Statin treatment increases the sialic acid content of LDL in hypercholesterolemic patients.

Lindbohm N, Gylling H, Miettinen TE, Miettinen TA.

Department of Medicine, Helsinki University Central Hospital, Finland.

Low density lipoprotein (LDL) with low sialic acid content has been reported to cause intracellular cholesterol accumulation, and therefore desialylation has been proposed to be an atherogenic modification of LDL. However, it is not known whether hypolipidemic treatment has any effect on LDL sialylation. Accordingly, we investigated the sialic acid/apolipoprotein (apo) B ratio of total LDL and its subfractions in 26 moderately hypercholesterolemic patients at baseline and after treatment with statins for 2-3 months. Cholesterol and triglyceride levels were reduced in all apo B-containing lipoproteins, including all LDL subfractions, while the sialic acid ratio was increased in total LDL and in all its subfractions. Cholesterol concentrations and sialic acid ratios were inversely correlated in light and dense LDL subfractions both before and during statin treatment, and the greater the decrease in cholesterol and apo B contents of dense LDL, the higher was the increase in its sialic acid ratio. Furthermore, the lower the baseline sialic acid ratio of dense LDL, the greater was the reduction in its lipid and apo B concentrations. In conclusion, inhibition of cholesterol synthesis by statin treatment increased sialic acid/apo B ratio in LDL proportionately to the decrease of LDL apo B and cholesterol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10924733&dopt=Abstract cholesterol




[Prevalence of coronary risk factors in 233 men with coronary heart disease. Role of HDL cholesterol]

[Article in German]

Hartmann G, Schmid R.

Medizinische Klinik, Ratisches Kantonsspital Chur.

In 233 male patients (age 35 to 90 years) with coronary heart disease, chiefly myocardial infarction, the prevalence of the established coronary risk factors was investigated: total cholesterol, HDL- and LDL-cholesterol, triglycerides, hypertension, smoking, overweight, diabetes, heredity, physical inactivity and psychosocial stress. Cigarette smoking shows the highest prevalence (54%), followed by hypertension (39%), overweight (38.6%) and hypercholesterolaemia (34.7%). In patients over 65 the prevalence of these coronary risk factors is lower, whereas physical inactivity and diabetes are more frequent than in the younger group. Combinations of the main coronary risk factors are much more frequent in the younger group. HDL-cholesterol was found to be lower than normal (below 0.91 mmol/l) in 27% irrespective of age. The lower the concentration of HDL-cholesterol the more frequent are the following coronary risk factors: smoking, overweight, diabetes, physical inactivity and hypertriglyceridaemia. We suspect that a low HDL-cholesterol concentration in many individuals may be the result of a clustering of the aforementioned risk factors. For practical purposes it seems important to evaluate all relevant risk factors in an individual and to concentrate intervention on those with a fair chance of success, especially smoking and hypertension in the younger subjects. Normal or elevated HDL-cholesterol in itself is not a reliable cardioprotective factor since it is normal or elevated in two thirds of our coronary heart disease patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10413821&dopt=Abstract cholesterol




[Apolipoprotein E gene polymorphism and risk of hypercholesterolemia: a case control study in a working population of Valencia]

[Article in Spanish]

Corella D, Guillen M, Portoles O, Sabater A, Cortina S, Folch J, Saiz C.

Departamento de Medicina Preventiva y Salud Publica, Universitat de Valencia. dolores.corella uv.es

