| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Advance of HDL-cholesterol measurement Sakurabayashi, I. (2001), Nippon Rinsho 59 Suppl 2: 788-91. |
| Advanced glycation end product precursors impair ABCA1-dependent cholesterol removal from cells Passarelli, M., C. Tang, et al. (2005), Diabetes 54(7): 2198-205. Abstract: Abnormal HDL metabolism may contribute to the increased atherosclerosis associated with diabetes. The ATP-binding cassette transporter A1 (ABCA1) is an atheroprotective cell protein that mediates cholesterol transport from cells to apolipoprotein (apo) A-I, the major protein in HDL. Because formation of advanced glycation end products (AGEs) is associated with diabetic vascular complications, we examined the effects of carbonyls implicated in AGE formation on the ABCA1 pathway in cultured fibroblasts and macrophages. Treating cells with glycolaldehyde (GA) and glyoxal (GO) strongly inhibited ABCA1-dependent transport of cholesterol from cells to apoA-I, while methylglyoxal had little effect. This occurred under conditions where other lipoprotein receptors or lipid metabolic pathways were little affected, indicating that ABCA1 was uniquely sensitive to these carbonyls. GA and GO destabilized ABCA1 and nearly abolished its binding of apoA-I, indicating that these carbonyls directly modified ABCA1. Immunohistology of coronary arteries from hyperlipidemic swine revealed that inducing diabetes with streptozotocin increased atherosclerotic lesion area and dramatically reduced the fraction of macrophages that expressed detectable ABCA1. These results raise the possibility that reactive carbonyl-mediated damage to ABCA1 promotes accumulation of cholesterol in arterial macrophages and thus contribute to the increased cardiovascular disease associated with diabetes, insulin resistance, and other inflammatory conditions. |
| Advanced glycation end products (AGE) inhibit scavenger receptor class B type I-mediated reverse cholesterol transport: a new crossroad of AGE to cholesterol metabolism Ohgami, N., A. Miyazaki, et al. (2003), J Atheroscler Thromb 10(1): 1-6. Abstract: Advanced glycation end products (AGE) -modified proteins behave as active ligands for several receptors belonging to the scavenger receptor family. Scavenger receptor class B type I (SR-BI) was identified as the first high density lipoprotein (HDL) receptor that mediates selective uptake of HDL-cholesteryl esters (HDL-CE). This study investigated whether AGE proteins serve as ligands for SR-BI and affect SR-BI-mediated cholesterol transport using Chinese hamster ovary (CHO) cells overexpressing hamster SR-BI (CHO-SR-BI cells). 125I AGE-bovine serum albumin (AGE-BSA) underwent active endocytosis and subsequent lysosomal degradation by CHO-SR-BI cells, indicating that SR-BI serves as an AGE receptor. SR-BI-mediated selective uptake of HDL-CE by CHO-SR-BI cells was efficiently inhibited by AGE-BSA although AGE-BSA had no effect on HDL binding to CHO-SR-BI cells. In addition, AGE-BSA significantly inhibited the efflux of 3H cholesterol from CHO-SR-BI cells to HDL. These findings suggest the possibility that AGE proteins in the circulation interfere with the functions of SR-BI in reverse cholesterol transport by inhibiting the selective uptake of HDL-CE, as well as cholesterol efflux from peripheral cells to HDL, thereby accelerating diabetes-induced atherosclerosis. |
| Advances in treatment of cholesterol abnormalities. The role of HMG-CoA reductase inhibitors Rackley, C. E. (1996), Postgrad Med 100(5): 61-5, 70-2. Abstract: The introduction of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has provided an important new class of agents that reduce levels of total and low-density lipoprotein cholesterol more powerfully than any previously used drugs. Multiple clinical trials have shown a significant decrease in lipid values and cardiovascular events and a slowing of the progression of atherosclerosis in men and women of all ages. The Scandinavian Simvastatin Survival Study demonstrated a significant reduction in all-cause mortality as a result of reduced cardiovascular mortality. The HMG-CoA reductase inhibitors should be considered as first-line therapy for hypercholesterolemia in all patients with established atherosclerosis involving the coronary, carotid, or peripheral vessels. |
