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Sample records for b-containing lipoprotein particle

  1. Apolipoprotein B-containing lipoprotein particle assembly: Lipid capacity of the nascent lipoprotein particle

    Energy Technology Data Exchange (ETDEWEB)

    Manchekar, Medha; Forte, Trudy M.; Datta, Geeta; Richardson, Paul E.; Segrest, Jere P.; Dashti, Nassrin

    2003-12-01

    We previously proposed that the N-terminal 1000 residue {beta}{alpha}{sub 1} domain of apolipoprotein B (apoB) forms a bulk lipid pocket homologous to that of lamprey lipovitellin (LV). In support of this ''lipid pocket'' hypothesis, apoB:1000 (residues 1-1000) was shown to be secreted by a stable transformant of McA-RH7777 cells as a monodisperse particle with HDL{sub 3} density and Stokes diameter of 112 {angstrom}. In contrast, apoB:931 (residues 1-931), missing only 69 residues of the sequence homologous to LV, was secreted as a particle considerably more dense than HDL with Stokes diameter of 110 {angstrom}. The purpose of the present study was to determine the stoichiometry of the lipid component of the apoB:931 and apoB:1000 particles. This was accomplished by metabolic labeling of cells with either [{sup 14}C]oleic acid or [{sup 3}H]glycerol followed by immunoprecipitation (IP) or nondenaturing gradient gel electrophoresis (NDGGE) of secreted lipoproteins and by immunoaffinity chromatography of secreted unlabeled lipoproteins. The [{sup 3}H]-labeled apoB:1000-containing particles, isolated by NDGGE, contained 50 phospholipids (PL) and 11 triacylglycerols (TAG) molecules per particle. In contrast, apoB:931-containing particles contained only a few molecules of PL and were devoid of TAG. The unlabeled apoB:1000-containing particles isolated by immunoaffinity chromatography and analyzed for lipid mass, contained 56 PL, 8 TAG, and 7 cholesteryl ester molecules per particle. The surface:core lipid ratio of apoB:1000-containing particles was approximately 4:1 and was not affected by incubation of cells with oleate. Although small amounts of microsomal triglyceride transfer protein (MTP) were associated with apoB:1000-containing particles, it never approached a 1:1 molar ratio of MTP to apoB. These results support a model in which: (1) the first 1000 amino acid residues of apoB are competent to complete the ''lipid pocket

  2. Apolipoprotein B-containing lipoproteins and atherosclerotic cardiovascular disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Michael D. Shapiro

    2017-02-01

    Full Text Available Cholesterol-rich, apolipoprotein B (apoB-containing lipoproteins are now widely accepted as the most important causal agents of atherosclerotic cardiovascular disease. Multiple unequivocal and orthogonal lines of evidence all converge on low-density lipoprotein and related particles as being the principal actors in the genesis of atherosclerosis. Here, we review the fundamental role of atherogenic apoB-containing lipoproteins in cardiovascular disease and several other humoral and parietal factors that are required to initiate and maintain arterial degeneration. The biology of foam cells and their interactions with high-density lipoproteins, including cholesterol efflux, are also briefly reviewed.

  3. Acute effects of interleukin-6 infusion on apo-B-containing lipoprotein subclasses in humans

    DEFF Research Database (Denmark)

    Bagdade, John; Pedersen, Bente K; Schwenke, Dawn

    2011-01-01

    B:E) apoB-containing subclasses present in VLDL. Therefore, we have directly measured these subclasses following their isolation by sequential immunoprecipitation in seven healthy male subjects during a 3-h infusion with recombinant human (rh) IL-6. Though plasma TG and apoB-containing particle number were...... unchanged by IL-6, the distribution of TG-rich subclasses was significantly altered. Compared to baseline values, LpB:E + LpB:C:E increased significantly at 0.5 h (p infused controls at 0.5 and 1 h (p

  4. Comparison of gemfibrozil versus simvastatin in familial combined hyperlipidemia and effects on apolipoprotein-B-containing lipoproteins, low-density lipoprotein subfraction profile, and low-density lipoprotein oxidizability

    NARCIS (Netherlands)

    Bredie, S. J.; de Bruin, T. W.; Demacker, P. N.; Kastelein, J. J.; Stalenhoef, A. F.

    1995-01-01

    We evaluated in a double-blind, placebo-controlled, randomized trial of 45 well-defined patients with familial combined hyperlipidemia, the effect of gemfibrozil (1,200 mg/day) or simvastatin (20 mg/day) on apolipoprotein-B (apo-B)-containing lipoproteins, low-density lipoprotein (LDL) subfraction

  5. Opposing effects of apolipoprotein m on catabolism of apolipoprotein B-containing lipoproteins and atherosclerosis

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Pedersen, Tanja Xenia; Gordts, Philip L S M

    2010-01-01

    Rationale: Plasma apolipoprotein (apo)M is mainly associated with high-density lipoprotein (HDL). HDL-bound apoM is antiatherogenic in vitro. However, plasma apoM is not associated with coronary heart disease in humans, perhaps because of a positive correlation with plasma low-density lipoprotein...... (LDL). Objective: We explored putative links between apoM and very-low-density (VLDL)/LDL metabolism and the antiatherogenic potential of apoM in vivo. Methods and Results: Plasma apoM was increased approximately 2.1 and approximately 1.5 fold in mice lacking LDL receptors (Ldlr(-/-)) and expressing...... dysfunctional LDL receptor-related protein 1 (Lrp1(n2/n2)), respectively, but was unaffected in apoE-deficient (ApoE(-/-)) mice. Thus, pathways controlling catabolism of VLDL and LDL affect plasma apoM. Overexpression ( approximately 10-fold) of human apoM increased (50% to 70%) and apoM deficiency decreased...

  6. Effects of saturated, mono-, and polyunsaturated fatty acids on the secretion of apo B containing lipoproteins by Caco-2 cells

    NARCIS (Netherlands)

    van Greevenbroek, M.M.J.; van Meer, G.|info:eu-repo/dai/nl/068570368; Erkelens, D.W.; de Bruin, T.W.A.

    1996-01-01

    We studied the effects of addition of physiological concentrations (0.5 mM) of fatty acids i.e., palmitic (16:0), stearic (18:0), oleic (18:1) and linoleic acid (18:2) on lipoprotein secretion by polarized Caco-2 cells. With saturated fatty acids, secreted lipoproteins were at IDL/LDL density, 1.009

  7. Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and their mechanisms of action on apolipoprotein B-containing lipoproteins in humans: a review.

    Science.gov (United States)

    Oscarsson, Jan; Hurt-Camejo, Eva

    2017-08-10

    Epidemiological and genetic studies suggest that elevated triglyceride (TG)-rich lipoprotein levels in the circulation increase the risk of cardiovascular disease. Prescription formulations of omega-3 fatty acids (OM3FAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduce plasma TG levels and are approved for the treatment of patients with severe hypertriglyceridemia. Many preclinical studies have investigated the TG-lowering mechanisms of action of OM3FAs, but less is known from clinical studies. We conducted a review, using systematic methodology, of studies in humans assessing the mechanisms of action of EPA and DHA on apolipoprotein B-containing lipoproteins, including TG-rich lipoproteins and low-density lipoproteins (LDLs). A systematic search of PubMed retrieved 55 articles, of which 30 were used in the review; 35 additional arrticles were also included. In humans, dietary DHA is retroconverted to EPA, while production of DHA from EPA is not observed. Dietary DHA is preferentially esterified into TGs, while EPA is more evenly esterified into TGs, cholesterol esters and phospholipids. The preferential esterification of DHA into TGs likely explains the higher turnover of DHA than EPA in plasma. The main effects of both EPA and DHA are decreased fasting and postprandial serum TG levels, through reduction of hepatic very-low-density lipoprotein (VLDL)-TG production. The exact mechanism for reduced VLDL production is not clear but does not include retention of lipids in the liver; rather, increased hepatic fatty acid oxidation is likely. The postprandial reduction in TG levels is caused by increased lipoprotein lipase activity and reduced serum VLDL-TG concentrations, resulting in enhanced chylomicron clearance. Overall, no clear differences between the effects of EPA and DHA on TG levels, or on turnover of TG-rich lipoproteins, have been observed. Effects on LDL are complex and may be influenced by genetics, such as APOE genotype. EPA and

  8. Lipoprotein Particle Concentrations in Children and Adults following Kawasaki Disease

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    Lin, Jonathan; Jain, Sonia; Sun, Xiaoying; Liu, Victoria; Sato, Yuichiro Z.; Jimenez-Fernandez, Susan; Newfield, Ron S.; Pourfarzib, Ray; Tremoulet, Adriana H.; Gordon, John B.; Daniels, Lori B.; Burns, Jane C.

    2014-01-01

    Objective To test the hypothesis that children and adults with history of Kawasaki disease (KD) are more likely to have abnormal lipoprotein particle profiles that could place them at increased risk of atherosclerosis later in life. Study design Fasting serum samples were obtained from 192 children and 63 adults with history of KD and 90 age-similar healthy controls. Lipoprotein particle (P) concentrations and sizes were measured by Nuclear Magnetic Resonance (NMR) spectroscopy (Liposcience Inc., Raleigh, NC) and serum was assayed for total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL)-C. Low-density lipoprotein cholesterol (LDL)-C was estimated using the Friedewald formula. Data were analyzed in a least-square means model adjusting for age and sex and using Holm correction for multiple comparisons. Results Compared with respective control groups, both adult and pediatric subjects with KD had significantly lower mean very-low-density lipoprotein-chylomicron particle concentrations (VLDLC-P), intermediate-density lipoproteins (IDL), TG, and TC concentrations. Pediatric subjects with KD had significantly lower LDL-P and LDL-C concentrations and lower mean TC/HDL-C ratio (ppediatric and adult subjects with KD regardless of their aneurysm status are no more likely than age-similar, healthy controls to have lipid patterns associated with increased risk of atherosclerosis. PMID:25039043

  9. Lipoprotein particle distribution and skeletal muscle lipoprotein lipase activity after acute exercise

    LENUS (Irish Health Repository)

    Harrison, Michael

    2012-06-06

    AbstractBackgroundMany of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS), it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects.MethodsUsing a randomized cross-over design, very low density lipoprotein (VLDL) responses were evaluated in eight men on the morning after i) an inactive control trial (CON), ii) exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF), and iii) after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL).ResultsThe intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG) determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70–120 nm (large) particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43–55 nm (medium) particle range. VLDL-TG in smaller particles (29–43 nm) was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL) activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state.ConclusionsThese findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in LPL activity.

  10. Apolipoproteins C-III and E in apoB- and non-apoB-containing lipoproteins in two populations at contrasting risk for myocardial infarction: the ECTIM study. Etude Cas Témoins sur 'Infarctus du Myocarde.

    Science.gov (United States)

    Luc, G; Fievet, C; Arveiler, D; Evans, A E; Bard, J M; Cambien, F; Fruchart, J C; Ducimetiere, P

    1996-03-01

    Apolipoprotein (apo) C-III and apoE are components of two major classes of plasma lipoproteins, i.e., apoB- and non-apoB-containing lipoproteins. To analyze the relationship between the distribution of apoC-III and apoE among lipoproteins and coronary heart disease, we compared the distribution of these two apolipoproteins in survivors of myocardial infarction (MI) and control subjects, within and between populations at contrasting risk for MI. ApoC-III and apoE concentrations were determined in plasma devoid of apoB-containing lipoproteins by immunoprecipitation using a specific anti-apoB antiserum. These assays referred to apoC-III-Lp non-B and apoE-Lp non-B, respectively. By examining the difference with total plasma apoC-III and apoE levels, we calculated apoC-III and apoE in apoB-containing lipoproteins (apoCIII-LpB and apoE-LpB, respectively). These determinations were performed in control subjects and in survivors of MI, all males aged 25 to 64 years. They were recruited in Northern Ireland and France, countries characterized by a large difference in the incidence of coronary heart disease. In univariate analysis, apoCIII-LpB appeared significantly higher and the apoC-III ratio (apoC-III-Lp non-B/apoC-III-LpB) significantly lower in MI survivors than in control subjects in both countries. ApoE-LpB was higher in MI survivors than in control subjects in Northern Ireland but not in France. The two French and Irish control populations differed for apoC-ILL-Lp non-B, apoC-III ratio, and apoE ratio, which were higher in France than in Northern Ireland, and for apoC-III-LpB, apoE, and apoE-LpB, which were lower. Multivariate analysis showed that no parameter involving apoC-III and apoE was more discriminatory than HDL-cholesterol, cholesterol, and triglycerides or apoA-I, apoB, and triglycerides between controls and MI subjects. In contrast, the apoC-III ratio was a better discriminatory parameter between the two control populations than the listed parameters. The

  11. Characterization and Purification of Polydisperse Reconstituted Lipoproteins and Nanolipoprotein Particles

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    Paul D. Hoeprich

    2009-07-01

    Full Text Available Heterogeneity is a fact that plagues the characterization and application of many self-assembled biological constructs. The importance of obtaining particle homogeneity in biological assemblies is a critical goal, as bulk analysis tools often require identical species for reliable interpretation of the results—indeed, important tools of analysis such as x-ray diffraction typically require over 90% purity for effectiveness. This issue bears particular importance in the case of lipoproteins. Lipid-binding proteins known as apolipoproteins can self assemble with liposomes to form reconstituted high density lipoproteins (rHDLs or nanolipoprotein particles (NLPs when used for biotechnology applications such as the solubilization of membrane proteins. Typically, the apolipoprotein and phospholipids reactants are self assembled and even with careful assembly protocols the product often contains heterogeneous particles. In fact, size polydispersity in rHDLs and NLPs published in the literature are frequently observed, which may confound the accurate use of analytical methods. In this article, we demonstrate a procedure for producing a pure, monodisperse NLP subpopulation from a polydisperse self-assembly using size exclusion chromatography (SEC coupled with high resolution particle imaging by atomic force microscopy (AFM. In addition, NLPs have been shown to self assemble both in the presence and absence of detergents such as cholate, yet the effects of cholate on NLP polydispersity and separation has not been systematically examined. Therefore, we examined the separation properties of NLPs assembled in both the absence and presence of cholate using SEC and native gel electrophoresis. From this analysis, NLPs prepared with and without cholate showed particles with well defined diameters spanning a similar size range. However, cholate was shown to have a dramatic affect on NLP separation by SEC and native gel electrophoresis. Furthermore, under

  12. Achieving secondary prevention low-density lipoprotein particle concentration goals using lipoprotein cholesterol-based data.

