| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Cholesterol-induced thrombogenicity of the vessel wall: inhibitory effect of fluvastatin Camera, M., V. Toschi, et al. (2002), Thromb Haemost 87(4): 748-55. Abstract: High cholesterol levels are a known risk factor for coronary events. The molecular links between high serum cholesterol and the increased thrombogenicity of the arterial wall are still matter of investigation. In the present study we investigate the relationship between plasma cholesterol, thrombus formation and TF expression in a atherosclerotic rabbit model. Hypercholesterolemic rabbits showed a pronounced TF staining as well as NF-kappaB activation in the aortic arch. A consistent vessel wall platelet deposition was also observed. Treatment with fluvastatin reduced lipid accumulation, TF overexpression (-60%), NF-kappaB activation, and platelet deposition (-56%). In vitro studies showed that the drug upregulated IkappaB alpha in unstimulated as well as in TNFalpha-stimulated cells and also impaired the TNFalpha-induced Cdc42 prenylation, indicating that fluvastatin interferes with the transcriptional activation of TF gene. These results indicate that the prothrombotic phenotype of arterial wall, associated with elevated serum cholesterol levels, is mediated by TF overexpression. Fluvastatin treatment reduces the prothrombotic tendency by inhibiting TF synthesis. |
| Cholesterol-induced upregulation of angiotensin II and its effects on monocyte-endothelial interaction and superoxide production Niebauer, J., P. S. Tsao, et al. (2001), Vasc Med 6(3): 133-8. Abstract: Atherogenesis involves an early endothelial dysfunction hallmarked by elevated free radical production and increased adhesiveness for monocytes. It was hypothesized that activation of the tissue renin angiotensin system may contribute to the endothelial alteration. To test this hypothesis, thoracic aortae were isolated from normocholesterolemic (NC; n = 6) and hypercholesterolemic (HC; n = 6; diet: 0.5% cholesterol; 6 weeks) New Zealand white rabbits, and incubated for 2 h with the angiotensin II (Ang II) receptor antagonist Sar-1,Ile-8-Ang II, the antioxidant pyrolidine dithiocarbamate (PDTC) and the protein kinase C (PKC) antagonist staurosporin. Superoxide production from aortic segments was measured by lucigenin-enhanced chemiluminescence. In comparison to the normocholesterolemic state, hypercholesterolemia led to a significant increase in superoxide production (221 +/- 44%, p < 0.02); this was reduced by ex vivo treatment of the vessel segment with Ang II-antagonist (to 130 +/- 29%; p < 0.04 vs HC), or PKC-antagonist (to 86 +/- 26%; p < 0.001 vs HC), or PDTC (to 103 +/- 27%; p < 0.02 vs HC). Monocyte-endothelial interaction was assessed by functional binding assay. When compared to normocholesterolemic rabbits, hypercholesterolemia led to a twofold increase in monocyte binding (74 +/- 13 vs 37 +/- 4 monocytoid cells per high power field (m/hpf); p < 0.03). The Ang II-antagonist and the PKC-antagonist led to a normalization of monocyte-endothelial binding (Ang II-antagonist: 37 +/- 9 m/hpf; PKC-antagonist: 41 +/- 17 m/hpf; p < 0.05). In conclusion, these results indicate that hypercholesterolemia activates the tissue renin angiotensin system, which results in an increased endothelial production of superoxide and monocyte adhesiveness. Ang II-antagonist inhibits free radical production and monocyte adhesion through a mechanism which may include PKC. |
| Cholesterol-induced variations in the volume and enthalpy fluctuations of lipid bilayers Halstenberg, S., T. Heimburg, et al. (1998), Biophys J 75(1): 264-71. Abstract: The sound velocity and density of suspensions of large unilamellar liposomes from dimyristoylphosphatidylcholine with admixed cholesterol have been measured as a function of temperature around the chain melting temperature of the phospholipid. The cholesterol-to-phospholipid molar ratio xc has been varied over a wide range (0 |
