| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| The role of cholesterol in the biosynthesis of beta-amyloid Frears, E. R., D. J. Stephens, et al. (1999), Neuroreport 10(8): 1699-705. Abstract: Addition of the beta-hydroxy-beta-methylglutaryl-CoA (HmG-CoA) reductase inhibitor lovastatin to human HEK cells transfected with the amyloid precursor protein (APP) reduces intracellular cholesterol/protein ratios by 50%, and markedly inhibits beta-secretase cleavage of newly-synthesized APP. Exogenous water-solubilized cholesterol at 200 microg/ml concentration increases newly synthesized beta-amyloidogenic products four-fold. These intracellular changes are detectable by immunoprecipitation and immunofluorescent labelling. Analyses of the fragments captured from culture medium by an N-terminal anti-beta-amyloid antibody on ProteinChip arrays and detected using surface-enhanced laser desorption/ionization (SELDI) mass spectrometry revealed that culture with cholesterol (200 microg/ml) increased secretion of beta-amyloid 1-40 by 1.8-fold, and increased secretion of beta-amyloid 1-42. Changes in APP processing by cholesterol may mediate the way in which the ApoE4 allele increases risk of developing Alzheimer's disease (AD) in western populations. |
| The role of cholesterol in the pathogenesis of Alzheimer's disease Michikawa, M. (2001), Nippon Ronen Igakkai Zasshi 38(6): 751-3. |
| The role of cholesterol management in coronary disease risk reduction in elderly patients Grundy, S. M. (1998), Endocrinol Metab Clin North Am 27(3): 655-75, x. Abstract: This article discusses the various factors that must be taken into account and balanced when making decisions about particular therapies for the management of high-serum cholesterol in older persons. |
| The role of cholesterol on the pressure sensing ability of kidneys in rats Edremitlioglu, M. and G. Oner (2003), J Basic Clin Physiol Pharmacol 14(4): 345-58. Abstract: We studied the effect of hypercholesterolemia on the pressure-sensing and regulating ability of the kidneys, using an acute hemorrhage model to provide 40% and 60% reduction in the blood pressure of hypercholesterolemic and control rats. The control group (n = 22) was fed a normal rat pellet diet and tap water; the experimental group (n = 22) received a diet containing 2% cholesterol/0.2% thaurocholate. Half the animals were subjected to 6 mL/kg bw and the others to 12 mL/kg bw of bleeding for 1 min. Blood pressure recording and proper samplings were done before bleeding and during the 20 min post-hemorrhagic period for analysis. Despite a finding of hypercholesterolemia in the experimental group, kidney cholesterol content as well as its function remained unchanged. Following an initial 40% decrease in rats bled 6 mL/kg bw, 20 min later the mean blood pressure returned to 90% of its initial value in control rats and to 70% of its basal level in hypercholesterolemic rats. A similar delay in pressure normalization occurred in rats subjected to 12 mL/kg of bleeding. Plasma renin activity remained unaffected. We conclude that dietary hypercholesterolemia delays the normalization of blood pressure after hemorrhage without affecting the sensing ability of kidneys, and that the kidneys are less sensitive than other organs to plasma cholesterol levels. |
| The role of cholesterol-lowering drugs in prevention of coronary heart disease Skaluba, Z. and R. Undas (1998), Przegl Lek 55(7-8): 382-7. Abstract: Hypercholesterolemia is an important risk factor of coronary heart disease. Pol-MONICA study performed in 1983-84 showed that at that time 65% of Polish population had an increased blood cholesterol level. After 10 years that percentage rose up to 70 in men and 67 in women. It is the reason for concern that prescription of cholesterol-lowering drugs is still insufficient. It has been proven that 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (HMG-CoA reductase inhibitors), named statins, which are recognized as the strongest cholesterol-lowering drugs, cause a significant decrease in the rate of acute coronary episodes and total mortality in both primary and secondary prevention of coronary heart disease. Moreover, statins induce the inhibition of progression, or even regression, of atherosclerotic lesions, as demonstrated by echocardiography. The aim of therapy is to decrease blood LDL-cholesterol level to 3.0-3.5 mmol/l (115-135 mg/dl). It should be emphasized, however, that any reduction in cholesterol concentration can provide distinct clinical benefits. Therefore, it seems important to present data on the recent progress in effective treatment of hypercholesterolemia and benefits arising from this approach. |
