| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effect of apoprotein B conformation on the activation of lysolecithin acyltransferase and lecithin: cholesterol acyltransferase. Studies with subfractions of low density lipoproteins Liu, M., E. S. Krul, et al. (1992), J Biol Chem 267(8): 5139-47. Abstract: In order to determine the role of apoprotein (apo) B conformation in the activation of the lysolecithin acyl-transferase reaction, we studied the activation of purified enzyme by various subfractions of low density lipoprotein (LDL), isolated by density gradient centrifugation. The activation of LAT correlated positively with the density of LDL and negatively with cholesterol/protein and triglyceride (TG)/protein ratios. The enzyme activation was also positively correlated with the number of trinitrobenzenesulfonic acid-reactive lysine amino groups, which increased with increasing density of LDL. The immunoaffinity of the LDL subfractions for B1B6, a monoclonal antibody directed to the receptor-binding region of apoB, increased with increasing density, while the affinity toward C1.4, a monoclonal antibody directed to the amino-terminal region of apoB, was not altered. Enrichment of normal whole LDL with TG resulted in a 45% reduction in enzyme activation, a 27% decrease in the number of trinitrobenzenesulfonic acid-reactive lysine groups, and a marked reduction in the immunoaffinity for B1B6. All these parameters reversed to normal when the TG-enriched LDL was treated with milk lipoprotein lipase, which specifically reduced the TG content of LDL. The LDL subfractions also supported cholesterol esterification by the purified enzyme, in parallel with lysolecithin esterification, indicating that apoB can also serve as an activator of the lecithin-cholesterol acyltransferase reaction. These results strongly suggest that the localized conformational change of apoB which occurs during the TG depletion of the precursor particle is critical for its activation of acyltransferase reactions, in a manner analogous to its interaction with the cellular receptors. |
| Effect of ascorbic acid administration on B and E apoproteins in rats fed a cholesterol enriched diet Santillo, M., F. Santangelo, et al. (1993), Horm Metab Res 25(3): 156-9. Abstract: The effect of ascorbic acid on cholesterol metabolism is very well documented; it is ascribed to the activation of this vitamin on cholesterol 7 alpha-hydroxylase (EC 1.14) that activates the catabolism of cholesterol. In this paper we have studied the effect of the administration of ascorbic acid on B and E apoproteins of rats fed a diet enriched with 1.5% of cholesterol. The results obtained show that ascorbic acid is able to affect cholesterol metabolism by modifying the serum levels of apo B in total serum and in lipoprotein classes of density less than 1.050 g/ml. Moreover the ascorbic acid treatment reduced the amount of cholesterol and triglycerides in all lipoprotein classes examined. No significant change of total serum apo E was observed following ascorbic acid administration. |
| Effect of aspirin on intimal hyperplasia and cholesterol uptake in experimental bypass grafts Landymore, R. W., M. A. MacAulay, et al. (1991), Can J Cardiol 7(2): 87-90. Abstract: The effects of aspirin on intimal and medial smooth muscle cell proliferation and cholesterol uptake in experimental bypass grafts were examined in a hypercholesterolemic canine model. Ten animals receiving a 2% cholesterol diet served as controls, while a further 10 animals received the same diet and 160 mg aspirin daily. Segments of external jugular vein were implanted between bilaterally divided femoral arteries. Tissue cholesterol and intimal and medial thicknesses were measured at six weeks. Graft cholesterol had increased 1.7 mumol/g at six weeks in the control group but only rose by 0.28 mumol/g in animals receiving aspirin (P less than 0.002). Intimal and medial smooth muscle cell proliferation was evident in all experimental bypass grafts and was unaffected by aspirin. It is concluded that cholesterol uptake and smooth muscle proliferation may be controlled by different mechanisms, and that aspirin reduces cholesterol uptake but does not prevent smooth muscle cell proliferation in experimental bypass grafts. |