| Advances in understanding of the role of lecithin cholesterol acyltransferase (LCAT) in cholesterol transport Dobiasova, M. and J. J. Frohlich (1999), Clin Chim Acta 286(1-2): 257-71. Abstract: We review the structure and function of lecithin cholesterol acyl transferase (LCAT), the advances in the studies of molecular genetics of LCAT and its deficiency states as well as the developments in assessment of LCAT activity particularly the concept of measurement of fractional esterification rate of plasma cholesterol in the absence of apoB lipoproteins (FER(HDL)) as an indication of atherogenic risk. We discuss LCAT reaction from two points of view: one that is consistent with the general belief in LCAT antiatherogenic potential and another, namely, a proposed concept of potentially opposing roles of LCAT in normal and dyslipidemic plasmas. While other plasma lipoproteins can (in addition to HDL) provide unesterified cholesterol (UC) for LCAT reaction, HDL may play an unique role in trafficking of newly formed cholesteryl esters (CE) rather than as a primary acceptor of cellular cholesterol. Thus, the plasma HDL, specifically the larger (HDL2b) particles, direct the efflux of most of (LCAT produced) CE to its specific catabolic sites rather than to potentially atherogenic VLDLs and back to LDLs. |
| Advantage of the ether linkage between the positive charge and the cholesteryl skeleton in cholesterol-based amphiphiles as vectors for gene delivery Ghosh, Y. K., S. S. Visweswariah, et al. (2002), Bioconjug Chem 13(2): 378-84. Abstract: Twelve novel cationic cholesterol derivatives with different linkage types between the cationic headgroup and the cholesteryl backbone have been developed. These have been tested for their efficacies as gene transfer agents as mixtures with dioleoyl phosphatidylethanolamine (DOPE). A pronounced improvement in transfection efficiency was observed when the cationic center was linked to the steroid backbone using an ether type bond. Among these, cholest-5-en-3b-oxyethane-N,N,N-trimethylammonium bromide (2a) and cholest-5-en-3b-oxyethane-N,N-dimethyl-N-2-hydroxyethylammonium bromide (3d) showed transfection efficiencies considerably greater than commercially available reagents such as Lipofectin or Lipofectamine. To achieve transfection, 3d did not require DOPE. Increasing hydration at the headgroup level for both ester- and ether-linked amphiphiles resulted in progressive loss of transfection efficiency. Transfection efficiency was also greatly reduced when a 'disorder'-inducing chain like an oleyl (cis-9-octadecenyl) segment was added to these cholesteryl amphiphiles. Importantly, the transfection ability of 2a with DOPE in the presence of serum was significantly greater than for a commercially available reagent, Lipofectamine. This suggests that these novel cholesterol-based amphiphiles might prove promising in applications involving liposome-mediated gene transfection. This investigation demonstrates the importance of structural features at the molecular level for the design of cholesterol-based gene delivery reagents that would aid the development of newer, more efficient formulations based on this class of molecules. |
| Advantages of initial population screen with determinations of total cholesterol in serum and of lipoproteins by electrophoresis Papadopoulos, N. M. (1990), Clin Chem 36(11): 2009-10. |
| Adverse effect of pregnancy on high density lipoprotein (HDL) cholesterol in young adult women. The CARDIA Study. Coronary Artery Risk Development in Young Adults Lewis, C. E., E. Funkhouser, et al. (1996), Am J Epidemiol 144(3): 247-54. Abstract: The authors analyzed data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study in order to examine associations between parity and lipoproteins. Of 2,787 women recruited in 1985-1986, 2,534 (91%) returned in 1987-1988 and 2,393 (86%) returned in 1990-1991 for repeat evaluations. Two-year change (1987-1988 to 1985-1986) in high density lipoprotein (HDL) cholesterol was significantly different among the parity groups. HDL cholesterol decreased in women who had their first pregnancy of at least 28 weeks duration during follow-up (mean +/- standard error, -3.5 +/- 1.2 mg/dl), and this change was significantly different from the increase in women parous at baseline who had no further pregnancies (2.5 +/- 0.3 mg/dl) and in nullipara (2.4 +/- 0.3 mg/dl). There was a nonsignificant trend for a greater decrease in HDL2 cholesterol fraction in the primipara compared with the other groups. The HDL cholesterol decrease remained significant after controlling for race, age, education, oral contraceptive use, and changes in body mass index, waist-hip ratio, physical activity, smoking status, and alcohol intake. Change in HDL cholesterol was also significantly different among the parity groups in analyses of pregnancies that occurred during the subsequent 3 years of follow-up. There were no differences for change in LDL cholesterol or triglycerides. Potential mechanisms for a detrimental effect of pregnancy on HDL cholesterol include hormonal, body composition, or life-style/behavioral changes. |