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    Simon C Mathews

    Full Text Available BACKGROUND: Epidemiologic studies suggest that LDL particle concentration (LDL-P may remain elevated at guideline recommended LDL cholesterol goals, representing a source of residual risk. We examined the following seven separate lipid parameters in achieving the LDL-P goal of <1000 nmol/L goal for very high risk secondary prevention: total cholesterol to HDL cholesterol ratio, TC/HDL, <3; a composite of ATP-III very high risk targets, LDL-C<70 mg/dL, non-HDL-C<100 mg/dL and TG<150 mg/dL; a composite of standard secondary risk targets, LDL-C<100, non-HDL-C<130, TG<150; LDL phenotype; HDL-C ≥ 40; TG<150; and TG/HDL-C<3. METHODS: We measured ApoB, ApoAI, ultracentrifugation lipoprotein cholesterol and NMR lipoprotein particle concentration in 148 unselected primary and secondary prevention patients. RESULTS: TC/HDL-C<3 effectively discriminated subjects by LDL-P goal (F = 84.1, p<10(-6. The ATP-III very high risk composite target (LDL-C<70, nonHDL-C<100, TG<150 was also effective (F = 42.8, p<10(-5. However, the standard secondary prevention composite (LDL-C<100, non-HDL-C<130, TG<150 was also effective but yielded higher LDL-P than the very high risk composite (F = 42.0, p<10(-5 with upper 95% confidence interval of LDL-P less than 1000 nmol/L. TG<150 and TG/HDL-C<3 cutpoints both significantly discriminated subjects but the LDL-P upper 95% confidence intervals fell above goal of 1000 nmol/L (F = 15.8, p = 0.0001 and F = 9.7, p = 0.002 respectively. LDL density phenotype neared significance (F = 2.85, p = 0.094 and the HDL-C cutpoint of 40 mg/dL did not discriminate (F = 0.53, p = 0.47 alone or add discriminatory power to ATP-III targets. CONCLUSIONS: A simple composite of ATP-III very high risk lipoprotein cholesterol based treatment targets or TC/HDL-C ratio <3 most effectively identified subjects meeting the secondary prevention target level of LDL-P<1000 nmol/L, providing a potential alternative to advanced lipid testing in many clinical

  13. Particle release in extracorporeal low-density lipoprotein lowering therapies.

    Science.gov (United States)

    Martins, K; Ahrenholz, P; Matic, G B; Hofmann, D; Tiess, M; Winkler, R E; Ramlow, W

    2000-07-01

    Release of microparticles into the blood during extracorporeal circulation must be kept low because of possibly serious acute and chronic adverse effects. Concentration and size distribution of microparticles were measured during simulated treatments (n = 7) on original equipment for 2 standard low-density lipoprotein (LDL) elimination procedures (DALI 750, Fresenius AG, St. Wendel, Germany and Liposorber, Kaneka Corporation, Osaka, Japan) and compared to hemofiltration solutions. For both systems as well as in hemofiltration solutions, the mean particle concentrations in 500 ml portions gathered from the efferent blood line stayed below 10% of pharmacopoeia standards for infusion solutions (United States Pharmacopoeia, European Pharmacopoeia) in all measured size classes. Although particle concentrations were comparable in all systems, the mean total number of particles > or =2 microm released per session was lowest in the DALI (167,000) compared to the Liposorber (465,000) and hemofiltration solutions (2,240,000). This was mainly due to different total processed blood volumes necessary to achieve the required LDL reduction.

  14. Changes in lipids and lipoprotein particle concentrations after interruption of antiretroviral therapy

    DEFF Research Database (Denmark)

    Lampe, Fiona C; Duprez, Daniel A; Kuller, Lewis H

    2010-01-01

    The effect of interruption of antiretroviral therapy (ART) on lipoprotein particle subclasses has not been studied. We examined short-term changes in lipids and lipoprotein particles among 332 HIV-infected individuals randomized to interrupt or continue ART in the "Strategies for Management...

  15. Changes in lipids and lipoprotein particle concentrations after interruption of antiretroviral therapy

    DEFF Research Database (Denmark)

    Lampe, Fiona C; Duprez, Daniel A; Kuller, Lewis H

    2010-01-01

    The effect of interruption of antiretroviral therapy (ART) on lipoprotein particle subclasses has not been studied. We examined short-term changes in lipids and lipoprotein particles among 332 HIV-infected individuals randomized to interrupt or continue ART in the "Strategies for Management...... of Antiretroviral Therapy" trial....

  16. The plasma concentration of HDL-associated apoM is influenced by LDL receptor-mediated clearance of apoB-containing particles

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Benn, Marianne; Christensen, Pernille Møller

    2012-01-01

    ApoM is mainly associated with HDL. Nevertheless, we have consistently observed positive correlations of apoM with plasma LDL cholesterol in humans. Moreover, LDL receptor deficiency is associated with increased plasma apoM in mice. Here, we tested the idea that plasma apoM concentrations...... are affected by the rate of LDL receptor-mediated clearance of apoB-containing particles. We measured apoM in humans each carrying one of three different LDL receptor mutations (n = 9) or the apoB3500 mutation (n = 12). These carriers had increased plasma apoM (1.34 ± 0.13 µM, P = 0.003, and 1.23 ± 0.10 µM, P...... = 0.02, respectively) as compared with noncarriers (0.93 ± 0.04 µM). When we injected human apoM-containing HDL into Wt (n = 6) or LDL receptor-deficient mice (n = 6), the removal of HDL-associated human apoM was delayed in the LDL receptor-deficient mice. After 2 h, 54 ± 5% versus 90 ± 8% (P

  17. Limited discriminant value of lipoprotein AI, lipoprotein Lp(a) and other lipoprotein particles in patients with and without early onset ischaemic heart disease.

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    Vallance, D T; Staunton, H A; Winder, A F

    1995-01-01

    AIMS--To assess whether the ability of lipoprotein related variables to discriminate between individuals with or without premature clinical ischaemic heart disease (IHD) was improved using data on high density lipoprotein-lipoprotein AI (HDL-LpAI) fractions, alone or in combination with data on Lp(a). METHODS--Lipid and apolipoprotein concentrations were measured in 26 middle-aged men (mean age 50.3 years) with early onset IHD and coronary artery bypass grafting prior to sampling, and in 26 matched lipaemic and 26 normolipaemic asymptomatic controls. RESULTS--Triglyceride and Lp(a) concentrations were higher, while HDL cholesterol and apolipoprotein A-I (apoA-I) concentrations were lower in patients than in controls. LpAI concentrations were also lower in IHD patients and were correlated with HDL and apoA-I in both IHD and control groups. Lp(a) was not correlated with any other lipid or apolipoprotein measured in either patients or controls. Univariate discriminant function analysis showed that the proportion correctly classified as patients or controls was marginally greater using LpAI concentrations as the discriminator, which was not increased in combination with Lp(a). Serum triglycerides, HDL cholesterol, apoA-I and Lp(a) alone all had similar, but weaker, discriminant power, which increased in various combinations with LpAI. CONCLUSIONS--LpAI particle measurement may be useful in research to define mechanisms of cardiovascular protection by HDL but the discriminating power for IHD was only marginally superior to measuring total apoA-I or Lp(a) concentrations. Little further advantage arose through combining LpAI data with other variables. PMID:7706525

  18. Reversible flow of cholesteryl ester between high-density lipoproteins and triacylglycerol-rich particles is modulated by the fatty acid composition and concentration of triacylglycerols

    Directory of Open Access Journals (Sweden)

    E.C.R. Quintão

    2010-12-01

    Full Text Available We determined the influence of fasting (FAST and feeding (FED on cholesteryl ester (CE flow between high-density lipoproteins (HDL and plasma apoB-lipoprotein and triacylglycerol (TG-rich emulsions (EM prepared with TG-fatty acids (FAs. TG-FAs of varying chain lengths and degrees of unsaturation were tested in the presence of a plasma fraction at d > 1.21 g/mL as the source of CE transfer protein. The transfer of CE from HDL to FED was greater than to FAST TG-rich acceptor lipoproteins, 18% and 14%, respectively. However, percent CE transfer from HDL to apoB-containing lipoproteins was similar for FED and FAST HDL. The CE transfer from HDL to EM depended on the EM TG-FA chain length. Furthermore, the chain length of the monounsaturated TG-containing EM showed a significant positive correlation of the CE transfer from HDL to EM (r = 0.81, P < 0.0001 and a negative correlation from EM to HDL (r = -041, P = 0.0088. Regarding the degree of EM TG-FAs unsaturation, among EMs containing C18, the CE transfer was lower from HDL to C18:2 compared to C18:1 and C18:3, 17.7%, 20.7%, and 20%, respectively. However, the CE transfer from EMs to HDL was higher to C18:2 than to C18:1 and C18:3, 83.7%, 51.2%, and 46.3%, respectively. Thus, the EM FA composition was found to be the rate-limiting factor regulating the transfer of CE from HDL. Consequently, the net transfer of CE between HDL and TG-rich particles depends on the specific arrangement of the TG acyl chains in the lipoprotein particle core.

  19. Manduca sexta lipid transfer particle acts upon a lipoprotein to catalyze lipid and apoprotein disproportionation.

    Science.gov (United States)

    Ryan, R O; Van Antwerpen, R; Van der Horst, D J; Beenakkers, A M; Law, J H

    1990-01-05

    A novel reaction, catalyzed by Manduca sexta lipid transfer particle (LTP), transforms low density lipophorin (LDLp) into two distinct lipoprotein species. A population of LDLp particles serves as lipid donor or acceptor in LTP-catalyzed production of a very low density lipophorin (VLDLp) and a high density lipophorin (HDLp) product. The products result from facilitated net transfer of lipid mass from donor LDLp particles to acceptor LDLp particles. Transfer of apolipophorin III (apoLp-III) from donor to acceptor lipoprotein occurs during the reaction to produce a lipid- and apoLp-III-enriched VLDLp species and lipid- and apoLp-III-depleted HDLp species. The VLDLp produced in this in vitro reaction contains more lipid and apoLp-III than any previous lipophorin species reported and further demonstrates the scope of the lipid binding capacity of lipophorin. Lipid analysis and radiolabeling studies confirmed that unidirectional net transfer of lipid mass and apoLp-III from donor to acceptor occurs. When 3H-lipid-LDLp was used as substrate in the LTP-catalyzed disproportionation reaction the density distribution of radioactivity and protein provided evidence of vectorial transfer of diacylglycerol, phospholipid, and free fatty acids. Electron micrographs of the original LDLp population and of the LTP-induced product lipoprotein population provided further support for the interpretation derived from biochemical studies. This LTP-catalyzed disproportionation was observed only with apoLp-III-rich LDLp suggesting that the presence of increased amounts of this apoprotein dramatically affects the properties of the particle and appears to be directly related to the capacity of the lipoprotein to bind lipid.

  20. Relations between particle size of HDL and LDL lipoproteins and cholesterol esterification rate

    Czech Academy of Sciences Publication Activity Database

    Dobiášová, Milada; Urbanová, Z.; Šamánek, M.

    2005-01-01

    Roč. 54, č. 2 (2005), s. 159-165 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NA6590; GA MZd(CZ) NR8328 Institutional research plan: CEZ:AV0Z5011922 Keywords : particle size of lipoproteins * FER(HDL) * Log(TG/HDL-C) Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.806, year: 2005

  1. Missense mutations in APOB within the betaalpha1 domain of human APOB-100 result in impaired secretion of ApoB and ApoB-containing lipoproteins in familial hypobetalipoproteinemia.