| Effect of aspirin on intimal proliferation and tissue cholesterol in long-term experimental bypass grafts Landymore, R. W., M. A. MacAulay, et al. (1992), Eur J Cardiothorac Surg 6(8): 422-6. Abstract: A single daily dose of aspirin (ASA) reduces the incidence of early graft thrombosis after coronary bypass operations. Recent data indicate that aspirin may not prevent intimal proliferation and cholesterol uptake in experimental bypass grafts which suggests that aspirin may not improve long-term graft patency. To further clarify the effects of aspirin on intimal proliferation and cholesterol metabolism, we performed femoral interposition vein grafts in 12 dogs receiving a 2% cholesterol diet. Six controls (CON) received the diet alone while the remaining animals received the diet with 160 mg aspirin daily before and for 9 months following operation. A segment of each graft was removed at 3 months for measurement of intimal thickness and tissue cholesterol. The entire graft was then harvested at 9 months. Intimal thickness increased rapidly during the first 3 months. A slow and progressive increase in intimal thickness was observed between 3 and 9 months. There was, however, no difference in intimal thickness between the two groups. Tissue cholesterol increased similarly in both groups. Rapid cholesterol uptake occurred within the first 3 months and then decreased between 3 and 9 months. Conclusions: (1) ASA failed to reduce intimal proliferation and cholesterol uptake in experimental bypass grafts suggesting that ASA may not prevent late graft failure, (2) Accelerated intimal proliferation and cholesterol uptake occurred within the first 3 months emphasizing the importance of developing and instituting anti-proliferative therapy immediately after aortocoronary bypass. |
| Effect of atherogenic diet on reverse cholesterol transport in vivo in atherosclerosis susceptible (C57BL/6) and resistant (C3H) mice Stein, O., Y. Dabach, et al. (2001), Atherosclerosis 156(2): 307-13. Abstract: Mice susceptible (C57BL/6) or resistant (C3H) to atherosclerosis induced by a high cholesterol-cholate containing diet (A-diet) were used to study reverse cholesterol transport (RCT) in vivo as measured by loss of cholesterol from a depot created by injection of cationized LDL into the rectus femoris muscle. Plasma total and HDL-cholesterol (HDL-C), total and HDL phospholipid (HDL-PL) levels in chow fed C3H male and female mice were higher than in C57BL/6 mice. After one month on A-diet, plasma cholesterol more than doubled in both strains and genders. The decrease in HDL-C and HDL-PL was twice as great in C57BL/6 as in C3H female mice, while in male C3H mice there was no decrease. The loss of exogenous cholesterol mass (ECM) after injection of cationized LDL was more rapid in C3H than in C57BL/6 mice. In chow fed mice, ECM retained in muscle on day 12 was 37% in C57BL/6 and 20% in C3H females; in males it was 39% and 18% in C57BL/6 and C3H, respectively. On A-diet, 76% were retained in C57BL/6 and 28% in C3H females; these values were 59% and 28% in C57BL/6 and C3H males. Thus, the slow clearance of ECM (which represents RCT) in C57BL/6 mice on A-diet, that could be related to a marked decrease of HDL-PL, might contribute towards their susceptibility to atherosclerosis. |
| Effect of atorvastatin 80 mg on endothelial cell function (forearm blood flow) in patients with pretreatment serum low-density lipoprotein cholesterol levels <130 mg/dl Wassmann, S., N. Ribaudo, et al. (2004), Am J Cardiol 93(1): 84-8. Abstract: The effect of 6-week treatment with 80 mg/day atorvastatin on vascular function in the forearm was investigated in 18 patients with mean pretreatment serum low-density lipoprotein cholesterol concentrations of 112 +/- 4 mg/dl in a double-blind, placebo-controlled, randomized study. Statin treatment improved hyperemic forearm blood flow and decreased serum markers of oxidative stress and inflammation. |
