| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Lowering of serum cholesterol in hypercholesterolemic humans by tocotrienols (palmvitee) Qureshi, A. A., N. Qureshi, et al. (1991), Am J Clin Nutr 53(4 Suppl): 1021S-1026S. Abstract: A double-blind, crossover, 8-wk study was conducted to compare effects of the tocotrienol-enriched fraction of palm oil (200 mg palmvitee capsules/day) with those of 300 mg corn oil/d on serum lipids of hypercholesterolemic human subjects (serum cholesterol 6.21-8.02 mmol/L). Concentrations of serum total cholesterol (-15%), LDL cholesterol (-8%), Apo B (-10%), thromboxane (-25%), platelet factor 4 (-16%), and glucose (-12%) decreased significantly only in the 15 subjects given palmvitee during the initial 4 wk. The crossover confirmed these actions of palmvitee. There was a carry over effect of palmvitee. Serum cholesterol concentrations of seven hypercholesterolemic subjects (greater than 7.84 mmol/L) decreased 31% during a 4-wk period in which they were given 200 mg gamma-tocotrienol/d. This indicates that gamma-tocotrienol may be the most potent cholesterol inhibitor in palmvitee capsules. The results of this pilot study are very encouraging. |
| Lowering of serum cholesteryl ester transfer protein--but not lecithin:cholesterol acyltransferase--activity levels by hypocholesterolemic drugs in the rabbit Meijer, G. W., J. E. Groener, et al. (1998), Cardiovasc Drugs Ther 12(1): 13-8. Abstract: Cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyltransferase (LCAT) are important factors in the regulation of serum lipoprotein metabolism. Rabbits were fed hypocholesterolemic drugs to investigate the effect on serum CETP and LCAT activity levels. The activities were assayed using exogenous substrate assays and are an estimate of CETP and LCAT mass. Groups of eight rabbits were fed a cholesterol-free diet containing either 0.03% simvastatin or 1% cholestyramine for 6 weeks. For comparison eight rabbits were fed a cholesterol-free control diet without drugs or a diet containing 0.1% cholesterol for 6 weeks. Total serum and lipoprotein triglyceride concentrations were not different after intervention with the hypocholesterolemic drugs or the cholesterol diet. Dietary cholesterol induced higher VLDL, IDL, and LDL cholesterol, as well as serum CETP activity, as expected. Serum LCAT activity showed little change with intervention. Both simvastatin and cholestyramine tended to lead to decreased cholesterol in all lipoprotein fractions and caused a significant decrease in serum CETP activity when compared with the control diet. Both drugs also caused a significant lower LDL particle concentration, as judged from differences in LDL protein levels. Intervention with simvastatin or cholestyramine led to relatively cholesterol-poor LDL. These effects on LDL concentration and composition were opposite from the effects of cholesterol feeding. Differences in the cholesterol contents of VLDL and IDL were comparable with those in LDL. The results suggest that decreasing serum CETP activity levels by treatment with simvastatin or cholestyramine may contribute to lowering of cholesterol apo B-containing lipoproteins. The effects are additional to the well-known increase in hepatic LDL receptor activity, which is likely to be the most important factor in LDL cholesterol lowering by these drugs. |
| Lowering patients' cholesterol. Excluding patients from trials increases uncertainty Jay, R. H. (1995), Bmj 311(7006): 690. |
| Lowering plasma cholesterol by raising ldl receptors. 1981 Brown, M. S. and J. L. Goldstein (2004), Atheroscler Suppl 5(3): 57-9. |
| Lowering serum cholesterol levels Stehbens, W. E. (1990), N Z Med J 103(898): 461. |
| Lowering serum cholesterol: who benefits? Allred, J. B. (1993), J Nutr 123(8): 1453-9. |
| Lowering the cholesterol content of MA104 cells inhibits receptor-mediated transport of folate Chang, W. J., K. G. Rothberg, et al. (1992), J Cell Biol 118(1): 63-9. Abstract: The folate receptor is clustered on the surface of MA104 cells in association with caveolae. This relationship is thought to be essential for the proper internalization and recycling of the receptor during the delivery of 5-methyltetrahydrofolate to the cytoplasm of folate-depleted cells. Both the clustered organization of the receptor and the integrity of caveolae are disrupted when cells are deprived of cholesterol. We now show that cholesterol depletion of MA104 cells markedly reduces the rate of 5-methyltetrahydrofolate internalization and causes a 70% decline in the number of receptors present in the internal, recycling compartment. This effect is consistent with morphologic data showing that cholesterol-depleted MA104 cells have a reduced number of caveolae as well as fewer receptors per caveolae. |
