Cholesterol Articles and Abstracts

For medical practitioners and the general public - Cholesterol Journal Article Catalog.

Cholesterol Journal Articles



Record 12021 to 12040
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Summary of 'Cholesterol' guideline (first revision) of the Dutch Society of Family Physicians
van der Laan, J. R. and S. Thomas (2000), Ned Tijdschr Geneeskd 144(9): 421-7.
Abstract: The revised guidelines on cholesterol of the Dutch College of General Practitioners (DCGP), which closely follow the consensus of the Dutch Institute for Health Care Improvement, provide thresholds for treatment with statins in patients with elevated risks for coronary heart disease (CHD): patients with a history of cardiovascular disease, with an annual CHD risk larger than 2.5-3%, or with a (suspected) hereditary lipid disorder. Unlike the consensus the DCGP guideline advises only to determine a total cholesterol/HDL cholesterol ratio if the accompanying risk table indicates that the patient might fall in the range where drug treatment is indicated. For this purpose an extra column has been added to the table. In patients with a possible hereditary lipid disorder a higher threshold for referral to a specialist is used because moderately raised levels are common in the population and indicate a familial lipid disorder in only part of the cases.

Summary of the 'Cholesterol' guideline (first revision) of the Dutch College of Family Practice
Bonneux, L. (2000), Ned Tijdschr Geneeskd 144(18): 862-3.

Summary of the third report of the National Cholesterol Education Program Adult Treatment Panel III
Lepor, N. E. and R. E. Vogel (2001), Rev Cardiovasc Med 2(3): 160-5.

Sunlight, cholesterol and coronary heart disease
Grimes, D. S., E. Hindle, et al. (1996), Qjm 89(8): 579-89.
Abstract: We investigated the relationship between geography and incidence of coronary heart disease, looking at deficiency of sunlight and thus of vitamin D as a factor that might influence susceptibility and thus disease incidence. Sunlight deficiency could increase blood cholesterol by allowing squalene metabolism to progress to cholesterol synthesis rather than to vitamin D synthesis as would occur with greater amounts of sunlight exposure, and the increased concentration of blood cholesterol during the winter months, confirmed in this study, may well be due to reduced sunlight exposure. We show evidence that outdoor activity (gardening) is associated with a lower concentration of blood cholesterol in the summer but not in the winter. We suggest that the geographical variation of coronary heart disease is not specific, but is seen in other diseases and sunlight influences susceptibility to a number of chronic diseases, of which coronary heart disease is one.

Sunlight, cholesterol and coronary heart disease
Walker, A. R. and A. Shor (1997), Qjm 90(2): 153-4.

Supercritical carbon dioxide extraction of lipids and cholesterol from dehydrated chicken meat
Froning, G. W., F. Fieman, et al. (1994), Poult Sci 73(4): 571-5.
Abstract: Supercritical carbon dioxide (SC-CO2) extraction was studied for removal of lipids and cholesterol from dried chicken meat powder and chunks. Two combinations of pressure and temperature were used: 299 atm and 45 C, and 381 atm and 55 C, both providing a fluid density of.90 g/cm3. For a given quantity of CO2, at the higher temperature and pressure, significantly (P <.05) more lipids and cholesterol were extracted from the powder. At 381 atm and 55 C, approximately 89% of the lipids and 90% of the cholesterol were removed from the dehydrated chicken meat powder. With respect to the chunk chicken meat, about 93% of the lipids and 82% of the cholesterol were extracted at 299 atm and 45 C. It seemed that the SC-CO2 extraction process was more efficient when chunks were used. Protein was concentrated as cholesterol and lipids were removed by SC-CO2 extraction of both chicken meat types, and Hunterlab L values increased but aL values decreased, indicating a lighter color with less redness. This research indicated that SC-CO2 extraction holds promise for substantially reducing lipids and cholesterol in chicken meat.

Supercritical fluid chromatographic determination of cholesterol and cholesteryl esters in serum on ODS-silica gel column
Nomura, A., J. Yamada, et al. (1993), Anal Chem 65(15): 1994-7.
Abstract: Cholesterol and cholesteryl esters in human serum were determined by supercritical fluid chromatography on an inert ODS-silica gel column using supercritical carbon dioxide as a mobile phase without a modifier. Chromatograms were obtained by monitoring the eluent simultaneously with an FID and UV detector at the wavelength of 190 nm. The retention behavior of cholesterol and cholesteryl esters was investigated in terms of the density of CO2 mobile phase. The separation mode was found to be reversed phase, as in liquid chromatography. The amounts of cholesterol and cholesteryl esters extracted from human serum reference material (NIST SRM 909) were determined individually using cholesteryl laurate as an internal standard to give good agreement of total cholesterol with the value certified by NIST.