| Effect of atorvastatin on endothelium-dependent vasodilation in postmenopausal women with average serum cholesterol levels Mercuro, G., S. Zoncu, et al. (2002), Am J Cardiol 90(7): 747-50. Abstract: After menopause, most healthy women show an impairment of peripheral vasodilation and an increase of plasma cholesterol levels. Statins have been shown to improve endothelial function in hypercholesterolemic men and women. The present study tests whether atorvastatin (10 mg) influences endothelium-dependent vasodilation in postmenopausal normocholesterolemic women. Twenty-eight healthy, postmenopausal women (mean age 51 +/- 2 years) with serum total cholesterol and low-density lipoprotein cholesterol within the desirable range entered a double-blind, single-crossover study. Postmenopausal women were randomized to receive either atorvastatin (10 mg/day) or placebo for 10 days and then crossed to the complementary treatment. Endothelium-dependent and -independent responses were assessed by means of strain-gauge plethysmography before and after intra-arterial infusion of acethylcholine (ACh) and sodium nitroprusside, in comparison to physiologic saline. The nitric oxide pathway was evaluated by repeating the infusion of ACh during admininstration of L-arginine and (G)-monomethyl-L-arginine (L-NMMA). Serum lipoproteins were not significantly modified by the active treatment. The vasodilation induced by ACh was significantly higher in the atorvastatin-treated women compared with the placebo-treated group (24 +/- 3 vs 13 +/- 2 ml/100 ml tissue/min, p <0.01). In contrast, responses to the endothelium-independent vasodilator sodium nitroprusside were not significantly modified by atorvastatin. The ACh-stimulated vasodilation induced by atorvastatin was additionally potentiated by L-arginine (800 +/- 105% vs 370 +/- 60%, p <0.05) and blunted by L-NMMA. No correlation was found between changes in plasma cholesterol and improvement in forearm blood flow. Our data show that the beneficial effect of atorvastatin on endothelium-dependent vasodilation is independent from changes in the lipid profile. |
| Effect of atorvastatin on high density lipoprotein cholesterol and its relationship with coronary events: a subgroup analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) Study Athyros, V. G., D. P. Mikhailidis, et al. (2004), Curr Med Res Opin 20(5): 627-37. Abstract: OBJECTIVE: To investigate the relationship between changes in high density lipoprotein cholesterol(HDL-C) levels after statin treatment and the risk for coronary heart disease (CHD)-related events in the secondary CHD prevention GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study. These findings suggested that dose titration with atorvastatin (10-80 mg/day, mean 24 mg/day)achieves the National Cholesterol Educational Program treatment goals and significantly reduces morbidity and mortality, in comparison to usual care. METHODS: Analysis of variance was used to assess the effect of atorvastatin on HDL-C over time (up to 48 months) in 1600 CHD patients. The time-dependent multivariate Cox predictive model,involving backward stepwise logistic regression,was used to evaluate the relation between coronary events and HDL-C changes. RESULTS: The mean increase in HDL-C levels during the study was 7%. All doses of atorvastatin significantly increased HDL-C levels. Increases were greater in men (7.8 vs 6.1%; p = 0.02), in combined hyperlipidaemia (7.9 vs 6.4% for hypercholesterolaemia; p = 0.04), and in the lower baseline HDL-C quartile (9.2 vs 5.3%, 1st vs 4th quartile; p = 0.001). After adjustment for 24 predictors of coronary events, multivariate analysis revealed a Hazards Ratio of 0.85 (95% confidence interval 0.76-0.94; p = 0.002) for every 4 mg/dL(0.1 mmol/L) increase in HDL-C. CONCLUSIONS: There was a significant beneficial effect on HDL-C levels across the dose range of atorvastatin. Clinical outcomes in the structured care arm of GREACE were determined in part by the extent of atorvastatin-induced HDL-C increase.This effect was independent from benefit induced by low density lipoprotein cholesterol (LDL-C)reduction, suggesting that the CHD risk reduction associated with a rise in a low HDL-C at baseline remains significant under aggressive (-46%) LDL-C lowering conditions. However, the relationship between HDL-C and vascular risk may be weaker when LDL-C levels are aggressively lowered. |
