| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Mechanism of separation on cholesterol-silica stationary phase for high-performance liquid chromatography as revealed by analysis of quantitative structure-retention relationships Al-Haj, M. A., P. Haber, et al. (1998), J Pharm Biomed Anal 18(4-5): 721-8. Abstract: The retention characteristics of a newly synthesized stationary phase were determined for reversed-phase high-performance liquid chromatography obtained by chemical immobilization of cholesterol on spherical silica gel. For a designed series of analytes the retention factors, log k, were determined at several compositions of the methanol-water mobile phase. Logarithms of retention factor corresponding to a hypothetical pure water eluent, log k(w), were calculated by extrapolation of the linear relationships of individual log k data versus volume percent of methanol. The series of 24 test analytes were characterized structurally by means of the logarithms of n-octanol-water partition coefficients, log P, by a set of the linear solvation energy relationship (LSER)-based descriptors of the polarity and bulkiness of the analytes and by structural descriptors of analyte size and polarity acquired by molecular modelling. Quantitative structure retention relationships (QSRR) were derived by multiple regression analysis using the three groups of structural descriptors of analytes and the log k(w) data determined on the new stationary phase. For the sake of comparison the corresponding QSRR equations were also derived for retention parameters determined on a standard octadecylsilica and on the so-called immobilized artificial membrane (IAM) stationary phase. The QSRR analysis clearly proved distinctive retention properties of the new cholesterol-silica stationary phase. It has been concluded that the new phase may possess valuable analytical specificity. Its application for modelling penetration of xenobiotics through biological membranes appears rather unlikely. |
| Mechanism of serum cholesterol reduction by oat bran Marlett, J. A., K. B. Hosig, et al. (1994), Hepatology 20(6): 1450-7. Abstract: Nine normolipidemic young men consumed a constant diet for 2 mo into which oat bran was incorporated during the second month so that we might test the hypotheses that oats lower serum cholesterol concentrations by decreasing bile acid and fat absorption and increasing bile acid synthesis. Bile acid kinetics were determined by measuring the 13C enrichment of serum cholic and chenodeoxycholic acids. Oat bran consumption decreased serum cholesterol levels (p < 0.01) and cholic acid pool size (p < 0.05). Deoxycholic acid pool size (p < 0.01) and the synthesis and fractional turnover rates of both primary bile acids (p < 0.05) increased. Total bile acid pool size did not change. Fecal excretion of total bile acids, the two secondary bile acids and fat increased significantly. The results demonstrate that oat bran lowers serum cholesterol levels in part by altering bile acid metabolism. In addition, the substantial increase in the proportion of the total bile acid pool that was deoxycholic acid is consistent with the hypothesis that oat bran also decreases cholesterol synthesis. |
| Mechanism of the gemfibrozil-induced decrease in the transfer of cholesterol esters from high density lipoproteins to very low and low density lipoproteins Ponsin, G., G. Girardot, et al. (1994), Biochem Med Metab Biol 52(1): 58-64. Abstract: To better understand the effects of lipid-lowering drugs on the transfer of esterified cholesterol (EC) between lipoproteins, we investigated the changes induced by gemfibrozil administration on the unidirectional transfer of radiolabeled EC from high density lipoproteins (HDL) to very low (VLDL) and low density lipoproteins (LDL) in 10 normolipidemic subjects. HDL, VLDL/LDL, and the d > 1.21 g/ml fraction containing cholesterol ester transfer protein (CETP) were isolated from plasma before and after 8 weeks of gemfibrozil administration. The same fractionation procedure was applied to aliquots of a control plasma pool to permit different recombination