Cholesterol Journal Articles

Record 7581 to 7600

Influence of the acyl-coenzyme A:cholesterol--acyltransferase inhibitor octimibate on cholesterol transport in rat mesenteric lymph
Windler, E., W. Rucker, et al. (1990), Arzneimittelforschung 40(10): 1108-11.
Abstract: The effect of the new inhibitor of acyl-coenzyme A:cholesterol-acyltransferase, octimibate (sodium 8-1,4,5-triphenyl-1H-imidazole-2yl)-oxy)octanoate), on the cholesterol transport in rat mesenteric lymph was evaluated. During intraduodenal infusion of a triglyceride-phospholipid emulsion, volume and triglyceride concentration of lymph collected from a mesenteric lymph fistula remained constant in control and treated rats. After addition of 3.75 mg 3H-cholesterol/h to the intraduodenal infusion, cholesterol content of lymph increased to about double the basic concentration in control rats. Yet there was no significant change of lymph cholesterol in treated animals, which had received 40 mg octimibate followed by ca. 120 mg/24 h x kg body weight octimibate added to the intraduodenal infusion. Up to 35% of the infused dose of 3H-cholesterol were recovered in lymph of control rats, in contrast to only 23% in lymph of treated rats. It is concluded that the inhibition of the intestinal acyl-coenzyme A:cholesterol-acyltransferase by octimibate may prevent the increase of cholesterol in mesenteric lymph induced by dietary cholesterol.

Influence of the bovine seminal plasma protein PDC-109 on cholesterol in the presence of phospholipids
Muller, P., A. Greube, et al. (2002), Eur Biophys J 31(6): 438-47.
Abstract: The interaction of the major bovine seminal plasma protein PDC-109 with cholesterol was studied by employing spin-labelled analogues. It could be shown that PDC-109 does not interact directly with cholesterol molecules. However, in the presence of phospholipids we found a strong reduction of cholesterol motion by PDC-109. The fraction of immobilized cholesterol was largest for phosphorylcholine-containing lipids. This is consistent with the preferential interaction between PDC-109 and phosphatidylcholine. It is concluded that a stronger association and interaction of PDC-109 with phosphatidylcholine leads to an enhanced fraction of immobilized cholesterol analogues, but not to a phospholipid-dependent specific interaction between the protein and cholesterol. Moreover, the interaction of PDC-109 with various spin-labelled analogues of phosphatidylcholine (lysoPC, diacylPC) was investigated. In membranes of lipid vesicles the protein caused an immobilization of the phosphatidylcholine analogues mainly in the outer membrane leaflet, with no differences between diacylPC and lysoPC. The results are of relevance for understanding the physiological role of PDC-109 in the genesis of sperm cells.

Influence of the HMG-CoA-reductase inhibitor lovastatin on cholesterol saturation index and nucleation time of duodenal bile
Nitsche, R., J. Schlage, et al. (1991), Z Gastroenterol 29(5): 242-5.
Abstract: Owing to the presence of hyperlipoproteinemia IIa, twelve patients without gallstones were treated daily with 20 mg, 40 mg and 80 mg of Lovastatin, each dose being administered for 4 weeks. At the conclusion of each 4-week treatment phase, bile was obtained from the fasting patient following injection of 5 micrograms ceruletid i.v. with the aid of a duodenal tube. The long nucleation time of bile was not shortened by the therapy. The bile cholesterol saturation index showed a decline with Lovastatin, which was particularly obvious in patients with an initially oversaturated bile. In contrast to other lipid-reducing agents (e.g. fibrates), Lovastatin does not lead to increased lithogenesis of the bile, but may in certain circumstances have an prophylactic effect against the formation of gallstones.

