| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Should intensive cholesterol lowering play a role in the management of acute coronary syndromes? Waters, D. D. and R. R. Azar (2000), Am J Cardiol 86(8B): 35J-42J; discussion 42J-43J. Abstract: Although several large, well-controlled trials with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) demonstrate the benefits of cholesterol lowering on cardiovascular morbidity and mortality, these trials excluded patients with recent unstable angina or myocardial infarction. Thus, the potentially beneficial effects that may accrue from early statin therapy have not been apparent. Mechanistic and experimental studies show that benefits from statin therapy may include improved endothelial function, a decrease in platelet thrombus deposition, and a reduction in inflammation at the site of the lesion. Large-scale clinical trials are now under way to determine the effect of aggressive cholesterol lowering in patients with acute coronary syndromes. If the findings of the smaller studies are confirmed, statin therapy should be considered early after infarction or unstable angina. |
| Should serum cholesterol be checked in children? Hussein, O. and Y. M. Traub (1993), Harefuah 125(7-8): 225-7. |
| Should the guidelines for monitoring serum cholesterol levels in the elderly be re-evaluated? Sparks, D. L., D. J. Connor, et al. (2002), J Mol Neurosci 19(1-2): 209-12. Abstract: Elevated circulating cholesterol can have profound effects on the health of an individual. Such excess cholesterol can promote coronary artery disease, production and accumulation of beta-amyloid in the brain, and possibly Alzheimer's disease (AD). In a clinical trial evaluating the benefit of a cholesterol-lowering drug in the treatment of AD, mean cholesterol levels at baseline among individuals participating in the trial were found to be relatively high. Based on this observation we suggest that cholesterol levels should be actively monitored in the elderly, as many individuals with AD are over 65 years of age and therefore excluded by currently accepted guidelines. |
| Should we be measuring blood cholesterol levels in young adults? Hulley, S. B., T. B. Newman, et al. (1993), Jama 269(11): 1416-9. Abstract: Should we measure blood cholesterol levels in all adults, or only in those at high risk of coronary heart disease (CHD)? Most men under the age of 35 years and women under the age of 45 years--roughly half the adult population--are at very low short-term risk of CHD. One consequence is that drug treatment to lower high blood cholesterol levels in the average young adult is an extremely expensive means of prolonging life; the estimated $1 million to $10 million per year of life is 100 to 1000 times the cost of other approaches. Individualized dietary treatment is somewhat cheaper but relatively ineffective. Another consequence of the low CHD risk in young adults is the greater likelihood that intervention may have harmful effects that outweight the benefits. Meta-analysis of primary prevention trials in middle-aged men reveal an increase in non-CHD deaths among those randomized to cholesterol interventions, an unexpected finding that is more substantial than the decrease in CHD deaths. This raises the possibility that one or more of the cholesterol interventions could have very serious adverse effects among young adults, whose risk of non-CHD death is normally 100 times their risk of CHD death. We conclude that the policy of screening and treating high blood cholesterol levels in young adults is neither cost-effective, nor does it satisfy ethical standards requiring strong evidence that preventive interventions do more good than harm. Fortunately, cholesterol screening in young adults is also not necessary: most CHD events associated with high blood cholesterol levels in this population will not occur for decades and can be prevented by treatment that is begun in middle age. Cholesterol screening and treatment in young adults should be limited to individuals with known coronary disease or other unusual factors that place them at high short-term risk of CHD death. |
| Should we reduce blood cholesterol to prevent cardiovascular disease among patients with chronic renal failure? Baigent, C. and D. C. Wheeler (2000), Nephrol Dial Transplant 15(8): 1118-9. |