| Effect of atorvastatin on postcardiac transplant increase in low-density lipoprotein cholesterol reduces development of intimal hyperplasia and progression of endothelial dysfunction See, V. Y., Jr., D. DeNofrio, et al. (2003), Am J Cardiol 92(1): 11-5. Abstract: Following cardiac transplantation, accelerated coronary disease limits long-term survival. Because statins may reduce the progression of the disease in part by their anti-inflammatory effects, this study was designed to assess if atorvastatin prevented neointimal hyperplasia and endothelial dysfunction independently of baseline cholesterol levels. Patients were randomized to usual therapy (n = 13) or to 10 to 20 mg of atorvastatin (n = 12). Control subjects received niacin when their low-density lipoprotein (LDL) cholesterol levels were >130 mg/dl (n = 4). Neointimal hyperplasia by intracoronary ultrasonography, endothelial dependent vascular reactivity, and coronary flow reserve were measured at baseline and 1 year. Control group total cholesterol (203 +/- 11 to 200 +/- 13 mg/dl) and LDL (116 +/- 10 to 119 +/- 11 mg/dl) remained stable, whereas there was a nonsignificant reduction at 12 months in the atorvastatin group (total cholesterol 216 +/- 28 to 178 +/- 21 mg/dl; LDL 126 +/- 17 to 100 +/- 18 mg/dl). At 2 to 3 months there was a significant increase in total cholesterol and LDL cholesterol that was reduced with atorvastatin. At 1 year, patients taking atorvastatin showed a decrease in new or progressing lesions (2.5 +/- 1.7 vs 4.2 +/- 1.8 lesions/patient, p = 0.02), progression of maximal intimal thickness (0.12 +/- 0.07 vs 0.52 +/- 0.17 mm, p = 0.04), and percent area stenosis (5.9 +/- 2.2% vs 19.0 +/- 5.5%, p = 0.04). Atorvastatin ameliorated progressive endothelial dysfunction, whereas coronary flow reserve was unchanged in both groups. Atorvastatin administered to patients with normal or mild hypercholesterolemia in the initial year after transplant reduced the initial increase in LDL cholesterol, and, by doing so, prevented the development and progression of coronary artery lesions and endothelial dysfunction with only mild long-term decreases in cholesterol levels. |
| Effect of atorvastatin, simvastatin, and lovastatin on the metabolism of cholesterol and triacylglycerides in HepG2 cells Scharnagl, H., R. Schinker, et al. (2001), Biochem Pharmacol 62(11): 1545-55. Abstract: We evaluated the effects of the hydroxymethylglutaryl coenzyme A reductase inhibitors (HMGRI) atorvastatin, lovastatin, and simvastatin on lipid homeostasis in HepG2 cells. The drugs were almost equally effective in inhibiting cholesterol synthesis and in decreasing cellular cholesterol. Atorvastatin and lovastatin increased low-density lipoprotein receptor mRNA (2.5-fold at 3 x 10(-7) M) and the transcription rate at the promoter of the low-density lipoprotein receptor gene (>5-fold at 10(-6) M). The three compounds enhanced the activity of the low-density lipoprotein receptor at a similar magnitude (1.6-2.1- fold at 10(-6) M). Atorvastatin and lovastatin increased the nuclear form of sterol regulatory element binding protein (SREBP)-2, but not of SREBP-1. Each of the drugs increased triacylglyceride synthesis (50% at 10(-7)-10(-6) M), cellular triacylglyceride content (16% at 10(-6) M), and expression of fatty acid synthase by reporter gene and Northern blot analysis (2-fold and 2.7-fold at 10(-6) M and 3 x 10(-7) M, respectively). All compounds reduced the secretion of apo B (30% at 3 x 10(-7) M). HMGRI decreased the ratio of cholesterol to apo B in newly synthesised apo B containing particles by approximately 50% and increased the ratio of triacylglycerides to apo B by approximately 35%. We conclude that regulatory responses to HMGRI are mediated by SREBP-2 rather than by SREBP-1, that HMGRI oppositely affect the cellular cholesterol and triacylglyceride production, that HMGRI moderately decrease the release of apo B containing particles, but profoundly alter their composition, and that atorvastatin does not significantly differ from other HMGRI in these regards. |
| Effect of baseline levels on response of high-density lipoprotein cholesterol to hypolipidemic treatment Kolovou, G. D., D. C. Daskalova, et al. (2003), Am J Cardiol 92(11): 1339-42. Abstract: The response of high-density lipoprotein cholesterol to hypolipidemic monotherapy with diet, statins, fibrates, or nicotinic acid was investigated prospectively in 801 patients with dyslipidemia. We hypothesized that the behavior of high-density lipoprotein cholesterol after treatment would depend on its baseline levels and the therapy used. |