| Lowest serum cholesterol values are associated with depressive symptoms but not with mood disorders Rozzini, R., T. Sabatini, et al. (2003), Int J Geriatr Psychiatry 18(5): 457-8. |
| Low-fat and high-monounsaturated fatty acid diets decrease plasma cholesterol ester transfer protein concentrations in young, healthy, normolipemic men Jansen, S., J. Lopez-Miranda, et al. (2000), Am J Clin Nutr 72(1): 36-41. Abstract: BACKGROUND: Cholesterol ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to apolipoprotein (apo) B-containing lipoproteins. The possible atherogenic role of this protein is controversial. Diet may influence plasma CETP concentrations. OBJECTIVE: The objective was to determine whether the changes in plasma lipids observed after consumption of 2 lipid-lowering diets are associated with changes in plasma CETP concentrations. DESIGN: We studied 41 healthy, normolipidemic men over 3 consecutive 4-wk dietary periods: a saturated fatty acid-rich diet (SFA diet: 38% fat, 20% saturated fat), a National Cholesterol Education Program Step I diet (NCEP Step I diet: 28% fat, 10% saturated fat), and a monounsaturated fatty acid-rich diet (MUFA diet: 38% fat, 22% monounsaturated fat). Cholesterol content (27.5 mg/MJ) was kept constant during the 3 periods. Plasma concentrations of total, LDL, and HDL cholesterol; triacylglycerol; apo A-I and B; and CETP were measured at the end of each dietary period. RESULTS: Compared with the SFA diet, both lipid-lowering diets significantly decreased plasma total and LDL cholesterol, apo B, and CETP. Only the NCEP Step I diet lowered plasma HDL cholesterol. Positive, significant correlations were found between plasma CETP and total (r = 0.3868, P < 0.0001) and LDL (r = 0.4454, P < 0.0001) cholesterol and also between changes in CETP concentrations and those of total (r = 0.4543, P < 0.0001) and LDL (r = 0.4554, P < 0.0001) cholesterol. CONCLUSIONS: The isoenergetic substitution of a high-saturated fatty acid diet with an NCEP Step I or a high-monounsaturated fatty acid diet decreases plasma CETP concentrations. |
| Low-fat diets and HDL cholesterol Baschetti, R. (1998), Am J Clin Nutr 68(5): 1143-4. |
| Low-fat diets do not lower plasma cholesterol levels in healthy men compared to high-fat diets with similar fatty acid composition at constant caloric intake Nelson, G. J., P. C. Schmidt, et al. (1995), Lipids 30(11): 969-76. Abstract: In most studies reporting the effects of high-fat (HF) and low-fat (LF) diets on human plasma fatty acids (FA) and lipoprotein levels, the design involved adding to the diet an oil that had an FA composition (FAC) very different from the FAC of the control diet. Thus, it is difficult to determine if simply reducing the fat content of the diet without changing the dietary FAC changes the tissue FAC or alters plasma lipid levels. In this study, we fed diets that contained either 22 or 39% of calories from fat, but had no differences in their FAC, for 50 d to a group (n = 11) of healthy men (20-35 y). Thus, the polyunsaturated/saturated ratios (1.0) of the diets were identical as were the n-3/n-6 ratio and the monounsaturated-to-total fat ratios. The diets contained (wt% of total fat) approximately 28% saturated FA, 33% monounsaturated cis-FA, 6% monounsaturated trans-FA, 22% n-6 polyunsaturated FA, and 7% n-3 polyunsaturated FA, and 4% other minor FA. The diets consisted of natural foods and were formulated to contain 16 en% protein, either 45 or 62 en% carbohydrate (CHO) and at least the recommended daily allowance for all micronutrients. Both diets contained 360 mg of cholesterol per day. All subjects were given the HF diet for 20 d, and then six were placed on the LF and the other five remained on the HF diet for 50 d. The two groups were crossed-over for the remaining 50 d of the study. The subjects' baseline total cholesterol level was 