BACKGROUND: The apolipoprotein E (apoE) gene is polymorphic with three common alleles (epsilon 2, epsilon 3, epsilon 4) whose allelic frequency and association with lipid levels varies from population to population. The aim of this study was to estimate the association between these genetic variants and the risk of hypercholesterolemia in a Mediterranean Spanish population. PATIENTS AND METHODS: A case-control study in a working population from Valencia was carried out. A total of 330 cases (148 men and 182 women) with moderate hypercholesterolemia (total cholesterol > 200 mg/dl or with lipid lowering treatment) and age range 20 to 60 years, were identified. 330 normocholesterolemic controls matched by age and sex were selected. From all of them data of apoE genotype, body mass index, lipid and lipoprotein levels, socioeconomic and life-style variables were obtained. RESULTS: The epsilon 2 allele frequency was statistically lower in cases (0.033) than in controls (0.086). The epsilon 4 allele frequency was higher in cases (0.115) than in controls (0.039). In the crude logistic regression analysis, the apoE polymorphism was related (p < 0.001) to the risk of hypercholesterolemia. After adjustment by age, body mass index, educational level, tobacco smoking, alcohol consumption and physical activity the epsilon 2 allele was associated with a lower risk of hypercholesterolemia (odds ratio [OR] = 0.36; 95% confidence interval (CI): 0.20-0.64), and the epsilon 4 allele was associated with a higher risk (OR = 3.04; 95% CI: 1.82-5.06). CONCLUSIONS: The apoE genotype was significantly related to the risk of moderate hypercholesterolemia in the Mediterranean Spanish population.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10996872&dopt=Abstract cholesterol




Polyunsaturated fatty acids up-regulate hepatic scavenger receptor B1 (SR-BI) expression and HDL cholesteryl ester uptake in the hamster.

Spady DK, Kearney DM, Hobbs HH.

Department of Internal Medicine, The University of Texas Southwest Medical Center at Dallas, Dallas, TX 75235, USA.

Diets rich in polyunsaturated fatty acids lower plasma HDL cholesterol concentrations when compared to diets rich in saturated fatty acids. We investigated the mechanistic basis for this effect in the hamster and sought to determine whether reduced plasma HDL cholesterol concentrations resulting from a high polyunsaturated fat diet are associated with a decrease in reverse cholesterol transport. Animals were fed semisynthetic diets enriched with polyunsaturated or saturated fatty acids for 6 weeks. We then determined the effect of these diets on the following parameters: 1) hepatic scavenger receptor B1 (SR-BI) mRNA and protein levels, 2) the rate of hepatic HDL cholesteryl ester uptake, and 3) the rate of cholesterol acquisition by the extrahepatic tissues (from de novo synthesis, LDL and HDL) as a measure of the rate of reverse cholesterol transport. Compared to saturated fatty acids, dietary polyunsaturated fatty acids up-regulated hepatic SR-BI expression by approximately 50% and increased HDL cholesteryl ester transport to the liver; as a consequence, plasma HDL cholesteryl ester concentrations were reduced. Although dietary polyunsaturated fatty acids increased hepatic HDL cholesteryl ester uptake and lowered plasma HDL cholesterol concentrations, there was no change in the cholesterol content or in the rate of cholesterol acquisition (via de novo synthesis and lipoprotein uptake) by the extrahepatic tissues.These studies indicate that substitution of polyunsaturated for saturated fatty acids in the diet increases SR-BI expression and lowers plasma HDL cholesteryl ester concentrations but does not affect reverse cholesterol transport.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10428974&dopt=Abstract cholesterol




Quantitative determination of cholesterol 5alpha-, 7alpha-, and 7beta-hydroperoxides in rat skin.

Yamazaki S, Ozawa N, Hiratsuka A, Watanabe T.

Toxicology and Efficacy Research, Tsukuba Research Laboratories, Pharmacia & Upjohn, Ltd., Ibaraki, Japan. shinji.yamazaki am.pnu.com

