| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Cholesterol, bile acid, and lipoprotein metabolism in two strains of hamster, one resistant, the other sensitive (LPN) to sucrose-induced cholelithiasis Ferezou, J., M. Combettes-Souverain, et al. (2000), J Lipid Res 41(12): 2042-54. Abstract: A comprehensive study of cholesterol, bile acid, and lipoprotein metabolism was undertaken in two strains of hamster that differed markedly in their response to a sucrose-rich/low fat diet. Under basal conditions, hamsters from the LPN strain differed from Janvier hamsters by a lower cholesterolemia, a higher postprandial insulinemia, a more active cholesterogenesis in both liver 3- to 4-fold higher 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoAR) activity and mRNA and small intestine, and a lower hepatic acyl-coenzyme A:cholesterol acyltransferase activity. Cholesterol saturation indices in the gallbladder bile were similar for both strains, but the lipid concentration was 2-fold higher in LPN than in Janvier hamsters. LPN hamsters had a lower capacity to transform cholesterol into bile acids, shown by the smaller fraction of endogenous cholesterol converted into bile acids prior to fecal excretion (0.34 vs. 0.77). In LPN hamsters, the activities of cholesterol 7alpha-hydroxylase (C7OHase) and sterol 27-hydroxylase (S27OHase), the two rate-limiting enzymes of bile acid synthesis, were disproportionably lower (by 2-fold) to that of HMG-CoAR. When fed a sucrose-rich diet, plasma lipids increased, dietary cholesterol absorption improved, hepatic activities of HMG-CoA reductase, C7Ohase, and S27OHase were reduced, and intestinal S27OHase was inhibited in both strains. Despite a similar increase in the biliary hydrophobicity index due to the bile acid enrichment in chenodeoxycholic acid and derivatives, only LPN hamsters had an increased lithogenic index and developed cholesterol gallstones (75% incidence), whereas Janvier hamsters formed pigment gallstones (79% incidence).These studies indicate that LPN hamsters have a genetic predisposition to sucrose-induced cholesterol gallstone formation related to differences in cholesterol and bile acid metabolism. |
| Cholesterol, but not cigarette smoke, decreases rabbit carotid artery relaxation Johnson, D., J. A. Freischlag, et al. (1999), Ann Vasc Surg 13(5): 480-3. Abstract: The purpose of this study was to determine the physiologic effects of cigarette smoke exposure and dietary cholesterol on the availability of nitric oxide in carotid vascular rings. New Zealand white rabbits were placed in an airflow chamber for 3 hr/day over an 8-week period and were exposed to smoke from 600 cigarettes/per day added to the chamber inflow by a robotic smoke generator. New Zealand white rabbits, made hypercholesterolemic, and one group fed a normal diet, were similarly placed in the chamber without exposure to cigarette smoke. In those exposed groups, serum cotinine and cholesterol levels were consistently elevated. After the 8-week period, the carotid arteries were harvested. The vessels were cut into 3-mm rings which were suspended from pressure transducers. The rings were contracted with potassium chloride (KCl) to determine vessel integrity. One ring from each carotid was maximally contracted with 1 x 10(-3) molar norepinephrine (NE) while the experimental ring was contracted to 50% of maximum. Relaxation of the rings was achieved by adding incremental doses of acetylcholine. Our results showed that endothelial dysfunction, as measured by acetylcholine-mediated vasorelaxation, occurs in the rabbit carotid artery when exposed to high dietary cholesterol. Cigarette exposure alone in this particular vessel did not result in significant alteration in acetylcholine-mediated vasorelaxation. |
| Cholesterol, but not its esters, triggers programmed cell death in human erythroleukemia K562 cells Maccarrone, M., L. Bellincampi, et al. (1998), Eur J Biochem 253(1): 107-13. Abstract: Cholesterol, its biosynthetic precursors and the cholesterol-lowering drug compactin were able to inhibit the growth of human erythroleukemia K562 cells. Compactin, farnesyldiphosphate and cholesterol were cytotoxic by the induction of apoptosis (programmed cell death, PCD). Compactin doubled the number of apoptotic cells compared to control numbers, whereas farnesyldiphosphate and cholesterol led to a fivefold increase in PCD over the control levels. At variance with cholesterol, cholesterol esters did not affect K562 cell viability and apoptotic body formation, regardless of chain length and degree of saturation. Compactin and farnesyldiphosphate reduced the membrane cholesterol content, thus increasing membrane fluidity. Conversely, cholesterol treatment reduced the membrane fluidity by increasing cholesterol content in the lipid bilayer. Unlike farnesyldiphosphate, the other cholesterol precursors and cholesterol esters were ineffective in increasing the cholesterol content and, thereby, the fluidity of cell membranes. Compactin and cholesterol precursors, apart from farnesyldiphosphate, did not affect the amount of the farnesylated proteins Ras and lamin B in the cytosolic and the membrane fractions of K562 cell extracts, whereas farnesyldiphosphate reduced the content of both proteins in both fractions. The level of lamin B in K562 cytosol and membranes was also reduced by cholesterol treatment, which did not significantly affect the amount of Ras. These findings highlight the role of cholesterol in promoting PCD. |