| Aerobic-hemodynamic support of physical exertion in virtually healthy persons with different levels of cholesterol in the blood and in patients with stenocardia of effort Vasil'ev, A. P., N. N. Strel'tsova, et al. (1999), Patol Fiziol Eksp Ter(4): 27-9. Abstract: Oxygen transport and central hemodynamics were studied in 66 healthy males with different blood cholesterol levels and 24 patients with angina of effort under standard exercise test. Increased blood cholesterol was found to influence exercise energy maintenance in healthy people. Subnormal efficacy of oxygen transport system provokes intensification of cardiac activity. Oxygen-hemodynamic maintenance of exercise in healthy subjects with hypercholesterolemia is similar to that in patients with ischemic heart disease. This indicates the same pathophysiological processes in the above individuals. |
| Affairs of the heart: cholesterol and coronary heart disease risk Shepherd, J., D. Gaffney, et al. (1991), Dis Markers 9(2): 63-71. |
| Affinity of Helicobacter pylori to cholesterol and other steroids Trampenau, C. and K. D. Muller (2003), Microbes Infect 5(1): 13-7. Abstract: Helicobacter pylori has a particular affinity to cholesterol. It is not known, however, whether other steroidal substances are bound as well. In order to characterize the specificity and nature of the H. pylori-steroid interaction, the affinity of H. pylori to cholesterol and several steroidal hormones was investigated. Seven strains of H. pylori (five reference strains, two wild strains) and one strain each of Staphylococcus epidermidis and Escherichia coli were cultured on a cholesterol-free medium. Cholesterol-free bacteria were incubated with cyclodextrin-mediated cholesterol and several cyclodextrin-mediated steroidal hormones (beta-estradiol, testosterone, progesterone, hydrocortisone, dexamethasone). The steroid contents of the bacteria were determined by gas liquid chromatography. High amounts of cholesterol were detected in all H. pylori strains, whilst steroidal hormones were not found. Neither S. epidermidis nor E. coli showed an appreciable amount of cholesterol in the chromatographic examinations. Bacterial pretreatment with proteinase K diminished cholesterol adsorption of H. pylori. These data indicate a specific affinity of H. pylori to cholesterol. This unique property might serve as a pathogenicity component enabling survival and colonization of H. pylori in the gastric environment. |
| Affinity of lipid transfer protein for lipid and lipoprotein particles as influenced by lecithin-cholesterol acyltransferase Nishida, H. I., H. Kato, et al. (1990), J Biol Chem 265(9): 4876-83. Abstract: The effects of lecithin-cholesterol acyltransferase (LCAT) on the transfer of cholesterol esters mediated by lipid transfer protein (LTP) and its affinity for lipid and lipoprotein particles were investigated. When the single bilayer vesicle preparations (containing phosphatidylcholine, cholesterol, cholesteryl ester, and apolipoprotein- (apo) A-I at the molar ratio of 90:30:1.2:0.18) or high density lipoprotein 3 (HDL3) were used as the cholesteryl ester donor and low density lipoproteins (LDL) as the acceptor, the transfer activity of LTP was enhanced by the addition of low concentrations of LCAT. In contrast, no enhancement of cholesteryl ester transfer was observed upon addition of LCAT to either the discoidal bilayer particle preparations (containing phosphatidylcholine, cholesterol, cholesteryl ester, and apo-A-I at the molar ratio of 90:30:1.2:1.0) or high density lipoprotein 2 (HDL2). Although both apo-A-I and apo-A-II promoted the transfer of cholesteryl ester from vesicles to LDL, the additional enhancement of the transfer by LCAT was observed only with the vesicles