| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effects of diets containing tallow and soybean oil with and without cholesterol on hepatic metabolism of lipids and lipoproteins in the preruminant calf Leplaix-Charlat, L., D. Durand, et al. (1996), J Dairy Sci 79(10): 1826-35. Abstract: The effects of long-chain fatty acids (230 g/kg of dietary DM) from tallow and from soybean oil, with or without cholesterol (10 g/kg of dietary DM), on hepatic lipid contents and on in vivo hepatic production rates of lipids and lipoproteins were investigated in 22 preruminant male calves fitted with chronic catheters and with electromagnetic blood flow probes implanted in the hepatic vessels. Diets containing soybean oil and soybean oil with cholesterol led to the development of triglyceride infiltration in the liver and to higher apparent hepatic secretion of very low density lipoproteins than did diets containing tallow or tallow with cholesterol. Addition of cholesterol to diets favored accumulation of low density lipoproteins in plasma and the net apparent secretion of these particles by the liver, especially for the diet containing soybean oil with cholesterol. Regardless of the diet, calf liver clearly removed large high density lipoproteins of type 1 that were rich in cholesteryl esters but secreted heavy high density lipoproteins that were rich in proteins. The intensity of removal of high density lipoproteins of type 1 by the liver depended on the plasma concentration of these particles, probably by mass action. This removal did not prevent the accumulation of high density lipoproteins of type 1 in plasma, such as it did in calves fed soybean oil. |
| Effects of diets enriched in n-6 or n-3 fatty acids on cholesterol metabolism in older rats chronically fed a cholesterol-enriched diet Fukushima, M., T. Ohhashi, et al. (2001), Lipids 36(3): 261-6. Abstract: Hypocholesterolemic effects in older animals after long-term feeding are unknown. Therefore, aged rats (24 wk of age) fed a conventional diet were shifted to diets containing 10% perilla oil PEO; oleic acid + linoleic acid + alpha-linolenic acid; n-6/n-3, 0.3; polyunsaturated fatty acid/saturated fatty acid (P/S), 9.6, borage oil oleic acid + linoleic acid + alpha-linolenic acid; n-6/n-3, 15.1; P/S, 5.3, evening primrose oil (EPO; linoleic acid + gamma-linolenic acid; P/S, 10.5), mixed oil (MIO; oleic acid + linoleic acid + gamma-linolenic acid + alpha-linolenic acid; n-6/n-3, 1.7; P/S, 6.7), or palm oil (PLO; palmitic acid + oleic acid + linoleic acid; n-6/n-3, 25.3; P/S, 0.2) with 0.5% cholesterol for 15 wk in this experiment. There were no significant differences in the food intake and body weight gain among the groups. The liver weight in the PEO (n-6/n-3, 0.3) group was significantly higher than those of other groups in aged rats. The serum total cholesterol and very low density lipoprotein (VLDL) + intermediate density lipoprotein (IDL) + low density lipoprotein (LDL)-cholesterol concentrations of the PLO (25.3) group were consistently higher than those in the other groups. The serum high density lipoprotein cholesterol concentrations of the PEO (0.3) and EPO groups were significantly lower than in the other groups at the end of the 15-wk feeding period. The liver cholesterol concentration of the PLO (25.3) group was significantly higher than those of other groups. There were no significant differences in the hepatic LDL receptor mRNA level among the groups. Hepatic apolipoprotein (apo) B mRNA levels were not affected by the experimental conditions. The fecal neutral steroid excretion of the PLO (25.3) group tended to be low compared to the other groups. The results of this study demonstrate that both n-6 fatty acid and n-3 fatty acids such as gamma-linolenic acid and alpha-linolenic acid inhibit the increase of serum total cholesterol and VLDL + IDL + LDL-cholesterol concentrations of aged rats in the presence of excess cholesterol in the diet compared with dietary saturated fatty acid. |