| Cholesterol, calcium and atherosclerosis: is there a role for calcium channel blockers in atheroprotection? Tulenko, T. N., L. Laury-Kleintop, et al. (1997), Int J Cardiol 62 Suppl 2: S55-66. Abstract: It is well known that the atherogenic dyslipidemias of either elevated serum LDL or reduced HDL levels correlate with the degree and severity of atherosclerosis. However, how this leads to atherogenesis is poorly understood. A role for cellular oxidative stress mediated by oxidized LDL has gained widespread acceptance, but this pathway is unlikely to be the sole atherogenic signal. Recent evidence obtained from arterial smooth muscle cells (SMC) and endothelial cells (EC) is consistent with another pathway that may explain, in part, the early alterations contributing to the initiation of cellular atherogenic modifications. This pathway involves enrichment of the cell plasma membrane with cholesterol. In SMC, in vitro (cell culture) and in vivo (cholesterol feeding) experiments demonstrate that cholesterol enrichment of the SMC membrane occurs rapidly and is associated with an increase in membrane bilayer width, calcium permeability, and cell proliferation. Removal of excess membrane cholesterol with human HDL restores these alterations, suggesting that this membrane structural 'defect' mediates these changes in cell function. In vitro, the increased calcium permeability is inhibitable by calcium channel blockers (CCBs), but in vivo, a calcium 'leak' pathway develops that is virtually uninhibitable. It is not surprising that the literature on the application of CCBs for atheroprotection is not wholly convincing. However, with the advent of the new third generation of CCBs, new hope arises. One of the first CCBs of this generation is amlodipine (Norvasc), a charged dihydropyridine that has a remarkable pharmacologic profile. First, it is markedly lipophilic allowing it to partition readily into cell membranes. Second, in the membrane it has the ability to re-order, or restore, the 'swollen' membrane bilayer back to normal in atherosclerotic SMC. Third, it has potent antioxidant properties. Fourth, it appears to inhibit the expression of a variety of genes implicated in atherogenesis. Fifth, it is a CCB. Amlodipine has demonstrated atheroprotection in both rabbit and subhuman primate models of this disease. We propose that cellular alterations induced by enrichment of the cell membrane with cholesterol, which appears to modulate SMC to the atherosclerotic phenotype, are inhibitable by amlodipine through a combination of its varied pharmacologic properties. The potential for atheroprotection with amlodipine is currently being investigated in a human trial (PREVENT trial) and the results of this trial will determine the relevance of the preclinical findings to humans. |
| Cholesterol, cholesterogenesis and cancer Siperstein, M. D. (1995), Adv Exp Med Biol 369: 155-66. |
| Cholesterol, cholesterol lowering, and endothelial function Vogel, R. A., M. C. Corretti, et al. (1998), Prog Cardiovasc Dis 41(2): 117-36. Abstract: A strong relationship between hypercholesterolemia and atherosclerosis has been established through epidemiological, experimental, and clinical trial data. Traditional theories on the pathophysiology of this relationship involve the deposition, modification, and cellular uptake of cholesterol, and the release of inflammatory and growth factors resulting in smooth muscle cell proliferation and collagen matrix production. The vasculature has recently been found to be an active and complex organ, with the endothelium playing a controlling role in vascular tone, lipid breakdown, thrombogenesis, inflammation, and vessel growth. In the presence of risk factors such as hypercholesterolemia, the endothelium promotes vasoconstriction, monocyte and platelet adhesion, thrombogenesis, and growth factor release. A high-fat diet also directly impairs endothelial function and increases coagulation factors. Endothelial dysfunction is associated with decreased availability of the predominant vasodilator nitric oxide, possibly by increased destruction by oxygen free radicals. This dysfunctional state appears before the earliest anatomic evidence of atherosclerosis and may represent an important initial step in its development. Several studies have shown improvements in endothelial function with cholesterol lowering in both normal individuals and those with coronary heart disease. Short-term improvements in endothelial-dependent vasodilation and adhesion molecule expression have also been reported with antioxidant therapy. These observations suggest that atherosclerosis is at least in part caused by endothelial dysfunction that favors cellular proliferation. This new understanding helps to explain the early and substantial reductions in major cardiovascular events associated with cholesterol lowering. |
