Cholesterol Journal Articles

Record 8301 to 8320

Lipid screening: is it enough to measure total cholesterol concentration?
Neil, H. A., D. Mant, et al. (1990), Bmj 301(6752): 584-7.
Abstract: OBJECTIVES--To determine whether measurement of total cholesterol concentration is sufficient to identify most patients at lipoprotein mediated risk of coronary heart disease without measurement of triglyceride and high density lipoprotein (HDL) cholesterol concentrations. DESIGN--Cross sectional screening programme. SETTING--Six general practices in Oxfordshire. PATIENTS--1901 Men and 2068 women aged 25-59. MAIN OUTCOME MEASURE--Cardiovascular risk as assessed by fasting venous plasma concentrations of total cholesterol, triglyceride, and HDL cholesterol. RESULTS--2931 Patients (74% of those screened) had a total cholesterol concentration of less than 6.5 mmol/l. If the triglyceride concentration had not been measured in these patients isolated hypertriglyceridaemia (greater than or equal to 2.3 mmol/l) would have remained undetected in 185. Among these 185 patients, however, 123 were overweight or obese and only 18 (0.6% of those screened) had an increased risk associated with both a raised triglyceride concentration (greater than or equal to 2.3 mmol/l) and a low HDL cholesterol concentration (less than 0.9 mmol/l). Conversely, in the 790 patients with predominant hypercholesterolaemia (cholesterol concentration greater than or equal to 6.5 mmol/l and triglyceride concentration less than 2.3 mmol/l) measurement of HDL cholesterol concentration showed that 348 (9% of those screened) had only a moderately increased risk with a ratio of total to HDL cholesterol of less than 4.5 and 104 had a low risk with a ratio of less than 3.5. CONCLUSIONS--Fasting triglyceride and HDL cholesterol concentrations identify few patients at increased risk of coronary heart disease if the total cholesterol concentration is less than 6.5 mmol/l. HDL cholesterol and triglyceride concentrations should, however, be measured in patients with a total cholesterol concentration exceeding this value. Total cholesterol concentration alone may overestimate risk in a considerable number of these patients, and measurement of HDL cholesterol concentration allows a more precise estimate of risk. Measurement of the triglyceride concentration is required to characterise the lipoprotein abnormality. A patient should not be started on a drug that lowers lipid concentrations without having had a full lipoprotein assessment including measurement of HDL cholesterol concentration.

Lipid screening: is measuring cholesterol enough?
Cooke, J. P. and A. H. Singer (1993), Cleve Clin J Med 60(2): 115-7.

Lipid therapy in risk patients. Do we concentrate too much on LDL cholesterol?
Marz, W. (2005), MMW Fortschr Med 147(14): 14.

Lipid trafficking and sorting: how cholesterol is filling gaps
Hoekstra, D. and I. S. C. van (2000), Curr Opin Cell Biol 12(4): 496-502.
Abstract: Recent research has highlighted a role for cholesterol homeostasis in the regulation of trafficking and sorting of sphingolipids. This sorting may dictate the nature of the acyl chain species of phospholipids in the plasma membrane which, in turn, may govern the selective partitioning of these lipids into lateral domains. Recently, several proteins have been identified that play a role in the flow and sorting of all major lipid classes.

Lipid transfer proteins, hypertriglyceridemia, and reduced high-density lipoprotein cholesterol
Sparks, D., J. J. Frohlich, et al. (1991), Am Heart J 122(2): 601-7.

Lipid transporters: membrane transport systems for cholesterol and fatty acids
Abumrad, N. A., Z. Sfeir, et al. (2000), Curr Opin Clin Nutr Metab Care 3(4): 255-62.
Abstract: Lipophilic molecules can passively diffuse across cell membranes, a process that is driven by the concentration gradient, by availability of acceptors to facilitate desorption from the bilayer, and by cellular metabolism. However, evidence has accumulated that supports the existence of specialized, protein-facilitated membrane transport systems for many lipophilic molecules. This has generated considerable debate regarding why such systems need to exist. The present review summarizes recent developments related to the membrane transport systems for cholesterol and fatty acids, which have been shown to involve structurally related proteins. General similarities of the cholesterol and fatty acid systems to other lipid transport systems (briefly discussed in the Introduction section) are highlighted in the Conclusion section. The overall aim of the present review is to illustrate why lipid transporters are needed in vivo, and how they accomplish specific functions that can not be met by lipid diffusion alone.

