| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Comparison of the associations of apolipoprotein B and low-density lipoprotein cholesterol with other cardiovascular risk factors in the Insulin Resistance Atherosclerosis Study (IRAS) Williams, K., A. D. Sniderman, et al. (2003), Circulation 108(19): 2312-6. Abstract: BACKGROUND: Risk factors for vascular disease include obesity, dyslipidemia, hypertension, dysglycemia, insulin resistance, inflammation, thrombosis, and subclinical atherosclerosis. This study compares the associations of apolipoprotein B (apoB) and LDL cholesterol (LDLC) with a wide array of measures of these risk factors. METHODS AND RESULTS: In 1522 individuals in the Insulin Resistance Atherosclerosis Study, anthropometric measures and measures of lipids, apoB, C-reactive protein, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), fasting and postglucose load glucose and insulin concentrations, and carotid artery intima-media thickness (IMT) were taken and insulin sensitivity was determined by frequently sampled intravenous glucose tolerance test. There were significant differences in measures of abdominal obesity, dyslipidemia, hyperinsulinemia, and thrombosis between subjects with elevated apoB but normal LDLC versus those with elevated LDLC but normal apoB. In each statistically significant comparison, the elevated-apoB group had higher associated risk than the elevated-LDLC group. Moreover, apoB is highly significantly (P<0.0001) correlated with each measure in the direction of higher risk, whereas LDLC was significantly correlated (P<0.05) only with blood pressure, triglyceride, fibrinogen, and C-reactive protein. After further adjustment for LDLC, apoB correlations remained significant, whereas several LDLC correlations adjusted for apoB became significant in the direction of lower risk. CONCLUSIONS: Elevated apoB is more strongly associated than LDLC with other risk factors, including measures in the National Cholesterol Education Program guidelines for lipid treatment and other more recently established risk factors. This may provide new insight into why apoB is a better predictor of vascular risk than LDLC. |
| Comparison of the associations of apolipoprotein B and non-high-density lipoprotein cholesterol with other cardiovascular risk factors in patients with the metabolic syndrome in the Insulin Resistance Atherosclerosis Study Sattar, N., K. Williams, et al. (2004), Circulation 110(17): 2687-93. Abstract: BACKGROUND: The metabolic syndrome (MetS) as defined by the National Cholesterol Education Panel definition has been proposed as an indicator of cardiovascular disease risk. Both apolipoprotein (apo)B and non-HDL cholesterol (NHDLC) have been proposed as an additional indicator to identify patients at higher risk in MetS patients. METHODS AND RESULTS: We studied 1522 individuals in the Insulin Resistance Atherosclerosis Study (IRAS) who were 40 to 69 years of age and from 3 ethnic groups. Their anthropometric measures, lipids, apoB, C-reactive protein, fibrinogen, plasminogen activator inhibitor-1, fasting and post-glucose load glucose, and insulin concentrations were measured, and insulin sensitivity was determined by intravenous glucose tolerance test. Differences in risk parameters in individuals with hyper-apoB/normo-NHDLC, and normo-apoB/hyper-NHDLC were compared in all IRAS subjects and again in those with MetS. In both cases, despite anticipated lower LDL cholesterol, the hyper-apoB/normo-NHDLC group had elevated risk indicated by greater waist circumference (both P<0.05) and fasting insulin (P<0.01) and lower insulin sensitivity (P<0.001). They also had higher C-reactive protein (P<0.05). Moreover, the Spearman correlation of apoB was significantly stronger (P<0.05) in the direction of greater associated risk than that of NHDLC with body mass index, waist circumference, systolic blood pressure, 2-hour glucose, fasting glucose, fasting insulin, 2-hour insulin, insulin sensitivity, C-reactive protein, fibrinogen, and plasminogen activator inhibitor-1. CONCLUSIONS: In conclusion, apoB is more closely associated with central adiposity, insulin resistance, thrombosis, and inflammation than NHDLC. Our data suggest that apoB is a better candidate risk parameter than NHDLC for identifying a subgroup of individuals with or without MetS with elevated cardiovascular risk. |
