groups and short or unsaturated hydrocarbon chains (e.g. DiIC(12) and FAST DiI) enter the endocytic recycling compartment efficiently, whereas lipid analogs with long, saturated tails (e.g. DiIC(16) and DiIC(18)) are sorted out of this pathway and targeted to the late endosomes/lysosomes (Mukherjee, S., Soe, T. T., and Maxfield, F. R. (1999) J. Cell Biol. 144, 1271-1284). This differential trafficking of lipid analogs with the same polar head group was interpreted to result from differential partitioning to different types of domains with varying membrane order and/or curvature. Here we investigate the system further by monitoring the trafficking behavior of these lipid analogs under conditions that alter domain properties. There was a marked effect of cholesterol depletion on the cell-surface distribution and degree of internalization of the lipid probes. Furthermore, instead of going to the late endosomes/lysosomes as in control cells, long chain DiI analogs, such as DiIC(16), were sorted to the recycling pathway in cholesterol-depleted cells. We confirmed that this difference was due to a change in overall membrane properties, and not cholesterol levels per se, by utilizing a Chinese hamster ovary cell line that overexpressed transfected stearoyl-CoA desaturase 1, a rate-limiting enzyme in the production of monounsaturated fatty acids. These cells have a decrease in membrane order because they contain a much larger fraction of unsaturated fatty acids. These cells showed alteration of DiI trafficking very similar to cholesterol-depleted cells. By using cold Triton X-100 extractability of different lipids as a criterion to determine the membrane properties of intracellular organelles, we found that the endocytic recycling compartment has abundant detergent-resistant membranes, in contrast to the late endosomes and lysosomes. |
| Effects of cholesterol depletion by cyclodextrin on the sphingolipid microdomains of the plasma membrane Ilangumaran, S. and D. C. Hoessli (1998), Biochem J 335 (Pt 2): 433-40. Abstract: Sphingolipid microdomains are thought to result from the organization of plasma membrane sphingolipids and cholesterol into a liquid ordered phase, wherein the glycosylphosphatidylinositol (GPI)-anchored proteins are enriched. These domains, resistant to extraction by cold Triton X-100, can be isolated as buoyant membrane complexes (detergent-resistant membranes) in isopycnic density gradients. Here the effects of methyl-beta-cyclodextrin (MBCD), a specific cholesterol-binding agent that neither binds nor inserts into the plasma membrane, were investigated on the sphingolipid microdomains of lymphocytes. MBCD released substantial quantities of GPI-anchored Thy-1 and glycosphingolipid GM1, and also other surface proteins including CD45, and intracellular Lck and Fyn kinases. From endothelial cells, MBCD released GPI-anchored CD59, and CD44, but only a negligible amount of caveolin. Most MBCD-released Thy-1 and CD59 were not sedimentable and thus differed from Thy-1 released by membrane-active cholesterol-binding agents such as saponin and streptolysin O, or Triton X-100. Unlike that released by Triton X-100, only part of the Thy-1 molecules released by MBCD was buoyant in density gradients and co-isolated with GM1. Finally, treatment of Triton X-100-isolated detergent-resistant membranes with MBCD extracted most of the cholesterol without affecting the buoyant properties of Thy-1 or GM1. We suggest that (1) MBCD preferentially extracts cholesterol from outside, rather than within the sphingolipid microdomains and (2) this partly solubilizes GPI-anchored and transmembrane proteins from the glycerophospholipid-rich membrane and releases sphingolipid microdomains in both vesicular and non-vesicular form. |
| Effects of cholesterol diets on vascular function and atherogenesis in rabbits Sun, Y. P., N. C. Lu, et al. (2000), Proc Soc Exp Biol Med 224(3): 166-71. Abstract: Vascular endothelial dysfunction is an important early event in atherogenesis. To evaluate the effects of different levels of cholesterol-containing diets on vascular function and atherogenesis, 17 New Zealand White male rabbits were randomized into four groups: Control with noncholesterol, 10-week 0.5% (0.5C-10) or 1% cholesterol (1C-10), and 14-week 0.5% cholesterol (0.5C-14) feedings. After 10 or 14 weeks, the aortas were harvested for studies of vascular endothelial function and percentage surface lipid