experiments. When the CETP fractions of the subjects studied were incubated in the presence of control HDL and VLDL/LDL, no effect of gemfibrozil was observed on the rate of EC transfer, indicating that the drug did not induce any change in the plasma transfer activity. When HDL of the subjects studied were recombined with the CETP fraction and VLDL/LDL isolated from the control plasma pool, the rate of EC transfer was decreased by 43% after gemfibrozil administration. Thus, the drug induced a decrease in the HDL-dependent transfer of EC. This effect was accompanied by a decrease of the triglyceride (TG)/EC ratio in HDL, a decrease of the Stokes radius of large HDL determined after gradient gel electrophoresis, and an increase of the HDL viscosity. Since both HDL size and viscosity are in part dependent upon their TG/EC ratio, further investigations will be necessary to answer the question as to whether one of these structural criteria is predominant for the regulation of the HDL-dependent transfer of EC. |
| Mechanism of transfer of LDL-derived free cholesterol to HDL subfractions in human plasma Miida, T., C. J. Fielding, et al. (1990), Biochemistry 29(46): 10469-74. Abstract: The transfer of 3Hcholesterol in low-density lipoprotein (LDL) to different high-density lipoprotein (HDL) species in native human plasma was determined by using nondenaturing two-dimensional electrophoresis. Transfer from LDL had a t1/2 at 37 degrees C of 51 +/- 8 min and an activation energy of 18.0 kCal mol-1. There was unexpected specificity among HDL species as acceptors of LDL-derived labeled cholesterol. The largest fraction of the major alpha-migrating class (HDL2b) was the major initial acceptor of LDL-derived cholesterol. Kinetic analysis indicated a rapid secondary transfer from HDL2b to smaller alpha HDL (particularly HDL3) driven enzymatically by the lecithin-cholesterol acyltransferase reaction. Rates of transfer among alpha HDL were most rapid from the largest alpha HDL fraction (HDL2b), suggesting possible protein-mediated facilitation. Simultaneous measurements of the transport of LDL-derived and cell-derived isotopic cholesterol indicated that the former preferably utilized the alpha HDL pathway, with little label in pre-beta HDL. The same experiments confirmed earlier data Castro, G.R., & Fielding, C.J. (1988) Biochemistry 27, 25-29 that cell-derived cholesterol is preferentially channeled through pre-beta HDL. We suggest that the functional heterogeneity of HDL demonstrated here includes the ability to independently process cell- and LDL-derived free cholesterol. |
| Mechanisms and (patho)physiological significance of biliary cholesterol secretion Kuipers, F., R. P. Oude Elferink, et al. (1997), Subcell Biochem 28: 295-318. |
| Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin Nguyen, L. B., S. Shefer, et al. (2001), J Lipid Res 42(2): 195-200. Abstract: The effects of feeding cholesterol, sitosterol, and lovastatin on cholesterol absorption, biosynthesis, esterification, and LDL receptor function were examined in the rat jejunal mucosa. Cholesterol absorption was measured by the dual-isotope plasma ratio method; the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, was measured as total and expressed enzyme activities (in the absence and presence of a phosphatase inhibitor, NaF, respectively); mucosal total and esterified cholesterol concentrations were determined by gas-liquid chromatography; LDL receptor function was assayed as receptor-mediated binding of (125)I-labeled LDL to mucosal membranes. Feeding 2% sitosterol or 0.04% lovastatin for 1 week significantly (P < 0.01) decreased the amounts of cholesterol absorbed per day (-85% and -63%, respectively). In contrast, feeding 2% cholesterol for 1 week increased the amounts of absorbed cholesterol 27-fold, even though the percent absorption significantly decreased. With all three treatments, there was a coordinate regulation of total HMG-CoA reductase activity and receptor-mediated LDL binding. Cholesterol feeding downregulated both total jejunal HMG-CoA reductase activity (P < 0.05) and receptor-mediated LDL binding (P < 