| Cholesterol-loading of membranes of normal erythrocytes inhibits phospholipid repair and arachidonoyl-CoA:1-palmitoyl-sn-glycero-3-phosphocholine acyl transferase. A model of spur cell anemia Allen, D. W. and N. Manning (1996), Blood 87(8): 3489-93. Abstract: Spur cell anemia may occur in severe liver disease including alcoholic cirrhosis. Spur cell anemia red blood cells (RBCs) have a characteristic morphology, with irregular projections, an increased ratio of membrane cholesterol (Ch) to phospholipid, evidence of oxidative damage, and shortened survival resulting in hemolytic anemia. Normal RBCs may acquire many of the features of spur cells either by transfusion into a spur cell patient or in an in vitro model system that loads the RBC membrane with Ch relative to phospholipid by means of Ch-rich, phospholipid-Ch sonicates. We found evidence of abnormal phospholipid repair metabolism in spur cell anemia RBCs characterized by decreased arachidonate (Ar) uptake into phospholipids and by increased uptake into a fatty acid membrane repair intermediate, acylcarnitine (AcylCn). To study the possible modulation of phospholipid repair metabolism in spur cells by Ch-loading, we compared the Ar metabolism of RBCs loaded with Ch in vitro with that of control cells incubated in autologous serum. Ar, a polyunsaturated fatty acid, is especially sensitive to peroxidation and, thus, is likely to be involved in phospholipid repair. Ch-loading decreased the incorporation of 14CAr into total lipids (Ch-loaded, 1,113 +/- 48 pmol/10(10) RBCs; control, 1,525 +/- 48 pmol/10(10) RBCs) including phosphatidylethanolamine, phosphatidylserine, and phosphatidylcholine. Uptake of 14CAr into AcylCn increased (control AcylCn, 169 +/- 31 pmol/10(10) RBCs; Ch-loaded AcylCn, 196 +/- 35 pmol/10(10) RBCs; P =.0012). Thimerosal, an inhibitor of arachidonoyl- CoA:l-palmitoyl-sn-glycero-3-phosphocholine acyl transferase or lysophosphocholine acyl transferase (LAT), produced a similar pattern of metabolic abnormality, with decreased incorporation into phospholipid but relative increase into AcylCn. We assayed LAT in RBC membranes from Ch-loaded RBCs, using 14Carachidonoyl CoA as precursor, and found similar decreased LAT activity at concentrations of 1-palmitoyllysophosphatidylcholine (LPC) from 1 to 30 micromol/L. Similar LAT assay results were obtained using 14Cpalmitoyl LPC as the precursor. We conclude that Ch-loading of RBC membranes results in inhibition of LAT in the cell-free system in vitro and may account for the inhibited phospholipid repair in Ch-loaded intact RBCs in vitro and in spur cell anemia RBCs in vivo. Decreased ability to replace peroxidized membrane fatty acid by this metabolic pathway may contribute to the hemolytic process in spur cell anemia. |
| Cholesterol-loading of peripheral tissues alters the interconversion of high density lipoprotein subfractions in rabbits Fragoso, Y. D. and E. R. Skinner (1996), Int J Biochem Cell Biol 28(2): 151-63. Abstract: High density lipoprotein (HDL) has been implicated in the process of reverse cholesterol transport,by which surplus cholesterol is removed from peripheral tissues and transported to the liver for excretion. It has been suggested that some subfractions of HDL may have a particular role in this process, though the underlying mechanism remains unclear. The present study was aimed at investigating the role of specific subfractions of HDL in reverse cholesterol transport. The interconversion of HDL subfractions in normal and cholesterol-loaded rabbits was studied in vivo. Rabbit HDL was separated by heparin-Sepharose affinity chromatography into six subfractions (HDL(I)-HDL(VI)), which were progressively enriched with apolipoprotein E (apo E), and varied in diameter and composition. Total HDL and its subfractions were individually labelled with 14C sucrose and injected in the rabbits. When rabbits which were not acutely loaded with 3Hcholesterol were injected with 14C-HDL(I), 70% of the label remained in this fraction while less than 5% was recovered in HDL(VI), containing the largest particles and those most enriched in apo E. No label was detectable in the liver of these animals. In rabbits which had received a prior loading of cholesterol, an average of only 18.3% of the 14C label was present in HDL(I) while approx. 40% of the label was recovered in HDL(VI). On average, 5.1% of the total 14C injected in these rabbits was recovered in the liver. It is concluded that two alternative routes for reverse cholesterol transport may be operative. While a continuous cholesterol-clearance route may be provided by particles of HDL of intermediate size, another route may be operative for clearance of excess cholesterol loaded into peripheral endothelial cells. |
