Cholesterol Journal Articles

Record 9201 to 9220

Myth about the disadvantage of lowering of serum cholesterol level refuted
van der Weijden, T. (1993), Ned Tijdschr Geneeskd 137(28): 1420-1.

N-2-N'-pentyl-(6,6-dimethyl-2,4-heptadiynyl)aminoethyl- (2-methyl-1-naphthylthio)acetamide (FY-087). A new acyl coenzyme a:cholesterol acyltransferase (ACAT) inhibitor of diet-induced atherosclerosis formation in mice
Nagata, Y., M. Yonemoto, et al. (1995), Biochem Pharmacol 49(5): 643-51.
Abstract: FY-087 (N-2-N'-pentyl-(6,6-dimethyl-2,4-heptadiynyl)aminoethyl- (2-methyl-1-naphthylthio)acetamide) was found to be a competitive inhibitor of human microsomal acyl coenzyme A:cholesterol acyltransferase (ACAT) with an IC50 value of 0.11 microM. Under our assay conditions, other ACAT inhibitors tested, specifically YM-750, E-5324, and melinamide, all of which are now in phase I clinical trials or in clinical use in Japan, inhibited this enzyme with IC50 values of 0.18, 0.14, and 3.2 microM, respectively. FY-087 also inhibited ACAT in acetyl-low density lipoprotein loaded human macrophages (THP-1 cells) with an IC50 of 0.17 microM. Following the oral administration of FY-087 (30 mg/kg) to rats, the plasma concentration of FY-087 reached 0.42 microgram/mL after 2 hr. This concentration of FY-087 was enough to inhibit blood vessel ACAT activity. Cholesterol-lowering and anti-atherogenic effects of FY-087 were examined using C57BL/6J mice fed an atherogenic diet. In this mouse model, treatment with FY-087 (28 mg/kg) inhibited the increase in plasma cholesterol levels by about 20% and decreased the hepatic accumulation of free and esterified cholesterol by 61 and 67%, respectively. FY-087 also significantly inhibited the atherogenic diet-induced increase in the fatty-streak lesion area of the proximal aorta by 57% in C57BL/6J mice. These results indicate that FY-087 is not only a therapeutically bioavailable ACAT inhibitor that lowers plasma cholesterol levels, but also an effective anti-atherogenic agent in mice fed an atherogenic diet.

n-3 and n-6 polyunsaturated fatty acids have different effects on acyl-CoA:cholesterol acyltransferase in J774 macrophages
Davis, P. J. (1992), Biochem Cell Biol 70(12): 1313-8.
Abstract: The effects of incubating J774 mouse macrophages with different fatty acids on cholesterol esterification were investigated. In cells incubated with n-3 polyunsaturated fatty acids, the rate of cholesterol esterification was significantly reduced compared with cells incubated with n-6 polyunsaturated fatty acids or with oleic acid. This change in cholesterol esterification appears to be the result of reductions in the activity of acyl-CoA:cholesterol acyltransferase (ACAT) in the endoplasmic reticulum of the macrophages incubated with the n-3 polyunsaturated fatty acids. No differences in microsomal cholesterol were observed among cells incubated with different fatty acids. However, cellular cholesterol levels were lower in cells incubated with n-3 polyunsaturated fatty acids. In microsomes from cells incubated with n-3 polyunsaturated fatty acids, both the Km and the Vmax of ACAT were lower than in microsomes from cells incubated with n-6 fatty acids or oleic acid. These findings may explain some of the reduction in atherosclerotic lesions that are observed with dietary fish oils that contain high levels of n-3 polyunsaturated fatty acids.