173 mg/dl, after 50 d on the HF diet it was 177 mg/dl and after 50 d on the LF diet, 173 mg/dl. The differences were not significant, and there were no significant changes in either the LDL or HDL cholesterol levels with either diet. Triglyceride levels, and consequently very low density lipoprotein levels, rose significantly on the LF, higher CHO diet compared to the levels found in the subjects on the HF diet (91.5 and 66.4 mg/dl respectively, P < 0.002). The linoleic acid content of the plasma, platelets, and red blood cells was significantly (P < 0.05) reduced in the LF diet compared to HF diet, without any obvious physiological effects. Hence, many earlier observations indicating reductions in plasma lipid levels when people are on LF diets may be due to changes in the FAC of the diet, not the reduction in fat calories. |
| Low-pH-dependent fusion of Sindbis virus with receptor-free cholesterol- and sphingolipid-containing liposomes Smit, J. M., R. Bittman, et al. (1999), J Virol 73(10): 8476-84. Abstract: There is controversy as to whether the cell entry mechanism of Sindbis virus (SIN) involves direct fusion of the viral envelope with the plasma membrane at neutral pH or uptake by receptor-mediated endocytosis and subsequent low-pH-induced fusion from within acidic endosomes. Here, we studied the membrane fusion activity of SIN in a liposomal model system. Fusion was followed fluorometrically by monitoring the dilution of pyrene-labeled lipids from biosynthetically labeled virus into unlabeled liposomes or from labeled liposomes into unlabeled virus. Fusion was also assessed on the basis of degradation of the viral core protein by trypsin encapsulated in the liposomes. SIN fused efficiently with receptor-free liposomes, consisting of phospholipids and cholesterol, indicating that receptor interaction is not a mechanistic requirement for fusion of the virus. Fusion was optimal at pH 5.0, with a threshold at pH 6.0, and undetectable at neutral pH, supporting a cell entry mechanism of SIN involving fusion from within acidic endosomes. Under optimal conditions, 60 to 85% of the virus fused, depending on the assay used, corresponding to all of the virus bound to the liposomes as assessed in a direct binding assay. Preincubation of the virus alone at pH 5.0 resulted in a rapid loss of fusion capacity. Fusion of SIN required the presence of both cholesterol and sphingolipid in the target liposomes, cholesterol being primarily involved in low-pH-induced virus-liposome binding and the sphingolipid catalyzing the fusion process itself. Under low-pH conditions, the E2/E1 heterodimeric envelope glycoprotein of the virus dissociated, with formation of a trypsin-resistant E1 homotrimer, which kinetically preceded the fusion reaction, thus suggesting that the E1 trimer represents the fusion-active conformation of the viral spike. |
| Low-saturated fat, low-cholesterol diet in 3-year-old children: effect on intake and composition of trans fatty acids and other fatty acids in serum phospholipid fraction-The STRIP study. Special Turku coronary Risk factor Intervention Project for children Salo, P., T. Seppanen-Laakso, et al. (2000), J Pediatr 136(1): 46-52. Abstract: OBJECTIVE: We evaluated whether replacing a proportion of saturated fat with vegetable oils in the diet of young children increases trans fatty acid intake. STUDY DESIGN: Dietary counseling aimed to reach a dietary fat ratio of unsaturated to saturated fat of 2:1 within a total fat intake of 30% to 35% of energy (E%). Four-day food records of 813 3-year-old children were analyzed, and serum phospholipid fatty acid compositions of 25 randomly selected intervention children and 17 control children were analyzed. RESULTS: trans fatty acid intake of the intervention and control children was small (0.8 E% and 0.6 E%, respectively; P <.001). The relative content of serum phospholipid trans 18:1 was closely similar in intervention and control children (1.0% and 0.9% of all fatty acids, respectively). Trans fatty acid intake and serum trans 18:1 correlated poorly with children's serum cholesterol and HDL cholesterol concentrations and inversely with serum phospholipid arachidonic to linoleic acid ratio (r = -0.373). CONCLUSIONS: Trans fatty acid intake of children in Finland is minimal. Dietary intervention replacing saturated with unsaturated fatty acids is safe because it does not increase trans fatty acid intake or the relative content of trans fatty acids in the serum phospholipid fraction. |