Lipid-cholesterol interactions in the P beta' phase. Application of a statistical mechanical model
Scott, H. L. and W. S. McCullough (1993), Biophys J 64(5): 1398-404.
Abstract: We describe a statistical mechanical model for lipid-cholesterol mixtures in the P beta' (ripple) phase of lipid bilayers. The model is a simple extension of an earlier model for the ripple phase in pure lipid bilayers. The extension consists of adding a degree of freedom to allow for the occupation of underlying lattice sites by cholesterol molecules, and adding a lipid-cholesterol interaction term to the model Hamiltonian. The interaction term was constructed based on numerical calculations of lipid-cholesterol energies for several different packing juxtapositions of the two molecules. Other than the lipid-cholesterol interactions, the extended model uses the same parameter set as the earlier model, so that comparison of the properties of the extended model with experimental data serves as a test of the validity of the original model. Properties of the model were calculated using the Monte Carlo method. Results are displayed as snapshots of the ripple configurations at different cholesterol concentrations. The spacing of the ripples increases with increasing cholesterol concentration and the rate of increase compares very well with experimental data. The success of this model supports the conclusion drawn earlier that frustration arising from anisotropic packing interactions is responsible for the ripple phase in lipid bilayers. In the extended model these packing interactions are responsible for the selective partitioning of cholesterol in the regions between the ripples.

Lipid-cholesterol interactions. Monte Carlo simulations and theory
Scott, H. L. (1991), Biophys J 59(2): 445-55.
Abstract: Results of Monte Carlo calculations of order parameter profiles of lipid chains interacting with cholesterol are presented. Cholesterol concentrations in the simulations are sufficiently large that it is possible to analyze profiles for chains which are near neighbors of two or more cholesterol molecules, chains which are neighbors to a single cholesterol, and chains which are not near any cholesterol molecules. The profiles, show that cholesterol acts to significantly decrease the ability of neighboring chains to undergo trans-gauche isomeric rotations, although these chains are not all forced into all-trans conformations. The effect is significantly greater for chains which are neighbors to more than one cholesterol. The Monte Carlo results are next used as a guide to develop a theoretical model for lipid-cholesterol mixtures. The properties of this model and the phase diagram which it predicts are described. The phase diagram is then compared with experimentally determined phase diagrams. The model calculations and the computer simulations upon which they are based yield a molecular mechanism for several of the observed phases exhibited by lipid-cholesterol mixtures. The theoretical model predicts that at low temperatures the system should exhibit solid phase immiscibility.

Lipid-lipid recognition in fluid bilayers: solving the cholesterol mystery
Regen, S. L. (2002), Curr Opin Chem Biol 6(6): 729-35.
Abstract: Nearest-neighbour recognition measurements take 'molecular-level snapshots' of lipid organization in fluid bilayers by detecting and quantifying the thermodynamic tendency of two lipids to become nearest-neighbours. Recent nearest-neighbour recognition experiments have clarified the structural role that cholesterol plays in biological membranes. They have also clarified the influence that the linkage region of sphingolipids, the sugar head group of glycolipids, and lipid-peptide interactions have on lipid-lipid recognition.