Supercritical fluid extraction and chromatography of cholesterol in food samples
Ong, C. P., H. K. Lee, et al. (1990), J Chromatogr 515: 509-13.
Abstract: A method based on supercritical fluid chromatography is presented which can be used for the determination of cholesterol in certain foods. The method involves the extraction with supercritical carbon dioxide and analysis of the extracts using a capillary column with supercritical carbon dioxide as mobile phase and flame ionization detection. Quantification is achieved using cholesteryl chloroacetate as an internal standard.

Superheated water extraction of cholesterol from solid food
Fernandez-Perez, V. and M. D. de Castro (2003), Anal Bioanal Chem 375(3): 437-42.
Abstract: A method based on superheated water extraction has been developed for the removal of cholesterol from solid food thus providing a clean approach by avoiding the use of organic solvents. A preconcentration step was also studied with the aim of solving the problem derived from low-cholesterol-content samples and dilution effect. The research also involved the optimisation of the parameters affecting the extraction process by a central composite experimental design as well as a univariate study of the optimisation of the preconcentration step. The time required for total removal of the target compound was 60 min. The method was validated using a certified reference material (NIST-CRM 1845) and was used to analyse food samples within a wide range of cholesterol concentrations. The efficiency for the CRM was 105%. The precision of the method yielded values less than 6.5% (expressed as relative standard deviation) in all instances.

Superior short-term cholesterol control and achievement of the adult treatment panel III low-density lipoprotein goals with initiation of statin therapy by the time of hospital discharge following acute myocardial infarction
Bybee, K. A., B. D. Powell, et al. (2004), Am J Cardiol 93(6): 776-9.
Abstract: In a community-based population, we compared serum cholesterol concentrations following hospital discharge after acute myocardial infarction based on statin therapy at the time of hospital discharge. At the time of follow-up cholesterol measurement, patients discharged from the hospital on a statin had lower mean low-density lipoprotein (LDL) (106.4 vs 116.7 mg/dl, p <0.01) and total cholesterol (182.2 vs 193.6 mg/dl, p <0.01) concentrations, larger absolute reductions in LDL (-24.7 vs -4.7 mg/dl, p <0.01) and total cholesterol (-24.2 vs -0.1 mg/dl, p <0.01) from pre-myocardial infarction levels, and superior attainment of the Adult Treatment Panel III LDL goal of <100 mg/dl at the time of follow-up compared with patients who were discharged without a statin (49% vs 33%; adjusted odds ratio 2.56; p <0.01).

Superiority of dietary safflower oil over olive oil in lowering serum cholesterol and increasing hepatic mRnas for the LDL receptor and cholesterol 7alpha-hydroxylase in exogenously hypercholesterolemic (exHC) rats
Sato, M., S. Yoshida, et al. (2000), Biosci Biotechnol Biochem 64(6): 1111-7.
Abstract: The exogenously hypercholesterolemic (ExHC) rat is a strain segregated from SD rats with a high response to dietary cholesterol. To understand the underlying mechanism(s) for this hypercholesterolemia, the interactive effects of dietary fatty acid and the susceptibility of rats to dietary cholesterol on the serum cholesterol concentration and hepatic mRNA abundance of the low-density lipoprotein (LDL) receptor, cholesterol 7alpha-hydroxylase (7alpha-hydroxylase) and 3-hydroxyl-3methylglutaryl (HMG) CoA reductase were examined. Both strains were fed on a diet supplemented with 10% each of olive, safflower or coconut oil with or without the addition of 1% cholesterol for one week. The ExHC rats fed on olive, safflower and coconut oil in combination with cholesterol respectively resulted in a 3.5-, 2.0- and 2.1-fold higher serum cholesterol concentration than that in the animals fed on the corresponding dietary fats without any supplementation of cholesterol (p < 0.01 by dietary cholesterol or type of fat). The dietary cholesterol dependent-elevation of serum cholesterol in the SD rats was less than 1.5-fold (p<0.01) and there was no dietary fat effect. The ExHC rats fed on the safflower oil-containing diet supplemented with cholesterol resulted in a higher mRNA abundance of the LDL receptor and 7alpha-hydroxylase than in the corresponding fat-fed rats without cholesterol (p<0.05). There was no dietary cholesterol-dependent change of mRNA abundance in either strain fed on olive or coconut oil, except for a decreased abundance of HMG CoA reductase mRNA in the olive oil-fed ExHC rats and coconut oil-fed Sprague-Dawley (SD) rats (p<0.05). These results indicate that the hepatic mRNA abundance of the LDL receptor and of 7alpha-hydroxylase depended on the dietary combination of cholesterol and a fatty acid and suggest that a linoleic acid-rich diet may alleviate exogenous hypercholesterolemia by activating the process involved in the hepatic uptake and biliary excretion of serum cholesterol.