0.01), whereas lovastatin- and sitosterol-supplemented diets significantly upregulated both of these parameters. In the control, cholesterol-fed, and sitosterol-fed animals, about half of the total jejunal HMG-CoA reductase activity was expressed (in functional dephosphorylated form). However, in the lovastatin-treated rats with 4-fold stimulation of HMG-CoA reductase, only 23% of the total enzyme activity was expressed. Changes in total HMG-CoA reductase activity and receptor-mediated LDL binding in all tested groups occurred with no change in total concentrations of mucosal cholesterol, and only cholesterol-fed animals had increased mucosal esterified cholesterol concentrations. Thus, in response to various fluxes of dietary or newly formed cholesterol, HMG-CoA reductase and receptor-mediated LDL binding are coordinately regulated to maintain constant cellular cholesterol concentrations in the jejunum. |
| Mechanisms of action of plant sterols on inhibition of cholesterol absorption. Comparison of sitosterol and sitostanol Heinemann, T., G. A. Kullak-Ublick, et al. (1991), Eur J Clin Pharmacol 40 Suppl 1: S59-63. Abstract: The effects of two different plant sterols on intestinal cholesterol absorption were compared in normal volunteers by an intestinal perfusion study during a control period followed by high dose infusion of sitosterol or sitostanol (3.6 mumol/min), to which subjects were allocated in a randomized manner. Cholesterol absorption during the control period was similar in the two groups, averaging 0.88 +/- 0.48 mumol/min (32 +/- 11%) for group I (sitosterol) and 0.68 +/- 0.33 mumol/min (29 +/- 9%) for group II (sitostanol). The infusion of a high dose of sitosterol resulted in a significant reduction of cholesterol absorption to 0.47 mumol/min (16%). Following the same dose of sitostanol, cholesterol absorption diminished significantly to 0.15 +/- 0.11 mumol/min (5.1 +/- 2.9%). Overall cholesterol absorption declined during sitosterol infusion by almost 50%, whereas sitostanol infusion caused a reduction of cholesterol absorption by almost 85%. These findings of a more effective inhibition of cholesterol absorption by sitostanol might confirm the observation recorded by others that an increase in hydrophobicity of a plant sterol results in a higher affinity but lower capacity to mixed micells. This may cause an effective displacement of cholesterol from micellar binding and therefore diminished cholesterol absorption. |
| Mechanisms of alpha-Sialosyl cholesterol action to suppress both cyclic AMP production and DNA synthesis of rat glial cells Ito, J., T. Kato, et al. (1993), J Neurochem 61(1): 80-4. Abstract: alpha-Sialosyl cholesterol (alpha-SC) that elicited morphological differentiation of rat astrocytes not only lowered intracellular cyclic AMP (cAMP) levels but also inhibited cAMP production induced by either alpha-isoproterenol, cholera toxin, or forskolin. The targets of alpha-SC in the cAMP production system of rat astrocytes were investigated to understand the mechanism of the alpha-SC action on cAMP production. cAMP production evoked by alpha-isoproterenol (1 microM) was entirely canceled by beta blockers such as propranolol and timolol (1 microM), but not by alpha-SC. Concentrations of alpha-SC greater than 15 microM were required for 50% inhibition of the activation by a beta agonist. Although alpha-SC inhibited in a dose-dependent manner the activities of membrane-associated adenylate cyclase that had been stimulated by either GTP gamma S of forskolin, alpha-SC inhibited neither GTP-binding activities nor GTPase activities of the membrane-associated G proteins. These findings suggest that alpha-SC suppresses adenylate cyclase directly, but not beta receptors or G proteins, and that it promotes the morphological differentiation of rat astrocytes through a mechanism regulating directly the cytoskeletal organization, regardless of intracellular cAMP level. alpha-SC (30 microM) suppressed 40% of DNA synthesis in the cell-free system, which contained the cytosolic extracts and the nucleus fraction prepared from rat astrocytoma C6 cells. Approximately 25% of alpha-SC incorporated in the astrocyte cytoplasm was transferred to the nuclei by 10 min after the addition.