lesions. The 0.5% and 1% cholesterol feedings resulted in the same degree of hypercholesterolemia independent of the level and period of cholesterol feeding. There was a decreased trend in vascular endothelial-dependent relaxation to acetylcholine in cholesterol-fed rabbits. Fourteen-week cholesterol feeding induced the least vascular dilation at a concentration of 10-7 M acetylcholine (-38 +/- 3%, -23 +/- 4%, -23 +/- 2%, and -15 +/- 5% in control, 0.5C-10, 1C-10, and 0.5C-14 groups, respectively, P = 0.003). More cumulative exposure of arterial walls to cholesterol induced more surface lipid lesions in the aorta (r = 0.877, P < 0.001). There was a negative relationship between aortic lesions and vasodilation (r = -0.557, P = 0.020 for calcium ionophore; r = -0.463, P = 0.062 for acetylcholine). We conclude that the 0.5% and 1% cholesterol feedings induce similar degrees of hypercholesterolemia. However, aortic lipid lesions and vascular reactivity are dependent on cumulative exposure to cholesterol rather than serum cholesterol level only. Furthermore, decreased vascular endothelial relaxation in cholesterol-fed rabbits was related to lipid plaques in the aorta. |
| Effects of cholesterol ester transfer protein Taq1B gene polymorphism on serum lipoprotein levels in Turkish coronary artery disease patients Yilmaz, H., T. Isbir, et al. (2005), Cell Biochem Funct 23(1): 23-8. Abstract: To evaluate the effect of cholesterol ester transfer protein (CETP) Taq1B gene polymorphism on serum lipid profile in Turkish coronary artery disease (CAD) patients, we investigated Taq1B gene polymorphism of CETP and serum lipid levels in 111 controls and in 173 CAD patients with myocardial infarction. There were no significant differences in the allele distribution at this polymorphic locus between the population sample and patients with coronary artery disease with myocardial infarction. To detect the association between the Taq1B RFLP and serum lipid levels, we determined the serum concentrations of total cholesterol, triglycerides and high density lipoprotein cholesterol (HDL-C) in the subjects studied and correlated the results to the Taq1B RFLP. Patients with Taq B1B1 genotypes had lower HDL-C levels than patients with B2B2 genotype (p = 0.003). Also in control subjects with Taq B1B1 genotype, lower HDL-C levels (p = 0.05) and higher triglyceride levels (p = 0.017) and body mass index (p = 0.05) were observed compared with control subjects with the B1B2 genotype. It was observed that in our population the distribution of CETP Taq1B genotypes is similar to other populations (except Greeks). The present study demonstrates that CETP Taq1B gene polymorphism may be responsible for low HDL cholesterol levels in patients with CAD and in healthy controls in Turkey. |
| Effects of cholesterol loading of mouse macrophages on carnitine palmitoyltransferase activity and sensitivity to inhibition by malonyl-CoA Kashfi, K., L. Dory, et al. (1991), Biochem Biophys Res Commun 177(3): 1121-6. Abstract: Scavenger receptor-mediated uptake of acetylated low density lipoprotein-derived cholesterol by peritoneal mouse macrophages resulted in decreased activity of the malonyl-CoA inhibitable carnitine palmitoyltransferase and a decrease in the sensitivity of this enzyme to inhibition by malonyl-CoA. |
| Effects of cholesterol loading on autoimmune MRL-lpr/lpr mice: susceptibility to hypercholesterolemia and aortic cholesterol deposition Yamaguchi, Y., S. Kitagawa, et al. (1993), Jpn J Pharmacol 61(4): 291-8. Abstract: Autoimmune MRL-lpr/lpr (MRL/l) mice, with a systemic lupus erythematosus-like disease, were shown to spontaneously develop hyperlipidemia and yet be susceptible to diet-induced hypercholesterolemia and aortic cholesterol deposition. Control animals on a basal diet showed significant increases in the serum total cholesterol, phospholipids, triglycerides, high density lipoprotein (HDL)-cholesterol and lipid peroxide levels, but a significant decline in the serum lecithin: cholesterol acyltransferase (LCAT) activity compared to those of 5-week-old mice. Animals on the high-cholesterol diet showed a rapid rise in serum total cholesterol to a plateau level (800 mg/100 ml) that was approximately 2.5 times higher than that in the control animals on a basal diet. However, the levels of serum triglycerides, HDL-cholesterol and lipid peroxides significantly decreased (by 61%, 23% and 53%, respectively) compared to those of the control animals, whereas LCAT activity and phospholipid level were not affected. The aortic contents of total cholesterol, free cholesterol and cholesteryl ester were significantly higher (by 35%, 36% and 31%, respectively) in animals fed the high-cholesterol diet than the control animals. These findings suggest that MRL/l mice are susceptible to diet-induced hypercholesterolemia and aortic cholesterol deposition. |
