| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| omega-6 and omega-3 fatty acids: monolayer packing and effects on bilayer permeability and cholesterol exchange Urquhart, R., R. Y. Chan, et al. (1992), Biochem Int 26(5): 831-41. Abstract: It has been suggested that the polyunsaturated omega-3 fatty acid, docosahexaenoic acid (DHA), can adopt unique closely packed arrays in lipid bilayers (Glomset and Applegate. (1986) J. Lipid Res. 27, 658-680). These conformations are predicted on the basis of molecular dynamics calculations and are in contrast to the expanded conformations characteristic of omega-6 unsaturated fatty acids. It has also been suggested that close packing of omega-3 acyl chains could have a substantial affect on the physical properties of lipid bilayers (e.g. permeability). We report here some experimental tests of these predictions. Surface pressure-area experiments have been carried out on DHA and its mixtures with stearic and oleic acids. At low surface pressures DHA is more expanded than oleic acid. Extrapolation to the high surface pressures characteristic of lipid bilayers indicates that the area per molecule of DHA is only marginally less than that for oleic acid. Thus there is no compelling evidence to suggest that the average area per molecule of the omega-3 fatty acid is substantially different from the omega-6 fatty acid at high surface pressures. Experiments also show that the permeability of bilayers to glucose and the rates of dissociation of pyrenyl cholesterol from bilayers were similar for bilayers containing DHA compared to bilayers containing oleic acid or linoleic acid. |
| On arguments about cholesterol Klimov, A. N. (1992), Kardiologiia 32(2): 5-8. |
| On call. I'm a 63-year-old man with arthritis but no other conditions. My only medicines were Naprosyn and vitamins until my last annual checkup, when my cholesterol was high. My doctor gave me Zocor, which helped. But I developed muscle aches, so he switched me to Zetia. I feel fine again, but I'd like to know what you think Simon, H. B. (2004), Harv Mens Health Watch 8(9): 8. |
| On correcting plasma cholesterol levels and preventing the clinical sequelae of atherosclerotic coronary heart disease Krut, L. H. (1998), Am J Cardiol 82(7): 918-20. |
| On the anti-atherogenic effect of the antioxidant BHT in cholesterol-fed rabbits: inverse relation between serum triglycerides and atheromatous lesions Freyschuss, A., A. Al-Schurbaji, et al. (2001), Biochim Biophys Acta 1534(2-3): 129-38. Abstract: We have shown that inclusion of the antioxidant butylated hydroxytoluene (BHT) in the diet protects against development of atherosclerotic lesions in cholesterol-fed rabbits. In parallel, BHT treatment results in increased plasma triglyceride levels. The present study explores the relationship between the triglyceride-inducing and protective effects of BHT in two different studies. The combined material contains 22 rabbits fed cholesterol and 18 rabbits fed cholesterol in combination with 1% BHT. In the BHT group there was an inverse relationship between triglyceride exposure/cholesterol exposure and extent of lesions with r=0.74 (P=0.0005). Our results show that increased triglyceride exposure parallels the anti-atherogenic effect of BHT. There was no significant correlation between atheromatosis and serum BHT levels. beta-very low density lipoprotein (beta-VLDL) from cholesterol and BHT animals was triglyceride-enriched and smaller compared to beta-VLDL from cholesterol-fed animals, but there was no significant association between the anti-atherogenic effect of BHT and particle size or apolipoprotein pattern of LDL or beta-VLDL. LDL isolated from rabbits treated with cholesterol and BHT was less sensitive to oxidative modification than LDL isolated from rabbits treated with cholesterol only. In conclusion, our results demonstrate that the degree of triglyceride exposure may be an important modulator of the anti-atherogenic effect of an antioxidant. |