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Mechanisms of angiotensin II type 1 receptor blocker for anti-atherosclerotic effect in monkeys fed a high-cholesterol diet Takai, S., S. Kim, et al. (2003), J Hypertens 21(2): 361-9. Abstract: OBJECTIVE To clarify the mechanism of the anti-atherosclerotic effect of angiotensin II type 1 receptor blocker (ARB) in primates, we investigated whether an ARB (CS-866) affects the serum markers of inflammation and growth factors, and the endothelial function in monkeys fed a high-cholesterol diet.DESIGN Monkeys fed a high-cholesterol diet for 6 months were divided into two groups: one group was given an ARB, CS-866 (10 mg/kg per day), and the other group was not. The control group was fed a normal diet.RESULTS Blood pressure and the plasma cholesterol level were not affected by CS-866. Plasma levels of angiotensin II, renin, angiotensin converting enzyme and chymase were not changed by the high-cholesterol diet, whereas vascular angiotensin converting enzyme, but not chymase, was significantly increased. Serum levels of macrophage-colony stimulating factor, transforming growth factor-beta1 and intracellular adhesion molecule-1 were significantly increased in monkeys fed a high-cholesterol diet but they were suppressed by CS-866. The relaxation response of isolated carotid arteries to acetylcholine was suppressed in the high-cholesterol group, whereas it was improved by CS-866.CONCLUSIONS CS-866 reduced lipid deposition along with the suppression of serum macrophage-colony stimulating factor, transforming growth factor-beta 1 and intracellular adhesion molecule-1, and the improvement of vascular functions, suggesting that ARB has multiple mechanisms for reducing lipid deposition in primates. |
| Mechanisms of cholesterol and sterol regulatory element binding protein regulation of the sterol 12alpha-hydroxylase gene (CYP8B1) Yang, Y., G. Eggertsen, et al. (2004), Biochem Biophys Res Commun 320(4): 1204-10. Abstract: Sterol 12alpha-hydroxylase (CYP8B1) is an obligatory enzyme for the synthesis of cholic acid and regulation of liver bile acid synthesis and intestine cholesterol absorption. The present study evaluates the roles for sterol regulatory element binding proteins (SREBPs) in the regulation of the CYP8B1 gene. Cholesterol feeding of mice and rats decreased the activity of CYP8B1, contrary to the up-regulation of cholesterol 7alpha-hydroxylase (CYP7A1). Cholesterol feeding also reduced mRNA levels for SREBP-1 but not for SREBP-2 in rat livers. Cholesterol and 25-hydroxycholesterol decreased the CYP8B1/luciferase reporter activity. Co-transfection of SREBP-1a and -1c stimulated CYP8B1 promoter activity, while SREBP-2 did not have any effects. Electrophoretic mobility shift assay and mutagenesis analyses identified several functional sterol regulatory elements (SRE) and E-box motifs in the rat CYP8B1 promoter. Our results indicate that SREBP-1a and -1c enhance transcription of the CYP8B1 gene through binding to SRE. Cholesterol loading reduces SREBP-1 mRNA expression in addition to reducing functional SREBP-1 protein, and results in decreasing CYP8B1 gene transcription. |
| Mechanisms of cholesterol gallstone formation Zijlstra, A. I., G. N. Tytgat, et al. (1995), Indian J Gastroenterol 14(2): 59-64. |
| Mechanisms of gallstone formation in women. Effects of exogenous estrogen (Premarin) and dietary cholesterol on hepatic lipid metabolism Everson, G. T., C. McKinley, et al. (1991), J Clin Invest 87(1): 237-46. Abstract: Our aim was to define mechanisms whereby conjugated estrogens (Premarin, exogenous estrogen; Ayerst Laboratories, New York) increase the risk of developing cholesterol gallstones and to determine the role, if any, of dietary cholesterol. We studied gallbladder motor function, biliary lipid composition and secretion, cholesterol absorption, cholesterol synthesis and esterification by peripheral blood mononuclear cells, the clearance of chylomicron remnants, and bile acid kinetics in 29 anovulatory women. 