| Comparison of the capacity of beta-cyclodextrin derivatives and cyclophanes to shuttle cholesterol between cells and serum lipoproteins Christian, A. E., H. S. Byun, et al. (1999), J Lipid Res 40(8): 1475-82. Abstract: Previous studies from this laboratory have demonstrated that low concentrations of cyclodextrins (<1.0 mm), when added to serum, act catalytically as cholesterol shuttles to accelerate the exchange of free cholesterol between cells and serum lipoproteins. As cholesterol shuttles, cyclodextrins have the potential to serve as pharmacological agents for modifying cholesterol metabolism. In the present study, we have quantitated the cholesterol-shuttling capacity of a series of newly synthesized beta-cyclodextrin derivatives (betaCDs), with varying structure, and two double-decker cyclophanes. The general protocol is as follows. (3)Hcholesterol-labeled CHOK1 cells are incubated for 2 h with the test compounds alone or together with 5% human serum, and efflux of the cellular (3)Hcholesterol is measured. As methyl beta-cyclodextrin (MbetaCD) served as the basis for comparison, initial experiments were conducted that demonstrated there was a dose-dependent stimulation of cell cholesterol efflux as the concentration of MbetaCD increased, with an EC(50) that was calculated to be 0.05 mm. To determine the cholesterol-shuttling capacity of the newly synthesized compounds, cell cholesterol efflux is measured when the compounds are present alone, at a concentration of 0.05 mm, or together with 5% human serum. Our results demonstrate that the double-decker cyclophanes are the most efficient cholesterol shuttles. Under our experimental conditions, methyl beta-cyclodextrin (MbetaCD) approximately doubles the efflux of cell cholesterol to serum, whereas one of the double-decker cyclophanes produces a 4-fold stimulation in efflux. Four of the beta-cyclodextrin derivatives (betaCDs) display shuttling ability similar to that of MbetaCD. Furthermore, there does not appear to be a structural pattern among the other betaCDs which could explain their shuttling capacity. |
| Comparison of the cholesterol-lowering effects and toxicity of D-003 and lovastatin in normocholesterolaemic rabbits Gamez, R., S. Mendoza, et al. (2003), Drugs R D 4(4): 219-29. Abstract: BACKGROUND: D-003 is a mixture of long-chain aliphatic primary acids isolated from sugar-cane wax and having cholesterol-lowering effects and a safety profile that have been proven in animals and in previous clinical studies in healthy volunteers. Lovastatin, the first member of the statin class, is an effective and well tolerated cholesterol-lowering drug. Some lovastatin-related adverse effects have been reported, and preclinical assessment has shown that the rabbit is the most sensitive species to lovastatin toxicity. OBJECTIVE: To compare the cholesterol-lowering effects and toxicity pattern of D-003 and lovastatin in normocholesterolaemic rabbits. METHODS: In order to study cholesterol-lowering effects, rabbits were randomly distributed into three groups (eight animals/group): one control group, only receiving the vehicle, and two groups treated with D-003 or lovastatin at 5 and 10 mg/kg/day, respectively. All treatments were orally administered for 30 days. To study toxicity, rabbits were distributed into four groups (six animals/group): one control group and three groups treated with D-003 200 and 400 mg/kg, respectively, or lovastatin 100 mg/kg. RESULTS: After 30 days, D-003 5 mg/kg and lovastatin 10 mg/kg significantly (p < 0.05) and similarly lowered serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels versus baseline. D-003, but not lovastatin, increased high-density lipoprotein-cholesterol (HDL-C) significantly (p < 0.05), whereas only lovastatin decreased (p < 0.05) triglycerides. Low doses of both drugs did not change safety indicators. D-003 (200 and 400 mg/kg) and lovastatin (100 mg/kg) administered for 10 days reduced TC and LDL-C levels significantly (p < 0.05). HDL-C values increased significantly (p < 0.05) with D-003, but were unchanged with lovastatin. Neither treatment affected triglycerides. No significant changes in lipid profile were observed in the control groups of the two series. Lovastatin 100 mg/kg impaired bodyweight gain and food consumption versus the controls, while D-003 did not. Lovastatin 100 mg/kg increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values (p < 0.05 versus baseline and controls) and liver weight (p < 0.05 versus controls). D-003 200 or 400 mg/kg did not affect AST, ALT or liver weight. Lovastatin 100 mg/kg, but not D-003 200 or 400 mg/kg, induced typical hepatocellular and renal tubular necrosis in the rabbits. CONCLUSIONS: D-003 5 mg/kg/day administered orally for 30 days to normocholesterolaemic rabbits lowered LDL-C and TC, as did lovastatin 10 mg/kg. D-003 was more effective in increasing HDL-C, while lovastatin was more effective in lowering triglycerides. Administration of higher doses for 10 days did not show D-003-related toxicity, but did demonstrate the typical pattern of lovastatin-induced toxicity in rabbits. |