| Effects of different cooking procedures on lipid quality and cholesterol oxidation of farmed salmon fish (Salmo salar) Al-Saghir, S., K. Thurner, et al. (2004), J Agric Food Chem 52(16): 5290-6. Abstract: Salmon fillets were steamed, or pan-fried without oil, with olive oil, with corn oil, or with partially hydrogenated plant oil. The exchange between the salmon and the pan-frying oils was marginal, but it was detectable as slight modifications in the fatty acid pattern and the tocopherol contents according to the oil used. Primary and secondary oxidation products were only slightly increased or remained unchanged, which indicated a slight lipid oxidation effect due to the heating procedures applied. The same was observed for tocopherol levels, which remained almost stable and were not affected by the oxidation process. The sum of cholesterol oxidation products (COPs) increased after the heating processes from 0.9 microg/g in the raw sample to 6.0, 4.0, 4.4, 3.3, and 9.9 microg/g extracted fat in pan-fried without oil, with olive oil, corn oil, partially hydrogenated plant oil, and steamed, respectively. A highly significant correlation was found between the fatty acid pattern and the total amount of COPs (r2 = 0.973, p < 0.001). No change has been determined in the n-3 fatty acids content and in the polyunsaturated/saturated-ratio of the cooked salmon fillets. Moderate pan-frying (6 min total) and steaming (12 min) of salmon did not accelerate lipid oxidation but significantly increased the content of COPs. The highest increase of COPs was found through steaming, mainly due to the longer heat exposure. The used frying oils did not influence the outcome; no significant difference between heat treatment with or without oil has been determined. |
| Effects of different dietary cholesterol concentrations on lipoprotein plasma concentrations and on cholesterol efflux from Fu5AH cells Blanco-Molina, A., G. Castro, et al. (1998), Am J Clin Nutr 68(5): 1028-33. Abstract: BACKGROUND: The fatty acid composition of the diet can modulate the effect of dietary cholesterol on plasma lipoproteins. However, HDL composition and its capacity to promote cholesterol efflux can be influenced by the diet. OBJECTIVE: Modifications in plasma lipids and in the capacity of serum to stimulate the cholesterol efflux induced by a low-fat diet National Cholesterol Education Program (NCEP) Step I diet, by a monounsaturated fatty acid (MUFA)-rich diet, and by addition of cholesterol to both diets was studied. DESIGN: Fifteen young, healthy men followed 2 NCEP Step I diets (<30% of fat as energy, with <10% saturated fat and 14% MUFAs) for 24 d, providing 0.027 or 0.068 mg cholesterol x kJ(-1) x d(-1), and 2 oleic acid-enriched diets (38% of energy as fat, with 24% MUFAs) providing the same amount of dietary cholesterol as the NCEP Step I diets. RESULTS: Total cholesterol, LDL cholesterol, apolipoprotein (apo) B, and apo A-I concentrations decreased after the NCEP Step I and MUFA diets compared with the usual diet. HDL cholesterol also decreased after the NCEP Step I diet. Total:HDL cholesterol, apo B, and apo B:apo A-I were lower after the MUFA diets than after the NCEP Step I diets. There were no significant differences between the lipid profiles obtained after the NCEP Step I and MUFA diets were enriched with cholesterol. The capacity of serum to promote cholesterol efflux was significantly higher after the cholesterol-enriched NCEP Step I diet than after the NCEP Step I diet. CONCLUSIONS: The MUFA diet induced a better lipid profile than the NCEP Step I diet; however, the increase in the cholesterol content of both diets produced similar plasma lipid changes. The cholesterol in the NCEP Step I diet increased the cholesterol efflux induced by total serum. |
| Effects of different doses of norethisterone on ovarian function, serum sex hormone binding globulin and high density lipoprotein-cholesterol Song, S., J. K. Chen, et al. (1993), Contraception 47(6): 527-37. Abstract: The ovarian effects of different doses of norethisterone (NET) were compared in 45 normally menstruating women in order to find the lowest effective dose of the Chinese NET "visiting pill". Subjects were randomly divided into 3 groups. Each subject in each group was taking 0.5, 1.5 or 3.0 mg per day from days 5 to day 18 of the cycle. Blood samples were taken on days 5, 8, 11, 14, 17, 20, 23, 26 and 29 of the cycle. Serum oestradiol (E2), progesterone (P), sex hormone binding globulin (SHBG), high density-lipoprotein cholesterol (HDL-C), and NET concentrations were measured. Ovulation, delayed ovulation, ovulation inhibition and follicular activity were classified by the analysis of the peripheral serum levels of sex hormones. Ovulation occurred in 7 women in the 0.5 mg group, in 2 women in the 1.5 mg group and in none of the 3.0 mg group. Mean serum SHBG levels were reduced progressively by 6.6% (Group 0.5), 15.5% (Group 1.5) and 23.4% (Group 3.0). There were no significant changes in HDL-C levels in any group. There was a significant correlation of mean serum NET concentrations with dose. The lack of complete inhibition of ovulation in most women in the 1.5 mg and 0.5 mg groups might suggest that the dose of NET required when used as a visiting pill could not be reduced below 3.0 mg. |
