| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Benefits of fibrate drugs in coronary heart disease patients with normal cholesterol levels Havel, R. J. (1997), Circulation 96(7): 2113-4. |
| Benefits of intensive reduction of low density lipoprotein cholesterol Posadas Romero, C. (2003), Arch Cardiol Mex 73 Suppl 1: S116-20. Abstract: The role of elevated cholesterol in the initiation and progression of atherosclerosis is universally recognized. In the last 14 years, the inhibitors of the 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase (statins) have become one of the most widely used therapeutic agents to lower cholesterol levels. Individual large clinical trials, as well as a meta-analysis of five of these studies, have clearly demonstrated the effect of statin-induced low-density lipoprotein cholesterol (LDL-C) lowering in significantly reducing the risk of coronary events in patients with a history of coronary artery disease (CAD). However, there are a few remaining questions, and the most important uncertainty is to what extent should cholesterol be reduced? The results of three large ongoing trials, specifically designed to answer this question, will be available in about two years. In the meantime, this paper presents a short review of the data derived from epidemiological studies and large intervention trials, suggesting that, in patients at high risk, the lower the LDL-C induced by treatment, the better the chance of reducing the incidence of cardiovascular events. |
| Benefits of lipid lowering on vascular reactivity in patients with coronary artery disease and average cholesterol levels: a mechanism for reducing clinical events? Cohen, J. D., J. H. Drury, et al. (2000), Am Heart J 139(4): 734-8. Abstract: BACKGROUND: The favorable effects of lowering low-density lipoprotein (LDL)-cholesterol on reducing clinical events in patients with coronary disease have been well established. The mechanisms responsible for this benefit, however, have not been fully understood. This study examined the impact of lipid-lowering therapy on endothelium-dependent vasoreactivity in a subgroup of patients after myocardial infarction with average cholesterol levels who participated in the Cholesterol Recurrent Events (CARE) study to determine whether an effect on endothelial function is a viable mechanism for the observed reduction in clinical events. METHODS AND RESULTS: Participants were recruited from among volunteers in the CARE trial at 2 university-based outpatient cardiology clinics. Patients were randomly assigned to pravastatin or placebo. Plasma lipids were measured at baseline and semiannually thereafter. During the final 6 months of the trial, vasoreactivity was assessed by change in ultrasound-determined brachial artery diameter in response to blood pressure cuff-induced ischemia (endothelium-dependent) and to nitroglycerin, a direct vasodilator. Differences in response were examined between the 2 randomized groups. The relation between change in LDL-cholesterol from baseline to year 5 and the magnitude of endothelium-dependent vasodilation also was examined. There was significantly greater endothelium-dependent vasodilation observed in the pravastatin group compared with the placebo group (13% vs 8%, P =.0002), with no difference between the groups in their response to the endothelium-independent vasodilator nitroglycerin. The magnitude of the endothelium-dependent vasodilation was significantly correlated with the percent change in LDL-cholesterol from baseline to final visit (r = 0.49, P =.015). CONCLUSIONS: These findings indicate that the use of pravastatin in patients after myocardial infarction with average cholesterol levels is associated with greater endothelium-dependent vasodilation compared with those who received placebo. The magnitude of this vasodilatory response is correlated to the reduction in LDL-cholesterol. This improvement in endothelium-dependent vasoreactivity may be a likely mechanism, at least in part, for the reduction in recurrent clinical events observed and reported in the CARE study. |