| Comparison of the effect of hyperinsulinemia on acyl-CoA:cholesterol acyltransferase activity in the liver and intestine of the rat Yang, L. Y., A. Kuksis, et al. (1994), Atherosclerosis 107(1): 25-34. Abstract: Recent studies have suggested that cholesteryl ester synthesis plays a critical role in the assembly of VLDL apo B and triacylglycerol in the liver. Chronic hyperinsulinemia is associated with increased TG production and since cholesteryl ester synthesis depends on acyl CoA:cholesterol acyltransferase (ACAT), we investigated the possibility that chronic hyperinsulinemia might increase ACAT activity. We also measured ACAT activity in the intestinal mucosa, where it has been suggested to play a role in induction of diabetes-associated hypercholesterolemia. Chronically hyperinsulinemic rats were produced by injecting insulin (2 weeks, 6U/day). To prevent profound hypoglycemia, these rats were given 10% sucrose in place of drinking water. Acute hyperinsulinemia was produced by injecting a single dose of 0.5 U insulin ip. Chronic hyperinsulinemia led to a significant increase in free cholesterol, cholesteryl esters, triacylglycerols and phospholipids in the whole liver (27%, P < 0.05; 60%, P < 0.05; 70%, P < 0.01; 37%, P < 0.01, respectively) and an increase in hepatic microsomal triacylglycerol (P < 0.05). In contrast, the microsomal lipids of the intestinal mucosa decreased significantly. In chronically hyperinsulinemic rats there was no change in hepatic ACAT, while ACAT in the intestine actually decreased (26%-50%, P < 0.01). Conclusions: since the effect of chronic hyperinsulinemia on hepatic ACAT did not parallel that seen previously on VLDL secretion, the effect of chronic hyperinsulinemia on VLDL production cannot be explained by its effect on hepatic ACAT. However, chronic hyperinsulinemia was associated with reduced ACAT activity in the intestine and this might result in decreased lipoprotein production in the hyperinsulinemic intestine. |
| Comparison of the effect of six compactin-related compounds on cholesterol synthesis in five human cell types Sviridov, D. D., A. Endo, et al. (1990), Lipids 25(11): 685-90. Abstract: We have investigated the effect of six compactin-related compounds--mevinolin, compactin, ML-236A, monacolin X, monacolin L and dihydromonacolin L--on cholesterol synthesis in human umbilical vein endothelial cells, human small intestine epithelial cells, human hepatoma cell line HEP G2, normal human skin fibroblasts and in skin fibroblasts from a patient with familial homozygous hypercholesterolemia. The inhibition of cholesterol synthesis was found to depend on both the cell type and the type of compound used. The most effective compounds were mevinolin and compactin. Monacolin X, monacolin L and ML-236A were less effective, and dihydromonacolin L was the least efficacious. Endothelial and epithelial cells were sensitive to very low concentrations of inhibitors (IC50 = 1.0-30 pg/mL), HEP G2 cells required higher concentrations (IC50 = 0.01-66 ng/mL) and fibroblasts needed even higher concentrations (IC50 = 0.1-200 ng/mL). Lactone and acid forms of the inhibitors were equally active. None of the inhibitors had any effect on either protein or fatty acid synthesis in any of the cell types studied. It can be concluded that different compactin-related compounds show a range of potencies as cholesterol synthesis inhibitors and a dose-dependent tissue-selectivity. |
| Comparison of the effects of cholesterol and oxysterols on phospholipid bilayer microheterogeneity: a study of fluorescence lifetime distributions Li, Q. T. and N. P. Das (1994), Arch Biochem Biophys 315(2): 473-8. Abstract: The homogenizing effect of cholesterol and its oxidative derivatives, 7-ketocholesterol, cholesterol 5 alpha, 6 alpha-epoxide and 25-hydroxycholesterol, in liquid-crystalline 1,2-dioleoyl-sn-glycero-3-phosphocholine(DOPC) bilayer vesicles was studied using the fluorescence lifetimes of 2-(3-(diphenylhexatrienyl)propanoyl)-1-hexadecanoyl-sn-glycero-3-p hosphocholine (DPH-PC). The phase and modulation data were fitted either to discrete exponential models or to models characterized by continuous distributional lifetimes. Among all the models tested, it was found that the best