containing apo-A-I. Gel permeation chromatography of LTP/vesicle and LTP/HDL3 mixtures in the presence and absence of LCAT showed that the affinity of LTP for both the vesicles and HDL3 increased upon addition of LCAT. In contrast, neither HDL2 nor discoidal bilayer particles showed any significant enhancement of LTP binding upon addition of LCAT. By using LCAT covalently bound to Sepharose 4B, a maximal interaction between LTP and bound LCAT was shown to occur at the ionic strength of 0.16. Deviation from this ionic strength reduced the extent of the interaction. At the ionic strength of 0.01 and 0.5, the elution volume of LTP was identical to that of bovine serum albumin. |
| AFM studies on Langmuir-Blodgett films of cholesterol Gupta, R. K. and K. A. Suresh (2004), Eur Phys J E Soft Matter 14(1): 35-42. Abstract: The Langmuir monolayer of cholesterol at the air-water interface exhibits a condensed phase in which the cholesterol molecules are aligned normal to the water surface. We have transferred the monolayer from water surface to different substrates by Langmuir-Blodgett (LB) technique and have studied their assembly by atomic force microscope (AFM). Our studies reveal that the aggregation of cholesterol molecules on hydrophobic surfaces leads to interesting structures. The cholesterol molecules assemble into a uniform film, elongated domains and uniformly distributed torus-shaped domains (doughnuts) for one, two and four cycles of deposition, respectively. Beyond four cycles, the molecules adsorb and desorb by an equal amount resulting in no further deposition. The formation of uniformly distributed doughnuts can be attributed to the hydrophobic interaction and reorganization of the molecules due to successive adsorption and desorption during deposition cycles. Our studies on hydrophilic surfaces show that cholesterol cannot form more than one layer of deposition. |
| African-American mothers' perceptions of cholesterol and its effects on their children Price, J. H. and S. M. Casler (1996), J Natl Med Assoc 88(3): 145-50. Abstract: This study examined African-American mothers' perceptions of cholesterol and its effects on their children. A random sample of middle- and upper-class women, Alpha Kappa Alpha sorority members, 26 to 53 years of age, responded to a 42-item questionnaire. Fifty-nine percent knew their cholesterol level and 13% knew the cholesterol level of their children. Two thirds of the parents believed that all elementary school children should have their cholesterol levels checked. A total of 79% had made lifestyle changes to reduce their child's risk of hypercholesterolemia, including 22% of this group who had purchased food supplements for this activity. Parents were more likely to receive most of their cholesterol information from the mass media, magazines (74%), newspapers (64%), and television (52%). The results of this study imply that these parents may be in need of further nutritional guidance from physicians to help them establish a safe and nutritious approach to maintaining normal cholesterol levels for their children. |
| After I had a heart attack and two bypass operations, I was put on Lipitor to lower my cholesterol. My cholesterol was never high--about 170-180 mg/dL. But my HDL was always low and triglycerides were somewhat high. Now my total cholesterol is 124 and my HDL has gone up slightly. My triglycerides are way down. My LDL cholesterol has fallen from 110 to 68. Is there any downside to such a low cholesterol level, other than the need to check my liver function tests? Lee, T. H. (1999), Harv Heart Lett 9(5): 7. |
| Age- and dietary fat-related effects on biliary lipids and cholesterol gallstone formation in African green monkeys Scobey, M. W., M. S. Wolfe, et al. (1992), J Nutr 122(4): 917-23. Abstract: The effects of age and dietary fat on bile cholesterol saturation index (CSI) and cholesterol gallstone formation were studied in three age groups of male African green monkeys. Animals were fed semipurified diets containing cholesterol (0.34 g/100 g diet) and 42% of energy as saturated or polyunsaturated fat. Animals were killed at 16 (pre-pubertal), 32 (peri-pubertal) or 60 (young adult) mo of age; the presence of gallstones was determined and gallbladder bile was analyzed for CSI and bile acid composition. Cholesterol gallstones were present in 9% of 60-mo-old animals, compared with a 42% incidence