| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Lateral ordering of lipid chains in cholesterol-containing membranes: high-field spin-label EPR Kurad, D., G. Jeschke, et al. (2004), Biophys J 86(1 Pt 1): 264-71. Abstract: High-field (i.e., 94 GHz) electron paramagnetic resonance is used to characterize the nonaxial ordering of spin-labeled lipid chains in membranes containing cholesterol. Employing high magnetic fields (and microwave frequencies) allows investigation of both the lateral and transverse ordering of the phospholipid chains by cholesterol, from the x-y and z-elements, respectively, of the spin-label g-tensor. Transverse ordering is described by the conventional order parameter, |
| Lateral organization of cholesterol molecules in lipid-cholesterol assemblies Sengupta, P., R. R. Singh, et al. (2004), Phys Rev E Stat Nonlin Soft Matter Phys 70(2 Pt 1): 021902. Abstract: We present results of an off-lattice simulation of a two-component planar system, as a model for lateral organization of cholesterol molecules in lipid-cholesterol assemblies. We explore the existence of "superlattice" structures even in fluid systems, in the absence of an underlying translational long-range order, and study their coupling to hexatic or bond-orientational order. We discuss our results in context of geometric superlattice theories and "condensation complexes" in understanding a variety of experiments in artificial lipid-cholesterol assemblies. |
| Lateral organization of liquid-crystalline cholesterol-dimyristoylphosphatidylcholine bilayers. Evidence for domains with hexagonal and centered rectangular cholesterol superlattices Virtanen, J. A., M. Ruonala, et al. (1995), Biochemistry 34(36): 11568-81. Abstract: The lateral organization of fluid cholesterol-dimyristoylphosphatidylcholine (DMPC) bilayers was studied by measuring the response of fluorescent membrane probes, dipyrenylphosphatidylcholines (diPyrxPCs) or merocyanine 540, to the variation of cholesterol concentration. Parallel absorbance and light-scattering measurements were also carried out. The excimer-to-monomer ratio of diPyrxPCs displayed abrupt deviations at particular cholesterol mole fractions (CMFs). The most notable of these occurred at CMFs of 0.15, 0.33, and 0.67. Deviations were also frequently observed at CMFs of 0.12, 0.20, 0.25, and 0.40. Merocyanine 540 reproducibly reported deviations at CMFs of 0.15 and 0.33 and frequently reported values close to 0.12, 0.20, and 0.25. In absorbance (turbidity) and light scattering versus CMF plots, well-defined kinks were observed at CMFs of 0.16, 0.33, 0.52, and 0.67. The occurrence of kinks or other deviations at those particular CMFs is most readily explained in terms of a superlattice model previously developed to explain the lateral distribution of pyrenylphospholipids in bilayers Somerharju, et al. (1985) Biochemistry 24, 2773-2781; Virtanen, J. A., et al. (1988) J. Mol. Electron. 4, 233-236. This model is based on the assumptions that (i) each cholesterol molecule replaces a single acyl chain in a hexagonal lattice, (ii) cholesterol molecules, because of their larger size, perturb the lattice, (iii) this perturbation is minimized when the cholesterol molecules are maximally separated from each other, and (iv) the maximal separation is achieved when the cholesterol molecules form a hexagonal or centered rectangular superlattice. All detected critical CMFs, except that at CMF 0.67, are predicted by the model, thus strongly supporting its validity. The critical CMF at 0.67 is a limiting case, which can be accounted for by assuming that cholesterol and phospholipid molecules form alternating rows, i.e., formation of a cholesterol superlattice with rectangular symmetry. As predicted by the superlattice model, composition-driven order-to-disorder transitions occur between the critical CMFs, as indicated by increased data scatter and sample fluctuations in those regions. Another important prediction of the superlattice model is that domains with different cholesterol superlattices should coexist at most cholesterol concentrations. Such domains do not have to be extensive to account for the critical events observed here; rather, they are expected to be dynamic entities of limited size. It is very likely that such microscopic domains with distinct cholesterol superlattices also coexist in biological membranes. This is expected to have remarkable effects on both the structure and functions of these membranes. |