| Effects of different exercise training intensities on lipoprotein cholesterol fractions in healthy middle-aged men Stein, R. A., D. W. Michielli, et al. (1990), Am Heart J 119(2 Pt 1): 277-83. Abstract: Exercise training has been associated with decreases in total cholesterol and increases in high-density lipoprotein (HDL) cholesterol. The effect of the intensity of the exercise on alterations in cholesterol and lipoprotein fractions has not been defined and is the subject of this study. We divided 49 healthy men (aged 44 +/- 8 years) into four groups and evaluated them before and after 12 weeks of cycle ergometer exercise training at (1) an intensity of 65% of maximal achieved heart rate, (2) 75% maximal heart rate, (3) 85% maximal heart rate, and (4) a 12-week nonexercise control period. Pre- and post-training evaluations included maximal ergometer exercise ECG examinations with measurement of maximal minute oxygen consumption and serum total cholesterol, HDL cholesterol, and triglyceride levels. Low-density (LDL) and very low-density lipoprotein (VLDL) cholesterol levels were calculated. Dietary histories were obtained before and after the training period, and body weight and percentage of body fat were measured. Post-training oxygen uptake was significantly increased (training effect) in the groups exercising to 65%, 75%, and 85% maximal heart rate. Results of within-group analysis showed significant increases in the HDL cholesterol fractions in the 75% and 85% groups but not in the 65% group or the control group. Significant decreases in calculated LDL fractions occurred only in the 75% exercise-trained group with maximal heart rate. Aerobic exercise training favorably alters plasma lipoprotein profiles. A minimum training intensity equal to 75% maximal heart rate is required to the increase HDL cholesterol level. |
| Effects of different fibre sources and fat addition on cholesterol and cholesterol-related lipids in blood serum, bile and body tissues of growing pigs Kreuzer, M., H. Hanneken, et al. (2002), J Anim Physiol Anim Nutr (Berl) 86(3-4): 57-73. Abstract: Knowledge is limited on the efficacy of hindgut-fermentable dietary fibre to reduce blood, bile and body tissue cholesterol levels. In three experiments with growing pigs the effects of different kinds and levels of bacterially fermentable fibre (BFS) on cholesterol metabolism were examined. Various diets calculated to have similar contents of metabolizable energy were supplied for complete fattening periods. In the first experiment, a stepwise increase from 12 to 20% BFS was performed by supplementing diets with fermentable fibre from sugar beet pulp (modelling hemicelluloses and pectin). Beet pulp, rye bran (modelling cellulose) and citrus pulp (pectin) were offered either independently or in a mixture in the second experiment. These diets were opposed to rations characterized in carbohydrate type by starch either mostly non-resistant (cassava) or partly resistant (maize) to small intestinal digestion. The third experiment was planned to explore the interactions of BFS from citrus pulp with fat either through additional coconut oil/palm kernel oil blend or full-fat soybeans. In all experiments the increase of the BFS content was associated with a constant (cellulose) or decreasing (hemicelluloses, pectin) dietary proportion of non-digestible fibre. In experiment 1 an inverse dose-response relationship between BFS content and cholesterol in blood serum and adipose tissue as well as bile acid concentration in bile was noted while muscle cholesterol did not respond. In experiment 2 the ingredients characterized by cellulose and hemicelluloses/pectin reduced cholesterol-related traits relative to the low-BFS-high-starch controls whereas, except in