| Effect of beta-carotene supplementation on the concentrations and distribution of carotenoids, vitamin E, vitamin A, and cholesterol in plasma lipoprotein and non-lipoprotein fractions in healthy older women Ribaya-Mercado, J. D., J. M. Ordovas, et al. (1995), J Am Coll Nutr 14(6): 614-20. Abstract: OBJECTIVE: We studied the effect of beta-carotene supplementation on the concentrations and distribution in plasma lipoprotein and non-lipoprotein fractions of carotenoids, alpha-tocopherol, retinol, and cholesterol. METHODS: Ten women ingested either 90 mg of beta-carotene or placebo daily for 3 weeks while residing in their homes and eating their usual meals. Carotenoids (beta-carotene, lycopene, lutein/zeaxanthin), retinol, alpha-tocopherol, and cholesterol were measured in plasma lipoprotein and non-lipoprotein fractions before and after treatment. RESULTS: In the beta-carotene-supplemented group, total plasma beta-carotene increased 14-fold from 0.48 +/- 0.13 to 6.83 +/- 2.12 mumol/L (p = 0.04). Although the greatest increase in beta-carotene was in low-density-lipoproteins (LDL), the magnitude of increase was similar in LDL, high-density-lipoproteins (HDL), and very-low-density-lipoproteins (VLDL). Thus, the relative distribution of beta-carotene in lipoproteins was unchanged: approximately 71% was in LDL, approximately 15% in HDL and approximately 12% in VLDL, before and after beta-carotene supplementation. There were no changes in amounts and distribution in lipoproteins of the other carotenoids, alpha-tocopherol, and cholesterol. There was no change in the amount of retinol in lipoprotein-deficient plasma. There were no changes in total plasma triglycerides. Significant positive correlations were found between LDL- or VLDL-cholesterol and alpha-tocopherol in LDL or VLDL, respectively; between LDL- or VLDL-cholesterol and lutein/zeaxanthin in LDL or VLDL, respectively; and between HDL-cholesterol and beta-carotene in HDL. CONCLUSIONS: beta-Carotene supplementation (90 mg/day for 3 weeks) in healthy older women results in an enrichment of all plasma lipoprotein fractions with beta-carotene, but does not alter the relative distribution of beta-carotene in lipoproteins. beta-Carotene supplementation has no effect on the amounts and relative distribution of lycopene, lutein/zeaxanthin, and alpha-tocopherol in lipoproteins, or of retinol in the non-lipoprotein fraction of plasma. Short-term beta-carotene supplementation has no effect on the concentrations of plasma total triglycerides, total cholesterol, HDL-, LDL-, and VLDL-cholesterol. |
| Effect of beta-cyclodextrin dietary supplementation on biliary proteins and their resulting cholesterol nucleating activity in pigs Catala, I., N. Domingo, et al. (1998), Biochim Biophys Acta 1394(1): 74-84. Abstract: We explored the possibility that the biliary protein fraction may support part of the variation in the nucleating activity previously measured in gallbladder biles of pigs. Eighteen gallbladder aspirates freshly obtained from three dietary groups (0, 5, or 10% beta-cyclodextrin) of six pigs were chromatographed to purify their total protein fraction. Proteins were quantified, and analysed through electrophoresis and immunoblotting or enzyme-linked immunosorbent assay for albumin, and five putative effectors of cholesterol crystallisation, mucins, immunoglobulin A, 130 kDa, apolipoprotein A-I, and anionic polypeptide fraction. Each total protein fraction was also assayed for its ability to influence cholesterol precipitation, when added to supersaturated model bile. The current data provided evidence that the cholesterol crystallisation-promoting activity of biliary proteins in model biles increased with the beta-cyclodextrin dietary content. This occurred without any significant change in the total biliary protein content, but was associated with a significant decrease in the concentration of albumin and apolipoprotein A-I, resulting in changes in the overall balance of proteins in bile. Comparison of these results with the crystallisation figures previously obtained from the corresponding native biles led us to conclude that biliary proteins might influence the outcome of the crystallisation process, namely the final crystal concentration at equilibrium, but would not systematically represent a major driving force for determining the velocity of crystal formation in native bile of pigs. |