| The role of cytochrome P450 in the regulation of cholesterol biosynthesis Gibbons, G. F. (2002), Lipids 37(12): 1163-70. Abstract: A ubiquitously expressed member of the cytochrome P450 superfamily, CYP51, encodes lanosterol 14alpha-demethylase, the first step in the conversion of lanosterol into cholesterol in mammals. The biosynthetic intermediates of lanosterol 14alpha-demethylation are oxysterols, which inhibit HMG-CoA reductase and sterol synthesis in mammalian cells in vitro. These oxysterols (5alpha-lanost-8-en-3beta,32-diol and 3beta-hydroxy-5alpha-lanost-8-en-32-al) are efficiently converted into cholesterol in vitro and are generally considered to be natural cholesterol precursors. When added to hepatocytes in high concentrations, besides their conversion into cholesterol, they are also rapidly metabolized into more polar sterols and into steryl esters. The 15alpha- and 15beta-hydroxy epimers of 5alpha-lanost-8-en-3beta-ol are also rapidly metabolized into more polar sterols and steryl esters but are not converted efficiently into cholesterol. Polar sterol formation from all these oxysterols is dependent on an active form of cytochrome P450. Oxysterols are potent regulators of the activities of transcription factors of the sterol regulatory element-binding protein family and of liver X-receptor alpha. It is proposed that the rapid, cytochrome P450-dependent metabolism of naturally occurring regulatory oxysterols provides a route for their deactivation so that they become incapable of affecting gene transcription. Inhibition of cytochrome P450 by the drug ketoconazole prevents the inactivation of such oxysterols, leading to a prolonged suppression of hepatic HMG-CoA reductase in vivo and in vitro. |
| The role of diet cholesterol changes on EEG Agar, A., P. Yargicoglu, et al. (1994), Int J Neurosci 75(1-2): 103-9. Abstract: Thirty three male albino rats, weight between 200 and 220 g were used in this experiment. Control animals consisting of 11 rats were fed with a normal lab diet for a period of 14 weeks and the others (22) were fed with a diet containing 1% cholesterol for the same period. At the end of the experimental period, plasma cholesterol level (Mean +/- SD) was 141.29 +/- 34.5 mg/dl in the cholesterol group and 70.66 +/- 10 mg/dl in the control group. Eleven of the rats from the cholesterol group were transferred to the normal diet for 14 weeks (normocholesterolemic group). Spectral analysis of EEG records from parietal lobes of animals showed that there was an obvious depression in the brain waves of hypercholesterolemic rats whereas no depression in normocholesterolemic rats. |
| The role of dietary cholesterol in infants Neu, J. (1992), Compr Ther 18(10): 35-7. |
| The role of dietary cholesterol in the regulation of postprandial apolipoprotein B48 levels in diabetes Taggart, C., J. Gibney, et al. (1997), Diabet Med 14(12): 1051-8. Abstract: The atherogenicity of intestinally derived postprandial lipoproteins has been confirmed in a number of recent studies. We have shown abnormalities in postprandial lipoprotein metabolism in diabetic patients, a group with an increased susceptibility to atherosclerosis. This study examined the relationship between dietary cholesterol and the postprandial, intestinally derived, apolipoprotein B48 and apolipoprotein B100 from the liver. We compared 10 non-insulin-dependent (Type 2, NIDDM) diabetic patients and 10 age-matched non-diabetic control subjects. Fasting blood was taken and subjects were fed a cholesterol-free, high fat meal. Blood samples were repeated at 2 h, 4 h, 6 h, and 8 h postprandial. The following week fasting blood was collected and subjects were given the same meal with 1 g of added cholesterol. Blood was collected at the same time points. Chylomicrons and very low density lipoprotein were isolated by sequential ultracentrifugation and their lipoprotein composition determined. Apolipoproteins B48 and B100 were separated by gradient gel electrophoresis and quantified by densitometric scanning using a low density lipoprotein apolipoprotein B100 standard. Post prandial chylomicron cholesterol and triglyceride increased after the high cholesterol meal in both groups (p < 0.001). The postprandial chylomicron apolipoprotein B48 response