13 were studied on both a low (443 +/- 119 mumol/d) and high (2,021 +/- 262 mumol/d) cholesterol diet. Premarin increased the lithogenic index of bile (P less than 0.05), increased biliary cholesterol secretion (P less than 0.005), lowered chenodeoxycholate (CDCA) pool (P less than 0.001) and synthesis (P less than 0.05), altered biliary bile acid composition (CA + DCA/CDCA increases, P less than 0.005), stimulated cholesterol esterification (P less than 0.03), and enhanced the clearance of chylomicron remnants (P = 0.07). Increases in dietary cholesterol stimulated the biliary secretion of cholesterol (P = 0.07), bile acid (P less than 0.05), phospholipid (P = 0.07), and as a result, did not alter lithogenic index. The reduction in CDCA pool and synthesis by Premarin was reversed by increasing dietary cholesterol. Off Premarin, only 24% of the increase in cholesterol entering the body in the diet was recovered as biliary cholesterol or newly synthesized bile acid. On Premarin, 68% of this increase in cholesterol was recovered as these biliary lipids. We conclude that Premarin increases biliary cholesterol by enhancing hepatic lipoprotein uptake and inhibiting bile acid synthesis. These actions of Premarin divert dietary cholesterol into bile. |
| Mechanisms of high density lipoprotein-mediated efflux of cholesterol from cell plasma membranes Phillips, M. C., K. L. Gillotte, et al. (1998), Atherosclerosis 137 Suppl: S13-7. Abstract: The participation of HDL in the reverse cholesterol transport (RCT) from peripheral cells to the liver is critical for the antiatherogenic properties of this lipoprotein. Experimental results showing that efflux of cholesterol from cells growing in culture is mediated by HDL and lipoprotein particles containing apo A-I, in particular, support this conclusion. A bidirectional flux of unesterified cholesterol molecules between the plasma membrane of cells and HDL particles in the extracellular medium occurs. Net efflux of cholesterol mass from the cells involves passive diffusion of cholesterol molecules through the aqueous phase and down their concentration gradient between the membrane and HDL; the concentration gradient is maintained by LCAT-mediated esterification of cholesterol molecules in the HDL particles. Fully lipidated apo A-I is important in promoting this aqueous diffusion mechanism because it: (1) acts as a cofactor for LCAT; and (2) solubilizes phospholipid into small HDL-sized particles that are efficient at absorbing cholesterol molecules diffusing away from the cell surface. Apo A-I also exists in an incompletely lipidated state in plasma. Apo A-I molecules in this state are able to solubilize phospholipid and cholesterol from the plasma membrane of cells. This membrane-microsolubilization process is enhanced by enrichment of the plasma membrane with cholesterol and is the mechanism by which pre-beta-HDL particles in the extracellular medium remove cholesterol and phospholipid from cells. The relative contributions in vivo of the aqueous diffusion and membrane-microsolubilization mechanisms of apo A-I-mediated cell cholesterol efflux are not predicted readily from cell culture experiments. Confounding issues are the variations with cell type and the dependence on the degree of cholesterol loading of the cell plasma membrane. |
| Mechanisms of high-density lipoprotein cholesterol effects on the endothelial function in hyperlipemia Lupattelli, G., S. Marchesi, et al. (2003), Metabolism 52(9): 1191-5. Abstract: High-density lipoprotein-cholesterol (HDL-c) has a favorable influence on the endothelial function, but the mechanisms of this protective action are not fully understood. We studied lipid parameters, soluble adhesion molecules (vascular cell adhesion molecule-1 VCAM-1, intercellular adhesion molecule ICAM-1, E-selectin) oxidized low-density lipoproteins (LDL), and brachial-artery flow-mediated vasodilation (FMV) in 184 hyperlipemic patients (90 men, age 54 +/- 10 years, waist/hip circumference ratio 0.89 +/- 0.07, LDL-cholesterol LDL-c 4.9 +/- 1.3 mmol/L, triglycerides 1.8 +/- 0.9 mmol/L, HDL-c 1.3 +/- 0.5 