| Effects of cholesterol lowering on the progression of coronary atherosclerosis in women. A Canadian Coronary Atherosclerosis Intervention Trial (CCAIT) substudy Waters, D., L. Higginson, et al. (1995), Circulation 92(9): 2404-10. Abstract: BACKGROUND: Although coronary disease is the leading cause of death in women and its clinical features differ from those in men, very few women have been included in angiographic trials of cholesterol lowering. METHODS AND RESULTS: Sixty-two women with diffuse but not necessarily severe coronary atherosclerosis documented on a recent angiogram and with fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a double-blind, placebo-controlled trial. More than one half had a history of hypertension, approximately one quarter were diabetics, and one third were current smokers. All women received dietary counseling. Lovastatin or placebo was begun at 20 mg/d and was titrated if necessary to 40 and then to 80 mg during the first 16 weeks to attain a fasting LDL cholesterol < or = 130 mg/dL. The mean lovastatin dose was 34 mg/d. Total and LDL cholesterol decreased by 24% and 32%, respectively, in lovastatin-treated women but by < 3% in women receiving placebo. Coronary arteriography was repeated after 2 years in 54 women (87%), and their 394 lesions were measured "blindly" on pairs of film with an automated computerized quantitative system. Progression, defined as a worsening in minimum diameter of one or more stenoses by > or = 0.4 mm, occurred in 7 of 25 lovastatin-treated women and 17 of 29 placebo-treated women (28% versus 59%, P =.031). New coronary lesions developed in 1 lovastatin-treated woman and 13 placebo-treated women (4% versus 45%, P <.001). The outcome for each of the angiographic end points was not significantly different between the women and the 245 men who completed the trial. CONCLUSIONS: Lovastatin slows the progression of coronary atherosclerosis and prevents the development of new coronary lesions in women. |
| Effects of cholesterol on conformational disorder in dipalmitoylphosphatidylcholine bilayers. A quantitative IR study of the depth dependence Davies, M. A., H. F. Schuster, et al. (1990), Biochemistry 29(18): 4368-73. Abstract: A method originally proposed by Snyder and Poore (1973) Macromolecules 6, 708-715 as a specific probe of trans-gauche isomerization in hydrocarbon chains and recently applied Mendelsohn et al. (1989) Biochemistry 28, 8934-8939 to the quantitative determination of phospholipid acyl chain conformational order is utilized to monitor the effects of cholesterol at various depths in dipalmitoylphosphatidylcholine (DPPC) bilayers. The method is based on the observation that the CD2 rocking modes from the acyl chains of specifically deuterated phospholipids occur at frequencies in the Fourier transform infrared spectrum which depend upon the local geometry (trans or gauche) of the C-C-C skeleton surrounding a central CD2 group. Three specifically deuterated derivatives of DPPC, namely, 4,4,4',4'-d4 DPPC (4-d4 DPPC), 6,6,6',6'-d4 DPPC (6-d4 DPPC), and 12,12,12',12'-d4 DPPC (12-d4 DPPC), have been synthesized, and the effects of cholesterol addition at 2:1 DPPC/cholesterol (mol:mol) on acyl chain order at various temperatures have been determined. At 48 degrees C, cholesterol inhibits gauche rotamer formation by factors of approximately 9 and approximately 6 at positions 6 and 4, respectively, of the acyl chains, thus demonstrating a strong ordering effect in regions of the bilayer where the sterol rings are presumed to insert parallel to the DPPC acyl chains. In contrast, the ability of the sterol to order the acyl chains is much reduced at the 12-position. The sterol demonstrates only a slight disordering of phospholipid gel phases. Finally, the contributions of different classes of gauche conformers to the spectra have been determined.