| Lateritin, a new inhibitor of acyl-CoA:cholesterol acyltransferase produced by Gibberella lateritium IFO 7188 Hasumi, K., C. Shinohara, et al. (1993), J Antibiot (Tokyo) 46(12): 1782-7. Abstract: A new inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), designated lateritin, was isolated from the mycelial cake of Gibberella lateritium IFO 7188 by successive purification procedure of solvent extraction, silica gel column chromatography and reverse phase HPLC. Spectroscopic analyses of the compound yielded 4-methyl-6-(1-methylethyl)-3-phenylmethyl-1,4-perhydrooxazine-2,5- dione as the proposed structure. Lateritin inhibited rat liver ACAT activity by 50% at a concentration of 5.7 microM. This inhibition was time-dependent and irreversible. |
| Lathosterol and other non-cholesterol sterols during treatment of hypercholesterolaemia with beta-glucan-rich oat bran Uusitupa, M. I., T. A. Miettinen, et al. (1997), Eur J Clin Nutr 51(9): 607-11. Abstract: OBJECTIVE AND SUBJECTS: Dietary fibre has been suggested to interfere with endogenous cholesterol synthesis in the liver. Therefore the effects of oat bran on the proportions of cholesterol synthesis precursors (squalene, delta(8-) cholesterol, desmosterol and lathosterol), cholestanol and plant sterols (campesterol and beta-sitosterol) to cholesterol were analysed in serum of 36 hypercholesterolaemic subjects. DESIGN: A randomized study of eight weeks duration when beta-glucan-rich oat bran (n = 20, subjects) or wheat bran (n = 16) was used as a part of a cholesterol lowering diet. Plant sterols and cholesterol synthesis precursors were analysed from frozen samples afterward. RESULTS: In the oat-bran group, but not in the wheat bran group, serum total cholesterol declined transiently. The proportions of plant sterols and cholesterol in serum, which reflect cholesterol absorption efficiency were unchanged. However, the proportions of squalene appeared to be transiently increased during the study. Subjects with apolipoprotein E 4 allele had higher serum campesterol and sitosterol levels (suggestive of efficient cholesterol absorption) than those with homozygous apolipoprotein E 3 allele. CONCLUSIONS: Since the cholesterol precursors in serum reflecting endogenous cholesterol synthesis remained almost unchanged the reduction in the serum cholesterol level by oat bran treatment can not be ascribed to an inhibition of the endogenous cholesterol synthesis. |
| Lathosterolosis: an inborn error of human and murine cholesterol synthesis due to lathosterol 5-desaturase deficiency Krakowiak, P. A., C. A. Wassif, et al. (2003), Hum Mol Genet 12(13): 1631-41. Abstract: Lathosterol 5-desaturase catalyzes the conversion of lathosterol to 7-dehydrocholesterol in the next to last step of cholesterol synthesis. Inborn errors of cholesterol synthesis underlie a group of human malformation syndromes including Smith-Lemli-Opitz syndrome, desmosterolosis, CHILD syndrome, CDPX2 and lathosterolosis. We disrupted the lathosterol 5-desaturase gene (Sc5d) in order to further our understanding of the pathophysiological processes underlying these disorders and to gain insight into the corresponding human disorder. Sc5d (-/-) pups were stillborn, had elevated lathosterol and decreased cholesterol levels, had craniofacial defects including cleft palate and micrognathia, and limb patterning defects. Many of the malformations found in Sc5d (-/-) mice are consistent with impaired hedgehog signaling, and appear to be a result of decreased cholesterol rather than increased lathosterol. A patient initially described as atypical SLOS with mucolipidosis was shown to have lathosterolosis by biochemical and molecular analysis. We identified a homozygous mutation of SC5D (137A>C, Y46S) in this patient. An unique aspect of the lathosterolosis phenotype is the combination of a malformation syndrome with an intracellular storage defect. |