n-3 FA increase liver uptake of HDL-cholesterol in mice
le Morvan, V., M. F. Dumon, et al. (2002), Lipids 37(8): 767-72.
Abstract: In humans, diets rich in fish oil (containing n-3 FA) decrease the incidence of coronary artery diseases. This is thought to be caused by the induction in liver and skeletal muscle of genes involved in lipid oxidation, and to the repression in liver and adipose tissue of genes responsible for lipogenesis. n-3 FA are known to reduce the synthesis of FA and TG in the liver, resulting in a decrease of plasma concentrations of TG-rich lipoproteins. On the other hand, little is known of a possible effect of n-3 FA on HDL metabolism. To investigate this question, female C57Bl/6J mice were fed an n-3 FA-enriched diet for 16 wk. As expected from previous studies, we found that total cholesterol, TG, and phospholipids were reduced in the plasma of treated mice. We also found that HDL-cholesterol decreased after this treatment and that the in vivo fractional catabolic rate of HDL-cholesteryl ester was significantly higher in treated mice than in control mice fed a standard diet. Consistent with these results, treated mice exhibited increased uptake of HDL-cholesteryl ester in the liver. Moreover, quantitative reverse transcriptase-PCR analysis showed a two- to threefold increase in scavenger receptor B-1 gene expression. Taken together, these results suggest that an n-3 FA-enriched diet stimulates one step in the reverse cholesterol transport in mice, probably by increasing the amount of the scavenger receptor class B-1. These effects of n-3 FA on HDL metabolism may contribute to their beneficial effects on the vasculature.

n-3 fatty acids of marine origin lower systolic blood pressure and triglycerides but raise LDL cholesterol compared with n-3 and n-6 fatty acids from plants
Kestin, M., P. Clifton, et al. (1990), Am J Clin Nutr 51(6): 1028-34.
Abstract: We compared the cardiovascular risk-reduction potential of three major polyunsaturated fatty acids in a double-blind study. Thirty-three normotensive and mildly hypercholesterolemic men were randomly allocated to one of three diets supplemented with linoleic acid (14.3 g/d), alpha-linolenic acid (9.2 g/d), or eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) (3.4 g/d). Diets were matched to provide similar amounts of the major classes of fatty acids and cholesterol. Blood pressure and plasma lipids were measured for 6 wk after a 3-wk run-in period on the linoleic acid supplement. For the diet supplemented with EPA plus DHA compared with the linoleic acid diet systolic blood pressure fell 5.1 mm Hg (p = 0.01); plasma triglyceride and VLDL cholesterol fell by 39% (p = 0.001) and 49% (p = 0.01), respectively; and LDL cholesterol rose by 9% (p = 0.01). There were no significant changes with the diet supplemented with alpha-linolenic acid. The net effect on cardiovascular risk therefore is complex and the systolic blood pressure reduction was substantial.

n-3 Fatty acids plus oleic acid and vitamin supplemented milk consumption reduces total and LDL cholesterol, homocysteine and levels of endothelial adhesion molecules in healthy humans
Baro, L., J. Fonolla, et al. (2003), Clin Nutr 22(2): 175-82.
Abstract: BACKGROUND AND AIMS: Numerous studies suggest n -3 polyunsaturated fatty acids (n -3 PUFA) and oleic acid intake have beneficial effects on health including risk reduction of coronary heart disease. The purpose of this study was to evaluate the effect of a commercially available skimmed milk supplemented with n -3 PUFA, oleic acid, and vitamins E, B(6), and folic acid (Puleva Omega3) on risk factors for cardiovascular disease. (CVD). METHODS: Thirty volunteers were given 500 ml/day of semi-skimmed milk for 4 weeks and then 500 ml/day of the n -3 enriched milk for 8 further weeks. Plasma and LDL lipoproteins were obtained from volunteers at the beginning of the study (T(pre)), and at 4, 8 and 12 weeks. RESULTS: The consumption of n -3 enriched milk produced a significant decrease in plasma concentration of total and LDL cholesterol accompanied by a reduction in plasma levels of homocysteine. Plasma and LDL oxidability and vitamin E concentration remained unchanged throughout the study. A significant reduction in plasma levels of vascular cell adhesion molecule 1, and an increase in plasma concentration of folic acid were also observed. CONCLUSION: Daily intake of n -3 PUFA and oleic acid supplemented skimmed milk plus folic acid and B-type vitamins has favourable effects on risk factors for CVD.