one to account for the experimental data was the unimodal Lorentzian distribution. Thus, the DPH-PC lifetime was adequately described by a distributional center and a full width at half-maximum, for DOPC vesicles these values being 6.23 and 0.48 ns, respectively. Increasing the concentration of cholesterol, 7-ketocholesterol, or cholesterol 5 alpha, 6 alpha-epoxide from 0 to 30 mol% resulted in an increase of the lifetime center (e.g., 7.16 ns at 30 mol% cholesterol) and a decrease of the distributional width (e.g., 0.05 ns at 30 mol% cholesterol). On the other hand, up to 30 mol% of 25-hydroxycholesterol incorporated into the bilayer vesicles showed little influence on both lifetime parameters. Our results support the use of lifetime distributional width to evaluate membrane heterogeneity and suggest that oxysterols, depending on their molecular structural particulars, may exert cholesterol-like homogenizing effect in membranes. |
| Comparison of the effects of cyclic AMP analogues on cholesterol metabolism in cultured rat and hamster hepatocytes Botham, K. M., V. Q. Hoang, et al. (1996), Comp Biochem Physiol B Biochem Mol Biol 113(1): 185-91. Abstract: The effects of two cell-permeable cyclic AMP analogues, 8-chloro cyclic AMP (8-Cl cAMP) and 8-(4-chlorophenylthio) cyclic AMP (8-CPT cAMP), on cholesterol esterification, cholesteryl ester hydrolysis and bile acid synthesis were compared in cultured rat and hamster hepatocytes. Cholesterol esterification, as measured by the incorporation of 3Holeate into cholesteryl ester, was increased by 58-88% by the analogues in rat hepatocytes and by 33-43% in hamster cells. The response in rat hepatocytes, however, was observed after a relatively short incubation time (28% increase after 1 hr), whereas that in hamster cells required a longer period (36% after 12 hr) to become apparent. The activity of the cytosolic neutral cholesteryl ester hydrolase in rat hepatocytes was also stimulated by both cyclic AMP analogues (31-37%, but the microsomal activity was unaffected. In hamster hepatocytes, however, microsomal cholesteryl ester hydrolase activity was increased (47-80%) in the presence of 8-Cl cAMP or 8-CPT cAMP. Bile acid synthesis was increased by 8-CPT cyclic AMP in rat cells (approximately 25%) but was unchanged by both analogues in hamster hepatocytes. These results indicate significant differences in the way in which cholesterol metabolism responds to cyclic AMP in cultured rat and hamster hepatocytes. |
| Comparison of the effects of gemfibrozil and clofibric acid on peroxisomal enzymes and cholesterol synthesis of rat hepatocytes Hashimoto, F., S. Taira, et al. (1998), Biol Pharm Bull 21(11): 1142-7. Abstract: We studied whether the peroxisomal proliferation, induction of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and activation of cholesterol synthesis by gemfibrozil shown in whole body (Hashimoto F., Ishikawa T., Hamada S. and Hayashi H., Biochemical. Pharm., 49, 1213-1221 (1995)) is also detected at a culture cell level, and we made a comparative analysis of the effects of clofibric acid. Gemfibrozil at 0.25 mM increased the activity of some peroxisomal enzymes (catalase and the cyanide-insensitive fatty acyl-CoA oxidizing system) after incubation for 72 h. However, contrary to whole body experiments, gemfibrozil decreased the activity of HMG-CoA reductase and cholesterol synthesis from 14Cacetate. At 1 mM, gemfibrozil decreased not only the activity of HMG-CoA reductase and cholesterol synthesis, but also the protein content of the cells and peroxisomal enzyme activity, indicating nonspecific inhibition at this concentration. Clofibric acid (0.25 and 1 mM) increased the activity of peroxisomal enzymes, but decreased the activity of HMG-CoA reductase and cholesterol synthesis. With respect to the direct effect on HMG-CoA reductase in the cell homogenate, gemfibrozil at 0.25 mm did not affect the activity, but it clearly inhibited the activity at 2 mM and above. Clofibric acid at 2 mM hardly affected the activity, but it clearly decreased the activity at 5 mM and over. That is, gemfibrozil directly inhibited the activity more strongly than clofibric acid. The direct inhibition of the enzyme itself required higher concentrations of both agents than did inhibition at the culture cell level. These results suggest that the cytotoxicity of gemfibrozil is greater than that of clofibric acid, and that gemfibrozil, as well as clofibric acid, can induce peroxisomal enzymes in the culture cell level. In contrast to whole body results, gemfibrozil may suppress cholesterol synthesis from 14Cacetate through the inhibition of HMG-CoA reductase at the culture cell level. The decreases in the reductase activity caused by gemfibrozil and clofibric acid at the culture cell level may not be caused by the direct inhibition of the enzyme. |