| L-Carnitine effects on chemical composition of plasma lipoproteins of rabbits fed with normal and high cholesterol diets Diaz, M., F. Lopez, et al. (2000), Lipids 35(6): 627-32. Abstract: L-Carnitine plays an important role in the mitochondrial uptake of long-chain fatty acids in mammals. It has recently been shown that this compound has a marked hypo-cholesterolemic effect when used in conjunction with lipid-rich diets. The aim of this study was to investigate the effects of L-carnitine on the fatty acid composition of plasma lipoproteins in rabbits fed with different diets. Four different groups were investigated: group I (standard diet), group II (standard diet supplemented with L-carnitine at 80 mg/kg), group III (standard diet supplemented with 0.5% cholesterol), and group IV (standard diet supplemented with 0.5% cholesterol plus L-carnitine at 80 mg/kg). The feeding period was 126 d. Total plasma cholesterol was indistinguishable in groups I and II, but increased nearly 40-fold in group III. This increment was reduced by 50% in group IV. Correspondingly, total cholesterol content in lipoprotein fractions very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) separated by agarose gel chromatography was the same for groups I and II, while for animals fed a cholesterol-rich diet (III) total cholesterol in VLDL + LDL increased nearly 100-fold when compared with groups I and II but, again, the increment was reduced by 50% in group IV. In contrast, total cholesterol in HDL increased only fivefold for both groups III and IV when compared with groups I and II, indicating no effects of L-carnitine on this parameter. The reduction of total cholesterol in VLDL + LDL particles in animals fed a cholesterol-rich diet plus L-carnitine was associated with a marked decrease in the ratio of cholesteryl ester to free cholesterol and a dramatic increase in their phospholipid content; opposite effects were observed for HDL. L-Carnitine induced a marked decrease in the saturated to unsaturated C16 + C18 fatty acid ratio in cholesteryl esters associated with VLDL and LDL from animals fed with both normal and cholesterol-rich diets. The opposite effect (a large increase in the saturated to unsaturated fatty acid ratio) was observed for both cholesteryl esters and phospholipids associated with HDL in animals fed with both diets. The results suggested that the hypocholesterolemic effects of L-carnitine could be associated with increased systemic breakdown of cholesteryl esters, a probable increase in reverse cholesterol transport, and the stabilization of a phospholipid-based structure of VLDL + LDL particles. |
| LCAT (lecithin:cholesterol acyltransferase) Kinoshita, M. and T. Teramoto (2001), Rinsho Byori Suppl 116: 125-30. Abstract: Lecithin:cholesterol acyltransferase (LCAT) is an enzyme which converts free cholesterol of lipoprotein into esterified cholesterol. LCAT plays an important role in lipid metabolism especially in the reverse cholesterol transport system. As LCAT protein is synthesized by the liver, patients with liver disease showed a decreased ratio of cholesteryl ester to total cholesterol. Familial LCAT Deficiency and Fish Eye Disease are disorders that lack LCAT activity congenitally. |
| LCAT inhibitors interfere with the enzymatic determination of cholesterol and triglycerides Harris, W. S. and A. Rayford (1990), Lipids 25(6): 341-3. Abstract: 5,5-Dithiobis-(2-nitrobenzoic acid) (DTNB) and p-chloro-mercuriphenylsulfonic acid (PCMPS) are well-known sulfhydryl inhibitors that are used to inhibit lecithin: cholesterol acyltransferase (LCAT). They were each found to interfere with the enzymatic assays of cholesterol and triglycerides. DTNB falsely reduced the measured plasma cholesterol content, and falsely increased triglyceride readings. The interference with the triglyceride assay could be largely prevented by blanking for glycerol. PCMPS had only a slight effect on the cholesterol assay, but falsely lowered the triglyceride readings to a great extent, even with glycerol-blanking. Thus, these inhibitors should be avoided when plasma samples are to be enzymatically analyzed for cholesterol or triglycerides. |