    Science.gov (United States)

    Burnett, John R; Zhong, Shumei; Jiang, Zhenghui G; Hooper, Amanda J; Fisher, Eric A; McLeod, Roger S; Zhao, Yang; Barrett, P Hugh R; Hegele, Robert A; van Bockxmeer, Frank M; Zhang, Hongyu; Vance, Dennis E; McKnight, C James; Yao, Zemin

    2007-08-17

    Familial hypobetalipoproteinemia (FHBL) is associated with mutations in the APOB gene. We reported the first missense APOB mutation, R463W, in an FHBL kindred (Burnett, J. R., Shan, J., Miskie, B. A., Whitfield, A. J., Yuan, J., Tran, K., Mc-Knight, C. J., Hegele, R. A., and Yao, Z. (2003) J. Biol. Chem. 278, 13442-13452). Here we identified a second nonsynonymous APOB mutation, L343V, in another FHBL kindred. Heterozygotes for L343V (n = 10) had a mean plasma apoB at 0.31 g/liter as compared with 0.80 g/liter in unaffected family members (n = 22). The L343V mutation impaired secretion of apoB-100 and very low density lipoproteins. The secretion efficiency was 20% for B100wt and 10% for B100LV and B100RW. Decreased secretion of mutant apoB-100 was associated with increased endoplasmic reticulum retention and increased binding to microsomal triglyceride transfer protein and BiP. Reduced secretion efficiency was also observed with B48LV and B17LV. Biochemical and biophysical analyses of apoB domain constructs showed that L343V and R463W altered folding of the alpha-helical domain within the N terminus of apoB. Thus, proper folding of the alpha-helical domain of apoB-100 is essential for efficient secretion.

  2. Polyphenol rich olive oils improve lipoprotein particle atherogenic ratios and subclasses profile: A randomized, crossover, controlled trial.

    Science.gov (United States)

    Fernández-Castillejo, Sara; Valls, Rosa-Maria; Castañer, Olga; Rubió, Laura; Catalán, Úrsula; Pedret, Anna; Macià, Alba; Sampson, Maureen L; Covas, María-Isabel; Fitó, Montserrat; Motilva, Maria-José; Remaley, Alan T; Solà, Rosa

    2016-07-01

    Lipoprotein particle measures performed by nuclear magnetic resonance (NMR), and associated ratios, may be better markers for atherosclerosis risk than conventional lipid measures. The effect of two functional olive oils, one enriched with its polyphenols (FVOO, 500 ppm), and the other (FVOOT) with them (250 ppm) and those of thyme (250 ppm), versus a standard virgin olive oil (VOO), on lipoprotein particle atherogenic ratios and subclasses profiles was assessed. In a randomized, double-blind, crossover, controlled trial, 33 hypercholesterolemic individuals received 25 mL/day of VOO, FVOO, and FVOOT. Intervention periods were of 3 weeks separated by 2-week washout periods. Lipoprotein particle counts and subclasses were measured by NMR. Polyphenols from olive oil and thyme modified the lipoprotein subclasses profile and decreased the total LDL particle/total HDL particle (HDL-P), small HDL/large HDL, and HDL-cholesterol/HDL-P ratios, and decreased the lipoprotein insulin resistance index (LP-IR) (p Olive oil polyphenols, and those from thyme provided benefits on lipoprotein particle atherogenic ratios and subclasses profile distribution. Polyphenol-enriched olive oil is a way of increasing the olive oil healthy properties while consuming the same amount of fat, as well as a useful and complementary tool for the management of cardiovascular risk individuals. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Low-density lipoprotein particle diameter and mortality: the Ludwigshafen Risk and Cardiovascular Health Study.

    Science.gov (United States)

    Grammer, Tanja B; Kleber, Marcus E; März, Winfried; Silbernagel, Günther; Siekmeier, Rüdiger; Wieland, Heinrich; Pilz, Stefan; Tomaschitz, Andreas; Koenig, Wolfgang; Scharnagl, Hubert

    2015-01-01

    The aim of the study was to examine whether differences in average diameter of low-density lipoprotein (LDL) particles were associated with total and cardiovascular mortality. We studied 1643 subjects referred to coronary angiography, who did not receive lipid-lowering drugs. During a median follow-up of 9.9 years, 398 patients died, of these 246 from cardiovascular causes. We calculated average particle diameters of LDL from the composition of LDL obtained by β-quantification. When LDL with intermediate average diameters (16.5-16.8 nm) were used as reference category, the hazard ratios (HRs) adjusted for cardiovascular risk factors for death from any cause were 1.71 (95% CI: 1.31-2.25) and 1.24 (95% CI: 0.95-1.63) in patients with large (>16.8 nm) or small LDL (<16.5 nm), respectively. Adjusted HRs for death from cardiovascular causes were 1.89 (95% CI: 1.32-2.70) and 1.54 (95% CI: 1.06-2.12) in patients with large or small LDL, respectively. Patients with large LDL had higher concentrations of the inflammatory markers interleukin (IL)-6 and C-reactive protein than patients with small or intermediate LDL. Equilibrium density gradient ultracentrifugation revealed characteristic and distinct profiles of LDL particles in persons with large (approximately even distribution of intermediate-density lipoproteins and LDL-1 through LDL-6) intermediate (peak concentration at LDL-4) or small (peak concentration at LDL-6) average LDL particle diameters. Calculated LDL particle diameters identify patients with different profiles of LDL subfractions. Both large and small LDL diameters are independently associated with increased risk mortality of all causes and, more so, due to cardiovascular causes compared with LDL of intermediate size. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  4. Human placenta secretes apolipoprotein B-100-containing lipoproteins

    DEFF Research Database (Denmark)

    Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B

    2004-01-01

    early during pregnancy in the placenta. To examine whether the human placenta produces lipoproteins, we examined apoB and microsomal triglyceride transfer protein (MTP) mRNA expression in placental biopsies. ApoB and MTP are mandatory for assembly and secretion of apoB-containing lipoproteins. Both...... genes were expressed in placenta and microsomal extracts from human placenta contained triglyceride transfer activity, indicating expression of bioactive MTP. To detect lipoprotein secretion, biopsies from term placentas were placed in medium with [(35)S]methionine and [(35)S]cysteine for 3-24 h. Upon...... lipoproteins secreted from placental tissue showed spherical particles with a diameter of 47 +/- 10 nm. These results demonstrate that human placenta expresses both apoB and MTP and consequently synthesize and secrete apoB-100-containing lipoproteins. Placental lipoprotein formation constitutes a novel pathway...

  5. Niacin extended-release/simvastatin combination therapy produces larger favorable changes in high-density lipoprotein particles than atorvastatin monotherapy

    Directory of Open Access Journals (Sweden)

    Toth PP

    2012-01-01

    Full Text Available Peter P Toth1, Kamlesh M Thakker2, Ping Jiang2, Robert J Padley21University of Illinois College of Medicine, Peoria, and CGH Medical Center, Sterling, 2Abbott, Abbott Park, IL, USABackground: The purpose of this research was to compare the effects of niacin extended-release in combination with simvastatin (NER/S versus atorvastatin monotherapy on high-density lipoprotein (HDL particle number and size in patients with hyperlipidemia or dyslipidemia from the SUPREME study.Methods: This was a post hoc analysis of patients (n = 137 who completed the SUPREME study and who had lipid particle number and size measurements at both baseline and at week 12 by nuclear magnetic resonance spectroscopy. Following ≥4 weeks without lipid-modifying therapy (washout period, the patients received NER/S 1000/40 mg/day for 4 weeks followed by NER/S 2000/40 mg/day for 8 weeks, or atorvastatin 40 mg/day for 12 weeks. Median percent changes in HDL particle number and size from baseline to week 12 were compared between the NER/S and atorvastatin treatment groups using the Wilcoxon rank-sum test. Distribution of HDL particle subclasses at week 12 was compared between the treatment groups using the Cochran–Mantel–Haenszel test.Results: Treatment with NER/S resulted in a significantly greater percent reduction in small HDL particle number at week 12 compared with atorvastatin monotherapy (-1.8% versus 4.2%, P = 0.014, and a numerically greater percent increase in large HDL particle number (102.4% versus 39.2%, P = 0.078 compared with atorvastatin monotherapy. A significantly greater percent increase in HDL particle size from baseline at week 12 was observed with NER/S compared with atorvastatin (6.0% versus 1.3%, P < 0.001. NER/S treatment also resulted in a significant shift in HDL particle size from small and medium at baseline to large at week 12 (P < 0.0001.Conclusion: Treatment with NER/S resulted in larger favorable changes in number and size of HDL particle

  6. Eicosapentaenoic acid inhibits oxidation of high density lipoprotein particles in a manner distinct from docosahexaenoic acid.

    Science.gov (United States)

    Sherratt, Samuel C R; Mason, R Preston

    2018-02-05

    The omega-3 fatty acid eicosapentaenoic acid (EPA) reduces oxidation of ApoB-containing particles in vitro and in patients with hypertriglyceridemia. EPA may produce these effects through a potent antioxidant mechanism, which may facilitate LDL clearance and slow plaque progression. We hypothesize that EPA antioxidant effects may extend to ApoA-containing particles like HDL, potentially preserving certain atheroprotective functions. HDL was isolated from human plasma and incubated at 37 °C in the absence (vehicle) or presence of EPA and/or DHA; 5.0 or 10.0 μM each. Samples were then subjected to copper-induced oxidation (10 μM). HDL oxidation was inhibited similarly by EPA and DHA up to 1 h. EPA (10 μM) maintained significant HDL oxidation inhibition of 89% (0.622 ± 0.066 μM MDA; p < .001) at 4 h, with continued inhibition of 64% at 14 h, vs. vehicle (5.65 ± 0.06 to 2.01 ± 0.10 μM MDA; p < .001). Conversely, DHA (10 μM) antioxidant benefit was lost by 4 h. At a lower concentration (5 μM), EPA antioxidant activity remained at 81% (5.53 ± 0.15 to 1.03 ± 0.10 μM MDA; p < .001) at 6 h, while DHA lost all antioxidant activity by 4 h. The antioxidant activity of EPA was preserved when combined with an equimolar concentration of DHA (5 μM each). EPA pretreatment prevented HDL oxidation in a dose-dependent manner that was preserved over time. These results suggest unique lipophilic and electron stabilization properties for EPA as compared to DHA with respect to inhibition of HDL oxidation. These antioxidant effects of EPA may enhance certain atheroprotective functions for HDL. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Effect of the Probiotic Saccharomyces boulardii on Cholesterol and Lipoprotein Particles in Hypercholesterolemic Adults: A Single-Arm, Open-Label Pilot Study.

    Science.gov (United States)

    Ryan, Jennifer Joan; Hanes, Douglas Allen; Schafer, Morgan Beth; Mikolai, Jeremy; Zwickey, Heather

    2015-05-01

    Elevated blood cholesterol levels are a major risk factor for coronary artery disease, the leading cause of death worldwide. Probiotics have been investigated as potential cholesterol-lowering therapies, but no previous studies have assessed the effect of the probiotic yeast Saccharomyces boulardii on cholesterol levels in human volunteers. The objective of this study was to examine the effect of S. boulardii on serum cholesterol and lipoprotein particles in hypercholesterolemic adults. This study was a single-arm, open-label pilot study. Twelve hypercholesterolemic participants were recruited into the study; one dropped out. Participants took 5.6×10(10) colony forming unit (CFU) encapsulated S. boulardii (Saccharomyces cerevisiae var. boulardii CNCM I-1079) twice daily for an 8-week period. Fasting concentrations of cholesterol (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], and triglycerides), lipoprotein particles (very-low-density lipoprotein-particle [VLDL-P], remnant lipoprotein particle [RLP-P], total LDL-P, LDL III-P, LDL IV-P, total HDL-P, and HDL 2b-P), and additional cardiovascular biomarkers (apo B-100, lipoprotein [a], high-sensitivity C-reactive protein, homocysteine, fibrinogen, and insulin) were measured at baseline, after 4 weeks, and after 8 weeks. Remnant lipoprotein particles decreased by 15.5% (p=0.03) over the 8-week period. The remaining outcome measures were not significantly altered. In this pilot study, 8 weeks of daily supplementation with S. boulardii lowered remnant lipoprotein, a predictive biomarker and potential therapeutic target in the treatment and prevention of coronary artery disease.

  8. Hyphenating size-exclusion chromatography with electrospray mass spectrometry; using on-line liquid-liquid extraction to study the lipid composition of lipoprotein particles.