| Benefits of lipid-lowering therapy in men with elevated apolipoprotein B are not confined to those with very high low density lipoprotein cholesterol Stewart, B. F., B. G. Brown, et al. (1994), J Am Coll Cardiol 23(4): 899-906. Abstract: OBJECTIVES. Do the benefits of intensive lipid-lowering therapy extend to patients with only borderline or moderately elevated levels of low density lipoprotein (LDL) cholesterol? BACKGROUND. The merits of the present LDL cholesterol treatment goal of < or = 100 mg/dl need to be clarified for patients without high levels of LDL cholesterol, particularly for those patients previously classified as having only borderline high (130 to 159 mg/dl) or desirable (101 to 130 mg/dl) levels. METHODS. Disease change and clinical events were examined in LDL cholesterol subgroups in the Familial Atherosclerosis Treatment Study (FATS) trial, a randomized, blinded, quantitative arteriographic comparison of one conventional and two intensive lipid-lowering strategies in men with coronary artery disease, a positive family history and apolipoprotein B > or = 125 mg/dl. The primary end point, disease change per patient, was measured as the mean change in severity of stenosis (delta %SProx) among nine standard proximal segments. RESULTS. Of the 120 patients completing the 30-month protocol, 60 had a baseline LDL cholesterol < 90th percentile (mean LDL cholesterol 152 mg/dl) and 60 > 90th percentile (mean LDL cholesterol 221 mg/dl). Thirty-one patients had levels < 160 mg/dl (mean LDL cholesterol 134 mg/dl) and 89 > 160 mg/dl (mean LDL cholesterol 205 mg/dl). Patients with LDL cholesterol < 90th percentile benefited angiographically from therapy (delta %SProx = -1.5% diameter stenosis regression during intensive therapy vs. +2.3% diameter stenosis progression during conventional therapy, p < 0.01), as did patients with LDL cholesterol < 160 mg/dl (delta %SProx = -4.2% vs. +3.3% diameter stenosis, p = 0.0001). By comparison, angiographic benefit was less pronounced among those entering with very high LDL cholesterol (delta %SProx = -0.2% vs. +1.9% diameter stenosis, p = 0.07) or with LDL cholesterol > or = 160 mg/dl (delta %SProx = +0.2% vs. +1.6% diameter stenosis, p = 0.13). Intensive therapy resulted in a statistically significant reduction in clinical events only in the subgroup with baseline LDL cholesterol < 90th percentile (2 of 42 vs. 8 of 29 patients initially enrolled, p = 0.01) and a trend toward fewer events in patients with LDL cholesterol < 160 mg/dl (2 of 20 vs. 6 of 15 patients, p = 0.05). No such difference was seen in the higher LDL cholesterol subgroups. CONCLUSIONS. Treatment benefit in the FATS trial was not confined to patients with very high levels of LDL cholesterol and was in fact particularly evident in those patients with levels < 160 mg/dl. Such patients should be considered more likely, not less, to benefit from intensive lipid-lowering therapy. |
| Benefits of simvastin in cholesterol lowering Farmer, J. A. (2003), Curr Atheroscler Rep 5(2): 93-4. |
| Benzophenone-containing cholesterol surrogates: synthesis and biological evaluation Spencer, T. A., P. Wang, et al. (2004), J Lipid Res 45(8): 1510-8. Abstract: Eight analogs of cholesterol (1) containing a benzophenone group have been synthesized as prospective photoaffinity labels for studies in cellular sterol efflux and HDL formation. Six of these compounds (4-9) have the photophore replacing different portions of the cholesterol alkyl side chain, and two (10 and 11) have it attached via nitrogen at carbon 3. The suitability of these analogs as cholesterol surrogates was determined by examining their ability to replace 3H1 in fibroblasts preequilibrated with 3H1. All eight analogs were effective in replacing natural 1 in competition with 3H1 for apolipoprotein A-I-induced efflux. These are the first compounds shown to replace cholesterol successfully in a complex pathway of multiple intracellular steps. The results suggest an unexpected tolerance of biological membranes regarding the incorporation of sterols of differing chemical structure. |
| Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins Kong, W., J. Wei, et al. (2004), Nat Med 10(12): 1344-51. Abstract: We identify berberine (BBR), a compound isolated from a Chinese herb, as a new cholesterol-lowering drug. Oral administration of BBR in 32 hypercholesterolemic patients for 3 months reduced serum cholesterol by 29%, triglycerides by 35% and LDL-cholesterol by 25%. Treatment of hyperlipidemic hamsters with BBR reduced serum cholesterol by 40% and LDL-cholesterol by 42%, with a 3.5-fold increase in hepatic LDLR mRNA and a 2.6-fold increase in hepatic LDLR protein. Using human hepatoma cells, we show that BBR upregulates LDLR expression independent of sterol regulatory element binding proteins, but dependent on ERK activation. BBR elevates LDLR expression through a post-transcriptional mechanism that stabilizes the mRNA. Using a heterologous system with luciferase as a reporter, we further identify the 5' proximal section of the LDLR mRNA 3' untranslated region responsible for the regulatory effect of BBR. These findings show BBR as a new hypolipidemic drug with a mechanism of action different from that of statin drugs. |
| Beta(2)-adrenergic receptor mutation and abdominal obesity risk: effect modification by gender and HDL-cholesterol Corbalan, M. S., A. Marti, et al. (2002), Eur J Nutr 41(3): 114-8. Abstract: OBJECTIVE AND DESIGN: A case-control study was conducted to examine the association between the 27Glu polymorphism of the beta(2)-adrenergic receptor gene (ADRB2) and the risk of abdominal obesity (defined by a waist/hip ratio: WHR higher than 0.85). METHODS: The case series encompassed 112 obese subjects with body mass index (BMI) > 30 kg/m(2) and WHR > 0.85 and no other major disease except for type 2 diabetes, while the controls were 127 healthy subjects, BMI < 25 kg/m(2) and WHR < 0.85. RESULTS: The association between the risk of abdominal obesity and the 27Glu polymorphism was estimated using multivariate logistic regression. A higher crude odds ratio (OR) of 4.08 (95 % confidence interval: 0.98-16.3) for the 27Glu allele was found among men, while no increased risk was apparent among female participants. Moreover, when the model was adjusted for age, male subjects carriers of the 27Glu allele had a significant ten-fold higher risk of abdominal obesity (OR = 10.31; 95 % CI: 1.4-76.8) and the product-term for the interaction (effect modification) between gender and the ADRB2 mutation was near to the limits of statistical significance (Likelihood ratio test p = 0.056). Interestingly, we also found an effect modification with higher OR among individuals with low HDL-cholesterol (< 1.5 mmol/l) after adjustment for age and gender (OR = 2.87 95 % CI 1.09-7.50) and the product-term for interaction between the 27Glu allele and HDL-cholesterol was statistically significant (Likelihood ratio test p = 0.003). CONCLUSIONS: Our results showed that the 27Glu allele of the ADRB2 gene appears to be a risk factor for abdominal obesity among male subjects, specially among those with lower HDL-cholesterol levels. |
| beta-Carotene oxidation products effect cholesterol biosynthesis and growth of human epidermoid carcinoma cultured cells Malakhova, M. V., V. F. Orlova, et al. (1998), Biull Eksp Biol Med 126(9): 321-4. |
| Beta-cyclodextrin facilitates cholesterol efflux from larval Manduca sexta fat body and midgut in vitro Jouni, Z. E., B. McGill, et al. (2002), Comp Biochem Physiol B Biochem Mol Biol 132(4): 699-709. Abstract: The ability of 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) and methyl-beta-cyclodextrin (MbetaCD) to promote cholesterol efflux from 3Hcholesterol-labeled larval Manduca sexta fat body and midgut was tested. In fat body, both beta-cyclodextrins induced a two-phase efflux of cholesterol. The first rapid phase depended on cyclodextrin concentration and was more rapid for MbetaCD than for HPbetaCD. The second, slower, phase was independent of cyclodextrin concentration and type. In midgut, only the concentration-dependent phase was observed; the rate constants are approximately 85% slower than for fat body. In both cases, a low activation energy for transfer was observed, consistent with a collision mechanism where cyclodextrin interacts directly with cholesterol in plasma membrane to affect transfer. In fat body, the second slower phase is suggestive of a second pool of exchangeable cholesterol and most likely represents transfer of cholesterol from internal membranes or different lateral domains of the plasma membrane. The lack of this second phase in midgut suggests that midgut has only a single pool of exchangeable cholesterol. Although the rates are somewhat different, the overall kinetic pattern for cyclodextrin-mediated cholesterol transfer in insect fat body closely resembles that for vertebrate cells, while the single pool behavior of the midgut is not found in vertebrate cells. |