| Cholesterol-lowering action of plant sterols Jones, P. J. (1999), Curr Atheroscler Rep 1(3): 230-5. Abstract: Plant sterols have an extended history of use as cholesterol-lowering agents. Until the 1970s, the principal interest in plant sterols lay in effects of sitosterol, but over the past decade interest has reemerged in using plant sterols in functional foods. Hydrogenated plant sterols have been shown efficacious in lowering lipid levels, inhibiting cholesterol absorption and regressing plaque in animals. Hydrogenated versus unhydrogenated plant sterol esters have been demonstrated to possess equal efficacy in low-density lipoprotein cholesterol lowering in humans. Unhydrogenated plants sterol esters show consistency in cholesterol-lowering across dosage levels in humans. Unhydrogenated, unesterifed plant sterols yield similar low-density lipoprotein cholesterol lowering efficacy as achieved with hydrogenated sitostanol esters. Solubility and miscibility are likely more important determinants in cholesterol-lowering potential of plant sterols than their specific composition. |
| Cholesterol-lowering action of psyllium mucilloid in the hamster: sites and possible mechanisms of action Turley, S. D., B. P. Daggy, et al. (1991), Metabolism 40(10): 1063-73. Abstract: These studies were undertaken to examine and compare the metabolic effects of psyllium mucilloid and two other nonabsorbable polymers (cholestyramine and surfomer) on sterol metabolism in the hamster. These three agents all significantly lowered the plasma total cholesterol concentration and the level of cholesterol carried in low-density lipoproteins (LDL). Rates of cholesterol synthesis were markedly increased in the livers of the psyllium-fed animals, but not in other tissues. In contrast, cholestyramine and surfomer feeding increased both hepatic and intestinal sterol synthesis. When cholesterol and saturated triacylglycerols were added to the diet, psyllium feeding essentially completely blocked the increase in the plasma cholesterol concentration and hepatic cholesterol content and the suppression of cholesterol synthesis. The pool of bile acid in the small intestine was increased from the control value (17.9 mumol/animal) by both psyllium (23.0 mumol) and cholestyramine (21.9 mumol) feeding. However, this pool was readily absorbed and secreted into the bile in the psyllium-fed animals (27.9 mumol/4 h), but not in the cholestyramine-treated hamsters (13.0 mumol/4 h). This was consistent with the further observation that there was no binding of bile acid by psyllium under in vitro conditions. Thus, these findings indicate that all three polymers lower plasma cholesterol concentrations by inducing a net negative cholesterol balance across the liver. With psyllium, this effect is presumably articulated through a reduction in cholesterol absorption, as well as an increase in the rate of degradation of cholesterol to bile acids. |
| Cholesterol-lowering activity of naringenin via inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl coenzyme A:cholesterol acyltransferase in rats Lee, S. H., Y. B. Park, et al. (1999), Ann Nutr Metab 43(3): 173-80. Abstract: The effects of dietary supplementation of a citrus bioflavonoid, naringenin, on the cholesterol metabolism were studied. For 42 days male rats were fed a 1% (wt/wt) high-cholesterol diet with or without a naringenin supplementation (0.1%, wt/wt) to study its effect on plasma lipid levels, hepatic lipid contents, activities of hepatic acyl coenzyme A:cholesterol O-acyltransferase (ACAT) and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and the excretion of fecal neutral sterols. Naringenin did not significantly alter the concentration of plasma triglycerides, but lowered the plasma cholesterol (3.80 vs. 3.12 