in adult animals fed these same diets for 5 y. Gallbladder bile from the 32-mo-old group contained significantly more cholesterol and had a higher CSI as compared with the other age groups. Dietary fat had no effect on biliary lipid composition. We conclude that the increase in CSI around the time of puberty in male monkeys is not clinically significant in terms of gallstone formation, and that polyunsaturated fat feeding is not associated with adverse effects. Because the incidence of gallstone formation in these young adults was lower than that seen in older adults, a minimal amount of time consuming a lithogenic diet as an adult seems to be required for stone genesis. |
| Age and dietary polyunsaturated fat alter high density lipoprotein subfraction cholesterol concentrations in a pediatric population of African green monkeys Wolfe, M. S., J. S. Parks, et al. (1991), Arterioscler Thromb 11(3): 617-28. Abstract: African green monkeys were raised from birth to 60 months of age on diets containing cholesterol (0.8 mg/kcal) and enriched in polyunsaturated (polyunsaturated to saturated fat ratio P:S = 2.5) or saturated (P:S = 0.3) fat. Lipoproteins were isolated from plasma of a group of animals (N = 123) and were separated by gel filtration chromatography at 9, 14, 26, 38, and 50 months of age, which covered a period through adolescence into young adulthood. Total plasma cholesterol (TPC) concentrations were 16% lower (p = 0.01) in the polyunsaturated fat-fed group, and high density lipoprotein (HDL) cholesterol concentrations averaged 20% lower (p = 0.008) in this group between 14 and 50 months of age, while plasma apolipoprotein A-I (apo A-I) averaged 7% lower (p = 0.06) over this age interval in the animals. The HDL cholesterol to apo A-I ratio was found to be significantly lower (p = 0.006) in the animals fed the polyunsaturated fat diet. This suggested that the HDL subfraction distribution might differ between groups. In a subset of animals (n = 105, 64 male and 41 female), HDL was subfractionated by density gradient ultracentrifugation into six subfractions, HDL-I to HDL-VI, from lowest to highest density. The saturated fat-fed animals had significantly higher cholesterol concentrations in HDL-I and significantly lower cholesterol concentrations in HDL-III, HDL-IV, and HDL-V. These effects held across all ages studied; therefore, these diet effects were not age dependent. In both diet groups, the HDL subfraction pattern changed with age such that the HDL-I and HDL-II cholesterol concentrations decreased, and those of HDL-IV, HDL-V, and HDL-VI increased as the animals matured. The decrease in HDL-I with age appeared to result primarily from a decrease in HDL-I in males, while the HDL-I cholesterol concentration in females did not change with age. We conclude that diet, age, and gender all affect HDL subfraction distribution and therefore can potentially modify the relative atherogenicity of the plasma HDL populations. It remains for future studies to demonstrate the effectiveness of each subfraction in promoting or preventing the cholesterol deposition of atherosclerosis. |
| Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes Clee, S. M., J. J. Kastelein, et al. (2000), J Clin Invest 106(10): 1263-70. Abstract: We and others have recently identified mutations in the ABCA1 gene as the underlying cause of Tangier disease (TD) and of a dominantly inherited form of familial hypoalphalipoproteinemia (FHA) associated with reduced cholesterol efflux. We have now identified 13 ABCA1 mutations in 11 families (five TD, six FHA) and have examined the phenotypes of 77 individuals heterozygous for mutations in the ABCA1 gene. ABCA1 heterozygotes have decreased HDL cholesterol (HDL-C) and increased triglycerides. Age is an important modifier of the phenotype in heterozygotes, with a higher proportion of heterozygotes aged 30-70 years having HDL-C greater than the fifth percentile for age and sex compared with carriers less than 30 years of age. Levels of cholesterol efflux are highly correlated with HDL-C levels, accounting for 82% of its variation. Each 8% change in ABCA1-mediated efflux is predicted to be associated with a 0.1 mmol/l change in HDL-C. ABCA1 heterozygotes display a greater than threefold increase in the frequency of coronary artery disease (CAD), with earlier onset than unaffected family members. CAD is more frequent in those heterozygotes with lower cholesterol efflux values. These data provide direct evidence that impairment of cholesterol efflux and consequently reverse cholesterol transport is associated with reduced plasma HDL-C levels and increased risk of CAD. |