| Cholesterol, copper, and accumulation of thioflavine S-reactive Alzheimer's-like amyloid beta in rabbit brain Larry Sparks, D. (2004), J Mol Neurosci 24(1): 97-104. Abstract: Accumulation of beta-amyloid (Abeta) in the Alzheimer's disease (AD) brain is considered to be causally related to the behavioral symptoms of the disorder. Transgenic mouse models of AD exhibit accumulation of Abeta in the brain and simultaneous memory deficits, and Abeta accumulation is enhanced if dietary cholesterol is administered. Likewise, dietary cholesterol induces neuronal accumulation of Abeta in New Zealand white rabbits. The cholesterol-induced accumulation of Abeta in rabbit brain is increased when distilled drinking water is supplemented with 0.12 ppm copper ion (as copper sulfate) compared to the cholesterol-induced accumulation of Abeta in rabbit brain of animals given unaltered distilled water. The numbers of affected neurons and the intensity of neuronal Abeta immunoreactivity is consistently increased among animals administered the copper ion in their drinking water. A copper-induced decrease in the clearance of overproduced Abeta from the brain is proposed as the mechanism causing Abeta accumulation and resulting in the observed memory deficits. Current studies reveal that intensely immunoreactive neurons, extracellular deposits of Abeta, and brain vessels in cholesterol-fed rabbits given copper-supplemented water were stained by thioflavine S. Thioflavine S-reactive features were not observed in cholesterol-fed rabbits given unaltered distilled drinking water. The data suggest that there is an accumulation of fibrillar Abeta induced in the brains of rabbits fed a cholesterol diet and administered trace levels of copper ion in their drinking water. |
| Cholesterol, coronary heart disease, and stroke in the Asia Pacific region Zhang, X., A. Patel, et al. (2003), Int J Epidemiol 32(4): 563-72. Abstract: BACKGROUND: Cholesterol levels in many Asian countries are rising. Predictions of the likely effects of this on the incidence of cardiovascular diseases have mostly relied on data from Western populations. Whether the associations between total cholesterol and cardiovascular diseases are similar in Asia is not established. METHODS: The Asia Pacific Cohort Studies Collaboration (APCSC) is an individual-participant data meta-analysis of prospective studies from the Asia-Pacific region. Cox models were applied to the combined data from 29 cohorts to estimate the region-, sex-, and age-specific hazard ratios of major cardiovascular diseases by the fifths of total cholesterol. RESULTS: At baseline, the age/sex-adjusted mean value of total cholesterol was higher in Australia and New Zealand (ANZ) (5.52 +/- 1.05 mmol/l) than in Asia (4.87 +/- 1.05 mmol/l). During 2 million person-years of follow-up among 352 033 individuals, 4841 cardiovascular deaths were recorded. The association of total cholesterol with coronary heart disease and stroke was similar in Asian and ANZ cohorts. Overall, each 1-mmol/l higher level of total cholesterol was associated with 35% (95% CI: 26-44%) increased risk of coronary death, 25% (95% CI: 13-40%) increased risk of fatal or non-fatal ischaemic stroke, and 20% (95% CI: 8-30%) decreased risk of fatal haemorrhagic stroke. CONCLUSIONS: In both Asian and non-Asian populations in the Asia-Pacific region, total cholesterol is similarly strongly associated with the risk of CHD and ischaemic, but not haemorrhagic, stroke. Rising population-wide levels of cholesterol would be expected to contribute to a substantial increase in the overall burden of cardiovascular diseases in this region. |
| Cholesterol, coronary heart disease, and total mortality in middle-aged and elderly men and women in Tecumseh Higgins, M. and J. B. Keller (1992), Ann Epidemiol 2(1-2): 69-76. Abstract: Relationships between serum cholesterol and coronary heart disease (CHD) were investigated in Tecumseh men and women who were 45 to 92 years old and initially free of CHD. Recruitment continued through three cycles of examinations over a period of 10 years, beginning in 1959. Follow-up for mortality ended in 1986 to 1987. Age-adjusted relative risks for CHD death for cholesterol levels of 5.2 to 6.2 mmol/L and greater than 6.2 mmol/L, compared with levels less than 5.2 mmol/L for men aged 45 to 64 years, were 1.2 and 1.7; for older men they were 1.0 and 1.8. Comparable relative risks for CHD death by cholesterol level were.7 and 1.4 for 45- to 64-year-old women and.8 and.7 for older women. Coefficients for cholesterol were significant for fatal CHD in men under and those 65 years and older when age, systolic blood pressure, body mass index, cigarette smoking status, and glucose intolerance were controlled in proportional hazards models. Cholesterol was a significant predictor of fatal CHD plus nonfatal myocardial infarction in middle-aged, but not elderly women. Relative risks for total mortality were lowest for middle-aged men and women with cholesterol levels of 5.2 to 6.2 mmol/L and the difference was significant in men. |