mmol/l) concentration and the hepatic cholesterol content (70.3 vs. 54.0 mg/g) significantly (p < 0.05) compared to those of the controls. HMG-CoA reductase (1,879.0 vs. 1,715.0 pmol/min/mg) and ACAT activities (806.0 vs. 563.0 pmol/min/mg) were significantly lower in the naringenin-supplemented group than in controls. Naringenin supplementation caused a marked decrease in the excretion of fecal neutral sterols (242.9 mg/day) compared to the controls (521.9 mg/day). These results show that naringenin lowers the plasma and hepatic cholesterol concentrations by suppressing HMG-CoA reductase and ACAT in rats fed a high-cholesterol diet. |
| Cholesterol-lowering activity of the aqueous extract of Spergularia purpurea in normal and recent-onset diabetic rats Jouad, H., A. Lemhadri, et al. (2003), J Ethnopharmacol 87(1): 43-9. Abstract: The purpose of this study was to examine the effect of single and repeated oral administration of the aqueous extract of Spergularia purpurea (SP) at a dose of 10mg/kg in normal and streptozotocin-induced diabetic rats. In normal rats, the aqueous extract of SP induced a significant decrease of the plasma cholesterol concentrations 6h after a single oral administration (P<0.05) and 2 weeks after repeated oral administration (P<0.05). The plasma triglycerides levels increased significantly 6h after a single oral administration (P<0.05) and decreased 2 weeks after repeated oral administration (P<0.05). In diabetic rats, SP treatment caused a significant decrease of plasma cholesterol levels after a single (P<0.01) and repeated (P<0.01) oral administration. A significant increase of triglycerides levels was observed 6h after a single oral administration of the SP aqueous extract (P<0.01). One week after repeated oral administration of SP aqueous extract, the plasma triglycerides levels were significantly decreased (P<0.005) and still dropped after 2 weeks (P<0.01). On the other hand, the repeated oral administration of SP aqueous extract caused a significant decrease of body weight after 2 weeks of treatment in both normal (P<0.001) and diabetic (P<0.01) rats. We conclude that the aqueous extract of SP exhibits a cholesterol and body weight-lowering activities in both normal and severe hyperglycaemic rats. |
| Cholesterol-lowering activity of various undigested fractions of soybean protein in rats Sugano, M., S. Goto, et al. (1990), J Nutr 120(9): 977-85. Abstract: The undigested high-molecular-weight fraction (HMF) of soybean protein prepared after exhaustive digestion by microbial proteases significantly decreased serum cholesterol levels to approximately 45% (p less than 0.05) of those observed with the parent protein in rats fed diets containing cholesterol (0.5%) and sodium cholate (0.125%). HMF bound conjugated bile salts in vitro and significantly increased fecal excretion of both neutral and acidic steroids by 65-95% and 80-170% more, respectively (p less than 0.05), than did the intact protein. Extraction of HMF with methanol slightly decreased the activity, but the methanol-soluble fraction was not regarded as a principal determinant. Soybean saponin at the dietary level equivalent to that contained in HMF did not effectively lower serum cholesterol. The activity was not necessarily duplicated even when methanol-treated fractions were recombined. Further degradation of the methanol-extracted HMF by various proteases resulted in loss of activity. HMF obtained after pepsin digestion exerted a potential similar to that of HMF prepared after digestion by microbial proteases. |
| Cholesterol-lowering and blood pressure effects of immune milk Sharpe, S. J., G. D. Gamble, et al. (1994), Am J Clin Nutr 59(4): 929-34. Abstract: The plasma cholesterol-lowering and blood pressure effects of a skim milk powder (immune milk) produced from dairy cows hyperimmunized with a multivalent bacterial vaccine were assessed in a double-blind crossover study of hypercholesterolemic subjects who consumed daily 90 g immune milk or a normal product. There was a significant reduction in plasma total and LDL cholesterol of 5.2% (95% CI 2.5, 7.9) and 7.4% (95% CI 4.1, 10.7), respectively, with 10 wk of immune milk consumption compared with control, but no change in HDL cholesterol or triglycerides. A significant systolic and diastolic blood pressure-lowering effect (5 and 4 mm Hg, respectively) was also demonstrated. Thus, immune milk may be a useful adjunct in the dietary management of hypercholesterolemia and the mechanisms of its cholesterol-lowering and blood pressure effects warrant further study. |