| Comparison of the effects of plant sterol ester and plant stanol ester-enriched margarines in lowering serum cholesterol concentrations in hypercholesterolaemic subjects on a low-fat diet Hallikainen, M. A., E. S. Sarkkinen, et al. (2000), Eur J Clin Nutr 54(9): 715-25. Abstract: OBJECTIVE: To investigate cholesterol-lowering effects of stanol ester (STAEST) and sterol ester (STEEST)-enriched margarines as part of a low-fat diet. DESIGN: According to a Latin square model randomized double-blind repeated measures design with three test margarines and three periods. SETTING: Outpatient clinical trial with free-living subjects. SUBJECTS: Thirty-four hypercholesterolaemic subjects completed the study. Interventions: Subjects consumed three rapeseed oil-based test margarines (STAEST, STEEST and control (no added stanols or sterols)) as part of a low-fat diet each for 4 weeks. RESULTS: Mean daily intake of total plant sterols plus stanols was 2.01-2.04 g during the two test margarine periods. In reference to control, serum total cholesterol was reduced by 9.2 and 7.3% with the STAEST and STEEST margarine, respectively (P<0.001 for both). The respective reductions for low-density lipoprotein (LDL) cholesterol were 12.7 and 10.4% (P<0. 001). The cholesterol-lowering effects of the test margarines did not differ significantly. The presence of apolipoprotein E4 allele had a significant effect on LDL cholesterol response during the STAEST margarine only. Serum sitosterol and campesterol increased by 0.83 and 2.77 mg/l with the STEEST (P<0.001), respectively and decreased by 1.18 and 2.60 mg/l with the STAEST margarine (P<0.001). Increases of serum sitostanol and campestanol were 0.11 and 0.19 mg/l with the STAEST margarine (P<0.001), repsectively. No significant changes were found in serum fat-soluble vitamin and carotenoid concentrations when related to serum total cholesterol. CONCLUSIONS: STAEST and STEEST margarines reduced significantly and equally serum total and LDL cholesterol concentrations as part of a low-fat diet. SPONSORSHIP: Grant to the University of Kuopio by Raisio Benecol Ltd, Raisio, Finland. |
| Comparison of the effects of ramipril versus telmisartan in reducing serum levels of high-sensitivity C-reactive protein and oxidized low-density lipoprotein cholesterol in patients with type 2 diabetes mellitus Koulouris, S., P. Symeonides, et al. (2005), Am J Cardiol 95(11): 1386-8. Abstract: The effect of ramipril (an angiotensin AT-converting enzyme inhibitor), telmisartan (an AT-II type 1 receptor blocker), or their combination on inflammation and lipid peroxidation was assessed in 37 patients with type 2 diabetes who were free of coronary artery disease. All regimens were associated with a significant reduction of C-reactive protein and oxidized low-density lipoprotein cholesterol serum levels (p <0.001). These results further enlighten the mechanisms underlying the cardiovascular beneficial effect of renin-AT system inhibition. |
| Comparison of the effects of sitostanol, sitostanol acetate, and sitostanol oleate on the inhibition of cholesterol absorption in normolipemic healthy male volunteers. A placebo controlled randomized cross-over study Sudhop, T., D. Lutjohann, et al. (2003), Arzneimittelforschung 53(10): 708-13. Abstract: Feeding of margarines containing sitostanol (CAS 19466-47-8), sitostanol acetate (CAS 73052-08-1), sitostanol oleate (CAS 107615-79-2), or placebo (equivalent of 0.5 g of sitostanol t.i.d) on cholesterol absorption and serum lipids were studied in 10 normolipemic volunteers in a randomized double blind cross-over trial. The study was divided into an open one-week run-in phase and four one-week treatment periods. Each treatment week was followed by a two-week washout period. Measurements of cholesterol absorption was performed by the continuous isotope feeding method using stable isotope labeled cholesterol and sitostanol. Cholesterol absorption during placebo, sitostanol, sitostanol acetate and sitostanol oleate feeding averaged 41.6 +/- (SD) 8.0, 10.2 +/- 6.6, 17.0 +/- 6.7, and 20.5 +/- 5.3%, respectively (p < 0.001 for all against placebo). Low density lipoprotein (LDL) cholesterol was proportionally reduced by 22 (p < 0.001), 14 (p < 0.05), and 8% (ns). Absorption efficiency was significantly lower with free sitostanol than with sitostanol acetate or oleate (p < 0.01). Percent reduction in cholesterol absorption with all preparations compared to placebo correlated positively with the percent reduction in LDL cholesterol (r = 0.404; p < 0.03). The results indicate that unesterified sitostanol is more effective in inhibiting cholesterol absorption and reducing LDL cholesterol than the acetate or oleate esters. |