    Science.gov (United States)

    Osei, Michael; Griffin, Julian L; Koulman, Albert

    2015-11-15

    Lipoproteins belong to the most commonly measured clinical biochemical parameters. Lipidomics is an orthogonal approach and aims to profile the individual lipid molecules that jointly form the lipoprotein particles. However, in the first step of the extraction of lipid molecules from serum, an organic solvent is used leading to dissociation of the lipoproteins. Thus far it has been impossible to combine lipidomics and lipoprotein analysis in one analytical system. Human plasma was diluted in phosphate-buffered saline (PBS) and injected onto a Superose 6 PC 3.2 column with PBS as a mobile phase to separate lipoproteins. The eluent was led to a Syrris FLLEX module, which also received CHCl3 /MeOH (3:1). The two phases were mixed and subsequently separated using a Teflon membrane in an especially designed pressurized flow chamber. The organic phase was led to a standard electrospray source of an Orbitrap mass spectrometer. Size-exclusion chromatography (SEC) has been commonly applied to separate lipoproteins and is considered a practical alternative to ultracentrifugation. Through the on-line liquid-liquid extraction method it becomes possible to obtained detailed mass spectra of lipids across different lipoprotein fractions. The extracted ion chromatograms of specific lipid signals showed their distribution against the size of lipoprotein particles. The application of on-line liquid-liquid extraction allows for the continuous electrospray-based mass spectral analysis of SEC eluent, providing the detailed lipid composition of lipoprotein particles separated by size. This approach provides new possibilities for the study of the biochemistry of lipoproteins. © 2015 The Authors. Rapid Communications in Mass Spectrometry Published by John Wiley & Sons Ltd.

  9. N-3 polyunsaturated fatty acids improve lipoprotein particle size and concentration in Japanese patients with type 2 diabetes and hypertriglyceridemia: a pilot study.

    Science.gov (United States)

    Ide, Kana; Koshizaka, Masaya; Tokuyama, Hirotake; Tokuyama, Takahiko; Ishikawa, Takahiro; Maezawa, Yoshiro; Takemoto, Minoru; Yokote, Koutaro

    2018-03-15

    Patients with type 2 diabetes are at high risk for cardiovascular disease. Although hydroxymethylglutaryl-CoA reductase inhibitors (statins) can reduce cardiovascular events, residual risk remains even after target low-density lipoprotein cholesterol (LDL-C) levels have been achieved. Lipoprotein particle size and fraction changes are thought to contribute to such risks. The purpose of this study was to evaluate the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs), predominantly eicosapentaenoic acid and docosahexaenoic acid, on lipoprotein particle size, concentration, and glycemic control in Japanese patients with type 2 diabetes and hypertriglyceridemia. This was a multicenter, prospective, open-label, single arm study. We enrolled 14 patients with type 2 diabetes and hypertriglyceridemia treated with statins and dipeptidyl peptidase-4 inhibitors with glycated hemoglobin (HbA1c) n-3 PUFAs for 12 weeks. Lipoprotein particle sizes, concentrations, lipoprotein insulin resistance (LPIR) scores, lipid profiles, HbA1c, and fasting plasma glucose (FPG) were measured before and after treatment. Lipoprotein profiles were measured by nuclear magnetic resonance spectroscopy. Data were analyzed using Wilcoxon signed-rank tests. Concentrations of total cholesterol (P n-3 PUFA administration. N-3 PUFAs decreased the size of very low-density lipoprotein (VLDL; P N-3 PUFAs partly improved atherogenic lipoprotein particle size and concentration, and produced less atherogenic lipoprotein subclass ratios in patients that achieved target LDL-C levels and glycemic control. These results suggest that n-3 PUFAs may reduce residual cardiovascular risk factors in statin-treated patients with type 2 diabetes and hypertriglyceridemia. The study was registered at UMIN-ID: UMIN000013776 .

  10. Magnetic Resonance Imaging Detection of Tumor Cells by Targeting Low-Density Lipoprotein Receptors with Gd-Loaded Low-Density Lipoprotein Particles

    Directory of Open Access Journals (Sweden)

    Simonetta Geninatti Crich

    2007-12-01

    Full Text Available Gd-DO3A-diph and Gd-AAZTAC17 are lipophilic magnetic resonance imaging (MRI agents that display high affinity for low-density lipoprotein (LDL particles. However, on binding to LDL, Gd-DO3A-diph shows a decreased hydration that results in a lower enhancement of water proton relaxation rate. Conversely, GdAAZTAC17 displays a strong relaxation enhancement at the imaging fields. Each LDL particle can load up to 100 and 400 UNITS of Gd-DO3A-diph and Gd-AAZTAC17, respectively. Their LDL adducts are taken up by human hepatoblastoma G2 (HepG2 and melanoma B16 tumor cells when added to the incubation medium. T, measurements of the labeled cells indicate that Gd-AAZTAC17 is significantly more efficient than Gd-DO3A-diph. Furthermore, it has been found that HepG2 hepatoma cells can internalize higher amounts of Gd-AAZTAC17 than B16 cells and the involvement of LDL receptors (LDLRs has been demonstrated in competition assays with free LDL. Gd-AAZTAC17/LDL adduct proved to be an efficient probe in the magnetic resonance (MR visualization of subcutaneous tumors in animal models obtained by injecting B16 melanoma cells into the right flank of mice. Finally, confocal microscopy validation of the distribution of LDL-based probes in the tumor has been obtained by doping the Gd-AAZTAC17/LDL adduct with a fluorescent phospholipid moiety.

  11. Insect lipid transfer particle catalyzes bidirectional vectorial transfer of diacylglycerol from lipophorin to human low density lipoprotein.

    Science.gov (United States)

    Ryan, R O; Wessler, A N; Price, H M; Ando, S; Yokoyama, S

    1990-06-25

    Insect plasma lipid transfer particle (LTP) catalyzes vectorial net transfer of diacylglycerol (DAG) from Manduca sexta larval high density lipophorin (HDLp-L) to human low density lipoprotein (LDL) producing an LDL of lower density and lipophorin subspecies of higher density. At equilibrium, a stable DAG-depleted very high density lipophorin species (density = 1.25 g/ml) is formed. Electrophoretic analysis of the substrate and product lipoproteins showed that apoprotein exchange or transfer between human LDL and lipophorin did not occur during the lipid transfer reaction. Facilitated net transfer of cholesteryl ester, free cholesterol, and phospholipid occurred to a much lower extent than DAG net transfer, indicating that under these conditions, LDL serves as a sink for lipophorin-associated DAG. This reaction, therefore, provides a method whereby the mass of lipid associated with human LDL can be modified in vitro without alteration of its apoprotein component. The DAG content of LDL increased in a linear manner with respect to LTP concentration and time during the initial phase of the reaction, demonstrating the utility of this system as a quantitative assay method for LTP-mediated net DAG transfer. When [3H]DAG-labeled LDL was prepared and employed in transfer experiments with unlabeled lipophorin, labeled DAG was recovered in the HDLp-L fraction. The amount of labeled DAG recovered in the HDLp-L fraction was dependent on the ratio of LDL to HDLp-L in the reaction. Thus, in this system, LTP-mediated DAG redistribution is bidirectional, suggesting that the final equilibrium distribution of lipid may be dictated by the properties of potential donor/acceptor lipoproteins rather than by an inherent particle substrate specificity of LTP.

  12. Disturbances of lipoprotein metabolism in metabolic syndro

    Directory of Open Access Journals (Sweden)

    Marta Czyżewska

    2010-01-01

    Full Text Available Dyslipidemia in metabolic syndrome (MS, called the atherogenic triad, includes elevated levels of plasma triglycerides (TGs, low levels of HDL-cholesterol (HDL-CH, and the presence of small dense low-density lipoproteins (sdLDLs with normal or slightly elevated LDL-CH levels. Insulin resistance drives the increase in the three main sources of TG for VLDL synthesis: fatty-acid flux from adipose tissue, de novo lipogenesis, and uptake of remnant lipoproteins. Overproduction of VLDL, predominantly triglyceride-rich large VLDL1 particles, induces the cascade of events which lead to abnormalities of other plasma lipoproteins. The accumulation of VLDL in plasma and decreased activity of lipoprotein lipase (LPL impair the catabolism of chylomicrons. Moreover, hyperinsulinemia induces increased intestinal production of chylomicrons. These factors cause augmented postprandial lipemia. Hepatic overproduction of VLDL leads to an increased level of VLDL remnants in plasma. Highly atherogenic sdLDLs are generated from VLDL1 particles by the action of LPL, cholesterol ester transfer protein (CETP, and hepatic lipase (HL. In the presence of hypertriglyceridemia, accelerated CETP-mediated lipid transfer generates TG-enriched HDL particles. This enhances HDL catabolism mediated by HL and endothelial lipase (EL. The assessment of risk of atherosclerotic cardiovascular disease in MS related to low HDL-CH and the presence of sdLDL particles may be improved by the incorporation of measurements of apolipoproteins (apo-B and apoA-I into clinical practice. In addition, the concentration of non-HDL-CH may be useful in quantifying apo-B-containing atherogenic lipoproteins.

  13. How Well Does BODIPY-Cholesteryl Ester Mimic Unlabeled Cholesteryl Esters in High Density Lipoprotein Particles?

    DEFF Research Database (Denmark)

    Karilainen, Topi; Vuorela, Timo; Vattulainen, Ilpo

    2015-01-01

    We compare the behavior of unlabeled and BODIPY-labeled cholesteryl ester (CE) in high density lipoprotein by atomistic molecular dynamics simulations. We find through replica exchange umbrella sampling and unbiased molecular dynamics simulations that BODIPY labeling has no significant effect...... on the partitioning of CE between HDL and the water phase. However, BODIPY-CE was observed to diffuse more slowly and locate itself closer to the HDL-water interface than CE due to the BODIPY probe that is constrained to the surface region, and because the CE body in BODIPY-CE prefers to align itself away from...

  14. Isolation and characterization of apolipoproteins from murine microglia. Identification of a low density lipoprotein-like apolipoprotein J-rich but E-poor spherical particle.

    Science.gov (United States)

    Xu, Q; Li, Y; Cyras, C; Sanan, D A; Cordell, B

    2000-10-13

    Amyloid Abeta deposition is a neuropathologic hallmark of Alzheimer's disease. Activated microglia are intimately associated with plaques and appear to facilitate Abeta deposition, an event believed to contribute to pathogenesis. It is unclear if microglia can modulate pathogenesis of Alzheimer's disease by secreting lipoprotein particles. Here we show that cultured BV2 murine microglial cells, like astrocytes, secrete apolipoprotein E (apoE) and apolipoprotein J (apoJ) in a time-dependent manner. To isolate and identify BV2 microglial particles, gel filtration chromatography was employed to fractionate BV2-conditioned medium. Analyses by Western blot, lipid determination, electron microscopy, and native gel electrophoresis demonstrate that BV2 microglial cells release spherical low density lipoprotein (LDL)-like lipid-containing particles rich in apoJ but poor in apoE. These microglial particles are dissimilar in size, shape, and lipoprotein composition to astrocyte-derived particles. The microglial-derived particles were tested for functional activity. Under conditions of suppressed de novo cholesterol synthesis, the LDL-like particles effectively rescued primary rat cortical neurons from mevastatin-induced neurotoxicity. The particles were also shown to bind Abeta. We speculate that the LDL-like apoJ-rich apoE-poor microglial lipoproteins preferentially bind the lipoprotein receptor, recognizing apoJ, which is abundant in the choroid plexus, facilitating Abeta clearance from the brain. BV2 cells also secrete an apoE-rich lipid-poor species that binds Abeta. Consistent with the role of apoE in Abeta fibril formation and deposition, this microglial species may promote plaque formation.

  15. Lipid core nanoparticles resembling low-density lipoprotein and regression of atherosclerotic lesions: effects of particle size

    Directory of Open Access Journals (Sweden)

    S.C.M.P. Freitas

    2018-03-01

    Full Text Available Particles are usually polydispersed and size is an important feature for lipid-based drug delivery systems in order to optimize cell-particle interactions as to pharmacologic action and toxicity. Lipid nanoparticles (LDE with composition similar to that of low-density lipoprotein carrying paclitaxel were shown to markedly reduce atherosclerosis lesions induced in rabbits by cholesterol feeding. The aim of this study was to test whether two LDE fractions, one with small (20–60 nm and the other with large (60–100 nm particles, had different actions on the atherosclerotic lesions. The two LDE-paclitaxel fractions, prepared by microfluidization, were separated by density gradient ultracentrifugation and injected (4 mg/body weight, intravenously once a week into two groups of rabbits previously fed cholesterol for 4 weeks. A group of cholesterol-fed animals injected with saline solution was used as control to assess lesion reduction with treatment. After the treatment period, the animals were euthanized for analysis. After treatment, both the small and large nanoparticle preparations of LDE-paclitaxel had equally strong anti-atherosclerosis action. Both reduced lesion extension in the aorta by roughly 50%, decreased the intima width by 75% and the macrophage presence in the intima by 50%. The two preparations also showed similar toxicity profile. In conclusion, within the 20–100 nm range, size is apparently not an important feature regarding the LDE nanoparticle system and perhaps other solid lipid-based systems.

  16. Relations of GlycA and lipoprotein particle subspecies with cardiovascular events and mortality: A post hoc analysis of the AIM-HIGH trial.