| On the effect of cholesterol on the fate of CYP11A1 imported into yeast mitochondria in vivo Kovaleva, I. E., S. I. Grivennikov, et al. (2000), Biochemistry (Mosc) 65(10): 1206-11. Abstract: It has earlier been shown that CYP11A1 (cytochrome P450scc precursor), synthesized in yeast cells, is imported into yeast mitochondria. However, in large part the foreign protein undergoes degradation or aggregates. In this work, we tried to prevent aggregation of CYP11A1 and stimulate its insertion into the mitochondrial inner membrane by substituting cholesterol (a substrate for cytochrome P450scc) for ergosterol in yeast cells. To this end, an ergosterol-deficient Saccharomyces cerevisiae mutant, growing in the presence of cholesterol and expressing a modified bovine CYP11A1 gene, was used. Under defined conditions, the mitochondrial respiratory system developed in this yeast and CYP11A1 with the CoxIV targeting presequence was imported into the mitochondria, being then proteolytically processed. However, substitution of cholesterol for ergosterol did not result in lowered aggregation of the imported CYP11A1 and its increased content in the SMP fraction. Hence, the presence of cholesterol is not instrumental in proper intramitochondrial compartmentalization and folding of CYP11A1. |
| On the evidence. Cholesterol and coronary heart disease screening & treatment Turner-Boutle, M., T. Sheldon, et al. (1998), Health Serv J 108(5593): 36-7. |
| On the importance of the phosphocholine methyl groups for sphingomyelin/cholesterol interactions in membranes: a study with ceramide phosphoethanolamine Terova, B., R. Heczko, et al. (2005), Biophys J 88(4): 2661-9. Abstract: In this study, we have examined how the headgroup size and properties affect the membrane properties of sphingomyelin and interactions with cholesterol. We prepared N-palmitoyl ceramide phosphoethanolamine (PCPE) and compared its membrane behavior with D-erythro-N-palmitoyl-sphingomyelin (PSM), both in monolayers and bilayers. The pure PCPE monolayer did not show a phase transition at 22 degrees C (in contrast to PSM), but displayed a much higher inverse isothermal compressibility as compared to the PSM monolayer, indicating stronger intermolecular interactions between PCPEs than between PSMs. At 37 degrees C the PCPE monolayer was more expanded (than at 22 degrees C) and displayed a rather poorly defined phase transition. When cholesterol was comixed into the monolayer, a condensing effect of cholesterol on the lateral packing of the lipids in the monolayer could be observed. The phase transition from an ordered to a disordered state in bilayer membranes was determined by diphenylhexatriene steady-state anisotropy. Whereas the PSM bilayer became disordered at 41 degrees C, the PCPE bilayer main transition occurred around 64 degrees C. The diphenylhexatriene steady-state anisotropy values were similar in both PCPE and PSM bilayers before and after the phase transition, suggesting that the order in the hydrophobic core in both bilayer types was rather similar. The emission from Laurdan was blue shifted in PCPE bilayers in the gel phase when compared to the emission spectra from PSM bilayers, and the blue-shifted component in PCPE bilayers was retained also after the phase transition, suggesting that Laurdan molecules sensed a more hydrophobic environment at the PCPE interface compared to the PSM interface both below and above the bilayer melting temperature. Whereas PSM was able to form sterol-enriched domains in dominantly fluid bilayers (as determined from cholestatrienol dequenching experiments), PCPE failed to form such domains, suggesting that the size and/or properties of the headgroup was important for stabilizing sphingolipid/sterol interaction. In conclusion, our study has highlighted how the headgroup in sphingomyelin affect its membrane properties and interactions with cholesterol. |
| On the mechanism of cholesterol interaction with apolipoproteins A-I and E Klimov, A. N., K. A. Kozhevnikova, et al. (1992), Chem Phys Lipids 62(3): 229-37. Abstract: It is shown that cholesterol may interact with some substances containing the guanidine group (guanidine itself, arginine, metformin and dodecylguanidine bromide) and with arginine-rich proteins--apoproteins A-I and E. In the latter case the interaction produces the formation of cholesterol-apoprotein complexes. Analysis of such complexes has shown that one apo A-I molecule binds 17-22 and one apo E molecule binds 30-35 sterol molecules, which approximately corresponds to the amount of arginine residues in these proteins. Formation of cholesterol-apoprotein complexes has been suggested to occur due to: (1) formation of hydrogen bond and/or ion-dipole interaction between cholesterol hydroxyl and guanidine groups of the apoprotein arginine residues and (2) hydrophobic interaction of the cholesterol aliphatic chain with nonpolar side chains of the amino acids occupying the third position from arginine in the protein molecule. |