| LDL and HDL enriched in triglyceride promote abnormal cholesterol transport Skeggs, J. W. and R. E. Morton (2002), J Lipid Res 43(8): 1264-74. Abstract: Hypertriglyceridemia induces multiple changes in lipoprotein composition. Here we investigate how one of these modifications, triglyceride (TG) enrichment, affects HDL and LDL function when this alteration occurs under conditions in which more polar components can naturally re-equilibrate. TG-enriched lipoproteins were produced by co-incubating VLDL, LDL, and HDL with cholesteryl ester (CE) transfer protein. The resulting 2.5-fold increase in TG/CE ratio did not measurably alter the apoprotein composition of LDL or HDL, or modify LDL size. HDL mean diameter increased slightly from 9.1 to 9.4 nm. Modified LDL was internalized by fibroblasts normally, but its protein was degraded much less efficiently. This likely reflects an aberrant apolipoprotein B (apoB) conformation, as suggested by its resistance to V8 protease digestion and altered LDL electrophoretic mobility. TG-enriched LDL ineffectively down-regulated cholesterol biosynthesis compared with control LDL at the same protein concentration, but was equivalent in sterol regulation when compared on a cholesterol basis. TG-enriched HDL promoted greater net cholesterol efflux from cholesterol-loaded J774 cells. However, cholesterol associated with TG-enriched HDL was inefficiently esterified by lecithin:cholesterol acyltransferase, and TG-enriched HDLs were poor donors of CE to HepG2 hepatocytes by selective uptake. We conclude that TG-enrichment, in the absence of other significant alterations in lipoprotein composition, is sufficient to alter both cholesterol delivery and removal mechanisms. Some of these abnormalities may contribute to increased coronary disease in hypertriglyceridemia. |
| LDL cholesterol Sakurabayashi, I. (2004), Nippon Rinsho 62 Suppl 12: 18-21. |
| LDL cholesterol and global risk stratification in referred hypertensive patients Pedrinelli, R., E. D. Esposti, et al. (2005), Atherosclerosis 180(1): 137-43. Abstract: BACKGROUND: Global risk status more than BP values per se drive nowadays treatment decisions and increasing emphasis is given to the role of lipid control in hypertension (HT). However, the distribution of circulating low density lipoproteins (LDL) levels as a function of risk profile and lipid-lowering treatment in hypertensive patients is unclear. METHODS: We analysed 1196 patients (677 males, age range: 20-80 years) referred to our Hypertension Unit with treatment history and a complete dataset (systolic blood pressure levels, being on anti-hypertensive treatment or not, total and high density lipoproteins (HDL) cholesterol, smoking status, sex, age) for 10-year absolute coronary heart disease (CHD) risk stratification by National Cholesterol Education Program (NCEP)/ATP III guidelines. LDL cholesterol <25.9 mmol/L (100 mg/dL) was the target for high-risk patients (vascular diseases, diabetes, hypertension with multiple risk factors at CHD risk >20%/10 years). LDL <33.6 mmol/L (130 mg/dL) and 41.4 mmol/L (160 mg/dL) were the thresholds for intermediate (10-20%/10 years) and low (<10%/10 years) CHD risk. RESULTS: At referral, 78% of high-risk patients were above target LDL and, overall, 56% had LDL cholesterol above the desired risk-specific thresholds. Lipid-lowering treatment was prescribed in 19% in whom LDL was actually higher than the untreated group. CONCLUSIONS: LDL cholesterol was out of target in most of a large series of referred high-risk hypertensive patients and LDL levels were largely unsatisfactory even in those undergoing lipid-lowering treatment. The data show the intensive effort still needed to implement global risk-oriented prevention strategies in hypertensive populations. |
| LDL cholesterol and troglitazone therapy Howard, B. V. and W. J. Howard (1998), Diabetes Care 21(12): 2201-3. |
| LDL cholesterol angiotensin II interactions in atherosclerosis Luft, F. C. (2001), J Mol Med 79(4): 157-8. |
| LDL cholesterol apheresis by adsorption to dextran sulfate Grunewald, R. W., H. H. Ditschuneit, et al. (1992), Infusionsther Transfusionsmed 19(4): 194-6. Abstract: Extracorporeal LDL cholesterol elimination may be the sole successful treatment in familial hypercholesterolemia. By treatment of 41 plasma both total cholesterol and LDL cholesterol were lowered by 69 +/- 1% and 78 +/- 1%, respectively. HDL cholesterol was decreased by 24 +/- 3%. This could be explained both by hemodilution (hematocrit was decreased by 9.3 +/- 2.8%) and unspecific adsorption of various plasma proteins (-15.3 +/- 3.7 g/l, i.e. -22 +/- 4%). Protein electrophoresis showed different affinities of the protein fractions. These data suggest that LDL apheresis by dextran sulfate is an effective method for the elimination of LDL cholesterol. However, other proteins besides apolipoprotein B are adsorbed to dextran sulfate. |