Influence of the SstI polymorphism at the apolipoprotein C-III gene locus on the plasma low-density-lipoprotein-cholesterol response to dietary monounsaturated fat
Lopez-Miranda, J., S. Jansen, et al. (1997), Am J Clin Nutr 66(1): 97-103.
Abstract: The plasma lipid response to changes in dietary fat and cholesterol can vary between individuals. The SstI polymorphism, arising from a cytosine to guanosine substitution in the 3' untranslated region of the APOC3 gene distinguishes between two alleles--S1 and S2. The S2 allele has been associated with elevated plasma triacylglycerol, cholesterol, and apolipoprotein (apo) C-III concentrations. In 90 young men we examined the effect of the same mutation on the response of low-density-lipoprotein (LDL) cholesterol to dietary monounsaturated fat. The frequency for the S2 allele was 0.14. Subjects were fed a low-fat diet for 25 d, followed by a diet rich in monounsaturated fatty acid (22% MUFA, 38% total fat) for 28 d; lipoproteins were measured at the end of each diet. There were no significant differences in initial total cholesterol between subjects with the APOC3*S1/APOC3*S1 (S1/S1) and APOC3*S1/APOC3*S2 (S1/S2) genotypes. After consumption of the diet high in MUFA, significant increases in LDL cholesterol (0.13 mmol/L, P < 0.027) were noted in the S1/S1 subjects whereas a significant decrease was observed in the S1/S2 subjects (-0.18 mmol/L, P < 0.046). Significant genotypic effects were seen for diet-induced changes in LDL cholesterol (P < 0.00034), total cholesterol (P < 0.009), and apo B (P < 0.0014). A study of the effect of the interaction between this mutation with that present in position -76 of the APOA1 gene promoter region (G/A) revealed that both mutations had an additive effect on changes in total cholesterol, LDL cholesterol, and apo B induced by diets. Plasma LDL-cholesterol responsiveness to the diet may be explained, at least in part, by variation at the APOC3 gene locus.

Influence of thiol balance on micellar cholesterol handling by polarized Caco-2 intestinal cells
Napolitano, M., G. Rainaldi, et al. (2003), FEBS Lett 551(1-3): 165-70.
Abstract: The in vitro thiol redox modulation of cholesterol homeostasis was investigated in polarized Caco-2 intestinal cells. Cells were pre-incubated with the pro-oxidant compound CuSO4 or with the antioxidant N-acetylcysteine (NAC), to induce a mild shift of the intracellular redox potential toward, respectively, a more oxidizing or a more reducing equilibrium, via a manipulation of intracellular soluble thiols (glutathione). Then, monolayers were exposed to micellar cholesterol and both the cholesterol uptake and export, as well as the cholesteryl ester cycle, were analyzed. We found that pro-oxidizing conditions induced a significant cholesterol retention within the cells, particularly in the unesterified form (FC), as a result of an augmented sterol incorporation coupled with a reduced rate of FC esterification. A reduction in FC export was also evident. Furthermore, the combination of FC retention and the oxidative imbalance leads to significant alterations of the monolayer integrity, evidenced by both the enhanced tight junction permeability and the lactate dehydrogenase release into the basolateral medium. In contrast, a more reducing environment generated by NAC pre-treatment favors the limitation of the resident time of FC into the cells, via a reduced cholesterol uptake and a concomitant increased cholesterol esterification. In addition, a significant higher FC extrusion into the basolateral medium was also appreciable. Our results indicate that the thiol balance of intestinal cells may be critical for the regulation of cholesterol homeostasis at the intestinal level, influencing the lipid transport throughout the intestinal barrier.