| Cholesterol, depression and suicide Su, K. P., S. Y. Tsai, et al. (2000), Br J Psychiatry 176: 399; author reply 399-400. |
| Cholesterol, depression and suicide Tanskanen, A., J. Tuomilehto, et al. (2000), Br J Psychiatry 176: 398-9; author reply 399-400. |
| Cholesterol, endothelial function and cardiovascular disease Wilkinson, I. B. and J. R. Cockcroft (1998), Curr Opin Lipidol 9(3): 237-42. Abstract: Hypercholesterolaemia is associated with endothelial dysfunction and increased risk of atheromatous disease. Although endothelial dysfunction has been demonstrated early in the course of the disease process, it remains difficult to establish a causal relationship. Despite this, endothelial function has been used as a surrogate marker in small trials to identify and assess the effectiveness of therapeutic interventions to reduce cardiovascular mortality, before large scale clinical trials are undertaken. Recently, arterial stiffness has emerged as an independent risk factor for cardiovascular disease and may provide a link between hypercholesterolaemia, endothelial dysfunction, hypertension and stroke. |
| Cholesterol, essential fatty acids, and suicide Brunner, J., K. G. Parhofer, et al. (2002), Pharmacopsychiatry 35(1): 1-5. Abstract: Epidemiological and clinical studies have described an association between lower serum cholesterol concentrations and increased suicide risk that is not entirely attributable to depression-related malnutrition and weight loss. Recent epidemiological studies with greater samples and longer follow-up periods, however, have even shown a positive correlation between cholesterol concentrations and suicide risk after controlling for potential confounding variables. A meta-analysis of earlier intervention trials suggested that cholesterol lowering could cause or worsen depressive symptoms and increase the risk of suicide. Large trials of statins (simvastatin, lovastatin, and pravastatin) did not show an increase of suicide mortality. The aim of this selective review is to critically discuss the current evidence for a potential link between cholesterol, essential fatty acids, depression, suicide, impulsivity, and aggression. Preclinical data support the hypothesis that cholesterol reduction may contribute to the serotonergic abnormalities that have been postulated in suicidal subjects. Recently, it was hypothesised that a decreased consumption of polyunsaturated fatty acids, especially omega-3 fatty acids, may be a risk factor for depression and suicide. Currently, we do not have sufficient evidence that cholesterol-lowering therapies increase the risk of depression and suicide. Increasing the dietary intake of omega-3 fatty acids may increase central serotonergic activity and reduce impulsive and aggressive behaviours. |
| Cholesterol, essential fatty acids, and suicide Terao, T. and A. Soya (2003), Pharmacopsychiatry 36(2): 86-7; author reply 87-8. |
| Cholesterol, fibre, and bile acids Spiller, R. C. (1996), Lancet 347(8999): 415-6. |
| Cholesterol, HDL-cholesterol, triglycerides and beta-lipoprotein in diabetic pregnancy Briese, V., H. Muller, et al. (1995), Zentralbl Gynakol 117(1): 17-22. Abstract: Follow up studies regarding lipid metabolism in diabetic pregnancy are important in maternal and fetal morbidity. OBJECTIVE: With this background it is particularly opportune to consider the difference of cholesterol, triglycerides and HDL-cholesterol of diabetics and nondiabetics in pregnancy. In addition the correlation of lipids to the glycosylated hemoglobin (HbA1), White groups and other clinical parameters is of interest. Attention is given to the comparison of insulin dependent diabetics (IDDM) and gestational diabetes (GDM) in the 3rd trimester. PATIENTS: A diabetic group of 84 patients (IDDM, GDM) was used for the prospective study over a two years period. The lipid metabolism was estimated preconceptionally, during pregnancy and on 7th day after delivery. 