mmol/L) after excluding those with current smoking, diabetes, hypertension, and vascular diseases. Patients were divided into 2 groups on the basis of HDL-c levels: < 1.03 mmol/L (n = 53) v >or= 1.03 mmol/L (n = 131). Patients with low HDL-c showed significantly lower LDL-c (P <.05), higher triglycerides (P <.001), higher body mass index (P <.02), lower FMV (3.7% +/- 2.0% v 4.9% +/- 3.4%, P <.002), higher VCAM-1 (1,195 +/- 395 ng/mL v 984 +/- 303 ng/mL, P <.01), and higher ICAM-1 (406 +/- 78 ng/mL v 364 +/- 68 ng/mL, P <.01). E-selectin and oxidized LDL showed no significant differences. In a multivariate age, oxidized LDL and brachial artery diameter predicted a lower FMV, while HDL-c was an independent predictor of a greater FMV (P =.003). Increasing levels of VCAM-1 and ICAM-1 were predicted by lower HDL-c, while higher oxidized LDL predicted higher VCAM-1 (P <.05). Our data suggest that in hyperlipemic subjects free of cardiovascular disease low HDL-c negatively modulates endothelial function through a lack of oxidation inhibition and a concomitant overexpression of adhesion molecules. |
| Mechanisms of high-density lipoprotein reduction after probucol treatment: changes in plasma cholesterol esterification/transfer and lipase activities Chiesa, G., S. Michelagnoli, et al. (1993), Metabolism 42(2): 229-35. Abstract: Probucol treatment results in a significant reduction of plasma high-density lipoprotein (HDL) levels. Since the remodeling of HDL within the plasma compartment is a crucial determinant of HDL levels, the activities of several factors participating in the process, ie, lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and lipoprotein and hepatic lipases (LPL, HL), were evaluated in 15 hypercholesterolemic patients treated with probucol (1 g/d) for 8 weeks. Drug treatment was associated with significant reductions of HDL cholesterol (HDL-C -32%), HDL2-C (-65%), HDL3-C (-22%), apolipoprotein (apo)A-I (-27%), and apo A-II (-11%) levels and with the accumulation of small HDL in plasma. CETP activity increased by 48%, with minor changes in LCAT (-7%), LPL (+4%), and HL (-7%) activities. By linear regression analysis, CETP activity correlated inversely with HDL-C, HDL2-C, and apo A-I levels (r = -.63, -.52, and -.73, respectively) and with HDL particle size. In multivariate analysis, CETP activity was the strongest predictor of HDL-C levels, apo A-I levels, and HDL particle size. The hypothetical mechanism of probucol is a stimulation of CETP activity, resulting in the formation of triglyceride (TG)-enriched HDL. These are acted on by HL, leading to the accumulation of small HDL in plasma. |
| Mechanisms of hypertriglyceridemia in the coconut oil/cholesterol-fed rabbit. Increased secretion and decreased catabolism of very low density lipoprotein Van Heek, M. and D. B. Zilversmit (1991), Arterioscler Thromb 11(4): 918-27. Abstract: Rabbits fed a 14% coconut oil/0.5% cholesterol (CNO/Chol) diet develop mild to severe hypertriglyceridemia compared with rabbits fed a 14% olive oil/0.5% cholesterol (OO/Chol) diet. Lipids and apolipoprotein (apo) B were significantly higher in the very low density lipoprotein (VLDL) and intermediate density lipoprotein fractions from CNO/Chol than from OO/Chol rabbits. Yet, the particle diameters of these lipoproteins were similar in both diet groups, indicating that CNO/Chol rabbits had a much larger number of VLDL and intermediate density lipoprotein particles in plasma. Although the composition of CNO/Chol VLDL differed from that of OO/Chol VLDL, the rates of triglyceride hydrolysis of CNO/Chol VLDL and OO/Chol VLDL by postheparin lipoprotein lipase in vitro were the same, suggesting that VLDLs from the two diet groups were equally good substrates for lipoprotein lipase. To determine the mechanisms of hypertriglyceridemia in the CNO/Chol rabbit, triglyceride and apo B of CNO/Chol VLDL and OO/Chol VLDL were labeled with tritium-containing triolein and iodine-131 and injected intravenously into CNO/Chol and OO/Chol rabbits. The fractional clearance rate for triglyceride in OO/Chol rabbits was twice that of CNO/Chol rabbits, which parallels the previously observed differences in postheparin lipoprotein lipase activity. Although the average fractional removal of apo B did not differ between diet groups, there was a significant inverse relation between plasma cholesterol and apo B fractional clearance rate. We conclude that the hypertriglyceridemia and the enhanced hypercholesterolemia in the CNO/Chol rabbit results primarily from increased hepatic secretion of VLDL and a modest decrease in VLDL triglyceride clearance capacity. |