of both diabetic and control subjects to the cholesterol meal was less than to the cholesterol-free meal (p < 0.001). Fasting very low density lipoprotein apolipoprotein B48 was higher in diabetic patients compared to control subjects and their postprandial increase following the cholesterol-free meal was significantly greater (p < 0.001). There was a 10-fold increase in the incremental postprandial VLDL apolipoprotein B48 area under the curve after the cholesterol-rich meal in the diabetic patients compared to a 3-fold increase in control subjects. The postprandial very low density lipoprotein apolipoprotein B100 was similar in the two groups with both meals. The study demonstrates a very significant increase in the amount of intestinally derived small apolipoprotein B48-associated particles in the very low density lipoprotein fraction following a cholesterol-rich meal in diabetic patients. Synthesis rather than clearance may be the major cause of the increase in these atherogenic postprandial particles. |
| The role of fat tissue in the cholesterol lowering and the pleiotropic effects of statins--statins activate the generation of metabolically more capable adipocytes Erol, A. (2005), Med Hypotheses 64(1): 69-73. Abstract: Statins have very important influences on adipocyte physiology, particularly via their effects on sterol regulatory element binding proteins (SREBPs), which are extremely important transcription factors for the regulation of adipocyte physiology. SREBP-1c activation in fat cell by the cytosolic cholesterol deprivation through HMG-reductase inhibition is responsible for most of the beneficial effects of statins. Glucose and lipid excess, and oxidative overload coming with energy dense nutrition, which might be deleterious, can be removed from the circulation by adipo-lipogenetic enhancement through the activated SREBP-1c. SREBP-1c causes formation of new small and competent adipocytes, which are insulin and leptin sensitive. Thus, adipocytes gain the ability of fat storing, and much more importantly, fat-burning machines. Statins already have a large and growing number of indications in the treatment of atherovascular diseases. General mechanism for the action of statins is their inhibitory effects on 3-hydroxy 3-methyl glutaryl CoA reductase, which is the rate-limiting enzyme in cholesterol biosynthesis, particularly in the liver. Recently, the beneficial effects of statins beyond their cholesterol lowering, which are called pleiotropic effects, have been the focus of great attention. Certain characteristics of the statin molecule itself have been proposed to explain these effects. Adipocytes are in the very heart of metabolic regulations. Therefore, the important elements of the pleiotropic effects of statins occur through executive improvements on impaired adipocyte functions by the activation of SREBP-1c. |
| The role of fats in the lifecycle stages. Adulthood--treatment: cholesterol-lowering with plant sterols Nestel, P. J. (2002), Med J Aust 176 Suppl: S122. Abstract: Margarines enriched with plant sterols are effective at lowering low-density lipoprotein (LDL) cholesterol levels when eaten as recommended. LDL-cholesterol level reductions of more than 10% are achieved in most people. Phytosterol-containing foods are valuable additions to other cholesterol-lowering treatments, including statins. They should be considered for all patients with increased cardiovascular risk factors in whom LDL reduction is desirable. The only recognised possible adverse effect is reduction in some carotenoids in plasma, but this can be overcome by eating an additional serving of a carotenoid-rich (yellow or orange) fruit or vegetable. |
| The role of fatty acid saturation on plasma lipids, lipoproteins, and apolipoproteins: II. The plasma total and low-density lipoprotein cholesterol response of individual fatty acids Derr, J., P. M. Kris-Etherton, et al. (1993), Metabolism 42(1): 130-4. Abstract: Regression analyses were performed on individual data from our two previous clinical investigations to establish the cholesterolemic effects of individual fatty acids. Our principal objective was to determine the effects of stearic acid on plasma total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol levels. Our second objective was to determine the variation in the cholesterolemic response of individuals to changes (delta) in the major dietary fatty acids. The best-fitting linear regression equations relating