Supernatant protein factor and tocopherol-associated protein: an unexpected link between cholesterol synthesis and vitamin E (review)
Porter, T. D. (2003), J Nutr Biochem 14(1): 3-6.
Abstract: Supernatant protein factor (SPF) is a recently cloned member of a family of cytosolic lipid-binding proteins that includes Sec14p, alpha-tocopherol transfer protein, and cellular retinal-binding protein. SPF stimulates the conversion of squalene to lanosterol in the downstream pathway for cholesterol biosynthesis, and overexpression of cloned SPF in hepatoma cells increases cholesterol synthesis. The mechanism of this stimulation has yet to be defined, but SPF appears to facilitate the transfer of squalene into and between intracellular membranes. The recent identification of SPF as alpha-tocopherol-associated protein (TAP) has called into question its long-standing association with cholesterol biosynthesis. TAP binds alpha-tocopherol, but not other isomers of tocopherol, with high affinity; in the presence of alpha-tocopherol TAP translocates to the nucleus and activates reporter gene transcription. Given the ability of alpha-tocopherol to down-regulate the expression of two scavenger lipoprotein receptors, SR-A and CD36, these observations raise some interesting questions regarding the role of SPF/TAP and vitamin E in cholesterol metabolism.

Supernatant protein factor in complex with RRR-alpha-tocopherylquinone: a link between oxidized Vitamin E and cholesterol biosynthesis
Stocker, A. and U. Baumann (2003), J Mol Biol 332(4): 759-65.
Abstract: The vast majority of monomeric lipid transport in nature is performed by lipid-specific protein carriers. This class of proteins can enclose cognate lipid molecules in a hydrophobic cavity and transport them across the aqueous environment. Supernatant protein factor (SPF) is an enigmatic representative of monomeric lipid transporters belonging to the SEC14 family. SPF stimulates squalene epoxidation, a downstream step of the cholesterol biosynthetic pathway, by an unknown mechanism. Here, we present the three-dimensional crystal structure of human SPF in complex with RRR-alpha-tocopherylquinone, the major physiological oxidation product of RRR-alpha-tocopherol, at a resolution of 1.95A. The structure of the complex reveals how SPF sequesters RRR-alpha-tocopherylquinone (RRR-alpha-TQ) in its protein body and permits a comparison with the recently solved structure of human alpha-tocopherol transfer protein (alpha-TTP) in complex with RRR-alpha-tocopherol. Recent findings have shown that RRR-alpha-TQ is reduced in vivo to RRR-alpha-TQH(2), the latter has been suggested to protect low-density lipoprotein (LDL) particles from oxidation. Hence, the antioxidant function of the redox couple RRR-alpha-TQ/RRR-alpha-TQH(2) in blocking LDL oxidation may reduce cellular cholesterol uptake and thus explain how SPF upregulates cholesterol synthesis.

Supernatant protein factor requires phosphorylation and interaction with Golgi to stimulate cholesterol synthesis in hepatoma cells
Mokashi, V. and T. D. Porter (2005), Arch Biochem Biophys 435(1): 175-81.
Abstract: Supernatant protein factor (SPF) is a poorly characterized cytosolic protein that stimulates HMG-CoA reductase and squalene monooxygenase in vitro and cholesterol synthesis when expressed in hepatoma cells. The activation of SPF by protein kinases A (PKA) and Cdelta enhances its ability to stimulate these cholesterolgenic enzymes in microsomal preparations. The present studies demonstrate that the ability of SPF to stimulate cholesterol synthesis in cell culture is also modulated by phosphorylation. Addition of dibutyryl-cAMP, a PKA activator, to hepatoma cells expressing SPF increased cholesterol synthesis by 62%, whereas addition of a cell-permeable PKA inhibitor blocked the SPF-mediated increase in cholesterol synthesis. To confirm a role for PKA in the regulation of SPF, substitution of alanine for serine-289 (a putative PKA recognition site) blocked the stimulation of cholesterol synthesis by SPF. Serine-289 is located at the junction of the proposed lipid-binding domain and the carboxyl-terminal Golgi dynamics domain, suggesting that phosphorylation may alter the interaction of these two domains. In a test of this hypothesis, deletion of the Golgi dynamics domain blocked the ability of SPF to stimulate cholesterol synthesis, supporting a role for Golgi in SPF function; this finding was buttressed by the observation that addition of brefeldin A, which disrupts Golgi formation, also abolished the ability of SPF to stimulate cholesterol synthesis. The activation of SPF by PKA suggests that cholesterol synthesis can be rapidly modulated in response to external stimuli by changes in cAMP levels, and that this regulation is dependent on an as yet undefined interaction with Golgi.