| Sialic acid content of low density lipoprotein and its relation to lipid concentrations and metabolism of low density lipoprotein and cholesterol Lindbohm, N., H. Gylling, et al. (2000), J Lipid Res 41(7): 1110-7. Abstract: A low sialic acid content in low density lipoprotein (LDL) has been associated with atherogenicity and coronary artery disease (CAD) in many but not all studies. We investigated associations of the sialic acid-to-apolipoprotein B (apoB) ratio of LDL with lipoprotein lipid concentrations, kinetics of LDL, metabolism of cholesterol, and the presence of CAD in 98 subjects (CAD(+), n = 56; CAD(-), n = 42). The sialic acid ratios of total, dense, and very dense LDL were lower in the CAD(+) than CAD(-) subjects, especially at high sialic acid ratios. The LDL sialic acid ratio was inversely associated with respective lipid and apoB concentrations and positively with lipid-to-apoB ratios of LDL. The transport rates (TRs) for total and dense LDL apoB were negatively associated with their sialic acid ratios. The sialic acid ratio of dense LDL, but not that of total LDL, was inversely correlated with serum levels of cholesterol precursor sterols, indicators of cholesterol synthesis, and positively with serum levels of plant sterols, indicators of cholesterol absorption. In addition, the TR for dense LDL was positively correlated with cholesterol synthesis.In conclusion, a low LDL sialic acid ratio was associated with CAD, high numbers of small LDL particles, and a high TR for LDL apoB, and in dense LDL also with high synthesis and low absorption of cholesterol. |
| Sialyl cholesterol enhances the development of grafted neurons and motor recovery Hashitani, T., F. Furuyama, et al. (1992), Brain Res Bull 29(6): 795-806. Abstract: Trophic actions of alpha-sialyl cholesterol (SC) and its sialidase-tolerant derivative, alpha-(3 beta-hydroxysialyl) cholesterol (SCt), were carried out on the development of midbrain neurons both in vitro and in vivo transplantation studies. Low to moderate concentrations of SC (0.01 to 0.05 micrograms/ml) facilitated neurite extension but had no effects on cell survival of primary cultured midbrain neurons. However, high concentration of SC (0.1 micrograms/ml) disturbed both neurite genesis and cell survival. SCt had a similar effect on midbrain neurons. At higher concentrations, SC and SCt induced concentration-dependent morphological changes in astrocytes from flat to fibrous. The effect on astrocytes was stronger in SCt than SC. At highest concentration tested (20 micrograms/ml), the proliferation of astrocytes was completely blocked, cells became detached and finally died. This effect of SC and SCt was partially blocked by simultaneous application of aFGF. Following dopaminergic cell grafting in vivo, SC and SCt had biphasic effects: a low dose (0.2 mg/kg, SC) enhanced motor recovery at 4 and 6 weeks after transplantation, while the highest dose (20 mg/kg, SC) disturbed motor recovery at all periods tested. These effects on motor recovery were paralleled by an effect on neurite genesis as studied by tyrosine hydroxylase immunostaining. Thus, at low concentrations, SC and SCt are neurotrophic agents that stimulate the development and differentiation of dopaminergic neurons. |
| Sialyl cholesterol is translocated into cell nuclei and it promotes neurite outgrowth in a mouse neuroblastoma cell line Yamashita, T., S. Tsuji, et al. (1991), Glycobiology 1(2): 149-54. Abstract: To determine the mechanisms of the neuritogenesis induced by synthetic sialyl cholesterol (SC) in a mouse neuroblastoma cell line, Neuro2a, the biochemical fate of SC and ganglioside GM1 (IV3NeuAc-GgOse4Cer) was investigated. The kinetics of incorporation of SC and GM1 into cells for the two compounds were similar. SC was not degraded nor modified for at least 24 h after the incorporation, indicating that SC itself and not its metabolites were responsible for the neuritogenic activity. Cell fractionation experiments showed that approximately 40% of the incorporated SC was localized in the nucleus, 25% in the plasma membrane fractions, and 11-14% in the granule fraction. This distribution was different from that of GM1. The nuclear SC was found to affect de novo RNA synthesis, indicating its biological effect may be mediated at the level of transcription. SC also increased the rates of both Ca2+ influx and efflux, although the intracellular level of total Ca2+ remained unchanged. Levels of inositol 1,4,5-triphosphate (IP3) also remained unchanged and the SC dependent neuritogenesis was not inhibited by an excess amount of W-7, an inhibitor of Ca2+/CaM kinases. These results again accord with the suggestion that SC and GM1 do not utilize Ca2+, IP3 or Ca2+/CaM as a second messenger for neuritogenesis. Rather it appears very likely that the nuclear localized SC may play a key role in neuritogenesis. |