adipose tissue cholesterol content, the pectinous ingredient had the opposite effect. However, the changes in serum cholesterol mainly affected HDL and not LDL cholesterol. Adipose tissue cholesterol also was slightly lower with partly resistant starch compared to non-resistant starch in the diet. Experiment 3 showed that the use of citrus pulp increased serum cholesterol concentrations when levels were low in the corresponding low-BFS diets (low-fat and soy bean diets), but caused no further increase in the coconut-oil/palm kernel oil blend diet. From the present results it seems that fermentable hemicelluloses have a more favourable effect of decreasing metabolic cholesterol and related traits than hardly digestible fibre, fermentable cellulose or, particularly, pectin. Furthermore, some types of fibre expressed a certain potential to reduce cholesterol content of fat pork and pork products by up to 10% (experiment 1) and 25% (experiment 2). |
| Effects of different forms of dietary hydrogenated fats on serum lipoprotein cholesterol levels Lichtenstein, A. H., L. M. Ausman, et al. (1999), N Engl J Med 340(25): 1933-40. Abstract: BACKGROUND: Metabolic studies suggest that fatty acids containing at least one double bond in the trans configuration, which are found in hydrogenated fat, have a detrimental effect on serum lipoprotein cholesterol levels as compared with unsaturated fatty acids containing double bonds only in the cis configuration. We compared the effects of diets with a broad range of trans fatty acids on serum lipoprotein cholesterol levels. METHODS: Eighteen women and 18 men consumed each of six diets in random order for 35-day periods. The foods were identical in each diet, and each diet provided 30 percent of calories as fat, with two thirds of the fat contributed as soybean oil (<0.5 g of trans fatty acid per 100 g of fat), semiliquid margarine (<0.5 g per 100 g), soft margarine (7.4 g per 100 g), shortening (9.9 g per 100 g), or stick margarine (20.1 g per 100 g). The effects of those diets on serum lipoprotein cholesterol, triglyceride, and apolipoprotein levels were compared with those of a diet enriched with butter, which has a high content of saturated fat. RESULTS: The mean (+/-SD) serum low-density lipoprotein (LDL) cholesterol level was 177+/-32 mg per deciliter (4.58+/-0.85 mmol per liter) and the mean high-density lipoprotein (HDL) cholesterol level was 45+/-10 mg per deciliter (1.2+/-0.26 mmol per liter) after subjects consumed the butter-enriched diet. The LDL cholesterol level was reduced on average by 12 percent, 11 percent, 9 percent, 7 percent, and 5 percent, respectively, after subjects consumed the diets enriched with soybean oil, semiliquid margarine, soft margarine, shortening, and stick margarine; the HDL cholesterol level was reduced by 3 percent, 4 percent, 4 percent, 4 percent, and 6 percent, respectively. Ratios of total cholesterol to HDL cholesterol were lowest after the consumption of the soybean-oil diet and semiliquid-margarine diet and highest after the stick-margarine diet. CONCLUSIONS: Our findings indicate that the consumption of products that are low in trans fatty acids and saturated fat has beneficial effects on serum lipoprotein cholesterol levels. |
| Effects of different hybrids, strains and age of laying hens on the cholesterol content of the table egg Kovacs, G., K. Dublecz, et al. (1998), Acta Vet Hung 46(2): 285-94. Abstract: Three experiments were carried out to investigate the effects of age, moulting and strain of hens on the weight, total cholesterol content (TCh) and cholesterol concentration (CCh) of egg yolk. Only slight differences were found in the TCh and CCh of eggs between white and brown egg layer hybrids (Shaver SC 288 vs. Shaver SC 579) of the same age. On the other hand, significant differences (p < 0.05) were found in yolk CCh and TCh of both hybrids during the production period. The change in yolk CCh was periodical: it decreased in both hybrids until 45 weeks of age, then it increased, reaching a plateau between weeks 51 and 54, and declined again at the end of production. TCh, however, increased until 51 (Shaver SC 579) or 54 (Shaver SC 288) weeks of age, which could be attributed to the steady increase in yolk weight throughout the production period. In the eggs of Tetra-SL hens yolk weight, yolk CCh and TCh were slightly higher after moulting (at 108 weeks of age) than in the first production period (at 48 weeks of age), but the differences were not significant (p > 0.05). Significant inter-strain differences (p < 0.05) were found, however, in the yolk parameters measured. The highest values were found in the eggs of New Hampshire hens, as compared to the traditional Hungarian breeds. The eggs of traditional pure-bred hens contained a substantially higher amount of cholesterol than those produced by the hybrids. |