Supernatant protein factor, which stimulates the conversion of squalene to lanosterol, is a cytosolic squalene transfer protein and enhances cholesterol biosynthesis
Shibata, N., M. Arita, et al. (2001), Proc Natl Acad Sci U S A 98(5): 2244-9.
Abstract: Squalene epoxidase, a membrane-associated enzyme that converts squalene to squalene 2,3-oxide, plays an important role in the maintenance of cholesterol homeostasis. In 1957, Bloch and colleagues identified a factor from rat liver cytosol termed "supernatant protein factor (SPF)," which promotes the squalene epoxidation catalyzed by rat liver microsomes with oxygen, NADPH, FAD, and phospholipid Tchen, T. T. & Bloch, K. (1957) J. Biol. Chem. 226, 921-930. Although purification of SPF by 11,000-fold was reported, no information is so far available on the primary structure or biological function of SPF. Here we report the cDNA cloning and expression of SPF from rat and human. The encoded protein of 403 amino acids belongs to a family of cytosolic lipid-binding/transfer proteins such as alpha-tocopherol transfer protein, cellular retinal binding protein, yeast phosphatidylinositol transfer protein (Sec14p), and squid retinal binding protein. Recombinant SPF produced in Escherichia coli enhances microsomal squalene epoxidase activity and promotes intermembrane transfer of squalene in vitro. SPF mRNA is expressed abundantly in the liver and small intestine, both of which are important sites of cholesterol biosynthesis. SPF is expressed significantly in isolated hepatocytes, but the expression level was markedly decreased after 48 h of in vitro culture. Moreover, SPF was not detectable in most of the cell lines tested, including HepG2 and McARH7777 hepatomas. Transfection of SPF cDNA in McARH7777 significantly stimulated de novo cholesterol biosynthesis. These data suggest that SPF is a cytosolic squalene transfer protein capable of regulating cholesterol biosynthesis.

Supplementation of Areca catechu L. extract alters triglyceride absorption and cholesterol metabolism in rats
Byun, S. J., H. S. Kim, et al. (2001), Ann Nutr Metab 45(6): 279-84.
Abstract: Areca extracts have already been found to exhibit a strong inhibitory activity on cholesterol absorption in high-cholesterol-fed rats. Accordingly, this study was performed to determine whether Areca extracts also exert an inhibitory activity on triglyceride absorption in triglyceride-fed rats. Male rats were fed a diet containing corn oil (10%, w/w) with or without an Areca nut extract supplement (0.5%, w/w). The supplementation of the Areca extract significantly lowered the absorption of triglyceride and the plasma lipid concentration. The absorbed triglyceride that appeared in the blood after an oral dose of 9,10(n)-(3)H triglyceride was significantly lower in the rats supplemented with the Areca nut extract, compared with the control group. The supplementation also significantly lowered the small intestinal pCEase (pancreatic cholesterol esterase) activity by 22.5% compared to the control group. The hepatic and intestinal ACAT (acyl-CoA:cholesterol acyltransferase) activities were significantly decreased in the Areca group compared with the control group. Hence, further studies are needed to elucidate the structure and chemical properties of the active compound in the water-soluble Areca extract that lowers cholesterol absorption.

Supplementation of naringenin and its synthetic derivative alters antioxidant enzyme activities of erythrocyte and liver in high cholesterol-fed rats
Lee, M. K., S. H. Bok, et al. (2002), Bioorg Med Chem 10(7): 2239-44.
Abstract: The antioxidative effects of naringenin (1) and its synthetic derivative, naringenin 7-O-cetyl ether (2), were tested. Male rats were fed a 1 g/100 g high-cholesterol diet for 6 weeks with supplements of either 1 or 2 (0.073 mmol/100 g diet) to study the effects on the antioxidant enzyme activities in the erythrocyte and liver. The erythrocyte catalase (CAT) and superoxide dismutase (SOD) activities were significantly higher in the compounds 1 or 2 supplemented groups than in the control group, whereas the hepatic SOD and CAT activities were significantly lower in the compound 2 supplemented group. The compounds 1 and 2 supplements to a high cholesterol diet lowered or tended to lower the plasma TBARS levels, that is, lipid peroxide products, while enhancing the plasma paraoxonase activity. These results indicate that the supplementation of 1 and 2 was effective in improving the antioxidant capacity of the erythrocyte and liver, plus the synthetic functional compound 2 appeared to be as potent as 1 in enhancing the antioxidant defense system.