Influence of total cholesterol levels on long-term mortality in coronary heart disease: a reappraisal
Gupta, R., A. K. Singh, et al. (2000), Indian Heart J 52(1): 23-8.
Abstract: To examine the prognostic significance of total cholesterol levels at baseline in subjects with stable coronary heart disease, 605 patients with stable coronary heart disease were enrolled; 45 of these did not meet inclusion criteria, 41 were lost to follow-up and 40 opted for coronary bypass surgery. Data of the remaining 479 (389 males, 90 females) were analysed. There were 102 males in group I (cholesterol < 200 mg/dL), 187 in group II (cholesterol 200-239 mg/dL), and 100 in group III (cholesterol > or = 240 mg/dL) and 49 females in group I and 41 in group II. The groups were evenly matched for age and numbers with stable angina or survivors of myocardial infarction. Proportion of smokers, hypertensives, diabetics or obese was also similar (p > 0.05). Mean follow-up in years in men was 6.82 +/- 3.15 in group I, 6.37 +/- 3.11 in group II and 6.81 +/- 2.84 in group III while in women it was 6.95 +/- 2.84 in group I and 7.03 +/- 2.58 years in group II and was not different in various groups (p > 0.05). The overall cardiovascular mortality in various groups in men was 20.6 percent in group I, 28.9 percent in group II and 23.0 percent in group III and in women it was 14.3 percent in group I and 22.0 percent in group II. The crude mortality rate was 2.51 percent per year in males and 1.77 percent per year in females. Actuarial survival at end of seven years in males was 0.76 +/- 0.05 in group I, 0.67 +/- 0.04 in group II, and 0.67 +/- 0.05 in group III and in females it was 0.85 +/- 0.05 in group I and 0.73 +/- 0.09 in group II. The cumulative hazard rates per 1000 person- year follow-up in group I, II and III in males were, at age less than 50 years: 5.4 +/- 5, 19.8 +/- 7, 17.4 +/- 8; at 50-59 years: 23.8 +/- 11, 38.5 +/- 9, 39.8 +/- 13; and at 60 years and over: 76.9 +/- 20, 112.6 +/- 20, 108.2 +/- 28, respectively (p < 0.001 on comparison of group I with groups II and III). In females the trends were not significant. Total cholesterol levels at baseline predict long-term cardiovascular mortality in men with stable coronary heart disease.

Influence of total cholesterol, high density lipoprotein cholesterol, and triglycerides on risk of cerebrovascular disease: the Copenhagen City Heart Study
Lindenstrom, E., G. Boysen, et al. (1994), Bmj 309(6946): 11-5.
Abstract: OBJECTIVE--To estimate the influence of plasma total cholesterol, high density lipoprotein cholesterol, and triglycerides on risk of cerebrovascular disease. DESIGN--The Copenhagen City Heart Study is a prospective observational survey with two cardiovascular examinations at five year intervals. Non-fasting plasma lipids were measured in participants once at each examination, along with other variables. The Cox regression model was used to establish the effect of the factors recorded on cerebrovascular events of mostly, but not exclusively, ischaemic origin. SUBJECTS--19,698 women and men at least 20 years old, randomly selected after age stratification from an area of central Copenhagen. MAIN OUTCOME MEASURES--Initial cases of stroke and transient ischaemic attack recorded from hospital records and death certificates from 1976 through 1988. RESULTS--660 non-haemorrhagic and 33 haemorrhagic events were recorded. Total cholesterol was positively associated with risk of non-haemorrhagic events, but only for levels > 8 mmol/l, corresponding to the upper 5% of the distribution in the study population. For lower plasma cholesterol values the relative risk remained nearly constant. Plasma triglyceride concentration was significantly, positively associated with risk of non-haemorrhagic events. The relative risk corresponding to an increase of 1 mmol/l was 1.12 (95% confidence interval 1.07 to 1.16). There was a negative, log linear association between high density lipoprotein cholesterol and risk of non-haemorrhagic events (0.53 (0.34 to 0.83)). There was no indication that the effects of plasma lipids were different in women and men. CONCLUSIONS--The pattern of the association between plasma cholesterol and risk of ischaemic cerebrovascular disease was not log linear, and the increased risk was confined to the upper 5% of the cholesterol distribution. Further studies should concentrate on the association between plasma cholesterol and verified haemorrhagic stroke.