    Science.gov (United States)

    Otvos, James D; Guyton, John R; Connelly, Margery A; Akapame, Sydney; Bittner, Vera; Kopecky, Steven L; Lacy, Megan; Marcovina, Santica M; Muhlestein, Joseph B; Boden, William E

    The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial showed no incremental benefit of extended-release niacin (ERN) therapy added to simvastatin in subjects with cardiovascular disease (CVD). To examine the effects of ERN treatment on lipoprotein particles and GlycA, a new marker of systemic inflammation, and their relations with incident CVD events including mortality. GlycA and very low-density lipoprotein, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) particle subclasses were quantified by nuclear magnetic resonance spectroscopy using available stored baseline (n = 2754) and 1-year in-trial (n = 2581) samples. Associations with CVD events and all-cause mortality were assessed using multivariable Cox proportional hazards regression adjusted for age, sex, diabetes, treatment assignment, and lipoproteins. Compared to placebo, ERN treatment lowered very low-density lipoprotein and LDL and increased HDL particle concentrations, increased LDL and HDL particle sizes (all P < .0001), but did not affect GlycA. Baseline and in-trial GlycA levels were associated with increased risk of CVD events: hazard ratio (HR) per SD increment, 1.17 (95% confidence interval [CI], 1.06-1.28) and 1.13 (1.02-1.26), respectively. However, none of the lipoprotein particle classes or subclasses was associated with incident CVD. By contrast, all-cause mortality was significantly associated with both GlycA (baseline HR: 1.46 [1.22-1.75]; in-trial HR: 1.41 [1.24-1.60]) and low levels of small HDL particles (baseline HR: 0.69 [0.56-0.86]; in-trial HR: 0.69 [0.56-0.86]). This Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial post hoc substudy indicates that inflammation, as indexed by GlycA, is unaffected by ERN treatment but is significantly associated with the residual risk of CVD and death in patients treated to low

  17. Secretion of hepatitis C virus envelope glycoproteins depends on assembly of apolipoprotein B positive lipoproteins.

    Directory of Open Access Journals (Sweden)

    Vinca Icard

    Full Text Available The density of circulating hepatitis C virus (HCV particles in the blood of chronically infected patients is very heterogeneous. The very low density of some particles has been attributed to an association of the virus with apolipoprotein B (apoB positive and triglyceride rich lipoproteins (TRL likely resulting in hybrid lipoproteins known as lipo-viro-particles (LVP containing the viral envelope glycoproteins E1 and E2, capsid and viral RNA. The specific infectivity of these particles has been shown to be higher than the infectivity of particles of higher density. The nature of the association of HCV particles with lipoproteins remains elusive and the role of apolipoproteins in the synthesis and assembly of the viral particles is unknown. The human intestinal Caco-2 cell line differentiates in vitro into polarized and apoB secreting cells during asymmetric culture on porous filters. By using this cell culture system, cells stably expressing E1 and E2 secreted the glycoproteins into the basal culture medium after one week of differentiation concomitantly with TRL secretion. Secreted glycoproteins were only detected in apoB containing density fractions. The E1-E2 and apoB containing particles were unique complexes bearing the envelope glycoproteins at their surface since apoB could be co-immunoprecipitated with E2-specific antibodies. Envelope protein secretion was reduced by inhibiting the lipidation of apoB with an inhibitor of the microsomal triglyceride transfer protein. HCV glycoproteins were similarly secreted in association with TRL from the human liver cell line HepG2 but not by Huh-7 and Huh-7.5 hepatoma cells that proved deficient for lipoprotein assembly. These data indicate that HCV envelope glycoproteins have the intrinsic capacity to utilize apoB synthesis and lipoprotein assembly machinery even in the absence of the other HCV proteins. A model for LVP assembly is proposed.

  18. Lipoprotein transport in the metabolic syndrome: pathophysiological and interventional studies employing stable isotopy and modelling methods.

    Science.gov (United States)

    Chan, Dick C; Barrett, P Hugh R; Watts, Gerald F

    2004-09-01

    The accompanying review in this issue of Clinical Science [Chan, Barrett and Watts (2004) Clin. Sci. 107, 221-232] presented an overview of lipoprotein physiology and the methodologies for stable isotope kinetic studies. The present review focuses on our understanding of the dysregulation and therapeutic regulation of lipoprotein transport in the metabolic syndrome based on the application of stable isotope and modelling methods. Dysregulation of lipoprotein metabolism in metabolic syndrome may be due to a combination of overproduction of VLDL [very-LDL (low-density lipoprotein)]-apo (apolipoprotein) B-100, decreased catabolism of apoB-containing particles and increased catabolism of HDL (high-density lipoprotein)-apoA-I particles. These abnormalities may be consequent on a global metabolic effect of insulin resistance, partly mediated by depressed plasma adiponectin levels, that collectively increases the flux of fatty acids from adipose tissue to the liver, the accumulation of fat in the liver and skeletal muscle, the hepatic secretion of VLDL-triacylglycerols and the remodelling of both LDL (low-density lipoprotein) and HDL particles in the circulation. These lipoprotein defects are also related to perturbations in both lipolytic enzymes and lipid transfer proteins. Our knowledge of the pathophysiology of lipoprotein metabolism in the metabolic syndrome is well complemented by extensive cell biological data. Nutritional modifications may favourably alter lipoprotein transport in the metabolic syndrome by collectively decreasing the hepatic secretion of VLDL-apoB and the catabolism of HDL-apoA-I, as well as by potentially increasing the clearance of LDL-apoB. Several pharmacological treatments, such as statins, fibrates or fish oils, can also correct the dyslipidaemia by diverse kinetic mechanisms of action, including decreased secretion and increased catabolism of apoB, as well as increased secretion and decreased catabolism of apoA-I. The complementary

  19. Open tubular capillary electrochromatography: A useful microreactor for collagen I glycation and interaction studies with low-density lipoprotein particles

    Energy Technology Data Exchange (ETDEWEB)

    D' Ulivo, Lucia; Witos, Joanna [Laboratory of Analytical Chemistry, Department of Chemistry, P.O. Box 55, FIN-00014 University of Helsinki (Finland); Ooerni, Katariina; Kovanen, Petri T. [Wihuri Research Institute, Kalliolinnantie 4, FIN-00140, Helsinki (Finland); Riekkola, Marja-Liisa, E-mail: marja-liisa.riekkola@helsinki.fi [Laboratory of Analytical Chemistry, Department of Chemistry, P.O. Box 55, FIN-00014 University of Helsinki (Finland)

    2010-04-07

    Diabetes, a multifunctional disease and a major cause of morbidity and mortality in the industrialized countries, strongly associates with the development and progression of atherosclerosis. One of the consequences of high level of glucose in the blood circulation is glycation of long-lived proteins, such as collagen I, the most abundant component of the extracellular matrix (ECM) in the arterial wall. Glycation is a long-lasting process that involves the reaction between a carbonyl group of the sugar and an amino group of the protein, usually a lysine residue. This reaction generates an Amadori product that may evolve in advanced glycation end products (AGEs). AGEs, as reactive molecules, can provoke cross-linking of collagen I fibrils. Since binding of low-density lipoproteins (LDLs) to the ECM of the inner layer of the arterial wall, the intima, has been implicated to be involved in the onset of the development of an atherosclerotic plaque, collagen modifications, which can affect the affinity of native and oxidized LDL for collagen I, can promote the entrapment of LDLs in the intima and accelerate the progression of atherosclerosis. In this study, open tubular capillary electrochromatography is proposed as a new microreactor to study in situ glycation of collagen I. The kinetics of glycation was first investigated in a fused silica collagen I-coated capillary. Dimethyl sulphoxide, injected as an electroosmotic flow marker, gave information about the charge of coating. Native and oxidized LDL, and selected peptide fragments from apolipoprotein B-100, the protein covering LDL particles, were injected as marker compounds to clarify the interactions between LDLs and the glycated collagen I coating. The method proposed is simple and inexpensive, since only small amounts of collagen and LDL are required. Atomic force microscopy images complemented our studies, highlighting the difference between unmodified and glycated collagen I surfaces.

  20. Targeted Measurements of O- and N-Glycopeptides Show That Proteins in High Density Lipoprotein Particles Are Enriched with Specific Glycosylation Compared to Plasma.

    Science.gov (United States)

    Kailemia, Muchena J; Wei, Wanghui; Nguyen, Khoa; Beals, Elizabeth; Sawrey-Kubicek, Lisa; Rhodes, Christopher; Zhu, Chenghao; Sacchi, Romina; Zivkovic, Angela M; Lebrilla, Carlito B

    2018-02-02

    High density lipoprotein (HDL) particles are believed to be protective due to their inverse correlation with the prevalence of cardiovascular diseases. However, recent studies show that in some conditions such as heart disease and diabetes, HDL particles can become dysfunctional. Great attention has been directed toward HDL particle composition because the relative abundances of HDL constituents determine HDL's functional properties. A key factor to consider when studying the structure and composition of plasma particles is the protein glycosylation. Here, we profile the O- and N-linked glycosylation of HDL associated-proteins including the truncated form of Apo CIII and their glycan heterogeneity in a site-specific manner. Apolipoprotein CIII, fetuin A, and alpha 1 antitrypsin are glycoproteins associated with lipoproteins and are implicated in many cardiovascular and other disease conditions. A targeted method (UHPLC-QQQ) was used to measure the glycoprotein concentrations and site-specific glycovariations of the proteins in human plasma and compared with HDL particles isolated from the same plasma samples. The proteins found in the plasma are differentially glycosylated compared to those isolated in HDL. The results of this study suggest that glycosylation may play a role in protein partitioning in the blood, with possible functional implications.

  1. High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: significance for cardiovascular risk: the IDEAL and EPIC-Norfolk studies

    DEFF Research Database (Denmark)

    van der Steeg, Wim A; Holme, Ingar; Boekholdt, S Matthijs

    2008-01-01

    : High plasma levels of HDL-C and apoA-I are inversely related to the risk of CAD. However, recent data suggest that this relationship does not hold true for very high HDL-C levels, particularly when a preponderance of large HDL particles is observed. METHODS: We conducted a post-hoc analysis of 2...... prospective studies: the IDEAL (Incremental Decrease in End Points through Aggressive Lipid Lowering; n = 8,888) trial comparing the efficacy of high-dose to usual-dose statin treatment for the secondary prevention of cardiovascular events, and the EPIC (European Prospective Investigation into Cancer...

  2. Remnant lipoproteins

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G.

    2017-01-01

    Purpose of review: To review recent advances in the field of remnant lipoproteins and remnant cholesterol with a focus on cardiovascular disease risk. Recent findings: In line with previous years' research, current observational, genetic, and mechanistic studies find remnant lipoproteins (defined...

  3. Heterogeneity of high-density lipoprotein particles and insulin output during oral glucose tolerance test in men with coronary artery disease.

    Science.gov (United States)

    Iwanejko, J; Kwaśniak, M; Wybrańska, I; Hartwich, J; Guevara, I; Zdzienicka, A; Kruszelnicka-Kwiatkowska, O; Piwowarska, W; Miszczuk-Jamska, B; Dembińska-Kieć, A

    1996-03-01

    We compared the high-density lipoprotein (HDL) composition and particle heterogeneity in 60 nonobese (normal body mass index, BMI) men suffering from coronary artery disease (CAD) with normolipemia and normoinsulinemia with lower and higher insulin output during the oral glucose tolerance test (silent hyperinsulinemia). The apolipoprotein apoAI, apoAII, and apoE levels were higher in the high insulin response (HI) group than in low insulin response (LI) group. The ratio of apoAI versus total protein and the ratio of apoAI versus total cholesterol were increased in HI compared with LI. The lipid components in HDL were higher in LI than in HI, while for HDL2 they were higher in HI. The fractioning of HDL by gradient gel electrophoresis revealed a different pattern of HDL particles in both groups. The larger particles, HDL2b and HDL2a (mean particle diameters 10.6 and 9.2 nm, respectively), occur more frequently in HI patients (up to 60%) than in LI patients, whereas the smaller particles, HDL3a and HDL3b (mean particle diameters 8.6 and 7.8 nm, respectively), predominate in LI patients. Our results demonstrate that even in the normoglycemic, normocholesterolemic CAD patients, a high insulin output observed during the oral glucose tolerance test may be connected with a different HDL particle pattern, which suggests changes in the reverse cholesterol transport.

  4. Beneficial Effects of Omega-3 Fatty Acids on Low Density Lipoprotein Particle Size in Patients with Type 2 Diabetes Already under Statin Therapy

    Directory of Open Access Journals (Sweden)

    Myung Won Lee

    2013-06-01

    Full Text Available Beyond statin therapy for reducing low density lipoprotein cholesterol (LDL-C, additional therapeutic strategies are required to achieve more optimal reduction in cardiovascular risk among diabetic patients with dyslipidemia. To evaluate the effects and the safety of combined treatment with omega-3 fatty acids and statin in dyslipidemic patients with type 2 diabetes, we conducted a randomized, open-label study in Korea. Patients with persistent hypertriglyceridemia (≥200 mg/dL while taking statin for at least 6 weeks were eligible. Fifty-one patients were randomized to receive either omega-3 fatty acid 4, 2 g, or no drug for 8 weeks while continuing statin therapy. After 8 weeks of treatment, the mean percentage change of low density lipoprotein (LDL particle size and triglyceride (TG level was greater in patients who were prescribed 4 g of omega-3 fatty acid with statin than in patients receiving statin monotherapy (2.8%±3.1% vs. 2.3%±3.6%, P=0.024; -41.0%±24.1% vs. -24.2%±31.9%, P=0.049. Coadministration of omega-3 fatty acids with statin increased LDL particle size and decreased TG level in dyslipidemic patients with type 2 diabetes. The therapy was well tolerated without significant adverse effects.