| Age related changes in the lipoprotein substrates for the esterification of plasma cholesterol in rats Lee, S. M., B. J. Kudchodkar, et al. (1991), Mech Ageing Dev 61(1): 85-98. Abstract: The activity of the enzyme lecithin:cholesterol acyltransferase (LCAT) and the properties of its lipoprotein substrates have been investigated in 6- and 19-month-old Fischer-344 rats. These studies were carried out to determine the nature of the relationship between the observed hypercholesterolemia and the age-related decrease in the fractional rate of lipoprotein cholesterol esterification. The distribution of LCAT activity of plasma fractions was determined following gel chromatography and ultracentrifugation respectively. LCAT activity was found to be associated with the high density lipoprotein (HDL) fraction when rat plasma was passed through a Bio-Gel A-5 M column. Upon density gradient ultracentrifugation for 24 h it was found associated with HDL fraction; d = 1.125-1.21 g/ml. However, following prolonged ultracentrifugation (40 h), the majority of the LCAT activity was displaced into the lipoprotein-free infranatant (d greater than 1.225 g/ml). The dissociation of LCAT from its complex with HDL occurred to a smaller extent in aged rat plasma than in young rat plasma. Substrate specificity studies indicated that HDL was a considerably better substrate for LCAT than very low density lipoproteins (VLDL) in both young and aged rats. In addition, HDL from young rats was a better substrate for LCAT than the HDL from aged rats. Incubation experiments followed by the isolation of lipoproteins and the subsequent analyses of their cholesterol contents revealed that the age-related hypercholesterolemia was mainly due to an increase in the cholesterol carried by lipoprotein fractions d = 1.025 -1.07 g/ml (LDL + HDL1). These and other low density lipoproteins (d less than 1.025 g/ml) were poor substrates for LCAT. However, these lipoproteins could provide free cholesterol for esterification by first transferring it to HDL (d = 1.07-1.21). The HDL isolated from the plasma of aged rats was enriched with apolipoprotein (apo) E and these lipoprotein particles were found to be inferior substrates for LCAT. These data suggest that the decreased fractional rate of esterification observed in aged rats is due to the slower utilization of the HDL lipid substrate pool by the enzyme LCAT as a result of the accumulation of unfavorable substrates (compositionally altered HDL particles) for the LCAT reaction. |
| Age specificity of the relationship between serum cholesterol and mood in obese women Troisi, A., S. Scucchi, et al. (2001), Physiol Behav 72(3): 409-13. Abstract: Despite increasing evidence of an association between lower cholesterol levels and negative mood, no study has specifically investigated this relationship in obese people, a population at high risk for both dyslipidaemia and depression. Data on serum cholesterol and mood were collected in a group of 73 healthy women, aged 16 to 76 years, with different degrees of obesity and widely varying total cholesterol concentrations. Mood was assessed using three self-rated scales: the Toronto Alexithymia Scale (TAS-20), the State-Trait Anger Scale (STAS), and the Beck Depression Inventory (BDI). The association between lower total cholesterol levels and negative mood was age-dependent. No significant association was found in the younger age group (<50 years). In contrast, in the subgroup of older women, serum cholesterol was negatively and significantly correlated with the TAS-20 and the STAS. The negative correlation between serum cholesterol and the BDI was nearly statistically significant. Restricting analysis to the subjects in the highest quartile of the age distribution (>60 years) yielded stronger correlations between cholesterol and mood. In this sample of obese women, the relationship between lower cholesterol levels and negative mood was age-specific and limited to the older age group. The results of this study suggest that preventive programs or drug treatments for reducing cholesterol levels in elderly obese women should include a careful evaluation of mood state. |