| Comparison of the efficacy of Questran Light, a new formulation of cholestyramine powder, to regular Questran in maintaining lowered plasma cholesterol levels Insull, W., Jr., N. R. Marquis, et al. (1991), Am J Cardiol 67(6): 501-5. Abstract: Sixty-one men with known hypercholesterolemia (plasma cholesterol greater than 265 mg/dl), most of whom were previous participants in the Coronary Primary Prevention Trial of the U.S. Lipid Research Clinic Program, were chosen to take part in this study to test the effectiveness of a new low-calorie (Questran Light) cholestyramine formulation against the proven effectiveness of the currently marketed formulation Questran in maintaining lowered plasma cholesterol levels. The study recorded changes in fasting plasma lipids, total cholesterol, high-density lipoprotein cholesterol, triglycerides, and calculated low-density lipoprotein cholesterol. After establishing baseline lipid/lipoprotein levels in a 3-week period during which all participants received the currently marketed formulation, the men were randomized into 2 groups, 1 group (n = 31) taking the new Questran Light formulation of 4 g of cholestyramine in 5 g of powder per pack, while the other group (n = 30) continued to take the marketed Questran formulation of 4 g of cholestyramine in 9 g of powder per pack. Each group consumed a total of 24 g/day of cholestyramine in 2 divided doses. At the end of the maintenance phase of the study there were no statistically significant mean changes in percentage from baseline to end-point lipid/lipoprotein levels within either group, nor were there any significant differences between the Questran Light group or the currently marketed Questran formulation group. The new low-calorie cholestyramine formulation appears to be equally as effective in maintaining lowered plasma cholesterol levels as the currently marketed formulation. |
| Comparison of the hepatic clearances of campesterol, sitosterol, and cholesterol in healthy subjects suggests that efflux transporters controlling intestinal sterol absorption also regulate biliary secretion Sudhop, T., Y. Sahin, et al. (2002), Gut 51(6): 860-3. Abstract: BACKGROUND: Recently identified ABCG5/8 transporters are responsible in part for the different absorption rates of campesterol, sitosterol, and cholesterol. These transporters are also expressed in the liver and might regulate biliary sterol secretion. AIMS: This study was therefore conducted to determine the biliary secretion rates and hepatic clearances of campesterol, sitosterol, and cholesterol. SUBJECTS: Six healthy, male volunteers. METHODS: Deuterium labelled sitosterol and campesterol, and unlabelled sitostanol were constantly infused together with a liquid formula using a duodenal perfusion technique. Biliary secretion and hepatic clearance rates were calculated from hourly bile and plasma samples. RESULTS: Plasma concentrations of cholesterol, campesterol, and sitosterol averaged 167.5 (50) mg/dl (SD), 0.50 (0.22) mg/dl, and 0.30 (0.10) mg/dl, respectively. Sitosterol showed a significantly higher biliary secretion rate (1.23 (0.87) mg/h) than campesterol (0.76 (0.54) mg/h, p=0.0321), but both plant sterols had significantly lower biliary secretion rates compared with cholesterol (47.7 (17.5) mg/h; p=0.001 for both). Hepatic clearance of cholesterol (0.31 (0.18) dl/h) was significantly lower compared with campesterol (2.11 (2.51) dl/h) and sitosterol (4.97 (4.70) dl/h; p=0.028 for both), and the clearance of campesterol was significant lower compared with sitosterol (p=0.028). CONCLUSION: The observed inverse relation between hepatic clearance and known intestinal absorption of cholesterol, campesterol, and sitosterol supports the hypothesis that the ABCG5/8 transporters regulating intestinal sterol absorption might also be involved in biliary sterol excretion. |