| Effects of different phenotypes of hyperlipoproteinemia and of treatment with fibric acid derivatives on the rates of cholesterol 7 alpha-hydroxylation in humans Bertolotti, M., M. Concari, et al. (1995), Arterioscler Thromb Vasc Biol 15(8): 1064-9. Abstract: Little is known about the relationships between hyperlipidemia and bile acid metabolism. However, hypolipidemic treatment with fibric acid derivatives has been shown to increase biliary cholesterol secretion, presumably by reducing bile acid synthesis. To clarify such relationships, we investigated the effects of different hyperlipoproteinemic conditions and of treatment with fibric acid derivatives on the rates of cholesterol 7 alpha-hydroxylation (the limiting step of bile acid synthesis) in humans. We studied 10 patients (aged 36 to 68 years) with lipoprotein phenotype IIa and with a clinical diagnosis of heterozygous familial hypercholesterolemia, a condition of reduced activity of LDL receptors, and 11 patients (aged 48 to 70 years) with lipoprotein phenotype IIb or IV and clinical diagnosis of familial combined hyperlipidemia, a condition probably related to increased hepatic lipoprotein synthesis. Cholesterol 7 alpha-hydroxylation rates were assayed in vivo by tritium release assay after an intravenous injection of 7 alpha-3Hcholesterol. The results were compared by ANOVA to the values obtained in a group of 28 normolipidemic patients (aged 34 to 83 years), with age as the covariate. Six patients were also studied after treatment with gemfibrozil (900 to 1200 mg/d for 6 to 8 weeks) and 5 patients were studied after treatment with bezafibrate (400 mg/d for 6 to 8 weeks). Hydroxylation rates were 0.82 +/- 0.22 mmol/d in the familial hypercholesterolemia group and 1.30 +/- 0.47 mmol/d in the familial combined hyperlipidemia group (P <.05 between the two groups and between patients with familial combined hyperlipidemia and control subjects; P = NS between patients with familial hypercholesterolemia and control subjects, as determined by ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS) |
| Effects of different types of polyunsaturated fatty acids on cholesterol esterification in human fibroblasts Pal, S. and P. J. Davis (1991), Biochem Int 25(2): 281-8. Abstract: We have enriched human fibroblasts with oleic acid, with linoleic acid and with eicosapentaenoic acid. The accumulation of cholesteryl esters in the cells and the rate of esterification of cholesterol by microsomal acyl-CoA:cholesterol acyltransferase (ACAT) were measured in these cells. Cholesteryl ester levels were lower in cells enriched with eicosapentaenoic acid compared with cells enriched with oleate or linoleate. We also observed significantly lower ACAT activities in the microsomes from fibroblasts enriched with the n-3 polyunsaturated fatty acids relative to cells enriched with oleic acid or linoleic acid. We suggest that the presence of n-3 polyunsaturated fatty acids might suppress cholesteryl ester accumulation and inhibit atherogenesis. |
| Effects of disodium ascorbyl phytostanol phosphates (FM-VP4) on cholesterol accumulation within rat intestinal cells Wasan, K. M., E. Yau, et al. (2003), AAPS PharmSci 5(1): E6. Abstract: The objective of this study was to determine whether FM-VP4, a novel compound derived from plant sterols, can effectively reduce cholesterol accumulation within rat intestinal epithelial crypt (IEC-6) cells. EC-6 cells were cultured in Dulbecco's minimal essential medium (DMEM) containing 5% fetal bovine serum, 100 U/mL penicillin, 100 micro g/mL streptomycin, and 0.1 units/mL insulin at 37 degrees C under a humidified 5% CO2 atmosphere and seeded at 6.4 x 10(4) cells/well in 48-well plates. Experiments were initiated 14 days postconfluence. IEC-6 cells were exposed to 3Hcholesterol micelles (containing oleic and taurcholic acids), co-incubated