  5. A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein

    DEFF Research Database (Denmark)

    Whorton, Matthew R; Bokoch, Michael P; Rasmussen, Søren Gøgsig Faarup

    2007-01-01

    G protein-coupled receptors (GPCRs) respond to a diverse array of ligands, mediating cellular responses to hormones and neurotransmitters, as well as the senses of smell and taste. The structures of the GPCR rhodopsin and several G proteins have been determined by x-ray crystallography, yet...... the organization of the signaling complex between GPCRs and G proteins is poorly understood. The observations that some GPCRs are obligate heterodimers, and that many GPCRs form both homo- and heterodimers, has led to speculation that GPCR dimers may be required for efficient activation of G proteins. However......, technical limitations have precluded a definitive analysis of G protein coupling to monomeric GPCRs in a biochemically defined and membrane-bound system. Here we demonstrate that a prototypical GPCR, the beta2-adrenergic receptor (beta2AR), can be incorporated into a reconstituted high-density lipoprotein...

  6. Lipoprotein metabolism in an apoB-80 familial hypobetalipoproteinemia heterozygote.

    Science.gov (United States)

    Hooper, Amanda J; Robertson, Ken; Champain, Danie; Hua, Jianmin; Song, Swithin; Parhofer, Klaus G; Barrett, P Hugh R; van Bockxmeer, Frank M; Burnett, John R

    2016-06-01

    Familial hypobetalipoproteinemia (FHBL) is characterized by mutations in APOB, the majority of these causing protein truncations, and low plasma levels of apolipoprotein (apo) B. The hypobetalipoproteinemia may be due to enhanced clearance and possibly reduced production of apoB-containing lipoproteins; the mechanism may depend on the length of the apoB truncation. We studied fasting lipoprotein metabolism in an FHBL subject heterozygous for a mutation causing a truncated apoB, apoB-80. Very low density lipoprotein (VLDL)-, intermediate density lipoprotein (IDL)-, and low density lipoprotein (LDL)-apoB kinetics were determined in the fasting state using stable isotope methods and compartmental modeling. Compared with lean normolipidemic controls the apoB-80 FHBL subject had an elevated VLDL-apoB fractional catabolic rate and lower LDL production. ApoB production rates and IDL- and LDL-apoB fractional catabolic rates were not different. FHBL subjects heterozygous for a mutation truncating apoB to 80% of full-length are able to produce VLDL-apoB normally, but have rapid clearance of these particles, resulting in low levels of circulating apoB. Copyright © 2016 The Canadian Society of Clinical Chemists. All rights reserved.

  7. Phytosterols, Phytostanols, and Lipoprotein Metabolism

    Directory of Open Access Journals (Sweden)

    Helena Gylling

    2015-09-01

    Full Text Available The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%–10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein

  8. Phytosterols, Phytostanols, and Lipoprotein Metabolism.

    Science.gov (United States)

    Gylling, Helena; Simonen, Piia

    2015-09-17

    The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL) cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%-10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a) or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL) cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein particles will be

  9. Aerosol preparation of intact lipoproteins

    Science.gov (United States)

    Benner, W Henry [Danville, CA; Krauss, Ronald M [Berkeley, CA; Blanche, Patricia J [Berkeley, CA

    2012-01-17

    A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

  10. Association of Air Pollution Exposures With High-Density Lipoprotein Cholesterol and Particle Number: The Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Bell, Griffith; Mora, Samia; Greenland, Philip; Tsai, Michael; Gill, Ed; Kaufman, Joel D

    2017-05-01

    The relationship between air pollution and cardiovascular disease may be explained by changes in high-density lipoprotein (HDL). We examined the cross-sectional relationship between air pollution and both HDL cholesterol and HDL particle number in the MESA Air study (Multi-Ethnic Study of Atherosclerosis Air Pollution). Study participants were 6654 white, black, Hispanic, and Chinese men and women aged 45 to 84 years. We estimated individual residential ambient fine particulate pollution exposure (PM 2.5 ) and black carbon concentrations using a fine-scale likelihood-based spatiotemporal model and cohort-specific monitoring. Exposure periods were averaged to 12 months, 3 months, and 2 weeks prior to examination. HDL cholesterol and HDL particle number were measured in the year 2000 using the cholesterol oxidase method and nuclear magnetic resonance spectroscopy, respectively. We used multivariable linear regression to examine the relationship between air pollution exposure and HDL measures. A 0.7×10 - 6 m - 1 higher exposure to black carbon (a marker of traffic-related pollution) averaged over a 1-year period was significantly associated with a lower HDL cholesterol (-1.68 mg/dL; 95% confidence interval, -2.86 to -0.50) and approached significance with HDL particle number (-0.55 mg/dL; 95% confidence interval, -1.13 to 0.03). In the 3-month averaging time period, a 5 μg/m 3 higher PM 2.5 was associated with lower HDL particle number (-0.64 μmol/L; 95% confidence interval, -1.01 to -0.26), but not HDL cholesterol (-0.05 mg/dL; 95% confidence interval, -0.82 to 0.71). These data are consistent with the hypothesis that exposure to air pollution is adversely associated with measures of HDL. © 2017 American Heart Association, Inc.

  11. Apolipoprotein AI tertiary structures determine stability and phospholipid-binding activity of discoidal high-density lipoprotein particles of different sizes

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Bin; Ren, Xuefeng; Neville, Tracey; Jerome, W. Gray; Hoyt, David W.; Sparks, Daniel L.; Ren, Gang; Wang, Jianjun

    2009-05-18

    Human high-density lipoprotein (HDL) plays a key role in the reverse cholesterol transport pathway that delivers excess cholesterol back to the liver for clearance. In vivo, HDL particles vary in size, shape and biological function. The discoidal HDL is a 140-240 kDa, disk-shaped intermediate of mature HDL. During mature spherical HDL formation, discoidal HDLs play a key role in loading cholesterol ester onto the HDL particles by activating the enzyme, lecithin:cholesterol acyltransferase (LCAT). One of the major problems for high-resolution structural studies of discoidal HDL is the difficulty in obtaining pure and, foremost, homogenous sample. We demonstrate here that the commonly used cholate dialysis method for discoidal HDL preparation usually contains 5-10% lipid-poor apoAI that significantly interferes with the high-resolution structural analysis of discoidal HDL using biophysical methods. Using an ultracentrifugation method, we quickly removed lipid-poor apoAI. We also purified discoidal reconstituted HDL (rHDL) into two pure discoidal HDL species of different sizes that are amendable for high-resolution structural studies. A small rHDL has a diameter of 7.6 nm, and a large rHDL has a diameter of 9.8 nm. We show that these two different sizes of discoidal HDL particles display different stability and phospholipid-binding activity. Interestingly, these property/functional differences are independent from the apoAI -helical secondary structure, but are determined by the tertiary structural difference of apoAI on different discoidal rHDL particles, as evidenced by two-dimensional NMR and negative stain electron microscopy data. Our result further provides the first high-resolution NMR data, demonstrating a promise of structural determination of discoidal HDL at atomic resolution using a combination of NMR and other biophysical techniques.

  12. Oxidized-phospholipids in reconstituted high density lipoprotein particles affect structure and function of recombinant paraoxonase 1.

    Science.gov (United States)

    Kar, Subhabrata; Patel, Mitulkumar A; Tripathy, Rajan K; Bajaj, Priyanka; Pande, Abhay H

    2013-12-01

    Paraoxonase 1 (PON1) is an HDL-associated enzyme and exhibits anti-inflammatory, anti-diabetic, and anti-atherogenic properties. Association of PON1 to HDL particles increases the stability and activity of PON1 and is important for the normal functioning of the enzyme. HDL particles are made up of lipid and protein constituents and apolipoprotein A-I (apoA-I) is a principal protein constituent of HDL that facilitates various biological activities of HDL. In many disease conditions the oxidized phospholipid (Ox-PL) content of HDL is found to be increased and an inverse correlation between the activity of PON1 and oxidation of the HDL is observed. However, the molecular details of the inhibitory action of the Ox-PL-containing HDL on the function of PON1 are not clear yet. In this study we have assembled reconstituted HDL (rHDL) particles with and without Ox-PL and compared their effect on the structure and function of (13)C-labeled recombinant PON1 ((13)C-rPON1) by employing attenuated total reflectance Fourier transformed infrared (ATR-FTIR) spectroscopy and enzymatic assay. Our results show that the presence of the Ox-PL in the rHDL particles alters the structure of rPON1 and decreases its lactonase activity. © 2013.

  13. The effect of fish oil enriched margarine on plasma lipids, low density lipoprotein particle composition, size and susceptibility to oxidation

    DEFF Research Database (Denmark)

    Nielsen, Nina Skall; Marckmann, Peter; Høy, Carl-Erik

    1998-01-01

    during intervention. The FO margarine increased the concentration of n-3 very-long-chain PUFAs in the LDL particles, showing 93% (P less than or equal to 0.0001), 8% (P = 0.05), and 35% (P = eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid, respectively......We investigated the effect of incorporating n-3 polyunsaturated fatty acids (PUFAs) into the diet on the lipid-class composition of LDLs, their size, and their susceptibility to oxidation. Forty-seven healthy volunteers incorporated 30 g sunflower-oil (SO) margarine/d into their habitual diet...

  14. Human placenta secretes apolipoprotein B-100-containing lipoproteins

    DEFF Research Database (Denmark)

    Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B

    2004-01-01

    Supply of lipids from the mother is essential for fetal growth and development. In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B-containing lipoproteins results in embryonic lethality. In humans, the yolk sac is vestigial. Nutritional functions are instead established very...... early during pregnancy in the placenta. To examine whether the human placenta produces lipoproteins, we examined apoB and microsomal triglyceride transfer protein (MTP) mRNA expression in placental biopsies. ApoB and MTP are mandatory for assembly and secretion of apoB-containing lipoproteins. Both...... genes were expressed in placenta and microsomal extracts from human placenta contained triglyceride transfer activity, indicating expression of bioactive MTP. To detect lipoprotein secretion, biopsies from term placentas were placed in medium with [(35)S]methionine and [(35)S]cysteine for 3-24 h. Upon...

  15. Cholesterol Efflux Capacity, High-Density Lipoprotein Particle Number, and Incident Cardiovascular Events: An Analysis From the JUPITER Trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin).

    Science.gov (United States)

    Khera, Amit V; Demler, Olga V; Adelman, Steven J; Collins, Heidi L; Glynn, Robert J; Ridker, Paul M; Rader, Daniel J; Mora, Samia

    2017-06-20

    Recent failures of drugs that raised high-density lipoprotein (HDL) cholesterol levels to reduce cardiovascular events in clinical trials have led to increased interest in alternative indices of HDL quality, such as cholesterol efflux capacity, and HDL quantity, such as HDL particle number. However, no studies have directly compared these metrics in a contemporary population that includes potent statin therapy and low low-density lipoprotein cholesterol. HDL cholesterol levels, apolipoprotein A-I, cholesterol efflux capacity, and HDL particle number were assessed at baseline and 12 months in a nested case-control study of the JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin), a randomized primary prevention trial that compared rosuvastatin treatment to placebo in individuals with normal low-density lipoprotein cholesterol but increased C-reactive protein levels. In total, 314 cases of incident cardiovascular disease (CVD) (myocardial infarction, unstable angina, arterial revascularization, stroke, or cardiovascular death) were compared to age- and gender-matched controls. Conditional logistic regression models adjusting for risk factors evaluated associations between HDL-related biomarkers and incident CVD. Cholesterol efflux capacity was moderately correlated with HDL cholesterol, apolipoprotein A-I, and HDL particle number (Spearman r = 0.39, 0.48, and 0.39 respectively; P JUPITER, cholesterol efflux capacity was associated with incident CVD in individuals on potent statin therapy but not at baseline. For both baseline and on-statin analyses, HDL particle number was the strongest of 4 HDL-related biomarkers as an inverse predictor of incident events and biomarker of residual risk. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681. © 2017 American Heart Association, Inc.

  16. Effect of pioglitazone on various parameters of insulin resistance including lipoprotein subclass according to particle size by a gel-permeation high-performance liquid chromatography in newly diagnosed patients with type 2 diabetes.