n-3 long-chain FA decrease serum levels of TG and remnant-like particle-cholesterol in humans
Hamazaki, K., M. Itomura, et al. (2003), Lipids 38(4): 353-8.
Abstract: A large number of papers have reported that administration of n-3 FA reduced serum TG concentrations in hypertriglyceridemic patients. However, few studies have examined the effect of n-3 FA on serum concentrations of remnant-like particle (RLP) cholesterol. Volunteers (n = 41) whose serum TG concentrations were 100-300 mg/dL were recruited and randomly assigned to either an n-3 FA group or a control group with stratification by sex, age, and serum TG level in a double-blind manner. The subjects in the n-3 FA group were administered 125 mL of fermented soybean milk with fish oil containing 600 mg of EPA and 260 mg of DHA/d for 12 wk. The controls consumed control soybean milk with olive oil. Fasting blood samples were obtained before the start of administration and at 4, 8, and 12 wk. EPA concentrations in red blood cells increased significantly in all but one subject in the n-3 FA group, with no significant changes in the control group. TG levels decreased more in the n-3 FA group than in the control group at weeks 4 (P < 0.05), 8 (P < 0.01), and 12 (P < 0.05) with their baseline as covariate. RLP cholesterol levels decreased more in the n-3 FA group than in the control at weeks 8 (P < 0.01) and 12 (P < 0.05) with their baseline as covariate. The groups did not differ in the other lipid levels. It is likely that n-3 long-chain FA may exert anti-atherosclerotic effects by lowering serum TG and RLP-cholesterol levels even at the dose of 860 mg/d.

N-3 polyunsaturated fatty acids enhance cholesterol efflux from human fibroblasts in culture
Pal, S. and P. J. Davis (1990), Biochem Biophys Res Commun 173(2): 566-70.
Abstract: Normal human skin fibroblasts were incubated in medium supplemented with 60 micrograms/ml linoleic acid (18:2n6) or eicosapentaenoic acid (20:5n3). After five days, cells lipids were enriched with linoleic acid or with docosapentaenoic acid (22:5n3). The HDL-mediated efflux of cholesterol from cells enriched with n-3 polyunsaturated fatty acids (PUFAs) was twice as fast as the rate of efflux of cholesterol from cells enriched with n-6 PUFAs. This suggests that the fatty acid composition of cellular lipids affects cholesterol efflux. The faster efflux when cells contain n-3 PUFAs may account for part of the reduction in risk of coronary disease with increases in dietary n-3 PUFAs (fish oils).

N-acyl phosphatidylethanolamines affect the lateral distribution of cholesterol in membranes
Terova, B., G. Petersen, et al. (2005), Biochim Biophys Acta 1715(1): 49-56.
Abstract: N-Acyl phosphatidylethanolamines are negatively charged phospholipids, which are naturally occurring albeit at low abundance. In this study, we have examined how the amide-linked acyl chain affected the membrane behavior of the N-acyl-1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine (N-acyl-POPE) or N-acyl-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine (N-acyl-DPPE), and how the molecules interacted with cholesterol. The gel-->liquid crystalline transition temperature of sonicated N-acyl phosphatidylethanolamine vesicles in water correlated positively with the number of palmitic acyl chains in the molecules. Based on diphenylhexatriene steady state anisotropy measurements, the presence of 33 mol% cholesterol in the membranes removed the phase transition from N-oleoyl-POPE bilayers, but failed to completely remove it from N-palmitoyl-DPPE and N-palmitoyl-POPE bilayers, suggesting rather weak interaction of cholesterol with the N-saturated NAPEs. The rate of cholesterol desorption from mixed monolayers containing N-palmitoyl-DPPE and cholesterol (1:1 molar ratio) was much higher compared to cholesterol/DPPE binary monolayers, suggesting a weak cholesterol interaction with N-palmitoyl-DPPE also in monolayers. In bilayer membranes, both N-palmitoyl-POPE and N-palmitoyl-DPPE failed to form sterol-rich domains, and in fact appeared to displace sterol from sterol/N-palmitoyl-sphingomyelin domains. The present data provide new information about the effects of saturated NAPEs on the lateral distribution of cholesterol in NAPE-containing membranes. These findings may be of relevance to neural cells which accumulate NAPEs during stress and cell injury.

NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol
Benjannet, S., D. Rhainds, et al. (2004), J Biol Chem 279(47): 48865-75.
Abstract: The discovery of autosomal dominant hypercholesterolemic patients with mutations in the PCSK9 gene, encoding the proprotein convertase NARC-1, resulting in the missense mutations suggested a role in low density lipoprotein (LDL) metabolism. We show that the endoplasmic reticulum-localized proNARC-1 to NARC-1 zymogen conversion is Ca2+-independent and that within the zymogen autocatalytic processing site SSVFAQ downward arrowSIP Val at P4 and Pro at P3' are critical. The S127R and D374Y mutations result in approximately 50-60% and > or =98% decrease in zymogen processing, respectively. In contrast, the double D374Y + N157K, F216L, and R218S natural mutants resulted in normal zymogen processing. The cell surface LDL receptor (LDLR) levels are reduced by 35% in lymphoblasts of S127R patients. The LDLR levels are also reduced in stable HepG2 cells overexpressing NARC-1 or its natural mutant S127R, and this reduction is abrogated in the presence of 5 mm ammonium chloride, suggesting that overexpression of NARC-1 increases the turnover rate of the LDLR. Adenoviral expression of wild type human NARC-1 in mice resulted in a maximal approximately 9-fold increase in circulating LDL cholesterol, while in LDLR-/- mice a delayed approximately 2-fold increase in LDL cholesterol was observed. In conclusion, NARC-1 seems to affect both the level of LDLR and that of circulating apoB-containing lipoproteins in an LDLR-dependent and -independent fashion.

Naringenin 7-O-cetyl ether as inhibitor of HMG-CoA reductase and modulator of plasma and hepatic lipids in high cholesterol-fed rats
Lee, M. K., S. S. Moon, et al. (2003), Bioorg Med Chem 11(3): 393-8.
Abstract: Numerous studies in vitro have shown a close relationship between the chemical structure and biologic activity of flavonoids, whereby their basic structure is modified to increase or decrease their biologic activity. The effects of naringenin (1) and its synthetic derivative, naringenin 7-O-cetyl ether (2), on the lipid profile, the cholesterol-regulating enzyme activity and the excretion of sterol were compared in rats fed a high-cholesterol (1% wt/wt) diet. Either 1 or 2 was supplemented with a high-cholesterol diet for 6 weeks at a dose of 0.073 mmol/100g diet. The supplementation of 1 or 2 significantly lowered the levels (mean+/-SE) of the plasma total cholesterol (4.93+/-0.19 and 4.75+/-0.16 mmol/L vs 5.87+/-0.36 mmol/L, p<0.05) and hepatic triglyceride (0.12+/-0.01 and 0.11+/-0.01 mmol/g vs 0.18+/-0.01 mmol/g, p<0.05) and cholesterol (0.23+/-0.01 and 0.21+/-0.01 mmol/g vs 0.31+/-0.01 mmol/g, p<0.05) compared to those of the control. The compound 1 or 2 supplementation appeared to decrease the excretion of neutral sterols. The plasma HDL-cholesterol concentration and ratio of HDL to total cholesterol were significantly higher in 1 and 2 groups than in control group. Although the biological effect of 2 on inhibiting hepatic HMG-CoA reductase and ACAT activities was only significant compared to the control group, both compounds exhibited a significant hypocholesterolemic effect in rats fed a high-cholesterol diet. The results suggest that cholesterol biosynthesis and esterification were concomitantly reduced by 2, as indicated by the decreased HMG-CoA reductase and ACAT activities.