with FM-VP4 (0, 10, 50, and 100 micro M) in Hepes Buffered Sterile Saline (HBSS). Cells were also preincubated with FM-VP4 prior to 3Hcholesterol micelle incubation to determine whether its effects are elicited intracellularly. The cellular localization of cholesterol was determined using digitonin. To determine the effects of cholesterol on the extent of FM-VP4 accumulation within IEC-6 cells, 3HFM-VP4 was incubated with IEC-6 cells in the presence of unlabeled cholesterol micelles (0, 10, and 50 micro M). The extent of 3Hcholesterol or 3HFM-VP4 associated with cell monolayers was determined after cell lysis using liquid scintillation counting in a Beckman LS6500 Scintillation Counter. Dose-response and time course studies were performed in which control (no FM-VP4 treatment) and FM-VP4 (10-100 micro M) were co-incubated with 50- micro M 3Hcholesterol micelles from 1 minute to 24 hours. Incubation with only 50- micro M FM-VP4 for less than 24 hours resulted in a 50% to 60% reduction (n = 6, P <.05) in 3Hcholesterol associated with the monolayer compared with control (n = 6). Preincubation of FM-VP4 did not elicit a significant reduction in cholesterol accumulation compared with control (n = 6). Approximately 25% of the total 3Hcholesterol associated with the cells was determined to be cytosolic, while 75% was noncytosolic in the presence and/or absence of FM-VP4. 3HFM-VP4 was also shown to associate with IEC-6 cells at similar concentrations to cholesterol with the most pronounced inhibition of FM-VP4 accumulation occurring at a cholesterol concentration of 50 micro M. However, cholesterol-induced inhibition was detectable only after 1 hour of incubation. FM-VP4 inhibits cholesterol accumulation within IEC-6 cells and is most effective at equimolar concentrations with cholesterol. Our findings further suggest that the action of FM-VP4 is likely at the cell surface and not elicited intracellularly. |
| Effects of doxazosin on atherosclerosis in cholesterol-fed rabbits Swindell, A. C., M. N. Krupp, et al. (1993), Atherosclerosis 99(2): 195-206. Abstract: Doxazosin was administered to rabbits fed diets enriched in cholesterol and peanut oil for 7.5 or 12 weeks, in 2 separate experiments. Doxazosin suppressed the accumulation of cholesterol and formation of atherosclerotic plaques in the aortas of treated rabbits and prevented a diet-induced increase in aortic collagen and wall mass. Doxazosin was more effective in the thoracic and abdominal segments of the aorta than in the aortic arch. Pharmacokinetic analysis indicated that treated rabbits were exposed to concentrations of doxazosin, integrated over 24 h, which were consistent with the therapeutic range of doxazosin measured in patients treated for hypertension. Doxazosin did not alter serum levels of cholesterol or triglycerides, nor were there any consistent effects on glucose, free fatty acid or ketone levels. Hypotheses of the mechanism of action of doxazosin are discussed, including the possible involvement of alpha 1-adrenergic receptors in recruitment of smooth muscle cells by subintimal macrophages and nonadrenergic mechanisms of inhibition of lipid infiltration. |
| Effects of doxazosin on functional alterations of isolated coronary arteries from cholesterol-fed rabbits Simonsen, U., D. Prieto, et al. (1996), J Pharm Pharmacol 48(6): 607-14. Abstract: Anti-hypertensive treatment is much less successful at reducing coronary artery disease than at reducing mortality from stroke and congestive heart failure. The effects of the alpha-adrenergic antagonist doxazosin on progression of atheromatous lesions and functional responses of isolated coronary arteries from cholesterol-fed rabbits have been investigated. Normotensive rabbits were fed either a standard chow (control, n = 8) or a 1% cholesterol-rich diet (n = 16) for 20 weeks. After 3 weeks the cholesterol-fed animals were assigned randomly to two groups either given placebo capsules (n = 8) or treated with doxazosin (5 mg kg-1 day-1; n = 8). Doxazosin reduced the mean arterial blood pressure by 10% that of the control and placebo-treated cholesterol-fed rabbits, but did not affect the plasma cholesterol, triacylglycerol and phospholipid levels, which were, after 20 weeks, severalfold increased in the cholesterol-fed rabbits compared with controls. Histological examination showed atheromatous