| Comparison of the hepatic uptake and processing of cholesterol from chylomicrons of different fatty acid composition in the rat in vivo Bravo, E., G. Ortu, et al. (1995), Biochim Biophys Acta 1258(3): 328-36. Abstract: The effect of the fatty acid composition of chylomicrons on the uptake and processing of the cholesterol they carry was investigated in the rat in vivo. Rats kept on a standard low fat pellet diet and tube fed a single dose of palm, olive, corn or fish oil (rich in saturated, n-9 monounsaturated, n-6 polyunsaturated and n-3 polyunsaturated fatty acids, respectively) were used to prepare 3Hcholesterol-labelled chylomicrons of different fatty acid composition. These were then injected intravenously into rats (kept on the standard diet), and the clearance of radioactivity from the blood, distribution in the plasma lipoprotein density fractions, uptake by the liver and appearance in the bile were studied. 3HCholesterol from fish and corn oil chylomicrons was cleared from the blood more rapidly than that from palm and olive oil chylomicrons. After 180 min the proportion of the radioactivity present in the plasma in high density lipoprotein (HDL) was less when the chylomicrons were derived from palm oil as compared to any of the other oils. Approx. 40% of the administered label was recovered in the liver after 180 min in all experiments. The percentage of the injected radioactivity secreted into bile during 180 min was significantly higher with corn and fish oil chylomicrons than with palm oil chylomicrons, with chylomicrons from olive oil in an intermediate position, and these differences were most pronounced between 60 and 120 min after administration of the label. These studies clearly demonstrate that the fatty acid composition of chylomicrons has important effects on the hepatic uptake and processing of the cholesterol they carry, with enrichment with polyunsaturated fatty acids leading to an increased rate of uptake and more rapid removal from the body via the bile as compared to enrichment with saturated or monounsaturated fatty acids. |
| Comparison of the intestinal uptake of cholesterol, plant sterols, and stanols in mice Igel, M., U. Giesa, et al. (2003), J Lipid Res 44(3): 533-8. Abstract: The recent identification of the aberrant transport proteins ABCG5 and ABCG8 resulting in sitosterolemia suggests that intestinal uptake of cholesterol is an unselective process, and that discrimination between cholesterol and plant sterols takes place at the level of sterol efflux from the enterocyte. Although plant sterols are structurally very similar to cholesterol, differing only in their side chain length, they are absorbed from the intestine to a markedly lower extent. In order to further evaluate the process of discrimination, three different sterols (cholesterol, campesterol, sitosterol) and their corresponding 5 alpha-stanols (cholestanol, campestanol, sitostanol) were compared concerning their concentration in the proximal small intestine, in serum, and in bile after a single oral dose of deuterated compounds. The data obtained support the hypothesis that i) the uptake of sterols and stanols is an extremely rapid process, ii) discrimination probably takes place on the level of reverse transport back into the gut lumen, iii) plant stanols are taken up, but not absorbed to a measurable extent, and iv) the process of discrimination probably also exists at the level of biliary excretion. The range of structural alterations that decrease intestinal absorption and increase biliary excretion is: 1) campesterol, 2) cholestanol-sitosterol, and 3) campestanol-sitostanol. |
| Comparison of the intracellular metabolism and trafficking of 25-hydroxycholesterol and cholesterol in macrophages Morel, D. W., M. E. Edgerton, et al. (1996), J Lipid Res 37(9): 2041-51. Abstract: Oxysterols arising from the diet or through lipid peroxidation may be important in the modulation of cellular cholesterol metabolism. In this study, the metabolism of one of the oxysterols, 25-hydroxycholesterol (25OHC), was examined in J774 and mouse peritoneal macrophages. Uptake of 25OHC from serum was rapid and substantial. Esterification of the cellular 25OHC was also rapid as was hydrolysis of pre-formed esters. Like cholesterol, 25OHC was removed from cells by an extracellular acceptor such as high density lipoprotein. Unlike cholesterol, 25OHC was also rapidly and extensively removed from cells by serum albumin, but not by ovalbumin. The differential removal of oxysterols and cholesterol from cells by albumin allows separation of cellular effects due to oxysterols and cholesterol. In order to understand more about this differential efflux of sterols, a computer model for sterol mass transport in cells was used to compare intracellular trafficking of cholesterol and 25OHC. The rate constants determined by this model for movement of sterols between cytoplasm and plasma membrane were similar for both cholesterol and 25OHC, whereas those for esterification and ester hydrolysis as well as those for bidirectional movement between plasma membrane and extracellular medium were greater for 25OHC than for cholesterol. For both sterols, the rate-limiting step for removal of cellular esters appeared to be the rate of cytoplasmic ester hydrolysis. As 25OHC and cholesterol differ significantly in aqueous solubility, the similarity in their rate constants for movement between cytoplasm and plasma membrane is consistent with facilitation of transport between these two loci. |