| Mechanisms of LDL-cholesterol lowering action of psyllium hydrophillic mucilloid in the hamster Turley, S. D. and J. M. Dietschy (1995), Biochim Biophys Acta 1255(2): 177-84. Abstract: Psyllium hydrophillic mucilloid (psyllium) is a soluble fiber that significantly lowers plasma low-density lipoprotein (LDL)-cholesterol levels in humans and experimental animals. These studies were designed to determine whether this action is the result of a reduction in LDL-cholesterol production, an increase in receptor-mediated LDL clearance by the tissues, or a combination of these mechanisms. Adult male Golden Syrian hamsters were fed ad libitum for 30 days a cereal-based diet containing added cholesterol (0.1%) and hydrogenated coconut oil (10%), as well as either microcrystalline cellulose (Avicel) (7.5%) or psyllium (7.5%). In contrast to their Avicel-fed controls, the hamsters given psyllium had markedly lower plasma total (122.1 +/- 4.1 vs. 399.4 +/- 39.4 mg/dl) and LDL-cholesterol (46.0 +/- 2.2 vs. 143.5 +/- 12.0 mg/dl) levels. Psyllium feeding also prevented both the dramatic increase in hepatic total cholesterol levels (2.6 +/- 0.1 vs. 16.6 +/- 1.1 mg/g), and the suppression of hepatic cholesterol synthesis (165.1 +/- 27.1 vs. 26.1 +/- 1.2 nmol/h per g) that occurred in the animals given Avicel. Compared to their controls, the psyllium-fed animals also manifested a 44% lower rate of LDL-cholesterol production (167.6 +/- 8.1 vs. 300.2 +/- 16.0 micrograms/h per 100 g bw), and a 2.2-fold higher rate of hepatic LDL clearance (50.1 +/- 2.3 vs. 22.6 +/- 2.1 microliters/h per g). When expressed as a percentage of corresponding values obtained for hamsters fed the basal diet without any additions, the relative rate of LDL-cholesterol production was 175 +/- 10% and 99 +/- 4% for the Avicel- and psyllium-fed groups, respectively. It was similarly determined that the level of whole animal relative LDL receptor activity was marginally higher in the hamsters given psyllium (55.9 +/- 1.4%) than in those fed Avicel (47.5 +/- 3.3%). Thus, it was concluded that while the LDL-cholesterol lowering action of psyllium in the hamster is mediated through two mechanisms, the major effect is exerted at the level of LDL-cholesterol production. |
| Mechanisms of the triglyceride- and cholesterol-lowering effect of fenofibrate in hyperlipidemic type 2 diabetic patients Forcheron, F., A. Cachefo, et al. (2002), Diabetes 51(12): 3486-91. Abstract: In humans, the precise mechanisms of the hypolipidemic action of fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, remain unclear. To gain insight on these mechanisms, we measured plasma lipids levels, lipids synthesis (hepatic de novo lipogenesis and cholesterol synthesis), and mRNA concentrations in circulating mononuclear cells (RT-PCR) of hydroxymethylglutaryl (HMG)-CoA reductase, LDL receptor, LDL receptor- related protein (LRP), scavenger receptor class B type I (SR-BI), ABCAI, and liver X receptor (LXR)-alpha in 10 control subjects and 9 hyperlipidemic type 2 diabetic patients. Type 2 diabetic subjects were studied before and after 4 months of fenofibrate administration. Fenofibrate decreased plasma triglycerides (P < 0.01) and total cholesterol (P < 0.05) concentrations and slightly increased HDL cholesterol (P < 0.05). Hepatic lipogenesis, largely enhanced in diabetic subjects (16.1 +/- 2.1 vs. 7.5 +/- 1.6% in control subjects, P < 0.01), was decreased by fenofibrate (9.8 +/- 1.5%, P < 0.01). Fractional cholesterol synthesis was normal in diabetic subjects (3.5 +/- 0.4 vs. 3.3 +/- 0.5% in control subjects) and was unchanged by fenofibrate (3.5 +/- 