| On the mechanism of oxidation of cholesterol at C-7 in a lipoxygenase system Lund, E., U. Diczfalusy, et al. (1992), J Biol Chem 267(18): 12462-7. Abstract: Incubation of 7-2H2cholesterol with soybean lipoxygenase and linoleic acid in the presence of oxygen gave a mixture of 5-cholestene-3 beta,7 alpha-diol, 5-cholestene-3 beta,7 beta-diol, 3 beta-hydroxy-5-cholesten-7-one,5 alpha,6 alpha-epoxycholestan-3 beta-ol, and 5 beta,6 beta-epoxycholestan-3 beta-ol. The conversion into the 7-oxygenated products was associated with a very high intermolecular isotope effect (KH/KD = 15-17), suggesting that the rate-limiting step in the overall conversion is likely to be the abstraction of hydrogen at C-7 in a radical reaction. Evidence that linoleic acid is to some extent directly involved was obtained with the use of 7-3Hcholesterol. Incubation of 7-3Hcholesterol resulted in a significant incorporation of 3H in the reisolated linoleic acid fraction. The isotope effect associated with conversion of 7 alpha-2Hcholesterol into 7-oxygenated products in the lipoxygenase system was 2-3, indicating that the extraction of hydrogen is nonstereospecific. Incubation of 7-2H2cholesterol with 13-hydroperoxy-9,11-octadecadienoic acid gave the above 7-oxygenated products with relatively small isotope effects (KH/KD = 3-4). It is concluded that the most important mechanism for oxidation of cholesterol at C-7 in the lipoxygenase system involves participation of radicals and that a carbon-centered linoleic acid radical can extract hydrogen directly from cholesterol. Fatty acid hydroperoxides and their secondary products seem to be less important as initiators in connection with oxidation of cholesterol. |
| On the mechanism of stimulation of cholesterol 7 alpha-hydroxylase by dietary cholesterol Bjorkhem, I., G. Eggertsen, et al. (1991), Biochim Biophys Acta 1085(3): 329-35. Abstract: In agreement with previous work, treatment of rats with cholesterol, 2% in diet, stimulated the cholesterol 7 alpha-hydroxylase activity more than 2-fold. With less than 1% in diet, no significant effect was obtained. Intravenous infusion of cholesterol-enriched Intralipid had no stimulatory effect. In accordance with some recent work by other groups, it was shown that the stimulation of the cholesterol 7 alpha-hydroxylase by dietary cholesterol was associated with elevated levels of mRNA corresponding to the enzyme. Most of the stimulation of the activity induced by dietary cholesterol could not be prevented by lymphatic drainage. Feeding lymph fistulated rats with 2% cholesterol in diet stimulated the cholesterol 7 alpha-hydroxylase almost 2-fold, indicating that under the conditions employed, a major part of the cholesterol-induced stimulation of the activity was due to factor(s) unrelated to the flux of cholesterol from the intestine to the liver. There was a good correlation between the amount of cholesterol excreted in faeces and the activity of the cholesterol 7 alpha-hydroxylase. The half-life of intraperitoneally administered labelled cholic acid was significantly shorter in rats treated with 2% cholesterol in diet (t1/2 = 1.2 +/- 0.1 days) than in control rats (t1/2 = 1.9 +/- 0.18 days). A notable finding was that the weight of faeces was considerably higher in rats fed cholesterol than in the controls. It is hypothesized that a high dietary load of cholesterol causes increased binding of bile acids in the intestine and increased loss of bile acids in faeces. This leads to a reduced suppression of the cholesterol 7 alpha-hydroxylase by the bile acids. The results support the contention that the flux of bile acids rather than the flux of cholesterol from the intestine is the major direct regulator of bile acid biosynthesis. |
| On the optimization of cholesterol screening Milsum, J. H. (1991), Methods Inf Med 30(1): 36-43. Abstract: Total serum cholesterol is a major risk factor for Coronary Heart Disease (CHD). Some guidelines have been published regarding treatment levels. However, before implementing cholesterol screening, the costs and benefits should be analyzed as a function of cholesterol level. Analysis is readily implemented on microcomputer spreadsheets using decision tree analysis. Because it is very difficult to establish some of the costs satisfactorily, the facility of spreadsheets in performing sensitivity analysis is crucial. Here, plausible numerical values are used as "default" conditions for estimating in a preliminary way the costs and benefits of a putative screening-intervention program. The cost-benefit condition remains very close to optimal over the range 200-240 mg/dl for cholesterol marker level. The optimal condition may shift considerably when the default parameter values are altered. With the default values, the maximal net benefit is around 5% of the estimated current costs of CHD deaths without screening. |