Lipid-lowering and antioxidative activities of 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate in cholesterol-fed rats
Lee, J. S., M. S. Choi, et al. (2001), Clin Chim Acta 314(1-2): 221-9.
Abstract: BACKGROUND: Polyphenols appear to have antioxidant activities and may mediate lipid lowering. METHODS: Four groups of rats, a high-cholesterol control (HC), HC+lovastatin, HC+3,4-di(OH)-cinnamate, and HC+3,4-di(OH)-hydrocinnamate, were given a semi-synthetic diet. The cinnamate derivative or lovastatin (0.1 g/100 g) supplements were given for 6 weeks. RESULTS: The plasma total cholesterol concentration was significantly lowered by the 3,4-di(OH)-cinnamate supplement compared to the control or lovastatin group. The 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate supplements significantly lowered both the hepatic cholesterol and triglyceride levels, while lovastatin only lowered the hepatic cholesterol. The hepatic HMG-CoA reductase activities were significantly lower in the 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate groups than in the control or lovastatin group. The ACAT activity was only significantly lower in the lovastatin group compared to the other groups. With regards the hepatic antioxidant enzyme system, the CAT activity was significantly higher in the 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate groups compared to the control or lovastatin group. The two cinnamate derivatives resulted in an increased hepatic GSH-Px activity. Meanwhile, all the supplements significantly lowered the hepatic thiobarbituric acid reactive substances (TBARS) content. However, the 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate supplements did not alter the neutral sterol and total fecal sterol. CONCLUSIONS: Both cinnamate derivatives were potent in lipid-lowering and altering the antioxidative enzyme. Furthermore, these results also suggest that 3,4-di(OH)-cinnamate is more effective than 3,4-di(OH)-hydrocinnamate in its lipid-lowering action.

Lipid-lowering drugs (statins), cholesterol, and coenzyme Q10. The Baycol case--a modern Pandora's box
Bliznakov, E. G. (2002), Biomed Pharmacother 56(1): 56-9.

Lipid-lowering efficacy of 3,4-di(OH)-phenylpropionic L-leucine in high-cholesterol fed rats
Kim, S. J., S. H. Bok, et al. (2005), J Biochem Mol Toxicol 19(1): 25-31.
Abstract: A preliminary study revealed that 3,4-di(OH)-hydrocinnamate (HC), a polyphenolic compound, lowered the plasma lipids in high-cholesterol fed rats. Accordingly, this study was designed to test the lipid-lowering efficacy of a synthetic derivative, 3,4-di(OH)-phenylpropionic (L-leucine) amide (PPLA), in rats fed a high-cholesterol (1%, wt/wt) diet. As such, HC or PPLA was given as supplement to a high-cholesterol diet for 6 weeks at a dose of 0.137 mmol/100 g diet. The supplementation of HC and PPLA significantly lowered the plasma and hepatic cholesterol and triglyceride levels compared to the control group. The activities of hepatic HMG-CoA reductase (164 +/- 9.12 and 124.74 +/- 17.09 pmol/min/mg protein vs. 245.41 +/- 13.01 pmol/min/mg protein, p < 0.05) and ACAT (411.49 +/- 11.48 and 334.35 +/- 17.68 pmol/min/mg protein vs. 490.41 +/- 16.69 pmol/min/mg protein, p < 0.05) were significantly lower in the HC- and PPLA-supplemented groups than in the control group. However, PPLA was more effective in inhibiting the enzyme activities than HC. The excretion of neutral sterol was significantly higher in HC- and PPLA-supplemented groups than in the control group. Therefore, these results indicate that PPLA, a leucine-attached version of HC, exhibited a similar significant hypocholesterolemic effect to HC in rats fed a high-cholesterol diet.

Lipid-lowering efficacy of hesperetin metabolites in high-cholesterol fed rats
Kim, H. K., T. S. Jeong, et al. (2003), Clin Chim Acta 327(1-2): 129-37.
Abstract: BACKGROUND: Hesperetin is a naturally occurring flavonoid that has hypolipidemic properties. METHODS: Male rats were fed a 1 g/100 g high-cholesterol diet for 5 weeks along with hesperetin (0.02%, 0.066 mmol/100 g diet) and hesperetin metabolites. The hesperetin metabolites, m-hydroxycinnamic acid (m-HC), 3,4-dihydroxyphenylpropionic acid (3,4-DHPP), and 3-methoxy-4-hydroxycinnamic acid (ferulic acid), were supplemented based on an equivalent amount of hesperetin. RESULTS: The supplementation of hesperetin and its metabolites significantly lowered the plasma total cholesterol and triglyceride concentrations compared to the control group. The hepatic HMG-CoA reductase and acyl-CoA:cholesterol acyltransferase (ACAT) activities were significantly lower in the hesperetin and its metabolite supplemented groups than in the control group. The excretion of acidic sterol was significantly higher in the hesperetin, m-HC, 3,4-DHPP, and ferulic acid supplemented groups than in the control group. CONCLUSIONS: These results demonstrated that the hesperetin metabolites played as potent a role as hesperetin in plasma lipid-lowering activities in vivo, and further suggest that cholesterol biosynthesis and esterification were concomitantly reduced by hesperetin and its metabolites, as indicated by the decreased HMG-CoA reductase and ACAT activities.