36 pregnant healthy women served as controls. The information obtained from each patient was entered into an SPSS data base. Statistical analysis were done by Mann-Whitney U and Kruskall-Wallis test and by means of Pearson's correlation coefficient to correlate with age, parity, body mass index, creatinin, albumiuria, HbA1, blood pressure. RESULTS: There were no any correlations between lipid parameters cholesterol, triglycerides, HDL-C, beta-lipoprotein and HbA1 as well as White groups (Pearson's coefficient). The triglyceride levels were significant lower in diabetic pregnants compared with healthy controls (p = 0.0095; Wilcoxon Test); diabetes: mean = 1,831 mmol/l; min 0.35; max 5.99 and control group mean = 2,133 mmol/l; min 0.36; max 4.70. Cholesterol levels were higher in the 3rd trimester of GDM patients than values of IDDM's (p = 0.0017; Wilcoxon Test). The longitudinal study during diabetic pregnancy resulted in significantly progressive increase in cholesterol and triglyceride levels (p = 0.0035 bzw. p = 0.0099; Kruskal-Wallis Test). CONCLUSIONS: Significant lower triglyceride levels had been found in diabetic pregnants than in healthy controls. There was no any correlation between lipid parameters cholesterol, triglycerides, HDL-cholesterol, beta-lipoprotein on the one side and HbA1 and White groups on the other side. Increased cholesterol levels were noted in the 3rd trimester of pregnancy in the gestational diabetes in comparison of insulin dependent pregnant diabetics. |
| Cholesterol, heart disease and the brain: an opportunity in research and a disaster in public health education? Young, S. N. (1993), J Psychiatry Neurosci 18(1): 1-3. |
| Cholesterol, hedgehog and embryogenesis Herz, J., T. E. Willnow, et al. (1997), Nat Genet 15(2): 123-4. |
| Cholesterol, hydroxycholesterols, and bile acids Javitt, N. B. (2002), Biochem Biophys Res Commun 292(5): 1147-53. Abstract: Although a variety of oxidation products of cholesterol occur in vitro, enzyme-catalyzed oxidations can occur at only 5 sites on the cholesterol molecule: C7alpha, C22R, C24S, C25, and C27. The genes coding for the synthesis of these enzymes were cloned, the tissue expressions of the mRNAs were identified, and the enzymes were characterized. The biologic properties of the hydroxycholesterol molecules that are initially generated and their metabolites are under study. Downregulation of cholesterol synthesis via the SREBP/SCAP regulatory pathway is common to the initial hydroxycholesterols, but more variations exist with respect to these intermediates functioning as ligands for the nuclear receptor LXRalpha. Because this receptor regulates the expression of cholesterol 7alpha-hydroxylase and ABC transporter proteins, hydroxycholesterols and their intermediate steroid metabolites modulate a number of biologic processes. Metabolism of 22S-hydroxycholesterol to steroid hormones differs from that of the other hydroxycholesterols which form mostly steroid acidic products, otherwise known as bile acids. In vivo estimates of their production rates in intact humans indicate that 24S and 25-hydroxycholesterol account for no more than 7% of total bile acid production per day. Current evidence indicates that cholesterol 7alpha-hydroxycholesterol generated in the liver is the major source of bile acids in older adults. It is also known that the cholesterol 27-hydroxylation pathway is the only one expressed in fetal and neonatal life. Precisely when the proportions contributed by these two metabolic pathways to bile acid synthesis begin to shift and the role of the cholesterol 27-hydroxylase pathway in reverse cholesterol transport mandate further study. |
| Cholesterol, linoleic acid or/and tyrosine yield different spectra of products when oxidized alone or in a mixture: studies in various oxidative systems Szuchman, A., M. Aviram, et al. (2003), Free Radic Res 37(12): 1277-88. Abstract: Identification of reliable biomarkers for oxidative stress for the prediction of the early development of pathological conditions is essential. The detection of biomarkers for oxidative stress such as degradation products of polyunsaturated fatty acid (PUFA), oxysterols, and oxidized proteins, as indicators of oxidative stress are in use, but suffers from insufficient specificity, accuracy and reliability. The overall aim of the present study was to develop new markers which will not only provide information about the presence and level of oxidative stress in biological systems but also on the type of reactive oxygen species (ROS) involved and their metabolic consequences. In the first stage of the study, we compared the level and type of oxidized products formed when different ROS were applied onto three major biomolecules, i.e. cholesterol, linoleic acid (LH) and tyrosine, representing sterols, PUFA and protein, when each compounds was exposed alone or in a mixture to the ROS copper ions, 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH) and hypochlorous acid (HOCl). It was found that different types of oxidants resulted in the formation of different types of oxidation products. Furthermore, oxidation pattern differs when the substrates (cholesterol, PUFA or amino acid) were present alone or in a mixture. As biological systems such as lipoproteins and cell membranes are composed of the above studied molecules, the need for simultaneous detection of the major oxidized products is requires for better characterization of the oxidative stress outcome. |