| On the origin of sphingolipid/cholesterol-rich detergent-insoluble cell membranes: physiological concentrations of cholesterol and sphingolipid induce formation of a detergent-insoluble, liquid-ordered lipid phase in model membranes Ahmed, S. N., D. A. Brown, et al. (1997), Biochemistry 36(36): 10944-53. Abstract: Detergent-insoluble membrane fragments that are rich in sphingolipid and cholesterol can be isolated from both cell lysates and model membranes. We have proposed that these arise from membranes that are in the liquid-ordered phase both in vivo and in vitro Schroeder et al. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 12130-12134. In order to detect formation of the liquid-ordered phase while avoiding possible detergent artifacts, we have now used fluorescence quenching to examine the phase behavior of mixtures of phosphatidylcholines, sphingolipids, and cholesterol. Phase separation was found in binary mixtures of either dipalmitoylphosphatidylcholine (DPPC) or sphingomyelin (SM) and a nitroxide-labeled phosphatidylcholine (12SLPC). A DPPC- or SM-enriched solidlike gel phase coexisted with a 12SLPC-enriched liquid-disordered fluid phase at 23 degrees C. As expected, phase separation was not seen at low concentrations of DPPC or SM. Instead, only a uniform fluid phase was present. Including 33 mol % cholesterol in model membranes greatly promoted phase separation. Phase separation was seen at higher temperatures and/or at lower concentrations of DPPC or SM in the presence of cholesterol than in its absence. Mixtures of DPPC or SM and cholesterol are known to form the liquid-ordered phase. Therefore, the fact that phase separation was observed in the cholesterol-containing membranes shows that liquid-ordered and liquid-disordered phase domains coexist. At 37 degrees C, the SM-enriched liquid-ordered phase was first seen at a SM/PC ratio of close to 0.25, when SM made up 17% of the total lipid including cholesterol. (This is similar to or less than the SM concentration of the plasma membranes of mammalian cells.) Furthermore, the detergent insolubility of cholesterol-containing model membranes correlated well with the amount of liquid-ordered phase as detected by fluorescence quenching. Thus, the detergent-insoluble membranes isolated from cells are likely to exist in the liquid-ordered phase prior to detergent extraction. The promotion of liquid-ordered phase formation may be an important function of cholesterol and sphingolipids in cells and may be a major distinction between the cholesterol- and sphingolipid-rich plasma membrane and most other cellular membranes. |
| On the ozonization of cholesterol 3-acyl esters in protic media Smith, L. L., E. L. Ezell, et al. (1996), Steroids 61(7): 401-6. Abstract: The structures of cholesterol 3 beta-acyl ester ozonides formed by reaction with ozone in participating alcoholic solvents are established by proton and carbon-13 spectra as a 3 beta-acyloxy-7 alpha-alkoxy-(5R,7R)-5 alpha-B-homo-6-oxacholestane-5-hydroperoxides (7a, 7b), and that of the dimeric cholesterol ozonide formed in nonparticipating solvents with cholesterol acting as alcohol is established as 7 alpha-cholest-5'-en-3'-yloxy-3 beta-hydroxy-(5R,7R)-5 alpha-B-homo-6-oxacholestane-5-hydroperoxide (7c). |
| On the relationship between cholesterol lowering and coronary disease event rate Fazio, S. and M. F. Linton (1998), Circulation 98(23): 2645-6. |
| On the turnover of brain cholesterol in patients with Alzheimer's disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells Bogdanovic, N., L. Bretillon, et al. (2001), Neurosci Lett 314(1-2): 45-8. Abstract: Evidence is accumulating for a link between cerebral cholesterol metabolism and Alzheimer's disease (AD). Here we focus on a possible relationship between AD and a newly discovered mechanism for cholesterol efflux from the brain, involving conversion of brain cholesterol into 24S-hydroxycholesterol by the neuronal oxidative enzyme CYP46. There was a marked difference in the distribution of CYP46 in brains of control and AD patients. The neuronal cells were less stained in AD brains than in controls while marked positive staining was found in glial cells in AD but not in controls. The dynamic changes in the mechanisms for cholesterol efflux from the brain are of interest in relation to the link between brain cholesterol and amyloid beta-protein in AD. |
| On the waves of the Seven Countries Study: a public health perspective on cholesterol Kromhout, D. (1999), Eur Heart J 20(11): 796-802. |