Naringin alters the cholesterol biosynthesis and antioxidant enzyme activities in LDL receptor-knockout mice under cholesterol fed condition
Kim, H. J., G. T. Oh, et al. (2004), Life Sci 74(13): 1621-34.
Abstract: The purpose of the current study was to evaluate the lipid lowering and antioxidant capacity of naringin in LDL receptor knockout (LDLR-KO) mice fed a cholesterol (0.1 g/100 g) diet. As such, naringin or lovastatin (0.02 g/100 g) was supplemented in a cholesterol diet for 6 weeks. The naringin and lovastatin supplementation significantly lowered the plasma total cholesterol level compared to the control group. The plasma and hepatic triglyceride level was only lowered by the lovastatin supplement, while the hepatic cholesterol content was lowered by both the naringin and lovastatin supplements compared to the control group. The hepatic HMG-CoA reductase activity was significantly lower in the naringin and lovastatin supplemented groups than in the control group, whereas the ACAT activity was unaffected. The excretion of total sterol was significantly higher in the naringin and lovastatin groups compared to the control group due to significant changes in the acidic and neutral sterol, respectively. When comparing the hepatic antioxidant enzyme activities, the superoxide dismutase, catalase, and glutathione reductase activities were all significantly higher in the naringin-supplemented group than in the control group, while only the lovastatin supplement increased the glutathione reductase activity. Accordingly, the current results confirmed that naringin lowers the plasma cholesterol level via the inhibition of hepatic HMG-CoA reductase activity and increases the excretion of fecal sterol. Naringin was also found to improve the activities of hepatic antioxidant enzymes against oxidative stress in a hypercholesterolemic animal model, i.e. cholesterol-fed LDLR-KO mice.

National alert campaign about increased cholesterol: determination of cholesterol levels in 81,262 Brazilians
Martinez, T. L., R. D. Santos, et al. (2003), Arq Bras Cardiol 80(6): 635-8, 631-4.
Abstract: OBJECTIVE: To determine the levels of total cholesterol in a significant sample of the Brazilian population. METHODS: Blood cholesterol was determined in 81.262 individuals > 18 years old (51% male, 44.7 +/- 15.7 years), using Accutrend equipment, in the cities Sao Paulo, Campinas, Campos do Jordao, Sao Jose dos Campos, Santos, Santo Andre, Ribeirao Preto, Porto Alegre, Rio de Janeiro, Belo Horizonte, Curitiba, Brasilia, Salvador and documented in the presence of other risk factors (RF) for coronary artery disease (CAD) (systemic hypertension, CAD in the family, smoking, and diabetes). Participants were classified according to sex, age, and the presence or absence of RF, respectively, as 0 RF, 1 RF and > 2 RF. The percentage of individuals with cholesterol > 200 mg/dL and > 240 mg/dL was evaluated. RESULTS: The prevalence of individuals with 0, 1, and > 2 risk factors was 30% (n = 24,589), 36% (n =29,324), and 34% (n = 27,349) respectively, (P=0.657), and the mean total cholesterol of the population was 199.0 +/- 35.0 mg/dL. Cholesterol levels above 200 and 240 mg/dL were found, respectively, in 40% (n = 32,515) and 13% (10.942) of individuals. The greater the number of risk factors the higher the levels of cholesterol (P<0.0001) and the greater the proportion of individuals with cholesterol > 200 mg/dL (P=0.032). No difference existed in the proportion of individuals with cholesterol > 240 mg/dL (P=0.11). CONCLUSION: A great percentage of individuals with cholesterol levels above those recommended to prevent coronary artery disease was found.

National cholesterol education program (NCEP) guidelines too complex
Feeman, W. E., Jr. (2005), Prev Cardiol 8(3): 188.