| Effect of beta-muricholic acid on the prevention and dissolution of cholesterol gallstones in C57L/J mice Wang, D. Q. and S. Tazuma (2002), J Lipid Res 43(11): 1960-8. Abstract: This study investigated whether beta-muricholic acid, a natural trihydroxy hydrophilic bile acid of rodents, acts as a biliary cholesterol-desaturating agent to prevent cholesterol gallstones and if it facilitates the dissolution of gallstones compared with ursodeoxycholic acid (UDCA). For gallstone prevention study, gallstone-susceptible male C57L mice were fed 8 weeks with a lithogenic diet (2% cholesterol and 0.5% cholic acid) with or without 0.5% UDCA or beta-muricholic acid. For gallstone dissolution study, additional groups of mice that have formed gallstones were fed chow with or without 0.5% beta-muricholic acid or UDCA for 8 weeks. One hundred percent of mice fed the lithogenic diet formed cholesterol gallstones. Addition of beta-muricholic acid and UDCA decreased gallstone prevalence to 20% and 50% through significantly reducing biliary secretion rate, saturation index, and intestinal absorption of cholesterol, as well as inducing phase boundary shift and an enlarged Region E that prevented the transition of cholesterol from its liquid crystalline phase to solid crystals and stones. Eight weeks of beta-muricholic acid and UDCA administration produced complete gallstone dissolution rates of 100% and 60% compared with the chow (10%). We conclude that beta-muricholic acid is more effective than UDCA in treating or preventing diet-induced or experimental cholesterol gallstones in mice. |
| Effect of beta-sitosterol on precipitation of cholesterol from non-aqueous and aqueous solutions Christiansen, L., M. Karjalainen, et al. (2003), Int J Pharm 254(2): 155-66. Abstract: The aim of the present work was to study the solubility and phase behaviour of the beta-sitosterol-cholesterol mixed crystals in the presence and absence of water. Cholesterol, beta-sitosterol and 3:1, 1:1 and 1:3 mixtures of these were co-precipitated from acetone and acetone-water solutions. Precipitated crystals were analysed using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), optical microscopy and Karl-Fischer titrimetry. The quantification of the sterols in solutions was preformed using GC-MS. The solubility of the sterols was mutually limiting. In the aqueous system, the solubility of both the sterols were significantly lower than in the absence of water, but the decrease in the solubility was considerably greater with the more hydrophobic beta-sitosterol. In the aqueous system, the total sterol solubility decreased with the increasing proportion of beta-sitosterol. The formation of new crystal structures, solid solutions of cholesterol and beta-sitosterol, was observed in non-aqueous as well as in aqueous environments except with the lowest cholesterol proportion in the system, in which case mixed crystals with eutectic behaviour were formed. |
| Effect of bezamidine on plasma cholesterol and triglyceride levels in patients with familial hyperlipoproteinemia Kukharchuk, V. V., V. A. Koshechkin, et al. (1990), Kardiologiia 30(12): 16-8. Abstract: The hypolipidemic agent bezamidine, a fibroic acid derivative (KPKA, Yugoslavia), was applied to treat Types 2a, 2b, 4 and 5 familial hyperlipoproteinemias. The highest reduction in plasma cholesterol and triglyceride concentrations was found in patients with Types 2b, 4 and 5 familial hyperlipoproteinemias. No clear-cut adverse effects of the drug were found during 3 months. |
| Effect of biological and analytical variation in cholesterol measurement on the cost-effectiveness of cholesterol-lowering therapy Martens, L. L. (1992), Pharmacoeconomics 2(5): 414-21. Abstract: A number of recently published studies on the cost-effectiveness of cholesterol-lowering therapy use data from the Framingham Study to model the effect of cholesterol lowering on coronary heart disease risk. However, the risk estimates from the Framingham Study underestimate the association between coronary heart disease risk and serum cholesterol level because they do not account for intraindividual biological variation and analytical variation in cholesterol measurement. Cost-effectiveness studies that use these risk estimates are therefore likely to overestimate the cost per year of life saved of cholesterol-lowering interventions. We have developed an algorithm that can be used to improve current estimates of the cost-effectiveness of cholesterol-lowering therapy. Our results show that adjusting for intraindividual biological variation and analytical variation lowers the cost per year of life saved by 17 to 29%, depending on sex, pretreatment cholesterol level, and age at initiation of therapy. |