delta TC and delta LDL (mg/dL) were as follows: delta TC = 2.3 delta C14:0 + 3.0 delta C16:0 - 0.8 delta C18:0 - 1.0 delta polyunsaturated fatty acids (PUFA) and delta LDL = 2.6 delta C14:0 + 2.9 delta C16:0 - 0.5 delta C18:0 - 0.7 delta PUFA, where delta fatty acid = change in intake expressed as percent of calories. Based on these equations, in which stearic acid has a significant, negative regression coefficient, and the other regression models analyzed, it appears that stearic acid has an independent cholesterol-lowering effect. Using the equation we developed, 75% of the actual cholesterolemic responses were within +/- 10 mg/dL of the predicted response. In summary, we have developed a predictive equation (similar to those developed by both Keys and Hegsted) to estimate changes in plasma TC and LDL cholesterol levels of young men in response to changes in dietary fatty acids. However, our predictive equation separates stearic acid from the other long-chain saturated fatty acids (SFA) and indicates that it has an independent cholesterol-lowering effect. Thus, stearic acid is a unique long-chain SFA because of its effect on plasma cholesterol level. |
| The role of fibrinolytic system proteins in cholesterol gallstone formation Havranek, E. G., S. Tierney, et al. (1999), Scand J Gastroenterol 34(5): 516-9. Abstract: BACKGROUND: Accelerated nucleation, supersaturation of bile, and biliary stasis are known to be key factors in cholesterol gallstone formation. The mechanisms through which these factors interact to form stones are still incompletely understood. Among the proteins now known to be present in bile are several components of the fibrinolytic system: tissue plasminogen activator, urokinase-like plasminogen activator, and plasminogen activator inhibitors 1 and 2. The concentrations of plasminogen activator inhibitors 1 and 2 in gallbladder bile are increased in patients with gallstones. The aim of this study was to determine whether these fibrinolytic system proteins act as pro-nucleating agents for cholesterol gallstone formation. METHODS: Nucleation assays were done on gallbladder bile from eight cholesterol stone patients and eight control patients. The effects of tissue plasminogen activator, urokinase-like plasminogen activator, and plasminogen activator inhibitors I and 2 on cholesterol crystal appearance time (CCAT) were tested, by direct observation using polarizing microscopy, after measurement of biliary lipids and calculation of cholesterol saturation indices. RESULTS: There was no significant difference in cholesterol saturation indices between bile that nucleated and bile that did not (mean, 2.0 +/- 1.5 versus 1.8 +/- 0.5). When all samples in which nucleation occurred were compared, tissue plasminogen activator significantly shortened CCAT median from 4.75 days (range, 2-21) to 3.5 days (2.5-18) (P < 0.05). This was similar to the effect of fibronectin (3.75 days; range, 2-20), a known pro-nucleator used as a nucleation accelerating control (P < 0.05). None of the other fibrinolytic system proteins significantly accelerated CCAT. CONCLUSIONS: The results of this study suggest that tissue plasminogen activator may act as a pro-nucleating agent for cholesterol gallstone formation in gallbladder bile. |
| The role of HDL in reverse cholesterol transport and its disturbances in Tangier disease and HDL deficiency with xanthomas Schmitz, G., T. Bruning, et al. (1990), Eur Heart J 11 Suppl E: 197-211. |
| The role of high-density lipoprotein (HDL) cholesterol in the prevention and treatment of coronary heart disease: expert group recommendations Sacks, F. M. (2002), Am J Cardiol 90(2): 139-43. |
| The role of intracellular cholesterol on the processing of the beta-amyloid precursor protein Austen, B. M., C. Sidera, et al. (2003), J Nutr Health Aging 7(1): 31-6. Abstract: The objectives of this article are to summarise evidence that amyloidogenesis is a causal factor in Alzheimer's disease, to outline the main pathways of amyloidogenesis in Alzheimer's disease, describe contemporary evidence showing that the processing of the amyloid precursor protein and amyloidogenesis is strongly influenced by the levels of intracellular cholesterol. Moreover, we shall suggest a mechanistic hypothesis that could explain the observed epidemiological links between the use of inhibitors of cholesterol biosynthesis in patients and the observed reduced risk of Alzheimer's disease. |