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Effects of cholesterol on dye leakage induced by multidrug-resistance modulators from anionic liposomes Castaing, M., A. Loiseau, et al. (2003), Eur J Pharm Sci 18(1): 81-8. Abstract: Multidrug-resistance (MDR) in cancer cells is often associated with marked changes in the membrane cholesterol levels. To assess the cholesterol-dependence of MDR modulator efficiency in terms of the drug-membrane interactions, the ability of 5 MDR-modulators to induce the leakage of Sulphan blue through anionic liposomes was quantified at various mole fractions x(chol) of cholesterol (0-0.42). Depending on the electric charge of the drug, cholesterol modified to a large extent either the permeation dose inducing 50% dye leakage (PD(50)) or the co-operativity (h) of the permeation process. The PD(50) of Triton X-100 (non-ionic) and that of diltiazem and verapamil (mono-basic amines) varied only slightly (0.3 mM) with the cholesterol level, whereas the co-operativity increased by 1.9-2.7. On the reverse, the PD(50) of a thioacridine derivative and mepacrine (di-basic amines) increased by 4.8-7.5 mM in the cholesterol range investigated, whereas the co-operativity (h) increased slightly (0.2-0.7). In the permeation process, the rate-limiting character of the electric charge (z) of the drug is likely to be strengthened by high cholesterol levels. The results provide evidence that in resistant tumours exhibiting high cholesterol levels, the MDR might be reversed by favourable drug-membrane interactions if the modulators are designed in the form of highly lipophilic mono-basic drugs that counteract the effects of cholesterol on the membrane dipolar potential and membrane fluidity. |
| Effects of cholesterol on proliferation and functional protein expression in rabbit bile duct fibroblasts Chen, B. Y., J. G. Wei, et al. (2004), World J Gastroenterol 10(6): 889-93. Abstract: AIM: To investigate the effect of cholesterol (Ch) on the growth and functional protein expression of rabbit bile duct fibroblasts. METHODS: The cultured bile duct fibroblasts were divided randomly into two groups: the control group and the experiment group (fibroblasts were incubated respectively with 0.6 g/L Ch for 12, 24, 36 and 48 h). The growth and DNA synthesis of bile duct fibroblasts were measured by the means of (3)H-TdR incorporation. The total protein content of fibroblast was measured by BSA protein assay reagent kit, then the expression of alpha-actin was analyzed semi-quantitatively by Western blot. RESULTS: After treatment with 0.6 g/L Ch for 12, 24, 36 and 48 h, the values of (3)H-TdR incorporation of bile duct fibroblasts were respectively 3.1+/-0.39, 3.8+/-0.37, 4.6+/-0.48 and 5.2+/-0.56 mBq/cell, and the values of the corresponding control groups were 3.0+/-0.33, 3.2+/-0.39, 3.7+/-0.49 and 4.3+/-0.43 mBq/cell. After comparing the values of experiment groups and their corresponding control groups, it was found that the (3)H-TdR incorporation of bile duct fibroblasts after treatment with 0.6 g/L Ch for 24, 36 and 48 h were significantly increased (P<0.05, P<0.01, P<0.01), while the (3)H-TdR incorporation of 12-h group was not different statistically from its control group. Ch had no obvious effect on the total protein content of fibroblasts. After incubated with 0.6 g/L Ch for 12, 24, 36 and 48 h, the total protein content of each experiment group was not altered markedly compared with its corresponding control group. The values of experiment groups were 0.246+/-0.051, 0.280+/-0.049, 0.263+/-0.044 and 0.275+/-0.056 ng/cell, and those of corresponding control groups were 0.253+/-0.048, 0.270+/-0.042, 0.258+/-0.050 and 0.270+/-0.045 ng/cell. Western blot analysis revealed that the alpha-actin expression in fibroblasts affected by Ch for 12 and 24 h was not markedly changed compared with their corresponding control groups (P>0.05), the values of total gray scale of 12- and 24-h groups were 1748+/-185 and 1756+/-173, respectively. But after stimulation with Ch for 36 h, the total gray scale of fibroblasts (1923+/-204) was significantly higher than that of control group (1734+/-197). When the time of Ch treatment was lengthened to 48 h, the alpha-actin expression was markedly elevated, the total gray scale was 2 189+/-231 (P<0.01 vs control group). CONCLUSION: Moderately concentrated Ch can promote the proliferation of bile duct fibroblasts at early stage. With the prolongation of Ch treatment, the alpha-actin expression of fibroblasts was also increased, but the hypertrophy of fibroblasts was not observed. |