An assay method for determination of cholesterol 5alpha-, 7alpha-, and 7beta-hydroperoxides (ChOOHs) in rat skin using high-performance liquid chromatography (HPLC) with a chemiluminescence detector has been developed. In the assay method, free form and free plus ester forms of ChOOHs could be separately determined by HPLC in combination with the treatment of a tissue extract by cholesterol esterase. Lower limits of quantitation for cholesterol 5alpha-, 7alpha-, and 7beta-hydroperoxides were 0.2, 0.1, and 0.5 nmol/g skin, respectively. This assay method showed that (i) good absolute recoveries of ChOOHs from rat skin (80-90% of radiolabeled ChOOHs added to rat skin); (ii) negligible autoxidation of cholesterol caused by the assay procedure (<9.4x10(-5)% of radiolabeled cholesterol added to rat skin); and (iii) good correlation between ChOOHs added to rat skin and ChOOHs determined, indicating this assay method is applicable to quantify ChOOHs in rat skin. By using this assay method, we observed that (i) cholesterol 5alpha-hydroperoxide was detected in skin of rats pretreated with oral doses of pheophorbide a and subsequent visible irradiation; (ii) concentrations of cholesterol 7-hydroperoxides in skin of rats in an ambient light room were not significantly different from those in a dark room for 12 weeks; and (iii) ultraviolet light B irradiation markedly enhanced the concentrations of cholesterol 7-hydroperoxides in the skin of rats.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10443927&dopt=Abstract cholesterol




Lipid profiles in untreated patients with rheumatoid arthritis.

Park YB, Lee SK, Lee WK, Suh CH, Lee CW, Lee CH, Song CH, Lee J.

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

OBJECTIVE: To investigate lipid profiles in patients with untreated active rheumatoid arthritis (RA) and to assess the relationship of the inflammatory condition of RA with lipid profiles. METHODS: Forty-two patients with RA and 42 age and sex matched healthy controls were studied. Patients with RA had not been treated with corticosteroid or disease modifying antirheumatic drugs prior to the study. Total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apolipoprotein A1 (apo A1), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], and C-reactive protein (CRP) were measured in both groups. RESULTS: The levels of apo A1 and HDL-cholesterol were significantly lower in patients than in controls (128.5 vs. 151.8 mg/dl, 41.2 vs. 54.9 mg/dl, respectively). The level of Lp(a) was significantly higher in patients than in controls (27.1 vs. 18.0 mg/dl). The ratios of apo B/apo A1, total cholesterol/HDL-cholesterol, and LDL-cholesterol/HDL-cholesterol were significantly higher in patients than in controls (0.82 vs. 0.67, 4.4 vs. 3.4, 2.8 vs. 1.9, respectively). CRP showed a significant correlation with apo A1 (r = -0.44, p<0.01) and HDL-cholesterol (r = -0.35, p<0.05). CONCLUSION: Our study suggests that patients with untreated active RA have altered lipoprotein and apolipoprotein patterns that may possibly expose them to higher risk of atherosclerosis. The inflammatory condition of RA may affect the metabolism of HDL-cholesterol and apo A1.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10451065&dopt=Abstract cholesterol




A mixture of organisms affects cholesterol metabolism together with rat cecal flora.

Fukushima M, Doi S, Ohashi T, Endo T, Saitoh H, Nakano M.

Department of Bioresource Science, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, Japan. fukshima obihiro.ac.jp

The effects of a mixture of organisms on cecal fermentation and cholesterol metabolism in sham-operated and cecectomized rats were investigated. Male F344 rats, allocated into four groups: cecectomized rats fed a mixture of organisms (CEMO), cecectomized rats fed rice bran (CERB), sham-operated rats fed a mixture of organisms (SHMO), and sham-operated rats fed rice bran (SHRB) for 4 weeks. The diets had 0.5% cholesterol and 0.125% sodium cholate added. There were no significant differences in the body weight gain and food intake among the groups. The cecal pH in the SHMO group was significantly lower than that in the other groups. The total cholesterol and (VLDL + IDL + LDL)-cholesterol concentrations in serum were significantly lower in the SHMO group than that in the SHRB group, and the triacylglycerol concentration in the sham-operated rats tended to decrease compared to the cecectomized rats. The fecal cholesterol excretion in the CERB group was higher than that in the other groups, and that in the SHMO group was significantly higher than in the SHRB group. The acetic acid, propionic acid, n-butyric acid, and total short-chain fatty acid concentrations in the cecum contents were significantly higher in the SHMO group than those in the other groups. Streptococcus, Bifidobacterium, and Lactobacillus in the SHMO group tended to be higher than the other groups and Bacteroidaceae in the CEMO and CERB groups were significantly higher than that in the SHMO group. The results demonstrate that the mixture of organisms was fermented with the cecal contents and that the metabolites such as short-chain fatty acid lowered the serum total cholesterol and liver cholesterol concentrations in the rats fed a cholesterol-containing diet.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10478442&dopt=Abstract cholesterol