| Comparison of the lipid and apolipoprotein composition of skeletal muscle and peripheral lymph in control dogs and in dogs fed a high fat, high cholesterol, hypothyroid-inducing diet Sloop, C. H., C. K. Castle, et al. (1993), Biochim Biophys Acta 1169(2): 196-201. Abstract: Most studies of peripheral interstitial fluid lipoprotein composition have been made on interstitial fluid-derived from skin and connective tissue. We developed techniques which allowed simultaneous comparison of lymph (a model of interstitial fluid) from skeletal muscle and skin in control (C) and cholesterol-fed (CF) dogs. Lipoprotein fractions were separated by ultracentrifugation. Skeletal muscle interstitial fluid HDL concentrations were approximately twice those of skin. However, the concentration of VLDL-LDL particles was similar in both interstitial spaces. HDL particles from both microvascular beds showed evidence of extensive remodelling when compared to plasma HDL from the same animal. Relative to apo A-I, skeletal muscle HDL was enriched in free cholesterol and apo E (C and CF dogs) and apo A-IV (CF dogs). Skin-derived HDL was consistently enriched in free cholesterol, apo E and A-IV in both C and CF dogs. These studies indicate that similar remodeling of plasma HDL occurs in widely different tissues which together constitute approximately 70% of the total interstitial space. The relatively high concentration of plasma-derived and remodeled HDL within the interstitial space of skeletal muscle is consistent with that tissue's importance in reverse cholesterol transport. |
| Comparison of the ratio HDL-cholesterol/total cholesterol on the Reflotron vs. conventional wet chemistry methods Herruer, M. H., W. E. Kluitenberg, et al. (1992), Eur J Clin Chem Clin Biochem 30(3): 153-5. Abstract: A new HDL-cholesterol assay using solid phase reagent chemistry on the Reflotron has become available recently. This raises the question of whether the Reflotron now is suited for the determination of the ratio, HDL-cholesterol/total cholesterol, as a supplement to the lipid profile, viz. cholesterol, triacylglycerol and HDL-cholesterol. We investigated this ratio, which is an additional measure for the risk of coronary heart disease and found a good agreement between the Reflotron and conventional wet chemistry methods. We conclude that the Reflotron can be used for establishing the complete lipid profile of a patient. |
| Comparison of the response of serum ceruloplasmin and cholesterol, and of tissue ascorbic acid, metallothionein, and nonprotein sulfhydryl in rats to the dietary level of cystine and cysteine Yang, B. S., M. Yamazaki, et al. (1996), Biosci Biotechnol Biochem 60(12): 1933-6. Abstract: The effects were compared of the addition of graded levels of L-cystine and of L-cysteine (0.3, 3, or 5%) to a 10% casein diet on several metabolic parameters in rats. The growth-promoting effect of cystine was equivalent to that of cysteine. Supplementation of these two amino acids elevated serum cholesterol, liver ascorbic acid, liver nonprotein sulfhydryl (SH) and kidney metallothionein, and reduced the activity of serum ceruloplasmin. The responses of serum cholesterol, liver nonprotein SH, and serum ceruloplasmin to cystine were greater than of those to cysteine. When the basal diet was supplemented with 0.3% of these amino acids, the elevation of liver ascorbic acid by cystine supplementation was less than that by cysteine supplementation. However, when supplemented with 5% of these amino acids, the elevation of liver ascorbic acid by cystine was greater than that by cysteine. There was no difference in the influence of cystine and cysteine on kidney metallothionein. This study demonstrates that dietary cystine and cysteine had the same influence on growth, but had a differential influence on such metabolic parameters as liver nonprotein SH, serum ceruloplasmin, serum cholesterol, and tissue ascorbic acid. |