Supplementation with vitamin E and/or zinc does not attenuate atherosclerosis in apolipoprotein E-deficient mice fed a high-fat, high-cholesterol diet
Paul, A., L. Calleja, et al. (2001), Int J Vitam Nutr Res 71(1): 45-52.
Abstract: Ever since oxidation has been known to be involved in atherogenesis, antioxidants have received considerable attention as potential antiatherogenic agents. The lipid-soluble vitamin E is the main antioxidant carried by lipoproteins. Zinc is a water-soluble trace element that acts as a cofactor of superoxide dismutase (SOD) and has an antioxidant role in several oxidative processes. To test the hypothesis that zinc could adjuvate the antioxidant activity of vitamin E and diminish atherogenesis, we explored how supplementing diet with vitamin E and/or zinc would affect an atherosclerosis-prone animal like Apo E-deficient mice. The increased plasma concentrations of both vitamin E and zinc showed that absorption was high. They had a significant hypolipidemic effect and the supplemented animals had 25% less plasma cholesterol and triglyceride than controls. The SOD activity was significantly higher in washed erythrocytes from mice supplemented with zinc. The plasma of supplemented animals was also significantly more resistant to oxidation. The size of lesions in the proximal aortic region did not differ among groups. Therefore, dietary supplementation resulted in the expected antioxidant effects but there was no substantial attenuation of atherosclerosis in this particular model.

Suppression of aortic atherosclerosis in cholesterol-fed rabbits by purified rabbit interferon
Wilson, A. C., R. G. Schaub, et al. (1990), Arteriosclerosis 10(2): 208-14.
Abstract: The effectiveness of rabbit interferon in suppressing atherosclerosis was evaluated in rabbits fed a diet containing 1% cholesterol. Ten male New Zealand White rabbits received intramuscular injections of 1 million units of interferon twice a week, while a control group of 10 rabbits received injections of buffer. Both groups had average serum cholesterol levels of over 2000 mg/dl during the 8-week experimental period. Interferon treatment resulted in no significant hypolipidemic effect or changes in lipoprotein composition. Atherosclerotic lesions in aortas were quantified both macroscopically and microscopically. Interferon treatment decreased the grossly visible lesion area significantly from 25 +/- 4% to 8 +/- 1% (mean +/- SEM, p less than 0.005) compared to the untreated group. Microscopic analysis of serial cross-sections of aortic segments revealed significant (p less than 0.01) reductions in both lesion size and frequency in the interferon-treated group. Electron microscopy also showed that interferon treatment reduced the pathological effects of cholesterol feeding. Tissue analysis showed that total aortic cholesterol was reduced by 28% by interferon treatment, while the aortic phospholipid concentration was increased by 25%. The possibility exists that the interferon preparation used contained other biological response modifiers and that the observed effects may be totally unrelated with interferon. These results suggest that the mechanism of atherosclerosis suppression in these cholesterol-fed rabbits is not related to the lowering of serum cholesterol but may be associated with inhibition of lesion initiation.

Suppression of atherogenesis by n-3 fatty acids in the cholesterol-fed rabbit
Demiroglu, C., A. Ozder, et al. (1991), Angiology 42(4): 323-30.
Abstract: The effects of n-3 fatty-acid supplementation on serum lipids, platelet aggregation, and the development of atherosclerotic lesions were studied in the cholesterol-fed rabbit. Serum total cholesterol and LDL cholesterol values were significantly reduced in comparison with those of the nonsupplemented cholesterol-fed group (p less than 0.005, p less than 0.0025, respectively), though still higher than those of the control group (p less than 0.0025, p less than 0.0125 respectively). Platelet aggregation was reduced below that of the cholesterol-fed and the control levels (p less than 0.0005, p less than 0.0025, respectively). The endothelial injury encountered in cholesterol-fed rabbits was inhibited in the supplemented group. It is concluded that n-3 fatty acids suppress atherogenesis in this animal model by interfering with platelet aggregation and lipid metabolism.


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