Ethanol-extracted soy protein isolate results in elevation of serum cholesterol in exogenously hypercholesterolemic rats.

Ni W, Yoshida S, Tsuda Y, Nagao K, Sato M, Imaizumi K.

Division of Bioresource and Bioenvironmental Sciences, Graduate School, Kyushu University, Fukuoka, Japan.

Soy protein preparations were reported to have hypocholesterolemic actions in experimental animals and humans, while the active components and the mechanism by which this occurs are not clarified yet. The objective of this study is to address these issues by using exogenously hypercholesterolemic rats which are susceptible to dietary cholesterol. Two groups of five rats (male, 12-wk-old) were fed on AIN 93G-based diet with soy protein isolate (SPI) or ethanol-extracted SPI (EE-SPI) for 2 wk. EE-SPI was prepared by ethanol extraction to remove isoflavones and other components. Concentrations of serum and liver total cholesterol were lower in rats fed SPI than in those fed EE-SPI. The abundances of mRNA for 7alpha-hydroxylase and low density lipoprotein receptor in the liver were lower in EE-SPI group than those in SPI group. These results suggest that the ethanol extract from SPI has a factor(s) to alleviate hypercholesterolemia by increasing the removal of cholesterol from serum through the receptor pathway and then from liver through enhancement of bile acid synthesis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10478929&dopt=Abstract cholesterol




Hypocholesterolemic effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in the guinea pig: atorvastatin versus simvastatin.

Conde K, Pineda G, Newton RS, Fernandez ML.

Department of Nutritional Sciences, University of Conneticut, Storrs 06269, USA.

Male Hartley guinea pigs were fed a hypercholesterolemic diet rich in lauric and myristic acids with 0, 10, or 20 mg/kg of simvastatin or atorvastatin for 21 days. Atorvastatin and simvastatin resulted in a lowering of plasma low-density lipoprotein (LDL) cholesterol in a dose-dependent manner by an average of 48 and 61% with 10 and 20 mg/kg, respectively. Both statins were equally effective in lowering plasma LDL cholesterol and apolipoprotein B (apo-B) levels. Atorvastatin and simvastatin treatments yielded LDL particles that differed in composition from the control. Due to the relevance of LDL oxidation and cholesteryl ester transfer in plasma to the progression of atherosclerosis, these parameters were analyzed after statin treatment. Atorvastatin and simvastatin treatment decreased the susceptibility of LDL particles to oxidation by 95% as determined by the formation of thiobarbituric acid reactive substances. An 80% decrease in the transfer of cholesteryl ester between high-density lipoprotein (HDL) and the apo-B-containing lipoproteins was observed after simvastatin and atorvastatin treatment. In addition, statin effects on plasma LDL transport were studied. Simvastatin- and atorvastatin-treated guinea pigs exhibited 125 and 175% faster LDL fractional catabolic rates, respectively, compared with control animals. No change in LDL apo-B flux was induced by either treatment; however, LDL apo-B pool size was reduced after statin treatment. Hepatic microsomal free cholesterol was lower in the atorvastatin and simvastatin groups. However, only atorvastatin treatment resulted in an 80% decrease of acyl-CoA:cholesterol acyltransferase activity (P < 0.001). In summary, atorvastatin and simvastatin had similar LDL cholesterol lowering properties, but these drugs modified LDL transport and hepatic cholesterol metabolism differently.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10484079&dopt=Abstract cholesterol