Influence of total lipid concentration, bile salt:lecithin ratio, and cholesterol content on inter-mixed micellar/vesicular (non-lecithin-associated) bile salt concentrations in model bile
Donovan, J. M., N. Timofeyeva, et al. (1991), J Lipid Res 32(9): 1501-12.
Abstract: We modified classic equilibrium dialysis methodology to correct for dialysant dilution and Donnan effects, and have systematically studied how variations in total lipid concentration, bile salt (taurocholate):lecithin (egg yolk) ratio, and cholesterol content influence inter-mixed micellar/vesicular (non-lecithin-associated) concentrations (IMC) of bile salts (BS) in model bile. To simulate large volumes of dialysant, the total volume (1 ml) of model bile was exchanged nine times during dialysis. When equilibrium was reached, dialysate BS concentrations plateaued, and initial and final BS concentrations in the dialysant were identical. After corrections for Donnan effects, IMC values were appreciably lower than final dialysate BS concentrations. Quasielastic light scattering was used to validate these IMC values by demonstrating that lipid particle sizes and mean scattered light intensities did not vary when model biles were diluted with aqueous BS solutions of the appropriate IMC. Micelles and vesicles were separated from cholesterol-supersaturated model bile, utilizing high performance gel chromatography with an eluant containing the IMC. Upon rechromatography of micelles and vesicles using an identical IMC, there was no net transfer of lipid between micelles and vesicles. To simulate dilution during gel filtration, model biles were diluted with 10 mM Na cholate, the prevailing literature eluant, resulting in net transfer of lipid between micelles and vesicles, the direction of which depended upon total lipid concentration and BS/lecithin ratio. Using the present methodology, we demonstrated that inter-mixed micellar/vesicular concentrations (IMC) values increased strongly (5 to 40 mM) with increases in both bile salt (BS):lecithin ratio and total lipid concentration, whereas variations in cholesterol content had no appreciable effects. For model biles with typical physiological biliary lipid compositions, IMC values exceeded the critical micellar concentration of the pure BS, implying that in cholesterol-supersaturated biles, simple BS micelles coexist with mixed BS/lecithin/cholesterol micelles and cholesterol/lecithin vesicles. We believe that this methodology allows the systematic evaluation of IMC values, with the ultimate aim of accurately separating micellar, vesicular, and potential other cholesterol-carrying particles from native bile.

Influence of trapidil and derivatives on cholesterol synthesis and esterification in cultured cells
Beitz, J., A. Corsini, et al. (1991), Pharmacol Res 24(3): 235-42.
Abstract: The effect of trapidil (Rocornal) and its derivatives AR 12456 and AR 12463 on endogenous cholesterol synthesis and on cholesterol esterification rate was studied in human skin fibroblasts (HSF), in human hepatoma cell line Hep G2 and in primary culture of peritoneal macrophages from mouse (PMM). The cholesterol esterification rate was not influenced by the drugs in the tested cell lines. The incorporation of 14Cacetate into cholesterol in HSF was inhibited by AR 12463 and AR 12456, but not by trapidil. The inhibitory potency of AR 12456 in HSF was enhanced after preincubation of the drug with Hep G2 and removal of the medium to HSF, suggesting that the formed metabolite(s) are more potent inhibitors than the parent substance. The metabolite(s) formed seem(s) to influence the first steps in the endogenous formation of cholesterol, because the incorporation of 14Cmevalonate into cholesterol was not significantly inhibited. These findings suggest that the demonstrated inhibition of the endogenous cholesterol synthesis by AR 12456, especially after transformation into a probably more active substance(s), together with the recently described enhanced expression of LDL receptors in Hep G2 cells may partially explain the hypocholesterolaemic activity of AR 12456.

Influence of triglyceride concentration on the relationship between lipoprotein cholesterol and apolipoprotein B and A-I levels
Leroux, G., I. Lemieux, et al. (2000), Metabolism 49(1): 53-61.
Abstract: A sample of 2,103 men aged 47 to 76 years from the Quebec Cardiovascular Study cohort was examined to quantify the influence of plasma triglyceride (TG) levels on the relationship between plasma lipoprotein cholesterol and either apolipoprotein A-I (apo A-I) or apo B concentrations. Regression analyses between high-density lipoprotein cholesterol (HDL-C) and apo A-I through TG tertiles showed highly significant correlations (62 < or = r < or =.75, P <.0001) in all TG tertiles between these 2 variables. The associations for plasma apo B versus low-density lipoprotein cholesterol (LDL-C) and non-HDL-C levels were also studied on the basis of TG concentrations, and correlation coefficients between either LDL-C or non-HDL-C and apo B were essentially similar among TG tertiles (78 < or = r < or =.85 and.83 < or = r < or =.86 for LDL-C and non-HDL-C, respectively, P <.0001). Regression analyses also showed that lower HDL-C levels were found for any given apo A-I concentration among men in the 2 upper TG tertiles, whereas lower LDL-C concentrations were observed at any given apo B level among subjects in the upper TG tertile. We further investigated whether there were synergistic alterations in the HDL-C/apo A-I and LDL-C/apo B ratios as a function of increasing plasma TG. A significant association was noted between these 2 ratios (r =.37; P <.0001). Mean HDL-C/apo A-I and LDL-C/apo B ratios were then calculated across quintiles of plasma TG concentrations. Increased TG concentrations were first associated with a reduced HDL-C/apo A-I ratio, followed by a decreased LDL-C/apo B ratio. These results suggest that a relatively modest increase in TG may rapidly alter the relative cholesterol content of HDL particles. Finally, the cholesterol content of the non-HDL fraction appears to be influenced less by TG levels than HDL-C and LDL-C fractions. Thus, the plasma apo B-containing lipoprotein cholesterol level may provide a better index of number of atherogenic particles than the LDL-C concentration, particularly in the presence of hypertriglyceridemia (HTG).