Lipid-lowering therapy and cholesterol levels following acute myocardial infarction: a German study of 5361 patients
Bergmann, A., J. Schulze, et al. (2003), Eur J Epidemiol 18(5): 407-11.
Abstract: BACKGROUND: Current studies on secondary prevention of cardiovascular events (CARE, LIPID, 4S) illustrate the necessity of an effective lipid-lowering therapy. An important part of secondary prevention is the prompt measurement of lipids following an infarct, to be able to start therapy as quickly as possible. AIMS: This study should show the general situation in the prescription of lipid-lowering drugs in patients with acute myocardial infarction (MI) and if there are gender differences in therapy and in the lipid parameters. The second aim was to determine the therapeutical conclusions for secondary prevention made in-hospital in patients with heart attacks. METHODS: Post-infarct lipid parameters (total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG) were examined in 5361 patients within 24 hours following an acute MI. Lipid parameters from 576 patients were measured again after 1 week. RESULTS: 80.1% of men under examination and 81.9% of the women had suffered from their first MI. Only 9% of all patients were already under lipid-lowering therapy before the MI. After the MI TC and LDL-C levels decreased significantly in a time-dependent manner. Around 50% of patients received lipid-lowering drug, or the recommendation of one, during their hospital stay. CONCLUSION: The range of TC values of the patients examined was comparable to those in the CARE and the 4S secondary prevention studies. It can therefore be assumed that the results of these studies are also applicable to Germany. Nevertheless, according to existing data, therapy with lipid-lowering drugs is currently unsatisfactory, even in secondary prevention.

Lipid-lowering treatment in coronary artery disease: how low should cholesterol go?
Jones, P. H. (2000), Drugs 59(5): 1127-35.
Abstract: The randomised clinical trial data, which supports preventing coronary heart disease (CHD) events by lowering low density lipoprotein cholesterol (LDL-C) levels, is substantial, consistent and highly significant. HMG-CoA reductase inhibitors (statins), which are the preferred medications for lowering LDL-C levels, are well tolerated, with greater efficacy than other lipid-altering medications. In 1993, the National Cholesterol Education Program (NCEP) guidelines recommended LDL-C target levels to be achieved with therapy in high-risk individuals. In particular, the LDL-C goal of therapy in patients with CHD was < or = 100 mg/dl (2.6 mmol/L), with no specific guidance as to the lower limit or whether additional clinical benefit could be expected. Because little clinical trial data existed at that time to offer support, and because some epidemiological data raised concern about the potential detriments associated with very low total cholesterol and LDL-C levels, the NCEP Adult Treatment Panel remained appropriately vague on the 'how low should you go' question. In the last few years, several additional clinical trials have provided sufficient efficacy and safety data to re-examine that question. Analyses of on-treatment LDL-C levels and subsequent CHD events from three landmark trials with HMG-CoA reductase inhibitors suggest that progressively lower LDL-C levels are associated with lower CHD events in a curvilinear fashion. The Post Coronary Artery Bypass Graft (Post-CABG) trial and Atorvastatin Versus Revascularisation Trial (AVERT) examined a more intensive versus less intensive drug regimen for LDL-C reduction, and concluded that the more aggressively treated patients had better angiographic and end-point outcomes. Most importantly, there did not appear to be any change in noncardiovascular end-points associated with lower LDL-C levels. In several ongoing clinical trials, patients with CHD have been randomised to receive HMG-CoA reductase inhibitors with targets for LDL-C levels of 100 mg/dl versus 75 mg/dl (1.94 mmol/L). These trials have sufficient patient numbers and power to definitely determine if reducing LDL-C levels to approximately 75 mg/dl can provide an acceptable benefit-to-risk-ratio.