| Oncologic diagnosis of serous effusions in body cavities (cytologic study and evaluation of cholesterol and carcinoembryonic antigen levels) Gulyas, M., G. Elek, et al. (1995), Orv Hetil 136(45): 2453-8. Abstract: Conventional cytological evaluation of serous effusions often yields border line result: apart from positive (malignant) or negative (benign) diagnoses, a relatively large part of the findings are "suspicious for malignancy" (P3). In the present paper the authors have analysed to what extent contributes the determination of cholesterol and CEA levels of ascites and pleural effusion to the diagnostic accuracy of cytologically "suspicious" (P3) cases. In 155 histologically controlled cases, specificity, sensitivity and diagnostic efficiency were assessed on the basis of cytology as well as the determination of CEA and cholesterol levels. Statistical parameters were determined for each method separately and for their combined application. According to the findings, cholesterol and CEA levels over 1.16 mmol/l and 2.5 ng/ml, respectively, indicate malignancy. In 19 out of 29 cytologically "suspicious" cases (66%), which histologically proved to be positive, cholesterol and/or CEA levels were elevated. In all of the 12 non-neoplastic "suspicious" cases the two parameters were under the cutoff values. The application of an easy and inexpensive cholesterol test proves to be a sensitive technique for indicating carcinomatosis and it completes adequately the specific cytological evaluation. If clinical symptoms speak for tumor, but the cytology is negative, the evaluation of CEA level may prove to be useful as far as it can indicate cancer not yet accompanied by carcinomatosis. |
| One measurement of serum total cholesterol is enough to predict future levels in healthy postmenopausal women Hetland, M. L., J. Haarbo, et al. (1992), Am J Med 92(1): 25-8. Abstract: PURPOSE: The purpose of this study was to investigate how well a single or double measurement of serum total cholesterol represents the spontaneous, future level in a particular person. SUBJECTS AND METHODS: The spontaneous fluctuations in serum total cholesterol levels in 169 healthy early postmenopausal women were followed during the course of 12 years. Serum total cholesterol was measured enzymatically. RESULTS: The initial measurement and the long-term level of serum total cholesterol were highly related (p less than 0.0001). The long-term level (calculated for each woman as the area under the curve of serum total cholesterol versus time) was not statistically significantly different from the initial level (mean difference: 0.036 +/- 0.046 mmol/L mean +/- SEM, NS). The initial serum total cholesterol level was then used to classify each woman into a high or a low cholesterol group, according to the current recommendations. The predictive value of an initial total cholesterol value in the high level (greater than or equal to 6.2 mmol/L) group was 84%, when compared with the long-term level. The predictive value of an initial total cholesterol level below 6.2 mmol/L was 80%. No improvement in these parameters was found when the average of the initial two (or three, when the difference exceeded 0.9 mmol/L) measurements were used as the baseline value. The fluctuations in serum total cholesterol levels were mainly due to short-term variations. CONCLUSION: For screening purposes, one measurement of serum total cholesterol in a woman gives a good estimate of the long-term level. The current data indicate that repeated measurements of serum total cholesterol do not improve the predictability of future cholesterol levels. The data also suggest that, at least in postmenopausal women with an elevated level of serum total cholesterol, one should proceed immediately to lipoprotein analysis for further risk assessment. |
| One state's approach to the regulation of cholesterol screening DeBoy, J. M. (1990), Public Health Rep 105(6): 584-8. Abstract: In 1989 Maryland became the first State to enact legislation, separate from existing laboratory law, authorizing a comprehensive, self-supporting program to regulate cholesterol screening conducted outside of laboratories and physicians' offices. This program requires a State permit to conduct cholesterol screening and oversees regulations that define minimum standards of quality assurance in such areas as personnel training, analytical quality control, counseling, and patient referral. This paper is a review of some of the political and technical problems that Maryland faced and solved in developing and implementing an effective regulatory program. |