| Low-serum high-density lipoprotein-cholesterol concentration as a sign of celiac disease Capristo, E., G. Addolorato, et al. (2000), Am J Gastroenterol 95(11): 3331-2. |
| Low-serum, high-density lipoprotein cholesterol concentration is an important coronary risk factor in Chinese patients with low serum levels of total cholesterol and triglyceride Lien, W. P., L. P. Lai, et al. (1996), Am J Cardiol 77(12): 1112-5. Abstract: The significance of low-serum high-density lipoprotein concentrations (<35 mg/dl) with respect to coronary atherogenesis in Chinese patients with low levels of total serum cholesterol (<200 mg/dl) and triglycerides (<250 mg/dl) was assessed. Persons with such a lipid profile pattern were still at high risk, and high-density lipoprotein. like smoking, appeared to be the most predictive independent coronary risk factor. |
| Luminal surface concentration of lipoprotein (LDL) and its effect on the wall uptake of cholesterol by canine carotid arteries Deng, X., Y. Marois, et al. (1995), J Vasc Surg 21(1): 135-45. Abstract: PURPOSE: The effect of near-wall blood flow velocity and plasma filtration velocity across the arterial wall on luminal surface concentration of low-density lipoproteins (LDL) and the uptake of tritium-cholesterol were investigated. METHODS: A numeric analysis of LDL transport in steady flow, over the range of physiologically relevant flow rates, predicted a surface concentration of LDL of 4% to 16% greater than that in the bulk flow. The LDL surface concentration increased linearly with filtration velocity and inversely with wall shear rate. RESULTS: These were validated experimentally in canine carotid arteries. When the transmural pressure was increased from 100 to 200 mm Hg, the filtration velocity increased from 5.13 x 10(-6) cm/sec to 8.41 x 10(-6) cm/sec, whereas the normalized uptake rate of tritium-cholesterol increased from 3.58 x 10(-4) cm/hour to 7.36 x 10(-4) cm/hour. CONCLUSION: These results indicate that lipids accumulate at the luminal surface in areas where blood flow velocity and wall shear stress are low and where the permeability of the endothelial layer is enhanced. Moreover, the rate of lipid infiltration into the blood vessel walls is affected by the luminal surface concentration. These findings are consistent with chronic hypertension and elevated blood cholesterol concentrations being major risk factors for atherosclerosis. |
| Lung retention of phosphatidylcholine and cholesterol from liposomes: effects of oxygen exposure and fasting Smith, L. J. and J. Anderson (1993), J Appl Physiol 74(4): 1899-904. Abstract: Antioxidants such as glutathione may play a role in prevention and treatment of several lung diseases. Liposomes can be used to deliver antioxidants to the lung and increase their retention. In addition, liposomes alone may protect against oxidant-induced damage. In addition, liposomes alone may protect against oxidant-induced damage. This study was designed to characterize the retention and distribution of liposomes in the lung under normal circumstances and during either fasting, exposure to 100% oxygen, or a combination of the two. Positively charged liposomes, consisting of phosphatidylcholine (PC), cholesterol, and stearylamine plus either 14Ccholesterol or 3HPC, were instilled intratracheally. Five minutes to 5 days later the lungs were removed and the radioactivity determined. Both 14Ccholesterol and 3HPC labels had prolonged and equal retention in the lung, but their distribution within lung compartments differed. The cholesterol label increased in lung tissue over time, comprising 78% of the remaining label after 5 days, whereas the PC label persisted at high levels in lavage fluid and became equally distributed between lung tissue and bronchoalveolar lavage fluid. Fasting had little effect on the retention of the labels and no effect on their distribution within the lung. Exposure to 100% oxygen increased lung retention of both radiolabels and altered their distribution such that 14Ccholesterol label decreased and 3HPC label increased in lung tissue. These results demonstrate the prolonged retention of intratracheally administered liposomes or their components in the lung and the effects of two clinically relevant conditions, fasting and hyperoxic exposure. Furthermore, they provide a basis for designing future studies using liposomes. |