| Beta-lactotensin and neurotensin rapidly reduce serum cholesterol via NT2 receptor Yamauchi, R., K. Ohinata, et al. (2003), Peptides 24(12): 1955-61. Abstract: Beta-lactotensin, a neurotensin NT2 agonist derived from beta-lactoglobulin, has hypocholesterolemic activity after administration for 2 days at a dose of 30 mg/kg (i.p.) or 100 mg/kg (p.o.) for 2 days in mice fed a high-cholesterol/cholic acid diet. The onset of hypocholesterolemic activity of beta-lactotensin was observed 90 min after a single i.p. or p.o. administration at the same dose as described above. Neurotensin also induced hypocholesterolemic activity 90 min after single i.p. administration at a dose of 2 microg per mouse but was ineffective after oral administration. The rapid onset of hypocholesterolemic activities of beta-lactotensin and neurotensin was blocked by levocabastine (50 microg/kg), an NT2 antagonist, and raclopride (0.5 mg/kg), a dopamine D2 antagonist. |
| Beta-VLDL in hepatic lipase deficiency induces apoE-mediated cholesterol ester accumulation in macrophages Huff, M. W., C. G. Sawyez, et al. (1993), Arterioscler Thromb 13(9): 1282-90. Abstract: Hepatic lipase-deficient subjects in the Ontario kindred are compound heterozygotes for hepatic lipase mutations (Ser267-->Phe and Thr383-->Met). Cholesteryl ester-rich beta-very-low-density lipoprotein (beta-VLDL) accumulates in plasma and such subjects have premature atherosclerosis. To determine a possible mechanism, we hypothesized that hepatic lipase-deficient beta-VLDL, homozygous for apolipoprotein (apo) E3, would cause cholesteryl ester accumulation and foam cell formation in macrophages. beta-VLDL and pre-beta-VLDL were isolated by Pevikon electrophoresis and incubated with J774 macrophages, cells that do not secrete apoE. beta-VLDL increased cellular cholesteryl ester content 13-fold, whereas pre-beta-VLDL increased cholesteryl ester sevenfold. beta-VLDL increased acyl CoA:cholesterol acyltransferase activity fourfold (measured as 14Coleate incorporation into cholesteryl ester). Preincubation of hepatic lipase-deficient beta-VLDL with the anti-apoE monoclonal antibody 1D7, which inhibits binding of apoE to low-density lipoprotein receptors, inhibited cellular cholesteryl ester accumulation by 75%, whereas the anti-apoB blocking monoclonal antibody 5E11 failed to inhibit cellular cholesteryl ester accumulation. In contrast to hepatic lipase deficiency, beta-VLDL from type III subjects (E2/E2) failed to increase cellular cholesteryl ester or acyl CoA:cholesterol acyltransferase more than 1.5-fold. Thus, hepatic lipase-deficient beta-VLDL readily induces cholesteryl ester accumulation in J774 macrophages, a process mediated by functional apoE3. This may explain the premature atherosclerosis observed in this kindred. |
| Beta-VLDL increases endothelial cell plasma membrane cholesterol Kim, J. A., K. Maxwell, et al. (1991), J Lipid Res 32(7): 1125-31. Abstract: In this study, the distribution of free cholesterol in cholesterol-loaded endothelial cells was examined. For these studies, cell fractionation methods were used to assess marker enzyme activity and cholesterol distribution. Treatment of rabbit aortic endothelial cells for 3 days with 50 micrograms/ml of beta-very low density lipoprotein (beta-VLDL) or malondialdehyde-low density lipoprotein (MDA-LDL) but not LDL caused a 50-100% increase in total cell unesterified cholesterol. The accumulation of free rather than esterified cholesterol in endothelial cells may be due to the ratio of hydrolysis to esterification, which we have shown in this study to be 10-fold higher in endothelial cells than in smooth muscle cells. This free cholesterol is found in the fractions enriched in plasma membrane markers and, to a lesser extent, in the Golgi-enriched fractions. The amount of cholesterol per mg of protein was increased approximately 50% in these fractions from cells treated for 3 days with 50 micrograms/ml of beta-VLDL. These increases in cholesterol content were reversible upon incubation of cells for 3 days in medium containing 15% fetal bovine serum. Alterations in several membrane functions were also observed in cholesterol-loaded cells. The activity of alkaline phosphatase, an enzyme marker for plasma membranes, was decreased by 25% and an alteration in membrane-associated microfilaments was seen with phalloidin staining. This morphological change in microfilaments was reflected in a decrease in filament ends as shown by cytochalasin binding and occurred without a change in total actin or vinculin. These microfilament changes were reversible.(ABSTRACT TRUNCATED AT 250 WORDS) |