| Cholesterol-lowering and coronary atherosclerosis: good news and bad news Kreisberg, R. A. (1996), Am J Med 101(5): 455-8. |
| Cholesterol-lowering and psychological well-being Griffin, K. W. and G. Weidner (1994), Compr Ther 20(9): 518-22. |
| Cholesterol-lowering benefits of oat-containing cereal in Hispanic americans Karmally, W., M. G. Montez, et al. (2005), J Am Diet Assoc 105(6): 967-70. Abstract: This randomized, controlled trial of cholesterol lowering by an oat bran cereal containing beta glucan vs a corn cereal without soluble fiber in Hispanic Americans was conducted for 11 weeks. One-hundred fifty-two men and women, ages 30 to 70 years, with baseline low-density lipoprotein cholesterol (LDL-C) levels between 120 and 190 mg/dL and triglycerides <400 mg/dL were included. After eating a National Cholesterol Education Program Step 1 diet for 5 weeks, subjects were randomly assigned to the corn or the oat cereal for the next 6 weeks. The daily dose of beta glucan was 3 g. Consumption of oat cereal was associated with a reduction in plasma levels of both total cholesterol (-10.9+/-21.6 mg/dL; -4.5%) and LDL-C (-9.4+/-20.3 mg/dL; -5.3%). Consumption of corn cereal did not affect either total cholesterol (+1.2+/-18.3 mg/dL; 1.1%) or LDL-C (+1.2+/-17.5 mg/dL; 2.2%). Differences between the effects of the two cereals on total cholesterol and LDL-C were significant, P =.0003 and P =.0007, respectively. |
| Cholesterol-lowering diets may increase the food costs for Danish children. A cross-sectional study of food costs for Danish children with and without familial hypercholesterolaemia Stender, S., F. Skovby, et al. (1993), Eur J Clin Nutr 47(11): 776-86. Abstract: Food costs for 30 children under dietary treatment for familial hypercholesterolaemia were compared with those of 105 other Danish children. The daily intake of macronutrients and the daily cost of the diet for each child were calculated from dietary intakes and average prices of 365 different food items. The mean +/- SE percentages of energy (E%) from fat in the diet of children with and without known familial hypercholesterolaemia were 23.6 +/- 0.8 E+ and 34.5 +/- 0.5 E%, respectively (P < 0.001). The dietary costs per MJ in these two groups were 3.79 +/- 0.12 Danish crowns (DKr) and 3.34 +/- 0.05 DKr (P < 0.001), taking into account food wastage due to preparation and cooking. The cost per unit of energy increased with decreasing fat energy percentage of the diet for all children as one group (r = -0.37, P < 0.001), as well as for the group of children without familial hypercholesterolaemia (r = -0.35, P < 0.001). Stepwise multiple regression analysis showed that the differences in cost per MJ between the groups could be explained primarily by differences in percentage of energy from fat. We conclude that a reduction of dietary fat from 35 E% to 25 E% may increase food costs by 10-20% for Danish children. |
| Cholesterol-lowering diets. A review of the evidence Denke, M. A. (1995), Arch Intern Med 155(1): 17-26. Abstract: To evaluate the efficacy of the high-risk approach and the population approach for cholesterol lowering, large trials of dietary intervention (n > or = 150) and smaller trials of angiographic assessment of the impact of diet on coronary disease were reviewed. Two trials of dietary therapy as intensive individualized counseling in individuals at usual risk for coronary disease achieved 75% to 80% of the cholesterol lowering predicted by metabolic ward studies and produced a 5% to 14% reduction in total cholesterol levels. Four studies in high-risk individuals exceeded predictions and achieved a 4% to 17% reduction in total cholesterol levels. Similar efficacy was observed in six of the seven trials of diet for secondary prevention. Four trials employing the population approach achieved smaller but often significant reductions in total cholesterol levels of 1% to 11%. No tachyphylaxis to dietary therapy occurred in trials in which dietary counseling was maintained during the trial. The effectiveness of diet is enhanced when individualized counseling is used, follow-up is maintained, and weight reduction is achieved. |