lesions in proximal (but not distal) coronary arteries from both groups of cholesterol-fed rabbits. Doxazosin either had no effect on reduced contractions to 125 mmol L-1 potassium saline solution or increased contractions to 5-hydroxytryptamine in proximal isolated coronary arteries from the cholesterol-fed rabbits. It did, however, abolish the hyper-responsiveness of the large atheromatous coronary arteries to noradrenaline. In both vehicle-and doxazosin-treated cholesterol-fed rabbits the maximum relaxation and sensitivity to acetylcholine were significantly reduced in proximal segments compared with the control group, whereas responses to acetylcholine in distal coronary segments were not significantly different. The relaxation to sodium nitroprusside, adenosine diphosphate and isoprenaline in proximal and distal coronary arteries were similar in the three experimental groups. These results indicate that treatment of normotensive cholesterol-fed rabbits with doxazosin prevents the hyper-responsiveness to noradrenaline of proximal coronary arteries, although it does not prevent the progression of other functional alterations observed in the coronary circulation. |
| Effects of doxazosin, an alpha 1-adrenergic inhibitor, on plasma lipid and lipoprotein levels, low density lipoprotein metabolism and cholesterol absorption in cynomolgus monkeys Stucchi, A. F., D. B. Vespa, et al. (1993), Atherosclerosis 103(2): 255-66. Abstract: The mechanism(s) by which doxazosin, an alpha 1 inhibitor, regulates plasma low density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) levels were investigated in 'normocholesterolemic' (average total cholesterol (TC) of 218 mg/dl) and 'hypercholesterolemic' (average TC of 350 mg/dl) cynomolgus monkeys. Twelve weeks of doxazosin treatment (1 mg/kg per day) significantly reduced plasma TC and LDL-C levels in both groups while high density lipoprotein cholesterol and apolipoprotein A-I concentrations rose. Despite these changes in plasma lipids, LDL and HDL lipid composition was not affected by doxazosin. The reduction in LDL-C and apo B in the doxazosin-treated 'hypercholesterolemic' group was associated with a significant increase in both receptor-dependent and -independent LDL apo B fractional catabolic rates. Similar associations were noted in the 'normocholesterolemic' group. LDL apo B production or transport rate was not affected by doxazosin. Cholesterol absorption was also significantly reduced by doxazosin which may also contribute to lowering plasma LDL-C levels. These studies suggest that doxazosin treatment can produce beneficial changes in the plasma lipid profile over a wide rage of plasma cholesterol levels by up-regulating LDL fractional clearance. |
| Effects of drugs affecting cholesterol biosynthesis pathway on BM 15.766-induced 7-dehydrocholesterol accumulation in rats. An animal model for testing compounds reducing cholesterol synthesis Pill, J., K. Stegmeier, et al. (1990), Methods Find Exp Clin Pharmacol 12(3): 167-74. Abstract: 7-Dehydrocholesterol (7DHC), an intermediate of cholesterol, accumulates in animals after administration of BM 15.766 and can be measured in addition to cholesterol photometrically. The effect of compounds acting at different points in the cholesterol biosynthetic pathway on BM 15.766-induced 7DHC accumulation was investigated in rats to evaluate its usefulness as in vivo test system for cholesterol lowering agents. 7DHC in liver of rats proved to be an appropriate measure for cholesterol de novo synthesis. In contrast to previously described methods no radiolabelled precursors are necessary. The extraction of 7DHC and its photometric determination is, in comparison with separation and measurement of radioactive cholesterol, a simple analytical procedure. |