| LDL cholesterol apheresis by dextran sulfate cellulose adsorption. Long-term experience in patients with familial hypercholesterolemia Olbricht, C. J. and P. Schulzeck (1991), ASAIO Trans 37(3): M492-3. Abstract: Five patients with diet and drug resistant familial hypercholesterolemia (FH) (low density lipoprotein LDL cholesterol, LDL greater than 230 mg/dl) were treated by LDL apheresis, using dextran sulfate cellulose adsorption (DSC), to prevent coronary heart disease (CHD). After membrane plasma separation, two 150 ml columns of DSC alternately adsorbed LDL, and were regenerated by 4.1% saline. Five patients received 230 treatments with 7 to 14 days intervals over 6 to 30 months. The treated plasma volume per session was 3.8 +/- 0.6 L. Post-apheresis values in percent of pre-apheresis were: total cholesterol, 42%; LDL, 27%; VLDL, 62%; HDL, 96%; triglycerides, 70%; WBC, 115%; platelets, 88%; C3 complement, 78%; fibrinogen, 67%; albumin, 94% (p less than or equal to 0.005 for all values). Safety parameters showed only slight changes. The initial LDL of 436 +/- 172 mg/dl decreased to nonatherogenic levels of between 150 and 100 mg/dl, whereas high density lipoprotein remained unchanged. Adverse events (hypotension, angina pectoris, technical problems) occurred in six treatments. Long-term treatment of patients with therapy resistant FH by extracorporeal DSC adsorption is effective and safe. |
| LDL cholesterol as a strong predictor of coronary heart disease in diabetic individuals with insulin resistance and low LDL: The Strong Heart Study Howard, B. V., D. C. Robbins, et al. (2000), Arterioscler Thromb Vasc Biol 20(3): 830-5. Abstract: Diabetes has been shown to increase the risk of coronary heart disease in all populations studied. However, there is a lack of information on the relative importance of diabetes-associated risk factors for cardiovascular disease (CVD), especially the role of lipid levels, because low density lipoprotein (LDL) cholesterol often is not elevated in diabetic individuals. The objective of this analysis was to evaluate CVD risk factors in a large cohort of diabetic individuals and to compare the importance of dyslipidemia (ie, elevated triglycerides and low levels of high density lipoprotein HDL cholesterol) and LDL cholesterol in determining CVD risk in diabetic individuals. The Strong Heart Study assesses coronary heart disease and its risk factors in American Indians in Arizona, Oklahoma, and South/North Dakota. The baseline clinical examinations (July 1989 to January 1992) consisted of a personal interview, physical examination, and drawing of blood samples for 4549 study participants (2034 with diabetes), 45 to 74 years of age. Follow-up averaged 4.8 years. Fatal and nonfatal CVD events were confirmed by standardized record review. Participants with diabetes, compared with those with normal glucose tolerance, had lower LDL cholesterol levels but significantly elevated triglyceride levels, lower HDL cholesterol levels, and smaller LDL particle size. Significant independent predictors of CVD in those with diabetes included age, albuminuria, LDL cholesterol, HDL cholesterol (inverse), fibrinogen, and percent body fat (inverse). A 10-mg/dL increase in LDL cholesterol was associated with a 12% increase in CVD risk. Thus, even at concentrations well below the National Cholesterol Education Program target of 130 mg/dL, LDL cholesterol is a strong independent predictor of coronary heart disease in individuals with diabetes, even when components of diabetic dyslipidemia are present. These results support recent recommendations for aggressive control of LDL cholesterol in diabetic individuals, with a target level of <100 mg/dL. |