| Cholesterol-lowering drug therapy in a patient with receptor-negative homozygous familial hypercholesterolaemia Feher, M. D., J. C. Webb, et al. (1993), Atherosclerosis 103(2): 171-80. Abstract: Familial hypercholesterolaemia (FH) is caused by mutations in the gene for the low density lipoprotein (LDL) receptor. It is generally believed that homozygous FH patients do not respond well to lipid-lowering drug therapy with inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase because they cannot respond to an increased demand for hepatic cholesterol by up-regulation of LDL-receptor activity. In this paper we show that serum cholesterol in a homozygous FH patient with a receptor-negative LDL-receptor phenotype was reduced by 30% after treatment with simvastatin alone and by a further 11% with simvastatin in combination with probucol and nicotinic acid. The patient was a true homozygote, with two identical alleles of the LDL receptor gene in which a previously undescribed point mutation in exon 11 introduces a premature termination codon at residue 540 in the protein; the mutant protein is predicted to be truncated in the domain with homology to the epidermal growth factor precursor. Cultured cells from the patient were unable to bind, internalise or degrade LDL by the receptor pathway and there was no immunodetectable LDL receptor protein in the cells. Thus the lipid lowering effect of simvastatin in this individual must involve mechanisms other than stimulation of LDL receptors. |
| Cholesterol-lowering drugs bring benefits to high-risk populations even when LDL is normal Braun, L. T. and M. H. Davidson (2003), J Cardiovasc Nurs 18(1): 44-9; quiz 75-6. Abstract: The Heart Protection Study (HPS) results were presented shortly after the National Cholesterol Education Program released the third report of clinical practice guidelines for the evaluation and management of elevated cholesterol in adults. Both the guidelines and the HPS results support an aggressive approach to managing high-risk individuals. The HPS showed that cardiovascular events and mortality were reduced in high-risk patients taking simvastatin regardless of baseline low-density lipoprotein (LDL) cholesterol levels. Some of these patients would not have met criteria for drug treatment according to the guidelines. The conclusion was that all high-risk patients with LDL > or = 100 mg/dL should be treated with drug therapy with the goal of reducing LDL to < 100 mg/dL. |
| Cholesterol-lowering drugs for primary prevention? The WOSCOP Study Muntoni, S. (1997), Pharmacol Res 35(3): 169-70. |
| Cholesterol-lowering effect of a low-fat diet containing lean beef is reversed by the addition of beef fat O'Dea, K., K. Traianedes, et al. (1990), Am J Clin Nutr 52(3): 491-4. Abstract: The aim of this study was to differentiate between lean beef and beef fat as risk factors for elevated plasma cholesterol concentrations. Ten healthy weight-stable subjects (five men, five women) participated. Energy intake was kept constant over the 5-wk study. Total cholesterol concentrations fell significantly within 1 wk of commencing the very-low fat (9%) energy from fat) lean-beef (500 g/d) diet (5.91 +/- 0.47 to 4.72 +/- 0.42 mmol/L, p less than 0.001) and rose as beef drippings were added in a stepwise manner in weeks 4 and 5 (5.45 +/- 0.56 mmol/L in week 5). The changes in total cholesterol concentrations were due almost entirely to changes in the concentration of low-density lipoprotein cholesterol levels. These results indicate that it is the beef fat, not lean beef itself, that is associated with elevations in cholesterol concentrations and that lean beef can be included in cholesterol-lowering diets provided it is free of all visible fat and the saturated fatty acid content of the diet is low. |