| Sibling aggregation of low- and high-density lipoprotein cholesterol and apolipoproteins B and A-I levels in black and white children: the Bogalusa Heart Study Chen, W., S. R. Srinivasan, et al. (1997), Ethn Dis 7(3): 241-9. Abstract: OBJECTIVE: To examine sibling aggregation of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) B and apo A-I in white versus black school-aged children. DESIGN: Study subjects included 790 full sibships representing 1305 sibpairs aged 5 to 17 years from a biracial community. METHODS: Intraclass correlation coefficients estimated by analyses of covariance were used to examine sibling aggregation of LDL-C, HDL-C, apo B and apo A-I. The influences of obesity and other lifestyle variables on sibpair differences in LDL-C, HDL-C, apo B and apo A-I were evaluated in black and white children by stepwise multiple regression analyses. RESULTS: Intraclass correlation coefficients for LDL-C and apo B in black children were lower than those in white children (0.17 and 0.11 versus 0.32 and 0.33, respectively, P < 0.05-0.01); no racial difference was found for HDL-C and apo A-I. Intraclass correlation coefficients for LDL-C and HDL-C were similar to that of apo B and apo A-I, respectively and the sibpair differences in LDL-C and HDL-C were correlated with those of apo B and apo A-I, respectively (P < 0.01). Obesity exerted a greater effect on sibpair differences in LDL-C, HDL-C and apo B in black children than in white children. CONCLUSIONS: These results suggest that the hereditary influence on LDL-C and apo B is more important in white children than in black children, especially for apo B. Further, genetic influence on LDL-C versus apo B, or HDL-C versus apo A-I may be similar. |
| Side-chain cleavage of cholesterol esters by human cytochrome P-450(scc) Tuckey, R. C., J. Lawrence, et al. (1996), J Steroid Biochem Mol Biol 58(5-6): 605-10. Abstract: In order to define the substrate binding site of human cytochrome P-450(scc) in the vicinity of the 3beta-hydroxyl group of cholesterol, we have tested the ability of the cytochrome to cleave the side chain of a range of cholesterol esters and cholesterol methyl ether. Using a Tween-20 detergent reconstituted system we found that cholesterol sulphate could undergo side-chain cleavage with the same turnover number (kcat) as that for cholesterol, but with a higher Km. Cholesterol methyl ether underwent side-chain cleavage to pregnenolone methyl ether with kcat and Km values 30% of those for cholesterol. Cholesterol fatty acid esters with acyl chain lengths of up to four carbons were able to undergo side-chain cleavage with Km values similar to those for cholesterol, but kcat values only 12-23% of those for cholesterol. Turnover numbers decreased as the acyl group length increased beyond four carbons, although some activity was still detected with cholesterol palmitate as substrate. Analysis of bovine cytochrome P-450(scc) revealed that it could also cleave the side chain of acyl and sulphate esters of cholesterol. This study indicates that the substrate binding site of cytochrome P-450(scc) in the vicinity of the 3beta-hydroxyl group is larger than previously believed. |
| Side-chain cleavage of cholesterol sulfate by ovarian mitochondria Tuckey, R. C. (1990), J Steroid Biochem Mol Biol 37(1): 121-7. Abstract: Mitochondria isolated from porcine corpora lutea and from the luteinized ovaries of gonadotropin-treated immature rats were found to efficiently cleave the side-chain of cholesterol sulfate to produce 3 beta-hydroxy-5-pregnen-20-one sulfate (pregnenolone sulfate). When mitochondria were preincubated with cholesterol sulfate, the time-course for the side-chain cleavage of cholesterol sulfate was biphasic. With 200 microM cholesterol sulphate, the initial rate of the reaction was the same as that observed for 25-hydroxycholesterol. This rate was not increased when both cholesterol sulfate and 25-hydroxycholesterol were incubated together. The rate of side-chain cleavage by isolated mitochondria supplied with 75 microM cholesterol sulfate as substrate was inhibited by 97% by aminoglutethimide, a specific inhibitor of cytochrome P-450scc. The slow phase of side-chain cleavage of cholesterol sulfate appeared to be limited by the rate of substrate movement to the mitochondrial site of the reaction. Cholesterol sulfate translocation rates were however up to 8 times greater than those observed for cholesterol when equivalent concentrations of the two substrates were added to the mitochondria. We conclude that cholesterol sulfate is a better substrate than cholesterol for side-chain cleavage by isolated mitochondria and that both reactions are catalysed by the same cytochrome P-450scc enzyme. |