| Effects of drugs on cholesterol esterification in normal and Niemann-Pick type C fibroblasts: AY-9944, other cationic amphiphilic drugs and DMSO Yoshikawa, H. (1991), Brain Dev 13(2): 115-20. Abstract: AY-9944 and other cationic amphiphilic drugs (CADs) have been reported to cause a reduction of acid sphingomyelinase activity in fibroblasts and various tissues in the rat, and DMSO has been known to correct a partial deficiency of acid sphingomyelinase activity in Niemann-Pick type C (NPC) fibroblasts. Furthermore, in the present study we demonstrated that AY-9944 and other CADs caused a marked reduction of cholesterol esterification in control fibroblasts and an excessive intracellular accumulation of unesterified cholesterol as in NPC cells, and that this reduction could partially be corrected by the addition of 2% DMSO to the medium. These characteristics of the drug-treated cells mimic the phenomena seen in NPC fibroblasts. Therefore, fibroblasts treated with CADs may be used as a model of drug-induced lipidosis of NPC. The effect of DMSO suggests the possibility of its usefulness in the treatment of NPC patients. |
| Effects of efonidipine hydrochloride on cholesterol esterification mediated by beta-very low density lipoprotein in J774 macrophages Kitahara, M., K. Toyoda, et al. (1995), Jpn J Pharmacol 69(2): 101-9. Abstract: The effects of efonidipine hydrochloride (efonidipine), a dihydropyridine calcium antagonist, on the cholesterol ester metabolism induced by beta-migrating very low density lipoprotein (beta-VLDL) in J774 macrophages were studied. The cholesteryl ester content in the macrophages was increased by incubation with beta-VLDL, and the increase was inhibited by efonidipine. Oleic acid incorporation into cellular cholesteryl ester was increased by beta-VLDL in J774 macrophages. The incorporation at an early phase of beta-VLDL induction (0-3 hr) was inhibited by efonidipine. This inhibitory effect of efonidipine was greater at an early phase of beta-VLDL induction (0-3 hr) than at a late phase of the induction (8-11 hr). Pretreatment of the cells with efonidipine enhanced the inhibitory effect. Efonidipine also inhibited beta-VLDL degradation but not the binding and association in macrophages without pretreatment. beta-VLDL binding and association to macrophages were decreased by pretreatment of the cells with efonidipine. beta-VLDL metabolism was also decreased by dibutyryl cyclic AMP pretreatment. The decrease of beta-VLDL metabolism by efonidipine was prevented by co-treatment with efonidipine and HA1004, a protein kinase A inhibitor. Furthermore, efonidipine increased the intracellular cyclic AMP content in J774 macrophages. These findings suggest that efonidipine suppresses cholesterol ester deposition in atherosclerotic foam cells by inhibiting the modified lipoprotein metabolism and cholesterol esterification mainly through elevation of the cellular cyclic AMP level. |
| Effects of eicosapentaenoic acids on remnant-like particles, cholesterol concentrations and plasma fatty acid composition in patients with diabetes mellitus Nakamura, N., T. Hamazaki, et al. (1998), In Vivo 12(3): 311-4. Abstract: Remnant lipoproteins are transient metabolites from chylomicron and/or very low density lipoproteins (VLDL), and remnant hyperlipoproteinemia has recently been reported to be a risk factor for atherosclerosis. Eicosapentaenoic acid (EPA), a major component of fish oil, has the following effects: anti-platelet aggregation, vaso-dilation, anti-inflammation, hypotriglyceridemia, and therefore has potential anti-atherosclerotic effects. We measured serum of remnant-like particle cholesterol (RLP-C) concentrations, and investigated the effects of EPA on serum RLP-C concentrations in patients with diabetes mellitus. Ten patients with non-insulin dependent diabetes mellitus were treated with 900-1800 mg EPA ethyl-ester daily for 3 months. We investigated serum RLP-C concentrations and plasma fatty acid composition before and after the administration of EPA. Serum RLP-C concentrations were significantly decreased 3 months after the administration of EPA (from 14.5 +/- 5.3 mg/dL to 3.3 +/- 0.8 mg/dL, P < 0.01). Plasma EPA concentrations and the ratios of EPA to arachidonic acids (AA) were significantly increased during the same period (from 86.2 +/- 12.4 mg/L to 194.6 +/- 27.3 mg/L, P < 0.01, from 0.571 +/- 0.074 to 1.242 +/- 0.163. P < 0.01, respectively). Serum RLP-C concentrations were inversely correlated with the ratios of EPA to AA in plasma (r = -.516, P < 0.05). These results suggested that administration of EPA was effective on remnant hyperlipoproteinemia which was a risk factor for atherosclerosis. |
| Effects of eicosapentanoic acid and soybean protein on plasma cholesterol, blood pressure and platelet aggregation in stroke-prone spontaneously hypertensive rats Kimura, S., M. T. Chiang, et al. (1990), Monogr Atheroscler 16: 26-35. |