| Effect of black tea polyphenols on plasma lipids in cholesterol-fed rats Matsumoto, N., K. Okushio, et al. (1998), J Nutr Sci Vitaminol (Tokyo) 44(2): 337-42. Abstract: The influence of black tea polyphenols on plasma lipid levels was investigated in rats fed a 15% lard and 1% cholesterol diet. The diet was supplemented with 1% black tea polyphenols extracted and condensed from black tea. Rats fed the lard-cholesterol diet showed an increase in plasma cholesterol and liver lipids compared to rats fed a basal diet. The supplementation of black tea polyphenols in this lard-cholesterol diet decreased the lipid levels in the plasma and increased the fecal excretion of total lipids and cholesterol. On the other hands, 1% supplementation of either instant black tea with a 20% polyphenol content of 0.2% supplementation of EGCg in the lard-cholesterol diet had no effect on plasma cholesterol and phospholipid levels. These results suggest that a high dose of black tea polyphenols exerts a hypocholesterolemic effect in cholesterol-fed rats. |
| Effect of BO-653 and probucol on c-MYC and PDGF-A messenger RNA of the iliac artery after balloon denudation in cholesterol-fed rabbits Inoue, K., O. Cynshi, et al. (2002), Atherosclerosis 161(2): 353-63. Abstract: Antioxidants have been proposed as a promising treatment for restenosis after percutaneous transluminal coronary angioplasty (PTCA), but their mechanism of action remains unclear. Here, we investigated the effect of antioxidants on gene expression in the artery after balloon denudation. We developed a sensitive ribonuclease (RNase) protection assay for the messenger RNA (mRNA) levels of immediate early (IE) genes (c-jun, c-fos and c-myc), as well as platelet-derived growth factor-A (PDGF-A), platelet-derived growth factor-beta receptor, transforming growth factor-beta 1, and vascular endothelial growth factor. New Zealand White rabbits were fed a 0.17% cholesterol diet containing vehicle, BO-653 or probucol, and balloon denudation for iliac arteries was performed. The iliac arteries were then removed at 4 h after the denudation, for IE genes, and 10 days after for growth factors and receptors. Both BO-653 and probucol significantly reduced neointimal thickening, compared with the control. In terms of gene expression, BO-653, but not probucol, significantly inhibited c-myc induction. On the other hand, probucol, but not BO-653, significantly inhibited PDGF-A expression. Neither treatment had any effect on the expression of other genes. These results suggest that antioxidants affect the gene expression of the neointimal response and that both BO-653 and probucol inhibit gene expression in specific manners. |
| Effect of bovine serum on the phase transition temperature of cholesterol-containing liposomes Gaber, M. H. (1998), J Microencapsul 15(2): 207-14. Abstract: The phase transition temperature of liposomes composed of dipalmitoylphosphatidylcholine (DPPC)/hydrogenated soy phosphatidylcholine (HSPC) at a 2:1 molar ratio was estimated in buffer, 30% and 50% bovine serum by monitoring the leakage of encapsulated self quenched doxorubicin (Dox) from the vesicles when exposed to a temperature increasing from 30-52 degrees C. The results showed that bovine serum caused a slight decrease in the phase transition temperature from 44 to 41 degrees C in 50% serum. Addition of 50% cholesterol to this liposomal composition resulted in the disappearance of transition temperature in buffer and 30% serum, whereas 50% bovine serum resulted in the reappearance of the transition temperature at 46 degrees C. The data suggest that bovine serum affects the transition temperature of liposomes in a concentration-dependent manner, and this effect is more pronounced in cholesterol-rich liposomes. The time course for the release of Dox from both kinds of liposomes (cholesterol rich and cholesterol free) during incubation in 50% bovine serum, at temperatures close to the transition temperature (42 degrees, 45 degrees C), was followed. The results showed an increased leakage of Dox from both kinds of liposomes, at both temperatures. However, liposomes with high cholesterol content released more drug at 42 degrees than at 45 degrees C. The size of these liposomes was monitored in 10% bovine serum at 25 degrees C for a period of 1 h using photon correlation spectroscopy. The data showed no variation in the size of both cholesterol-rich and cholesterol-free liposomes for this period, which indicates that bovine serum does not affect the size of either cholesterol-rich or cholesterol-free liposomes. |