| LDL cholesterol in normal range.The lower the better? Implications of the GREACE study Marz, W. (2003), MMW Fortschr Med 145(50): 46-9. Abstract: The higher an individual patient's risk, the greater the clinical effect of lipid lowering drug therapy. According to present guidelines, therapeutic decisions should be guided by the patient's overall risk. This depends not only on the LDL cholesterol, but also on the number and degree of other risk factors. This paper will show that LDL cholesterol before treatment determines the clinical efficacy of a statin: for instance, using a statin to lower the LDL cholesterol by one third gives a greater risk reduction the higher the baseline value. For a given baseline value, greater risk reduction results from a larger reduction in LDL cholesterol. LDL cholesterol measurement is thus essential before and on treatment. |
| LDL cholesterol is associated with small abdominal aortic aneurysms Hobbs, S. D., M. W. Claridge, et al. (2003), Eur J Vasc Endovasc Surg 26(6): 618-22. Abstract: OBJECTIVE: To examine the relationship between serum lipids and abdominal aortic aneurysms (AAA). METHODS: Two hundred and six males (>50 years) with AAA (> or =30 mm) detected in a population based screening programme were compared with 252 age-matched male controls in a nested case-control study. Smoking status, previous medical and family histories, height, weight, blood pressure, ankle brachial pressure index (ABPI) and non-fasting lipid profile were recorded. RESULTS: Cases were found to have significantly higher LDL cholesterol than controls. LDL cholesterol was an independent predictor of the risk for aneurysms in a logistic regression model adjusting for smoking status, family history of AAA, history of ischaemic heart disease, presence of peripheral vascular disease, use of lipid lowering medication and treatment for hypertension. There was a linear effect with increased levels of LDL cholesterol increasing the risk of having a small aneurysm (test for trend p=0.03). CONCLUSION: The highly significant association between LDL cholesterol and small aneurysms suggests that LDL, possibly acting via inflammatory mediated matrix degeneration, could be an initiating factor in the development of AAA. The ability of statin therapy to prevent AAA formation requires further investigation. |
| LDL cholesterol lowering by bile acid malabsorption during inhibited synthesis and absorption of cholesterol in hypercholesterolemic coronary subjects Gylling, H. and T. A. Miettinen (2002), Nutr Metab Cardiovasc Dis 12(1): 19-23. Abstract: BACKGROUND AND AIMS: Recent large-scale trials have consistently documented the fact that a 25-35% reduction in low-density lipoprotein cholesterol (LDL-C) can delay the progression of atherosclerosis. This raises the question as to how much it is possible to reduce serum cholesterol using feasible therapies. The aim of this study was to investigate the cholesterol-lowering efficacy of a triple therapy combining bile acid malabsorption with the inhibition of cholesterol synthesis and absorption. METHODS AND RESULTS: Eleven consecutive hypercholesterolemic coronary patients from Lipid Clinics on a low-fat, low-cholesterol baseline diet added simvastatin (20 mg/day) for three months, and then dietary plant stanol ester margarine (2.25 g of stanols/day) for eight weeks; finally, cholestyramine 8 g/day was added for another eight weeks. This was a before-after trial, in which the results of each period were compared with baseline and those of the previous period. Serum lipids were quantitated using commercial kits, and serum sterols by means of gas-liquid chromatography. Simvastatin lowered LDL-C by 39% (p < 0.001), and additional stanol ester margarine by a further 13% (p < 0.05). The triple treatment led to 67% reduction from baseline (p < 0.001), with all LDL-C values being < 2.6 mmol/L, and increased high-density lipoprotein cholesterol (HDL-C) by 15% (p < 0.01). It also increased the serum lathosterol/cholesterol ratio (p < 0.01), thus indicating an upregulation of cholesterol synthesis, and increased the serum sitosterol ratio (p < 0.01) despite the simultaneous consumption of plant stanols. CONCLUSIONS: The massive reduction in LDL and increase in HDL-C obtained using our triple therapy suggests that the combination of stanol ester with only moderate doses of statin and resin makes it possible to control LDL-C levels effectively in hypercholesterolemic subjects. |