Influence of two guar preparations on glycosylated hemoglobin, total cholesterol and triglycerides in patients with diabetes mellitus
Kirsten, R., B. Heintz, et al. (1992), Int J Clin Pharmacol Ther Toxicol 30(12): 582-6.
Abstract: Guar smoothens postprandial glucose peaks and reduces serum cholesterol. Both properties are advantageous for diabetic patients and can be realized, in part, by adding fiber to the diet. Depending on the blood glucose concentration, a small portion is incorporated into hemoglobin (HbA1), building a largely irreversible complex, making it a long-term indicator of blood glucose status. HbA1 may increase from a normal value of about 5% to as much as 20% of total hemoglobin in diabetics. This study tested the efficacy of two guar preparations in diabetic patients over 3 months by measuring HbA1, cholesterol and triglycerides. Forty diabetic patients with HbA1 > 10% ingested either 3 x 4 g daily of a new guar preparation (GU-052, Steigerwald, Darmstadt, Germany) or 3 x 5 g daily of Glucotard (Boehringer, Mannheim, Germany) for 12 weeks. Before and after 30, 60 and 90 days of treatment, HbA1, cholesterol and triglycerides were determined. After 90 days of treatment, GU-052 caused a reduction in HbA1 from 12.6 +/- 2.6% to 10.5 +/- 1.5% (-15.6 +/- 9.0%) in the GU-052 group and from 12.0 +/- 2.6% to 10.9 +/- 1.82% (-8.6 +/- 7.2%) in the Glucotard group. Cholesterol was reduced from 269 +/- 28 mg/100 ml on day 0 to 227 +/- 18 mg/100 ml on day 90 in the GU-052 group and from 261 +/- 40 to 235 +/- 26 mg/100 ml in the Glucotard group. Both GU-052 and Glucotard had little effect on plasma triglycerides. Fewer unpleasant side effects were reported for the GU-052 preparation than for Glucotard.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of use of the direct LDL-cholesterol (LDL-C) assay on diagnosis and treatment for patients with hyperlipidemia--analysis using the hospital information system
Goto, S., I. Ohsawa, et al. (2005), Rinsho Byori 53(6): 509-13.
Abstract: Many hospitals have recently begun to use the direct LDL-C assay which can provide an accurate value of LDL-C concentration in serum with hyper-triglyceridemia. This may have altered diagnosis and treatment of patients with hyperlipidemia. To evaluate the influence of the use of the direct LDL-C assay, we analyzed medical data from the hospital information system. The total number of the direct LDL-C assays amounted to around 1,000 per month, while that of beta-lipoprotein fell to around 50 per month. The monthly number of patients who were treated with statin drugs did not increase: from 37.4+/-2.2 (mean+/-SD) to 37.5+/-1.3 per 1,000 outpatients (p=0.932). Also the monthly number of patients who were prescribed statin drugs for the first time remained at a similar level: from 1.6+/-0.5 to 1.3+/-0.2 per 1,000 outpatients (p=0.063). These results suggest that the determination of the LDL-C value has not significantly changed the diagnosis and treatment of patients with hyperlipidemia.