| The role of investigating the fractional composition of high-density cholesterol lipoproteins and dys-alpha-lipoproteinemia for detection of atherogenic disorders Kamyshnikov, V. S. (1994), Klin Lab Diagn(3): 19-22. Abstract: Disorders of cholesterol-acceptor and cholesterol-transporting properties of antiatherogenic lipoproteins are associated with changes in etherification and fractional composition of high-density lipoprotein (HDLP) cholesterol. The said metabolic shifts prompted us to develop a new method for assessment of the cholesterol coefficient of plasma lipoprotein spectrum atherogenicity calculated by the formula: (CS--alpha-CS)/alpha-CS.(ECS/FCS), where alpha-CS, ECS, and FCS are total, ether-bound, and free HDLP cholesterols, respectively. For detection of atherogenic disorders assessment of HDLP loading with ether-bound cholesterol is recommended, as well as of dyslipoproteinemia, from the ratio of atherogenic lipoproteins and HDLP2, of lipoprotein cholesterols of these two classes, and of the type and severity of dys-alpha-lipoproteinemia from HDLP2/HDLP3 ratio. A reduced value of this ratio is a sensitive indicator of disorders in antiatherogenesis metabolic system leading to impaired cholesterol outflow from the tissues. Efficacy of diagnosis of atherosclerosis by each of the suggested methods is higher than that of the prototype method. Authors' certificates for invention of these methods were granted. |
| The role of lipoprotein cholesterol in biliary steroid secretion. Studies with in vivo experimental models Botham, K. M. and E. Bravo (1995), Prog Lipid Res 34(1): 71-97. |
| The role of microsomal triglyceride transfer protein and dietary cholesterol in chylomicron production in diabetes Gleeson, A., K. Anderton, et al. (1999), Diabetologia 42(8): 944-8. Abstract: AIMS/HYPOTHESIS: The aim of this study was to examine factors involved in chylomicron production in the streptozotocin diabetic rat, our hypothesis being that the synthesis of the chylomicron is abnormal in diabetes. METHODS: Diabetic rats (n = 20) were paired with control rats (n = 20). Cholesterol emulsion was given by gavage and the lymph duct was cannulated. Lymph was collected for 4 h. Chylomicrons were prepared from the lymph by ultracentrifugation. Lymph apolipoprotein B48 was isolated by gradient gel electrophoresis and quantified by densitometric scanning. Intestinal microsomal triglycerol transfer protein mRNA was measured by solution hybridisation nuclease protection, using a rat specific 32P-labelled cRNA probe. RESULTS: Serum triglyceride and cholesterol were greatly increased in diabetic compared with control animals (258 +/- 77 and 8.9 +/- 6.4 mg/ml vs 1.04 +/- 0.37 and 0.54 +/- 0.03 mg/ml, p < 0.0001). Lymph chylomicron triglyceride and cholesterol were also higher in diabetic rats (29.4 +/- 27.3 and 0.28 +/- 0.3 mg/h vs 16.8 +/- 10.6 and 0.18 +/- 0.09 mg/h, p < 0.05). Lymph chylomicron apo B48 was similar in the two groups. Intestinal microsomal triglycerol transfer protein mRNA was higher in the diabetic rats (12.6 +/- 3.2 vs 3.8 +/- 3.0 amol/microgram RNA, p < 0.0001) and there was a positive correlation between lymph triglyceride and microsomal triglycerol transfer protein mRNA in the whole group (r = 0.65, p < 0.01). CONCLUSION/INTERPRETATION: The study shows that microsomal triglycerol transfer protein mRNA is raised in diabetes without an increase in apolipoprotein B48 in the lymph suggesting that microsomal triglycerol transfer protein regulates chylomicron triglyceride content but not particle number. |
| The role of orphan nuclear receptors in the regulation of cholesterol homeostasis Repa, J. J. and D. J. Mangelsdorf (2000), Annu Rev Cell Dev Biol 16: 459-81. Abstract: Cholesterol balance is maintained by a series of regulatory pathways that control the acquisition of cholesterol from endogenous and exogenous sources and the elimination of cholesterol, facilitated by its conversion to bile acids. Over the past decade, investigators have discovered that a family of membrane-bound transcription factors, sterol regulatory element-binding proteins (SREBPs), mediate the end-product repression of key enzymes of cholesterol biosynthesis. Recently orphan members of another family of transcription factors, the nuclear hormone receptors, have been found to regulate key pathways in bile acid metabolism, thereby controlling cholesterol elimination. The study of these orphan nuclear receptors suggests their potential as targets for new drug therapies. |