0.5%). Absolute cholesterol synthesis was, however, increased in diabetic subjects before and after fenofibrate (P < 0.05 vs. control subjects). HMG-CoA reductase, LDL receptor, LRP, and SR-BI mRNA concentrations were not different in type 2 diabetic and control subjects and were unchanged by fenofibrate. LXR-alpha mRNA levels were increased (P < 0.05) by fenofibrate. ABCAI mRNA concentrations, which were decreased in diabetic subjects (P < 0.05) before fenofibrate, were increased (P < 0.05) by fenofibrate to values comparable to those of control subjects. The plasma triglyceride-lowering effect of fenofibrate is explained in part by a decrease in hepatic lipogenesis, the moderate fall in total plasma cholesterol is not explained by a reduction of whole-body cholesterol synthesis, and the increase in LXR-alpha and ABCAI mRNA levels suggests that fenofibrate stimulated reverse cholesterol transport. |
| Medical nutrition therapy lowers serum cholesterol and saves medication costs in men with hypercholesterolemia Sikand, G., M. L. Kashyap, et al. (1998), J Am Diet Assoc 98(8): 889-94; quiz 895-6. Abstract: This study was designed to evaluate whether medical nutrition therapy administered by registered dietitians could lead to a beneficial clinical and cost outcome in men with hypercholesterolemia. Ninety-five subjects participating in a cholesterol-lowering drug study took part in an 8-week nutrition intervention program before initiating treatment with a cholesterol-lowering medication, Patient records were reviewed via a retrospective chart review to determine plasma lipid levels at the beginning and end of the program and the number and length of sessions with a dietitian. Complete information was available for 74 subjects aged 60.8 n+/- 9.8 years (mean +/- SD). Medical nutrition therapy lowered total serum cholesterol levels 13% (P <.001), low-density lipoprotein cholesterol (LDL-C) 15% (P <.0001), triglyceride 11% (P <.05), and high-density lipoprotein-cholesterol (HDL-C) 4% (P <.05). Total dietitian intervention time was 144 +/- 21 minutes (range = 120 to 180 minutes) in 2.8 +/- 0.7 sessions (range = 2 to 4) during 6.81 +/- 0.7 weeks of medical nutrition therapy (range = 6 to 8 weeks). Analysis of covariance was conducted to examine whether mean change in LDL-C differed by number of dietitian visits. Results showed a marginal difference between the number of dietitian visits and change in LDL-C (f = 2.6, P <.084). However, the magnitude of LDL-C reduction was significantly higher with 4 dietitian visits (180 minutes) than with 2 visits (120 minutes) (21.9% vs 12.1%; P =.027). Lipid drug eligibility was obviated in 34 of 67 (51%) subjects per the National Cholesterol Treatment Program guidelines algorithm. The estimated annualized cost savings from the avoidance of lipid medications was $60,561.68. Therefore, we conclude that 3 or 4 individualized dietitian visits of 50 minutes each over 7 weeks are associated with a significant serum cholesterol reduction and a savings of health care dollars. |
| Medical treatment of cholesterol crystal embolism Hachulla, E. and B. Devulder (1991), Presse Med 20(5): 215-9. Abstract: Cholesterol crystal embolization is an often fatal disorder in the elderly. Clinical manifestations consist of skin lesions arterial hypertension and renal failure. In some cases the clinical picture is suggestive of vasculitis. The most frequent predisposing factors are operative and radiological vascular procedures and the use of anticoagulants. The diagnosis can be confirmed by skin, muscle or kidney biopsy. Data concerning management are scarce and contradictory. A review of the literature has revealed some controversy as to how and when cholesterol crystal embolization should be treated, and controlled studies are lacking. We discuss the use of various drugs such as anticoagulants, antiplatelet agents and corticosteroids. In practice, the usual treatment is symptomatic and includes therapy of the peripheral vascular disease, adequate control of blood pressure and appropriate management of renal insufficiency. The most effective measure is prevention. |