Lipid-protein complexes as cholesterol pronucleating agents in human bile
Mala, I., J. Zikova, et al. (1998), Int J Biochem Cell Biol 30(2): 251-60.
Abstract: Among the various substances which accelerate the formation of cholesterol crystals in cholesterol supersaturated bile are proteins obtained from the bile by affinity chromatography on con A-Sepharose. Several such con A binding proteins have been identified and shown to mediate acceleration of cholesterol crystal formation in vitro. However, the major protein fraction, which does not bind con A, has been studied rarely. Investigation of the effect of this latter bile protein fraction on cholesterol crystallization is the aim of this study. Contrary to results published to date, the con A nonbinding protein fraction exerted a higher cholesterol crystallization promoting activity than the con A binding fraction. Delipidation as well as proteolytic degradation sharply decreased the activity of both fractions. Albumin was identified as the main component of the con A nonbinding fraction. A lipid-protein complex formed from the lipid and albumin possessed a very high cholesterol crystallization promoting activity whereas albumin or the lipid alone showed much lower activity. Bivalent ions, especially Mn2+ and Ca2+, increased the promoting activity of the lipid-protein complex. Thus, albumin and other bile protein can bind noncovalently biliary lipid material and such lipid-protein complexes may act as the main cholesterol crystallization promoter in the human bile.

Lipid-related prevention of coronary disease without reduction of LDL-cholesterol. Two new intervention studies show that the old truths must be modified
Olsson, A. G. (2000), Lakartidningen 97(12): 1368-70.

Lipids rich in phosphatidylethanolamine from natural gas-utilizing bacteria reduce plasma cholesterol and classes of phospholipids: a comparison with soybean oil
Muller, H., L. I. Hellgren, et al. (2004), Lipids 39(9): 833-41.
Abstract: We compared the effects of three different high-lipid diets on plasma lipoproteins and phospholipids in mink (Mustela vison). The 18 mink studied were fed one of the three diets during a 25-d period in a parallel group design. The compared diets had 0, 17, and 67% extracted lipids from natural gas-utilizing bacteria (LNGB), which were rich in PE. The group with 0% LNGB was fed a diet for which the lipid content was 100% soybean oil. The total cholesterol, LDL cholesterol, and HDL cholesterol of animals consuming a diet with 67% LNGB (67LNGB-diet), were significantly lowered by 35, 49, and 29%, respectively, and unesterified cholesterol increased by 17% compared with the animals fed a diet of 100% lipids from soybean oil (SB-diet). In addition, the ratio of LDL cholesterol to HDL cholesterol was 27% lower in mink fed the 67LNGB-diet than those fed the SB-diet. When the mink were fed the 67LNGB-diet, plasma PC, total phospholipids, lysoPC, and PI were lowered significantly compared with the mink fed a SB-diet. Plasma total cholesterol was correlated with total phospholipids as well as with PC (R = 0.8, P< 0.001). A significantly higher fecal excretion of unesterified cholesterol, cholesteryl ester, PC, lysoPC, and PE was observed in the 67LNGB-fed mink compared with the SB-fed mink. We conclude that phospholipids from the 67LNGB-diet decreased plasma lipoprotein levels, the LDL/HDL cholesterol ratio, and plasma phospholipid levels, especially lysoPC and PC, compared with the highly unsaturated soybean oil. Our findings indicate that the decrease of plasma cholesterol is mainly caused by a specific mixture of phospholipids containing a high level of PE, and not by the dietary FA composition. The lack of significant differences in the level of plasma PE due to the diets indicates that most of the PE from LNGB has been converted to PC in the liver. Thus, plasma cholesterol may at least be partly regulated by phospholipid methylation from PE to PC in the liver.