| Signal transduction in atherosclerosis: second messengers and regulation of cellular cholesterol trafficking Pomerantz, K. B., A. C. Nicholson, et al. (1995), Adv Exp Med Biol 369: 49-64. Abstract: The data summarized in this review demonstrate that the regulation of intracellular cholesterol trafficking is mediated not only by extracellular lipoprotein concentrations and transcriptional responses to alterations in intracellular free cholesterol content. Rather, the modulation of cholesterol trafficking is also regulated by the products synthesized following activation of signal transduction pathways originating at the cell surface. Furthermore, we have identified those cell-derived factors which utilize these signal transduction pathways to elicit alterations in cholesterol trafficking, and demonstrated the importance of the generation of second messengers, most notably eicosanoids, and cyclic AMP in promoting a modulatory influence on specific pro-atherogenic effects of mitogens. |
| Signal transduction via glycosyl phosphatidylinositol-anchored proteins in T cells is inhibited by lowering cellular cholesterol Stulnig, T. M., M. Berger, et al. (1997), J Biol Chem 272(31): 19242-7. Abstract: Glycosylphosphatidylinositol (GPI)-anchored proteins can deliver costimulatory signals to lymphocytes, but the exact pathway of signal transduction involved is not yet characterized. GPI-anchored proteins are fixed to the cell surface solely by a phospholipid moiety and are clustered in distinct membrane domains that are formed by an unique lipid composition requiring cholesterol. To elucidate the role of membrane lipids for signal transduction via GPI-anchored proteins, we studied the influence of reduced cellular cholesterol content on calcium signaling via GPI-anchored CD59 and CD48 in Jurkat T cells. Lowering cholesterol by different inhibitors of cellular cholesterol synthesis suppressed calcium response via GPI-anchored proteins by about 50%, whereas stimulation via CD3 was only minimally affected (<10%). The decrease in overall calcium response via GPI-anchored proteins was reflected by inhibition of calcium release from intracellular stores. Cell surface expression of GPI-anchored proteins was not changed quantitatively by lowering cellular cholesterol, and neither was the pattern of immunofluorescence in microscopic examination. In addition, the distribution of GPI-anchored proteins in detergent-insoluble complexes remained unaltered. These results suggest that cellular cholesterol is an important prerequisite for signal transduction via GPI-anchored proteins beyond formation of membrane domains. |
| Signaling molecules derived from the cholesterol biosynthetic pathway Jackson, S. M., J. Ericsson, et al. (1997), Subcell Biochem 28: 1-21. |
| Signaling molecules derived from the cholesterol biosynthetic pathway: mechanisms of action and possible roles in human disease Edwards, P. A. and J. Ericsson (1998), Curr Opin Lipidol 9(5): 433-40. Abstract: The association of high plasma cholesterol levels with the development of atherosclerosis is well known. The metabolic pathways that are regulated by cholesterol and the mechanisms involved are less well understood. Recent studies have identified not only cholesterol, but also oxysterols and isoprenoids, derived from the cholesterol biosynthetic pathway, as new signaling molecules. The transcriptional and post-transcriptional regulation of specific genes and metabolic pathways by these newly discovered signaling molecules may be important in the development of human disease and forms the topic of this review. |
| Significance of a polymorphism (G-->A transition) in the -75 position of the apolipoprotein A-I gene promoter on serum high density lipoprotein-cholesterol levels in Japanese hyperlipidemic subjects Tashiro, J., N. Morisaki, et al. (2001), J Atheroscler Thromb 8(3): 95-100. Abstract: High density lipoprotein-cholesterol (HDL-C) levels are inversely related to the incidence of coronary artery disease. We studied the influence of a G(-75)-->A transition in the promoter of the apolipoprotein (apo) A-I gene, a major protein component of HDL, on serum HDL-C levels in hyperlipidemic subjects. Seventy three hyperlipidemic subjects with serum levels of high HDL-C (HDL-C > or = 70 mg/dl, Group H) were compared with hyperlipidemic subjects with levels of HDL-C between 40 and 70 mg/dl (Group N) and those with HDL-C < 40 mg/dl (Group L). Group H showed a higher incidence (45.2%) of low plasma cholesteryl ester transfer protein (CETP) activity than Groups N (9.1%) and L (5.3%) (p < 0.001). Group H had a higher incidence of the G(-75)-->A transition (0.275) than Groups N (0.117, p < 0.05) and L (0.056, p < 0.01), among subjects with normal CETP activities. The HDL-C levels in subjects with the transition (84 +/- 16 mg/dl) were higher than those in subjects without the transition (56 +/- 12 mg/dl) (p < 0.05). These data suggest that a G(-75)-->A transition of the apo A-I gene promoter, in addition to the common mutation of CETP gene, contributes to high HDL-C levels among hyperlipidemic patients in Japan. |