Influence of vesicle surface composition on the interfacial binding of lecithin:cholesterol acyltransferase and apolipoprotein A-I
Miller, K. R. and J. S. Parks (1997), J Lipid Res 38(6): 1094-102.
Abstract: Interfacial binding affinities and capacities of lecithin:cholesterol acyltransferase (LCAT) and apolipoprotein A-I (apoA-I) for surfaces of different phosphatidylcholine (PC) composition, cholesterol content, and apolipoprotein content were measured with a vesicle model system. Native polyacrylamide gel electrophoresis was used to separate free protein from vesicle-bound protein. ApoA-I was isolated from human plasma and radiolabeled with iodine, whereas radiolabeled LCAT was purified from the media of Chinese hamster ovary cells that were transfected with human LCAT cDNA and incubated in the presence of 35S cysteine and methionine. Bound and free radiolabeled LCAT and apoA-I were quantified by phosphorimage analysis. ApoA-I binding was not influenced by cholesterol content (14 mole%) but was influenced by the PC fatty acyl composition of the vesicle. PC species containing long chain, polyunsaturated fatty acids (PUFA) in the sn-2 position resulted in increased binding affinity (Kd = 75-177 nM) but reduced capacity (0.1-0.3 apoA-I/ 1000 PC) in comparison to sn-1 palmitoyl, sn-2 oleoyl PC (POPC, 750 nM and 1.4 apoA-I/1000 PC). LCAT binding affinity to POPC (2190 nM) was stronger in the presence of cholesterol (530 nM), and LCAT binding capacity was reduced (2.63 and 0.6 molecules LCAT/1000 PC, respectively). In comparison to POPC, LCAT binding affinity to sn-1 palmitoyl, sn-2 arachidonyl PC was stronger (611 nM) and binding capacity was reduced (0.7 LCAT/1000 PC). LCAT binding affinity and capacity to sn-1 palmitoyl, sn-2 eicosapentaneoyl PC (2041 nM, and 2.5 LCAT/1000 PC) were similar to those observed for POPC. We conclude that vesicle surface PC fatty acyl composition and cholesterol content significantly influence LCAT and apoA-I interfacial binding and therefore may alter LCAT enzymatic activity.

Influence of weight reduction on plasma high-density-lipoprotein cholesterol concentrations in severe obesity: interrelationships with plasma insulin levels
Cominacini, L., U. Garbin, et al. (1991), Ann Nutr Metab 35(6): 339-46.
Abstract: The influence of caloric restriction and of weight loss during a weight-maintaining diet on lipid profile and in particular on high density lipoprotein (HDL) is controversial. In this study we analyzed the effect of a period of very low caloric diet (VLCD) and of a period of hypocaloric diet followed by 30 days of weight stabilization on lipoprotein levels, especially on HDL cholesterol and its subfractions (HDL2 and HDL3) and on the summated means of glucose (sigma glucose) and insulin levels (sigma IRI) after an oral tolerance test in a group of obese females. Body weight decreased significantly during the VLCD and hypocaloric diet. Total cholesterol decreased significantly after the VLCD and hypocaloric diet, but after the period of the weight-maintaining diet it was superimposable to the initial value. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol behaved like total cholesterol. HDL2, HDL3 and HDL cholesterol decreased significantly after the period of VLCD. Then, after the hypocaloric diet the values of HDL2, HDL3 and HDL cholesterol returned towards the initial values and only after the period of the weight-maintaining diet did their values increase significantly. sigma glucose did not vary significantly at any time of the study, while sigma IRI reduced significantly both after the hypocaloric diet and the weight-maintaining diet. HDL2 and HDL cholesterol changes were found to be positively correlated to the variations of sigma IRI both at day 45 and 75 of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of withdrawal of statin treatment on proinflammatory response and fibrinolytic activity in humans: an effect independent on cholesterol elevation
Lai, W. T., K. T. Lee, et al. (2005), Int J Cardiol 98(3): 459-64.
Abstract: BACKGROUND: In addition to lowering lipid profile, statins have pleiotropic effects on improving vascular function. Changes of these pleiotropic effects and their relationship to lipid profile after withdrawal of statin treatment remained unclear. METHODS: We investigated the changes of lipid profile and plasma concentrations of human soluble vascular cell adhesion molecule-1 (sVCAM-1) and human tissue type plasminogen activator (tPA) after withdrawal of statin treatment. Twenty-two patients (14 F, 8 M, aged 63+/-13 years) with hypercholesterolemia were treated with atorvastatin (ATOR; 10 mg/day) for 12 weeks. Blood samplings for serum lipid and markers were collected before, after and withdrawal of statin treatment. RESULTS: The total cholesterol, LDL-cholesterol and sVCAM-1 (from 394.4+/-251.7 to 321.0+/-198.9 ng/ml, p<0.05) all decreased significantly and the tPA (from 9.47+/-3.57 to 11.62+/-3.99 ng/ml, p<0.05) increased significantly after atorvastatin treatment. During the following 3 days after withdrawal of atorvastatin, the total cholesterol and LDL-cholesterol did not show any significant change. However, the plasma sVCAM-1 significantly elevated on day 2 (from 321.0+/-198.9 to 371.2+/-220.4 ng/ml, p<0.05) and the plasma tPA significantly decreased on day 1 (from 11.62+/-3.99 to 10.52+/-3.55 ng/ml, p<0.05) and day 3 (from 11.62+/-3.99 to 10.27+/-3.69 ng/ml, p<0.05). Both the significant elevation of sVCAM-1 and decrease of tPA after withdrawal of atorvastatin treatment occurred within 3 days, while the serum cholesterol and LDL-chol levels did not have any significant change and were still within the therapeutic range. CONCLUSIONS: After 12 weeks of atorvastatin treatment, the beneficial pleiotropic effects can be demonstrated simultaneously with lowering the lipid profile. However, after withdrawal of atorvastatin, the beneficial pleiotropic effects are abrogated rapidly within days and are independent on elevation of serum cholesterol.