National Cholesterol Education Program Adult Treatment Panel III guidelines and obesity: implications for Canada
Ardern, C. I. and P. T. Katzmarzyk (2003), Can J Cardiol 19(10): 1171-7.
Abstract: BACKGROUND: The National Cholesterol Education Program Adult Treatment Panel (ATP) III recommendations incorporate new evidence for treating elevated low-density lipoprotein cholesterol. OBJECTIVES: Comparisons between the prevalence of drug-eligible Canadians under the old ATP II and the new ATP III guidelines were made, and the impact of obesity on current and future drug eligibility was explored using various models. METHODS: Participants from the Canadian Heart Health Surveys (1986 to 1992; n=17,728; 20 to 74 years of age) were assigned to therapeutic lifestyle change or drug-eligible groups in the event of elevated low-density lipoprotein cholesterol. Body mass index was used to classify participants as having normal weight, or as being overweight or obese. The prevalence of overweight and obese status for 2001, 2006 and 2011 were projected from past trends by linear regression. Population attributable risk was used to model reductions or increases in the prevalence of obesity in drug-eligible participants using several nationally representative population health surveys. RESULTS: In 2001, an additional 1.1 million Canadians were drug-eligible under ATP III (16.0% of men, 9.5% of women), compared with ATP II (7.7% of men, 7.7% of women). Drug eligibility was elevated in overweight participants (men: OR=1.87 1.51 to 2.31; women: OR=1.60 1.13 to 2.28) and the obese (men: OR=2.86 1.86 to 4.38; women: OR=2.28 1.63 to 3.18) versus normal weight participants. The population attributable risk was higher in men (overweight 22.6%, obese 11.5%) than in women (overweight 9.4%, obese 9.2%). IMPLICATIONS: A 10% reduction in overweight and obesity prevalence could have prevented 69,530 cases of drug eligibility in 2001. On the other hand, by 2011 over one million Canadians will be drug-eligible because of an elevated body mass index, if the recent trends in overweight and obese status continue.

National cholesterol education program keeps a priority on lifestyle modification to decrease cardiovascular disease risk
Ernst, N. D. and J. I. Cleeman (2002), Curr Opin Lipidol 13(1): 69-73.
Abstract: The National Cholesterol Education Program's updated third Adult Treatment Panel report on clinical guidelines for cholesterol testing and management adds to the base of knowledge provided by two previous Adult Treatment Panel reports. Similar to the other reports, it has distinctive features and goals that are in accord with the most currently available clinical trial evidence. The major new feature of the third report is a focus on primary prevention of coronary heart disease in persons with multiple coronary heart disease risk factors. The guidelines provide the rationale for intensive cholesterol-lowering therapy in clinical management, and they provide detailed information to help inform clinical judgment for implementation of both medical nutrition management (therapeutic lifestyle changes) and drug therapy for treatment of high blood cholesterol.

National Cholesterol Education Program recommendations for cholesterol testing in young adults. A science-based approach
Cleeman, J. I. and S. M. Grundy (1997), Circulation 95(6): 1646-50.

National Cholesterol Education Program recommendations for measurement of high-density lipoprotein cholesterol: executive summary. The National Cholesterol Education Program Working Group on Lipoprotein Measurement
Warnick, G. R. and P. D. Wood (1995), Clin Chem 41(10): 1427-33.

National Cholesterol Education Program recommendations for measurement of low-density lipoprotein cholesterol: executive summary. The National Cholesterol Education Program Working Group on Lipoprotein Measurement
Bachorik, P. S. and J. W. Ross (1995), Clin Chem 41(10): 1414-20.

National Cholesterol Education Program's recommendations, and implications of "missing" high-density lipoprotein cholesterol in cardiac rehabilitation programs
Lavie, C. J. and R. V. Milani (1991), Am J Cardiol 68(10): 1087-8.

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Cholesterol Journal Articles