| LuXuRies of lipid homeostasis: the unity of nuclear hormone receptors, transcription regulation, and cholesterol sensing Zhang, Y. and D. J. Mangelsdorf (2002), Mol Interv 2(2): 78-87. Abstract: Cholesterol homeostasis is maintained by a regulatory network that controls both the acquisition and elimination of cholesterol. Recent studies have elucidated a mechanism by which cholesterol metabolism is transcriptionally regulated by several classes of orphan nuclear receptors. In particular, the liver X receptors, LXRalpha and LXRbeta, appear to serve as key sensors of intracellular sterol levels by regulating the expression of genes that control cholesterol absorption, storage, transport, and elimination. LXRs are also involved in fatty acid metabolism by their ability to increase the expression of sterol regulatory element-binding protein 1c (SREBP-1c). These findings define LXRs as potential therapeutic targets for the treatment of lipid disorders. |
| LXR (liver X receptor) and HNF-4 (hepatocyte nuclear factor-4): key regulators in reverse cholesterol transport Crestani, M., E. De Fabiani, et al. (2004), Biochem Soc Trans 32(Pt 1): 92-6. Abstract: Cholesterol homoeostasis is the result of the fine tuning between intake and disposal of this molecule. High levels of cholesterol in the blood are detrimental as they may lead to excessive accumulation in vessel walls, a condition predisposing to the development of atherosclerotic lesions. Cholesterol is removed from the vessel wall and transported to the liver through a process called reverse cholesterol transport. Nuclear receptors are among the most important transcription factors regulating genes involved in different steps of reverse cholesterol transport. Here, we discuss the role of the nuclear receptors LXR (liver X receptor) and HNF-4alpha (hepatocyte nuclear factor-4alpha) in different steps of reverse cholesterol transport. LXR controls the transcription of crucial genes in cholesterol efflux from macrophages and its transport to the liver, such as ABCA1 (ATP binding cassette A1), CYP27A1 (sterol 27-hydroxylase), CLA-1 (scavenger receptor type B1) and apolipoprotein E. Some oxysterols present in oxidized low-density lipoproteins and proinflammatory cytokines modulate the activity of LXR by antagonizing the effect of activators of this receptor, thus contributing to cholesterol accumulation in macrophages. Bile acid synthesis, which represents the final step of reverse cholesterol transport, is transcriptionally regulated by several nuclear receptors at the level of the liver-specific cytochrome P450 cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme of this metabolic pathway. Bile acids returning to the liver through the enterohepatic circulation down-regulate CYP7A1 transcription via the bile acid sensors farnesoid X receptor and HNF-4alpha. Based on this evidence, these nuclear receptors are candidate targets of new drugs for the treatment and prevention of atherosclerotic disease. |
| LXR activation and cholesterol efflux from a lipoprotein depot in vivo Stein, Y., O. Stein, et al. (2004), Biochim Biophys Acta 1686(1-2): 24-9. Abstract: Activation of LXR in cultured cells results in enhancement of cholesterol efflux to apo Al. To study cholesterol efflux, in vivo cationized LDL was injected into the rectus femoris muscle of mice to create a lipoprotein depot. LXR ligand TO901317, 10 mg/kg, was given by gavage for 8 days, starting 4 days after injection of the lipoprotein. The rate of cholesterol efflux from the depot was compared in treated and control mice. Administration of the ligand resulted in a 70% increase in plasma cholesterol and 40% in phospholipids, but HDL-cholesterol and HDL-phospholipids increased by 43% and 24% only. Efflux of the injected cholesterol from the lipoprotein depot of treated mice was not enhanced but even somewhat delayed. This impairment was unexpected and its cause could be multifactorial. A plausible explanation seems that induced hypercholesterolemia, and a decrease in HDL-cholesterol to total cholesterol ratio, delayed the clearance. |