Influence of yogurt and acidophilus yogurt on serum cholesterol levels in mice
Akalin, A. S., S. Gonc, et al. (1997), J Dairy Sci 80(11): 2721-5.
Abstract: The effects of yogurt and acidophilus yogurt on the weight gain, serum cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, and the numbers of fecal lactobacilli and coliforms were investigated in mice assigned to three dietary treatments for 56 d: 1) commercial rodent chow and water (control), 2) commercial rodent chow and yogurt made from milk inoculated with a 3% (vol/vol) liquid culture of Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus (yogurt), and 3) commercial rodent chow plus yogurt made from milk inoculated with a 0.01% (wt/vol) freeze-dried culture of Streptococcus thermophilus plus Lactobacillus acidophilus. The weight gains of mice receiving yogurt or acidophilus yogurt were higher than those of the mice in the control group. The mean values for serum cholesterol concentrations and LDL cholesterol concentrations were significantly decreased when acidophilus yogurt was fed on d 28 and 56. High density lipoprotein cholesterol and triglycerides were not affected by yogurt or acidophilus yogurt. The highest number of fecal lactobacilli was found in mice receiving acidophilus yogurt, and the number of fecal coliforms of that group was also lower than in the other two groups.

Influence on hazelnut oil administration on peroxidation status of erythrocytes and apolipoprotein B 100-containing lipoproteins in rabbits fed on a high cholesterol diet
Balkan, J., A. Hatipoglu, et al. (2003), J Agric Food Chem 51(13): 3905-9.
Abstract: Hazelnut oil (HO) is rich in monounsaturated fatty acids (MUFA). The effect of a high cholesterol (HC) diet with and without HO on lipids and lipid peroxide levels in plasma, apolipoprotein B 100-containing lipoproteins (VLDL + LDL), and erythrocytes as well as hematological data was investigated in rabbits. A HC diet caused significant increases in lipid peroxide levels in plasma and apo B-containing lipoproteins together with histopathological atherosclerotic findings in aorta. In addition, this diet resulted in hemolytic anemia associated with increased endogenous diene conjugate (DC) levels, but H(2)O(2)-induced malondialdehyde (MDA) levels remained unchanged in erythrocytes. HO supplementation reduced lipid peroxide levels in plasma and apolipoprotein B 100-containing lipoproteins as well as aortic atherosclerotic lesions in rabbits fed an HC diet without any decreasing effect on lipid levels. In addition, HO was found to reduce hemolytic anemia together with significant decreases in DC and H(2)O(2)-induced MDA levels.