| Significance of cholesterol for cardiovascular disease mortality Klemsdal, T. O. (2005), Tidsskr Nor Laegeforen 125(4): 464. |
| Significance of cholesterol in health and disease Ranade, V. V. (1993), Int J Clin Pharmacol Ther Toxicol 31(6): 276-84. Abstract: A large number of studies indicate that the process of atherosclerosis begins in childhood; and that this process is related to elevated levels of serum cholesterol which are often predictive of elevated serum cholesterol levels in adulthood. Despite substantial success in reducing coronary heart disease (CHD) mortality in the past two decades, CHD disease remains the leading cause of death worldwide. Preventing or slowing the atherosclerotic process in childhood and adolescence could mean years of healthy life for many people. The US Department of Health and Human Services has recently published a report on these findings National Cholesterol Education Program: Report of the expert panel on blood cholesterol levels in children and adolescents 1991. In this and following series of articles, a summary from these data is discussed. The articles have been arranged in the following sub groups: 1) Cholesterol levels in children and adolescents. 2) Nutrition recommendations for healthy children and adolescents for cholesterol control. 3) Cholesterol detection, diagnosis and evaluation in individuals, and 4) treatment for normalizing levels of cholesterol. |
| Significance of HDL cholesterol/apolipoprotein A-I ratio Okamoto, Y., H. Tsujii, et al. (1990), Rinsho Byori 38(10): 1193-7. Abstract: HDL cholesterol (HDL-Ch)/apolipoprotein A-I (A-I) ratio was studied in fourteen healthy students, fifteen male habitual drinkers, five male patients with chronic hepatitis (CH) and seven controls. HDL-Ch/A-I ratio in male students, female students, male drinkers, CH and control were 0.36 +/- 0.029, 0.39 +/- 0.03, 0.41 +/- 0.065, 0.40 +/- 0.02, and 0.36 +/- 0.039, respectively. Elevation of HDL-Ch/A-I ratio in female students, male drinkers and CH were statistically significant compared with control, while there was no significant change in HDL-Ch or A-I in female students but the elevations of both in male drinkers or the reduction of A-I in CH. Positive correlations were found between HDL-Ch/A-I ratio and HDL2-Ch, and HDL2-Ch/HDL3-Ch ratio in students and CH. The elevation of HDL-Ch/A-I ratio in CH appeared to be related to the reduction of HDL3-Ch. It is suggested that HDL-Ch/A-I ratio could indicate HDL2-Ch/HDL3-Ch ratio and is useful parameter for analysis of HDL metabolism. |
| Significance of high density lipoprotein-cholesterol in cardiovascular risk prevention: recommendations of the HDL Forum Ascaso, J. F., A. Fernandez-Cruz, et al. (2004), Am J Cardiovasc Drugs 4(5): 299-314. Abstract: In the approach to lipid-related risk factors for cardiovascular diseases, serum high density lipoprotein-cholesterol (HDL-C) levels bear a particular significance as this lipoprotein is considered to be an antiatherogenic factor mainly, but not only, because of its influence and impact on reverse cholesterol transport. Hence the need and requirement to consider serum HDL-C levels for both primary and secondary prevention of cardiovascular disease. A particularly important aspect is the association of the 'low HDL syndrome' with the metabolic syndrome. These factors force us to consider serum HDL-C level as a therapeutic target by itself, or even in association with low density lipoprotein-cholesterol (LDL-C) levels when the latter are increased. This review stresses the aspects connecting serum HDL-C levels and cardiovascular risk, and looks at the populations that should be considered amenable to therapeutic management because of low serum HDL-C levels. We review therapeutic strategies, both pharmacological and nonpharmacological. The aim of this review is to present therapeutic management recommendations for correcting the proportion of cardiovascular risk that is attributable to changes in HDL-C. Serum HDL-C levels of >40 mg/dL must be a therapeutic target in primary and secondary prevention. This goal is particularly important in patients with low serum HDL-C levels and ischemic heart disease (IHD) or its equivalents, even if the therapeutic target for serum LDL-C levels (<100 mg/dL) has been achieved. The first choice for this clinical condition is fibric acid derivates. The same therapeutic option should be considered in patients without IHD with low serum HDL-C levels and high cardiovascular risk (>20%), hypertriglyceridemia, type 2 diabetes mellitus, or metabolic syndrome. |