Lipodystrophy-associated morphological, cholesterol and triglyceride abnormalities in a population-based HIV/AIDS treatment database
Heath, K. V., R. S. Hogg, et al. (2001), Aids 15(2): 231-9.
Abstract: OBJECTIVE: To provide population-based estimates of the prevalence of lipodystrophy syndrome and constituent symptoms and to identify correlates of prevalent symptomology. METHODS: Participants in a province-wide HIV/AIDS treatment programme reported morphological and metabolic abnormalities. Probable lipodystrophy was defined as self-report of at least one morphological abnormality or both high cholesterol and triglyceride levels. Explanatory variables investigated included: age; sex; ethnicity; transmission risk group; CD4 cell count; plasma viral load; AIDS diagnosis; duration of infection; alternative therapy use; past, current and duration of use of antiretroviral therapy (ART) by class and specific drug; total duration of ART; and current adherence. Stepwise logistic regression identified possible determinates of lipodystrophy. RESULTS: Of 1035 participants, 50% appeared to have probable lipodystrophy, with 36% reporting peripheral wasting, 33% abdominal weight gain, 6% buffalo hump, and 10 and 12% increased triglyceride or cholesterol levels, respectively. In multivariate analysis, lipodystrophy was associated with older age (per year) (AOR 1.03; 95% CI 1.01, 1.04), the use of ingested alternative therapies (AOR 1.46; 95% CI 1.06, 2.01), having ever used protease inhibitors (PI) (AOR 2.63; 95% CI 1.89, 3.66), and duration of stavudine treatment (per year) (AOR 1.35; 95% CI 1.15, 1.58). In analysis limited to participants exposed to PI, after similar adjustment, the duration of lamivudine rather than stavudine treatment was associated with lipodystrophy (AOR 1.32; 95% CI 1.13, 1.53). CONCLUSION: Increased risk of abnormalities is associated with the use of PI, and the duration of stavudine and lamivudine treatment after adjustment for personal characteristics, clinical disease stage, duration of infection and detailed treatment history.

Lipolytic activities in rats fed a sucrose-rich diet supplemented with either cystine or cholesterol: relationships with lipoprotein profiles
Mathe, D., C. Serougne, et al. (1991), Ann Nutr Metab 35(3): 165-73.
Abstract: To study the relationships between lipolytic activities and plasma lipoprotein levels in rats, three diets were given for 8 weeks: a semipurified diet (based on sucrose, casein and lard) and this diet enriched with 5% cystine or with 1% cholesterol. Both supplemented diets induced hypercholesterolemia. Lipoprotein analysis by density gradient ultracentrifugation of plasma indicated that hypercholesterolemia of cystine-fed rats (+52%) was characterized by an increased cholesterol level in high-density lipoprotein (HDL; +131%) and low-density lipoprotein 2 (LDL2; +147%), the lipoprotein fraction containing essentially apolipoprotein-E-rich high-density lipoproteins (HDL1), and was associated with a decreased cholesterol level in triglyceride-rich lipoproteins (TRL: -69%). That obtained by cholesterol feeding (+28%) was due to a large increase in the TRL cholesterol level (+315%) whereas cholesterol was reduced in HDL (-40%) and in LDL2 (-60%). Under these dietary conditions, the activity of hepatic lipase (HL) was measured in liver homogenates and those of both HL and lipoprotein lipase were measured in plasma after heparin injection. The activity of HL (1,783 +/- 132 mU/g liver in control rats) was increased by 48% in cystine-fed rats and decreased by 40% in cholesterol-fed rats. Similar changes were observed in the activity of both lipases measured in postheparin plasma. Highly significant positive correlations linked each lipolytic activity with the level of cholesterol, phospholipids and proteins in LDL2 (HDL1-rich fraction) and in HDL. In contrast, significant negative correlations were found between all of the TRL components and the activity of the lipases.(ABSTRACT TRUNCATED AT 250 WORDS)

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