Influences of alpha-tocopherol on cholesterol metabolism and fatty streak development in apolipoprotein E-deficient mice fed an atherogenic diet
Peluzio, M. C., A. P. Homem, et al. (2001), Braz J Med Biol Res 34(12): 1539-45.
Abstract: Although the role of oxidized lipoproteins is well known in atherogenesis, the role of vitamin E supplementation is still controversial. There is also little information about cholesterol metabolism (hepatic concentration and fecal excretion) in the new models of atherosclerosis. In the present study, we evaluated the effect of moderate vitamin E supplementation on cholesterol metabolism and atherogenesis in apolipoprotein E (apo E)-deficient mice. Apo E-deficient mice were fed an atherogenic diet containing 40 or 400 mg/kg of alpha-tocopherol acetate for 6 weeks. Total cholesterol in serum and liver and 3-OH-alpha-sterols in feces, and fecal excretion of bile acids were determined and histological analyses of aortic lesion were performed. A vitamin E-rich diet did not affect body weight, food intake or serum cholesterol. Serum and hepatic concentrations of cholesterol as well as sterol concentration in feces were similar in both groups. However, when compared to controls, the alpha-tocopherol-treated mice showed a reduction of about 60% in the atherosclerotic lesions when both the sum of lesion areas and the average of the largest lesion area were considered. These results demonstrate that supplementation of moderate doses of alpha-tocopherol was able to slow atherogenesis in apo E-deficient mice and to reduce atherogenic lipoproteins without modifying the hepatic pool or fecal excretion of cholesterol and bile acids.

Influences of supplementary dietary tungsten on methionine metabolism in rabbits fed a low-cholesterol plus methionine diet
Takagi, S., S. Nakajima, et al. (1998), J Atheroscler Thromb 5(1): 13-20.
Abstract: Hyperhomocysteinemia results from an impaired methionine metabolism. Sulfite oxidase, which is an important enzyme in methionine metabolism, contains molybdenum. In contrast, tungsten has a molybdenum-antagonistic effect. Thus, we hypothesized that dietary tungsten may decrease plasma homocysteine levels and influence methionine metabolism. Male New Zealand White rabbits (n=15) were fed a low-cholesterol basal diet and then placed on three different diets: 0.1% cholesterol (Chol), Chol plus 1% methionine (Met), and Chol plus Met plus 0.1% tungsten (W). The animals received these diets for 20 weeks. Biochemical tests of blood and urine were performed. Plasma homocysteine levels were significantly lower in the Chol+Met+W group than in the Chol+Met group. Plasma levels of total cholesterol, triglyceride, lipid peroxide, and urinary 24-h taurine concentrations were higher in the Chol + Met + W group than in the Chol + Met group. In comparison, concentrations of 2, 3-diphosphoglycerate (2, 3-DPG), reduced glutathione (GSH) in erythrocytes, and urinary 24-h SO4(2) were lower in the Chol+Met+W group than in the Chol+Met group. From these results, tungsten could be expected to exhibit an antiatherogenic effect. Conversely, it may have effects on atherogenic factors. Thus, tungsten may play a number of roles in the methionine metabolism.

Influences of the PPAR alpha-L162V polymorphism on plasma HDL(2)-cholesterol response of abdominally obese men treated with gemfibrozil
Bosse, Y., A. Pascot, et al. (2002), Genet Med 4(4): 311-5.
Abstract: PURPOSE: The effect of gemfibrozil is mediated by the activation of peroxisome proliferator-activated receptor alpha (PPAR alpha). The objective of this study was to determine whether the lipid response to gemfibrozil therapy is influenced by the PPAR alpha-L162V polymorphism. METHODS: Sixty-three abdominally obese men were randomly assigned to a 6-month-intervention program with either receiving a placebo (N = 31) or gemfibrozil (N = 32). RESULTS: In response to gemfibrozil therapy, L162-homozygotes exhibited a 5.5% increase in high-density lipoprotein 2 cholesterol (HDL(2)-C) levels compared with a 50.0% increase among carriers of the V162 allele (P = 0.03). CONCLUSION: These results suggest that the HDL(2)-C response to gemfibrozil is modulated by the PPAR alpha-L162V polymorphism.

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