    Science.gov (United States)

    Nakano, Koji; Hasegawa, Goji; Fukui, Michiaki; Yamasaki, Masahiro; Ishihara, Kiyoshi; Takashima, Tooru; Kitagawa, Yoshihiro; Fujinami, Aya; Ohta, Mitsuhiro; Hara, Hirokazu; Adachi, Tetsuo; Ogata, Masakazu; Obayashi, Hiroshi; Nakamura, Naoto

    2010-01-01

    Pioglitazone is an insulin-sensitizing agent that has been reported to have anti-arteriosclerotic effects. The aim of this study was to obtain a better understanding of the mechanism involved in the insulin sensitizing effect of pioglitazone. A total of 50 newly diagnosed patients with type 2 diabetes were enrolled in this study and divided into two groups, 25 of who were treated with 15 mg/day pioglitazone and 25 with 500 mg/day metformin for 12 weeks. Changes in various parameters of insulin resistance including lipoprotein subclass according to particle size determined by high performance liquid chromatography, as well as glucose metabolism, were monitored to determine the relationship between lipoprotein subclass and other insulin resistance parameters. Both pioglitazone and metformin treatment were associated with significant reductions in hyperglycemia, HOMA-IR and HbA1c levels. Pioglitazone treatment, but not metformin treatment resulted in significant reductions in serum large very low-density lipoprotein (VLDL: 44.5-64.0 nm) and increases in serum adiponectin levels (both net electronegative charged modified-LDL (r=0.412, P=0.0399), and inversely with changes in adiponectin level (r=-0.526, P=0.0061). The results in this study suggest that the hypoglycemic effect of pioglitazone is achieved mainly through improvement of hepatic insulin resistance, and that pioglitazone may have an antiatherosclerotic effect by decreasing serum atherogenic modified-LDL and by increasing adiponectin.

  17. Plasma Lp-PLA2 mass and apoB-lipoproteins that carry Lp-PLA2 decrease after sodium

    NARCIS (Netherlands)

    Constantinides, Alexander; Kerstens, Michiel N.; Dikkeschei, Bert D.; van Pelt, L. Joost; Tellis, Constantinos C.; Tselepis, Alexandros D.; Dullaart, Robin P. F.

    2012-01-01

    Eur J Clin Invest 2012; 42 (11): 12351243 Abstract Background Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel cardiovascular risk marker, which is predominantly complexed to apolipoprotein (apo) B-containing lipoproteins in human plasma. As increasing dietary sodium intake may decrease

  18. Lipoprotein(a)

    DEFF Research Database (Denmark)

    Langsted, Anne; Kamstrup, Pia R; Nordestgaard, Børge G

    2014-01-01

    OBJECTIVE: There are no recommendations in guidelines on measuring lipoprotein(a) in the fasting or nonfasting state, or on the influence of inflammation. We tested the hypotheses that lipoprotein(a) levels change only minimally in response to normal food intake, and to inflammation. Also, we......(a) levels did not change in response to normal food intake: median fasting levels were 17.3 mg/dL, while median levels at 3-4 h since last meal were 19.4 mg/dL(p = 0.38). Lipoprotein(a) levels increased minimally with increasing levels of C-reactive protein(CRP): median lipoprotein(a) levels at CRP ... tested whether normal food intake or inflammation influenced lipoprotein(a)'s ability to predict ischemic heart disease. METHODS: We studied 34 829 individuals from the Danish general population using the Copenhagen General Population Study and the Copenhagen City Heart Study. RESULTS: Lipoprotein...

  19. Glycation and glycoxidation of low-density lipoproteins by glucose and low-molecular mass aldehydes. Formation of modified and oxidized particles

    DEFF Research Database (Denmark)

    Knott, Heather M; Brown, Bronwyn E; Davies, Michael Jonathan

    2003-01-01

    by the adduction of glucose or species derived from glucose, such as low-molecular mass aldehydes, to proteins. These reactions can be nonoxidative (glycation) or oxidative (glycoxidation) and result in the conversion of low-density lipoproteins (LDL) to a form that is recognized by the scavenger receptors...... with glucose. These processes are rapid and unaffected by low concentrations of copper ions. In contrast, lipid and protein oxidation are slow processes and occur to a limited extent in the absence of added copper ions. No evidence was obtained for the stimulation of lipid or protein oxidation by glucose...... or methylglyoxal in the presence of copper ions, whereas glycolaldehyde stimulated such reactions to a modest extent. These results suggest that the earliest significant events in this system are metal ion-independent glycation (modification) of the protein component of LDL, whilst oxidative events (glycoxidation...

  20. Lipoprotein Lipase releases esterified oxylipins from Very Low Density Lipoproteins

    Science.gov (United States)

    Shearer, Gregory C.; Newman, John W.

    2009-01-01

    We previously demonstrated that defects in lipoprotein metabolism alter the distribution of oxygenated polyunsaturated fatty acids (PUFAs) in lipoprotein particles. If these oxidation products are released by lipoprotein lipase (LpL), then their delivery to peripheral tissues with bulk lipids could influence cellular function. Using 26 week old normolipidemic and hyperlipidemic Zucker rats, we measured PUFA alcohols, epoxides, diols, ketones and triols (i.e. oxylipins) in esterified and non-esterified fractions of whole plasma, VLDL, and LpL-generated VLDL-lipolysates. Whole plasma, VLDL, and lipolysate oxylipin profiles were distinct and altered by hyperlipidemia. While >90% of the whole plasma oxylipins were esterified, the fraction of each oxylipin class in the VLDL varied: 46% of alcohols, 30% of epoxides, 19% of diols, <10% of ketones, <1% triols. Whole plasma was dominated by arachidonate alcohols, while the linoleate alcohols, epoxides and ketones showed an increased prevalence in VLDL. LpL-mediated VLDL lipolysis of PUFA alcohols, diols and ketones was detected and the relative abundance of oxygenated linoleates was enhanced in the lipolysates, relative to their corresponding VLDL. In summary esterified oxylipins were seen to be LpL substrates with heterogeneous distributions among lipoprotein classes. Moreover, oxylipin distributions are changes within the context of obesity-associated dyslipidemia. These results support the notion that the VLDL-LpL axis may facilitate the delivery of plasma oxylipins to the periphery. The physiological implication of these findings are yet to be elucidated, however these molecules are plausible indicators of systemic oxidative stress, and could report this status to the peripheral tissues. PMID:19042114

  1. A clustering analysis of lipoprotein diameters in the metabolic syndrome

    Science.gov (United States)

    The presence of smaller low-density lipoproteins (LDL) has been associated with atherosclerosis risk, and the insulin resistance (IR) underlying the metabolic syndrome (MetS). In addition, some research has supported the association of very low-, low- and high-density lipoprotein (VLDL HDL) particle...

  2. Postprandial Hyperlipidemia and Remnant Lipoproteins

    Science.gov (United States)

    Yamashita, Shizuya

    2017-01-01

    Fasting hypertriglyceridemia is positively associated with the morbidity of coronary heart disease (CHD), and postprandial (non-fasting) hypertriglyceridemia is also correlated with the risk status for CHD, which is related to the increase in chylomicron (CM) remnant lipoproteins produced from the intestine. CM remnant particles, as well as oxidized low density lipoprotein (LDL) or very low density lipoprotein (VLDL) remnants, are highly atherogenic and act by enhancing systemic inflammation, platelet activation, coagulation, thrombus formation, and macrophage foam cell formation. The cholesterol levels of remnant lipoproteins significantly correlate with small, dense LDL; impaired glucose tolerance (IGT) and CHD prevalence. We have developed an assay of apolipoprotein (apo)B-48 levels to evaluate the accumulation of CM remnants. Fasting apoB-48 levels correlate with the morbidity of postprandial hypertriglyceridemia, obesity, type III hyperlipoproteinemia, the metabolic syndrome, hypothyroidism, chronic kidney disease, and IGT. Fasting apoB-48 levels also correlate with carotid intima-media thickening and CHD prevalence, and a high apoB-48 level is a significant predictor of CHD risk, independent of the fasting TG level. Diet interventions, such as dietary fibers, polyphenols, medium-chain fatty acids, diacylglycerol, and long-chain n-3 polyunsaturated fatty acids (PUFA), ameliorate postprandial hypertriglyceridemia, moreover, drugs for dyslipidemia (n-3 PUFA, statins, fibrates or ezetimibe) and diabetes concerning incretins (dipeptidyl-peptidase IV inhibitor or glucagon like peptide-1 analogue) may improve postprandial hypertriglyceridemia. Since the accumulation of CM remnants correlates to impaired lipid and glucose metabolism and atherosclerotic cardiovascular events, further studies are required to investigate the characteristics, physiological activities, and functions of CM remnants for the development of new interventions to reduce atherogenicity. PMID

  3. Endogenous androgen deficiency enhances diet-induced hypercholesterolemia and atherosclerosis in low-density lipoprotein receptor-deficient mice.

    Science.gov (United States)

    Hatch, Nicholas W; Srodulski, Sarah J; Chan, Huei-Wei; Zhang, Xuan; Tannock, Lisa R; King, Victoria L

    2012-10-01

    Despite numerous clinical and animal studies, the role of sex steroid hormones on lipoprotein metabolism and atherosclerosis remain controversial. We sought to determine the effects of endogenous estrogen and testosterone on lipoprotein levels and atherosclerosis using mice fed a low-fat diet with no added cholesterol. Male and female low-density lipoprotein receptor-deficient mice were fed an open stock low-fat diet (10% of kcals from fat) for 2, 4, or 17 weeks. Ovariectomy, orchidectomy, or sham surgeries were performed to evaluate the effects of the presence or absence of endogenous hormones on lipid levels, lipoprotein distribution, and atherosclerosis development. Female mice fed the study diet for 17 weeks had a marked increase in levels of total cholesterol, triglycerides, apolipoprotein-B containing lipoproteins, and atherosclerosis compared with male mice. Surprisingly, ovariectomy in female mice had no effect on any of these parameters. In contrast, castration of male mice markedly increased total cholesterol concentrations, triglycerides, apolipoprotein B-containing lipoproteins, and atherosclerotic lesion formation compared with male and female mice. These data suggest that endogenous androgens protect against diet-induced increases in cholesterol concentrations, formation of proatherogenic lipoproteins, and atherosclerotic lesions formation. Conversely orchidectomy, which decreases androgen concentrations, promotes increases in cholesterol concentrations, proatherogenic lipoprotein formation, and atherosclerotic lesion formation in low-density lipoprotein receptor-deficient mice in response to a low-fat diet. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

  4. Thyrotropin interaction with high-density lipoproteins.

    Science.gov (United States)

    Bifulco, M; Saroff, H A; Kohn, L D; Aloj, S M

    1985-07-09

    Human high-density lipoproteins (HDL), but not other lipoprotein classes, bind bovine thyrotropin (TSH) with moderately high affinity. Binding of 125I-labeled HDL to TSH has been measured in a solid-phase assay; it is saturable and can be displaced by unlabeled HDL but not by other lipoproteins or bovine serum albumin. The interaction of HDL with TSH has been studied by fluorescence spectroscopy: HDL specifically modifies the fluorescence properties of the biologically active dansyl derivative (DNS, (5-dimethyl-aminonaphtalene-1-sulfonyl) chloride) of TSH (DNS-TSH) causing a 12 nm shift to lower wavelength of the emission maximum, a two-fold increase of the quantum yield and a significant increase of fluorescence polarization. The primary site of TSH binding on the HDL particle is likely to be located on its protein moieties, since other lipoprotein classes, which share similar lipids with HDL, do not bind TSH. 125I-labeled apolipoprotein A-I binds TSH in the solid-phase assay and titration of DNS-TSH with apolipoprotein A-I causes perturbations nearly identical to those observed with intact HDL. One HDL particle has at least 12 binding sites for TSH with an association constant, K = 10(7) M-1 whereas one apolipoprotein A-I molecule binds one or two TSH molecules with an association constant slightly lower than that for HDL (K = 10(6) M-1). The lipid moieties of HDL also appears to be perturbed by the interaction with TSH.

  5. Sex steroids and lipoprotein metabolism

    NARCIS (Netherlands)

    Gevers Leuven, J.A.

    1994-01-01

    Lipoprotein metabolism is involved in atherogenesis. Female sex-hormones have substantial effects on both lipoprotein metabolism and the vessel wall. Cholesterol, one of the major lipids in lipoproteins, is both the substrate for, and the target of, the steroidal sex hormones.

  6. Changes in plasma low-density lipoprotein (LDL)- and high-density lipoprotein cholesterol in hypo- and hyperthyroid patients are related to changes in free thyroxine, not to polymorphisms in LDL receptor or cholesterol ester transfer protein genes

    NARCIS (Netherlands)

    Diekman, M. J.; Anghelescu, N.; Endert, E.; Bakker, O.; Wiersinga, W. M.

    2000-01-01

    Thyroid function disorders lead to changes in lipoprotein metabolism. Both plasma low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) increase in hypothyroidism and decrease in hyperthyroidism. Changes in LDL-C relate to altered clearance of LDL particles

  7. The effect of atorvastatin on serum lipide, lipoproteins and NMR-spectroscopy defined lipoprotein subclasses in type 2 diabetic patients with ischaemic heart disease

    NARCIS (Netherlands)

    Soedamah-Muthu, S.S.; Colhoun, H.M.; Thomason, M.J.; Betteridge, D.J.; Durrington, P.N.; Hitman, G.A.; Fuller, J.H.; Julier, K.; Mackness, M.I.; Neil, H.A.W.