| beta-VLDL of patients with type III hyperlipoproteinemia interferes with homogeneous determination of HDL-cholesterol based on polyethylene glycol-modified enzymes Lackner, K. J. and G. Schmitz (1998), Clin Chem 44(12): 2546-8. |
| Beta-VLDL-induced cholesterol ester deposition in macrophages may be regulated by neutral cholesterol esterase activity Ishii, I., M. Oka, et al. (1992), Arterioscler Thromb 12(10): 1139-45. Abstract: We examined the role of enzyme activities involved in cholesterol ester metabolism in the accumulation of cholesterol ester in macrophages. When 3Hcholesterol linoleate-beta-very low density lipoproteins (beta-VLDLs) were incubated with rat resident peritoneal macrophages (RPMs), thioglycolate-elicited macrophages (TEMs), or alveolar macrophages (AMs), cholesterol ester accumulation was the greatest in TEMs and the least in AMs. The uptake of 3Hcholesterol linoleate-beta-VLDL into AMs was four times that into RPMs, and the uptake into TEMs was twice that into RPMs. The 3Hcholesterol released from 3Hcholesterol linoleate-beta-VLDL-loaded AMs was five times higher than from TEMs and RPMs, whereas those from RPMs and TEMs were almost the same. In studies using cell homogenates, the acid cholesterol esterase activity in AMs was 1.7 times that in TEMs and six times that in RPMs. The acyl-coenzyme A:cholesterol acyltransferase (ACAT) activities in AMs and TEMs were similar but were higher than that in RPMs. The neutral cholesterol esterase activity was seven times higher in AMs than in RPMs and TEMs. In the study using intact cells, the hydrolysis of loaded 3Hcholesterol linoleate-beta-VLDL in the presence of the ACAT inhibitor CL277,082 and the cholesterol 14Coleate synthesis from 14Coleate were enhanced in AMs about twofold compared with RPMs and TEMs. The reduction of de novo synthesized cholesterol 14Coleate in the presence of CL277,082 was enhanced in AMs four times compared with TEMs or RPMs.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Better outcome after stroke with higher serum cholesterol levels Steiner, I. and I. Biran (2000), Neurology 55(12): 1941-2. |
| Better outcome after stroke with higher serum cholesterol levels Vauthey, C., G. R. de Freitas, et al. (2000), Neurology 54(10): 1944-9. Abstract: OBJECTIVE: To examine whether serum cholesterol levels have any prognostic value in the first month following acute ischemic stroke. BACKGROUND: Although the association between serum cholesterol levels and cerebrovascular disorders has been extensively studied, the relationship between cholesterol levels and outcome following ischemic stroke has not been investigated. METHODS: Using data from 3,273 consecutive patients with first-ever ischemic stroke, the authors compared poor functional outcome (severe disability or death) at 1 month in patients with high cholesterol (total serum cholesterol greater than 6.5 mmol/L or 250 mg/dL) and normal cholesterol (level equal to or less than 6.5 mmol/L or 250 mg/dL). Data were analyzed by univariate and multivariate analysis. RESULTS: In comparison with patients with normal cholesterol levels, patients with high cholesterol levels had a 2.2-fold lower risk of death (p = 0.002) and a 2.1-fold lower risk of poor functional outcome at 1 month (p < 0.001). After adjustment for known confounding variables, multivariate analysis showed that higher cholesterol levels remained an independent predictor of better functional outcome (OR 0.48, CI 0. 34 to 0.69, p < 0.001). CONCLUSIONS: The authors' findings suggest that higher levels of cholesterol are associated with a better outcome in the early phase after ischemic stroke. |
| Beyond cholesterol Kluger, J. (1997), Time 150(5): 48. |
| Beyond cholesterol concentration: other abnormalities of lipid metabolism associated with coronary heart disease Reaven, G. (1991), Diabetes Metab Rev 7(3): 137-8. |
| Beyond cholesterol. Inflammation is emerging as a major risk factor--and not just in heart disease Park, A. (2002), Time 160(22): 74-5. |