    2003-01-01

    The effect of statin therapy on subclasses of LDL, VLDL and HDL lipoproteins is unclear. We compared changes in serum lipids, apolipoproteins and nuclear magnetic resonance (NMR) spectroscopy measured lipoprotein subclass concentration and average particle size over a minimum 6 months treatment

  8. Spirochetal Lipoproteins and Immune Evasion

    Science.gov (United States)

    Christodoulides, Alexei; Boyadjian, Ani; Kelesidis, Theodoros

    2017-01-01

    Spirochetes are a major threat to public health. However, the exact pathogenesis of spirochetal diseases remains unclear. Spirochetes express lipoproteins that often determine the cross talk between the host and spirochetes. Lipoproteins are pro-inflammatory, modulatory of immune responses, and enable the spirochetes to evade the immune system. In this article, we review the modulatory effects of spirochetal lipoproteins related to immune evasion. Understanding lipoprotein-induced immunomodulation will aid in elucidating innate pathogenesis processes and subsequent adaptive mechanisms potentially relevant to spirochetal disease vaccine development and treatment. PMID:28424696

  9. Pharmacokinetics and metabolites of 10B-containing compounds in biological fluids

    International Nuclear Information System (INIS)

    Mauri, P.L.; Basilico, F.; Wittig, A.; Sauerwein, W.; Heimans, J.; Huiskamp, R.

    2006-01-01

    Mass spectrometry method has been applied for determining the pharmacokinetics profile of 10 B-containing compounds in urine and plasma of patients treated in the trials EORTC 11001 and 11011 with BSH or BPA. For these analyses a very small volume (1μl) of diluted samples (urine and plasma, diluted 10000 and 1000-fold, respectively) were used. These data were compared with those obtained using other analytical methods. (author)

  10. Genetics of non-conventional lipoprotein fractions

    Science.gov (United States)

    Lipoprotein subclass measures associate with cardiometabolic disease risk. Currently the information that lipoproteins convey on disease risk over that of traditional demographic and lipid measures is minimal, and so their use is clinics is limited. However, lipoprotein subclass perturbations repres...

  11. Relation Between Cigarette Smoking, Body Fat Distribution and Density of Lipoprotein Cholesterol in Women.

    Science.gov (United States)

    1992-08-01

    may be directly atherogenic and 2) metabolic consequences of hypertriglyceridemia such as elevated postprandial lipoproteins, large VLDL particles...adverse changes in lipid metabolism that could promote CFD and atherosclerosis. Nicotine has been shown to stimulate the sympathoadrenal system which...associations between variables, they may tend to oversimplify the complex biological processes involved in lipid metabolism , lipoprotein transport

  12. Native and Reconstituted Plasma Lipoproteins in Nanomedicine: Physicochemical Determinants of Nanoparticle Structure, Stability, and Metabolism.

    Science.gov (United States)

    Pownall, Henry J; Rosales, Corina; Gillard, Baiba K; Ferrari, Mauro

    2016-09-01

    Although many acute and chronic diseases are managed via pharmacological means, challenges remain regarding appropriate drug targeting and maintenance of therapeutic levels within target tissues. Advances in nanotechnology will overcome these challenges through the development of lipidic particles, including liposomes, lipoproteins, and reconstituted high-density lipoproteins (rHDL) that are potential carriers of water-soluble, hydrophobic, and amphiphilic molecules. Herein we summarize the properties of human plasma lipoproteins and rHDL, identify the physicochemical determinants of lipid transfer between phospholipid surfaces, and discuss strategies for increasing the plasma half-life of lipoprotein- and liposome-associated molecules.

  13. Cellular uptake of lipoproteins and Persistent Organic Compounds - An update and new data

    DEFF Research Database (Denmark)

    Hjelmborg, Philip Sebastian; Andreassen, Thomas Kjærgaard; Bonefeld-Jørgensen, Eva Cecilie

    2008-01-01

     There are a number of interactions related to transport of lipophilic xenobiotic compounds in the blood stream of mammals. This paper will focus on the interactions between lipoproteins and persistent organic pollutants (POPs) and how these particles are taken up by cells. A number of POPs...... study was to determine the role of lipoprotein receptors in mouse embryonic fibroblast (MEF) cells in conjunction with uptake of DDT-lipoprotein complexes from supplemented media in vitro. Uptake of DDT by MEF cells was investigated using MEF1 cells carrying the receptors LRP (low-density lipoprotein...

  14. Increased oxidizability of low-density lipoproteins in hypothyroidism

    NARCIS (Netherlands)

    Diekman, T.; Demacker, P. N.; Kastelein, J. J.; Stalenhoef, A. F.; Wiersinga, W. M.

    1998-01-01

    Hypothyroidism leads to an increase of plasma low-density lipoprotein (LDL) cholesterol levels. Oxidation of LDL particles changes their intrinsic properties, thereby enhancing the development of atherosclerosis. T4 has three specific binding sites on apolipoprotein B; furthermore it inhibits LDL

  15. Lipoprotein biogenesis and evolution of lipid transport: an insect perspective

    NARCIS (Netherlands)

    Smolenaars, Martinus Maria Wilhelmus

    2006-01-01

    Lipids are essential to organisms as they constitute membranes, and function as energy source and reserve. In animals, lipid transport in the circulation is accomplished by lipoproteins. These macromolecular particles, consisting of one or more proteins and up to hundreds of lipid molecules, have

  16. Existence of B/E and E receptors on Hep-G2 cells: a study using colloidal gold- and 125I-labeled lipoproteins

    International Nuclear Information System (INIS)

    Hesz, A.; Ingolic, E.; Krempler, F.; Kostner, G.M.

    1987-01-01

    The presence of specific receptors for apolipoprotein B (low-density lipoproteins) and apolipoprotein E (HDL-E) on Hep-G2 cells and human skin fibroblasts was studied by chemical methods and by electron microscopy using a differential gold labeling technique. Fibroblasts bound both types of lipoproteins to one and the same receptor (B/E receptor) as deduced from competition experiments with HDL-E and LDL. Labeled HDL-E, on the other hand, was only partially displaced by cold LDL but was completely displaced by unlabeled HDL-E. Scatchard analysis of lipoprotein binding to Hep-G2 cells revealed an approx 10 times higher binding affinity of apoE-containing lipoproteins as compared to apoB-containing ones. No differences between apoE- or apoB-containing lipoproteins with respect to the morphology of cell binding and intracellular processing were observed. The results are compatible with the concept that Hep-G2 cells possess two kinds of receptors, one specific for apoB- and apoE-containing lipoproteins (B/E receptor) and another specific for apoE only. From these studies we conclude that Hep-G2 cells may serve as a suitable model for studying the lipoprotein metabolism in the liver

  17. Interfacial Tension and Surface Pressure of High Density Lipoprotein, Low Density Lipoprotein, and Related Lipid Droplets

    DEFF Research Database (Denmark)

    Ollila, O. H. S.; Lamberg, A.; Lehtivaara, M.

    2012-01-01

    Lipid droplets play a central role in energy storage and metabolism on a cellular scale. Their core is comprised of hydrophobic lipids covered by a surface region consisting of amphiphilic lipids and proteins. For example, high and low density lipoproteins (HDL and LDL, respectively....... Here we use coarse-grained molecular-dynamics simulations to consider a number of related issues by calculating the interfacial tension in protein-free lipid droplets, and in HDL and LDL particles mimicking physiological conditions. First, our results suggest that the curvature dependence...

  18. Transendothelial lipoprotein exchange and microalbuminuria

    DEFF Research Database (Denmark)

    Jensen, Jan Skov; Feldt-Rasmussen, Bo; Jensen, Kurt Svarre

    2004-01-01

    . METHODS: Using an in vivo isotope technique, transendothelial exchange of low density lipoprotein (LDL) was measured in 77 non-diabetic individuals. Autologous 131-iodinated LDL was reinjected intravenously, and the 1-h fractional escape rate was calculated as index of transendothelial exchange. RESULTS......OBJECTIVE: Microalbuminuria associates with increased risk of atherosclerosis in individuals without diabetes. We hypothesized that transendothelial lipoprotein exchange is elevated among such individuals, possibly explaining increased intimal lipoprotein accumulation and thus atherosclerosis......: There was no difference in transendothelial LDL exchange between subjects with microalbuminuria versus normoalbuminuria (mean (95% confidence interval) 3.8%/h (3.3-4.3%/h) versus 4.2%/h (3.7-4.7%/h); P=0.33). In contrast, there was a positive correlation between transendothelial LDL exchange and (logarithmically...

  19. Regulation of high-density lipoprotein metabolism.

    Science.gov (United States)

    Rye, Kerry-Anne; Barter, Philip J

    2014-01-03

    There is compelling evidence from human population studies that plasma levels of high-density lipoprotein (HDL) cholesterol correlate inversely with cardiovascular risk. Identification of this relationship has stimulated research designed to understand how HDL metabolism is regulated. The ultimate goal of these studies has been to develop HDL-raising therapies that have the potential to decrease the morbidity and mortality associated with atherosclerotic cardiovascular disease. However, the situation has turned out to be much more complex than originally envisaged. This is partly because the HDL fraction consists of multiple subpopulations of particles that vary in terms of shape, size, composition, and surface charge, as well as in their potential cardioprotective properties. This heterogeneity is a consequence of the continual remodeling and interconversion of HDL subpopulations by multiple plasma factors. Evidence that the remodeling of HDLs may impact on their cardioprotective properties is beginning to emerge. This serves to highlight the importance of understanding not only how the remodeling and interconversion of HDL subpopulations is regulated but also how these processes are affected by agents that increase HDL levels. This review provides an overview of what is currently understood about HDL metabolism and how the subpopulation distribution of these lipoproteins is regulated.

  20. HeLp, a heme-transporting lipoprotein with an antioxidant role.

    Science.gov (United States)

    Maya-Monteiro, Clarissa M; Alves, Liliane R; Pinhal, Nelson; Abdalla, Dulcineia S P; Oliveira, Pedro L

    2004-01-01

    Plasma lipoproteins involved in lipid transport are target for free radical-evoked pathological conditions in several mammalian models. The main hemolymphatic protein of Boophilus microplus is a heme-binding lipoprotein (HeLp, for Heme LipoProtein) that carries dietary heme produced from degradation of vertebrate hemoglobin to tissues of the tick. Addition of heme to phospholipid liposomes resulted in intense lipid peroxidation, which was inhibited by addition of HeLp. HeLp prevented lysis of red blood cells by heme. HeLp also inhibited reactions of heme with tert-butyl hydroperoxide (t-BOOH) or hydrogen peroxide. HeLp, quite differently from other lipoproteins, presents a protective intrinsic mechanism to counteract heme toxicity, while preserving the heme molecule to be reused by the tick. This is the first report of a lipoprotein acting as an antioxidant particle against heme-induced radical damage.

  1. Butter, margarine and serum lipoproteins.

    NARCIS (Netherlands)

    Zock, P.L.; Katan, M.B.

    1997-01-01

    Intake of trans fatty acids unfavorably affects blood lipoproteins. As margarines are a major source of trans, claims for the advantages of margarines over butter need to be scrutinized. Here we review dietary trials that directly compared the effects of butter and margarine on blood lipids. We

  2. Revisiting the gram-negative lipoprotein paradigm

    Science.gov (United States)

    The processing of lipoproteins (lpps) in Gram-negative bacteria is generally considered to be an essential pathway. Mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by Lnt, an apolipoprotein n-acyltransferase. The mature lipoproteins are then sorted...

  3. Lipoprotein Apheresis for Lipoprotein(a)-Associated Cardiovascular Disease

    DEFF Research Database (Denmark)

    Roeseler, Eberhard; Julius, Ulrich; Heigl, Franz

    2016-01-01

    OBJECTIVE: Lipoprotein(a)-hyperlipoproteinemia (Lp(a)-HLP) along with progressive cardiovascular disease has been approved as indication for regular lipoprotein apheresis (LA) in Germany since 2008. We aimed to study the long-term preventive effect of LA and to assess hypothetical clinical...... correlations of apolipoprotein(a) (apo(a)) by analyzing genotypes and phenotypes. APPROACH AND RESULTS: This prospective observational multicenter study included 170 patients with Lp(a)-HLP and progressive cardiovascular disease (48.9 years median age at diagnosis) despite other cardiovascular risk factors......-nucleotide polymorphisms rs10455872 or rs3798220. CONCLUSIONS: Results of 5 years of prospective follow-up confirm that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP. Patients clinically selected by progressive cardiovascular disease were characterized by a highly frequent...

  4. Lipoprotein(a) and dietary proteins: casein lowers lipoprotein(a) concentrations as compared with soy protein1-3

    DEFF Research Database (Denmark)

    Nilausen, Karin Johanne; Meinertz, H.

    1999-01-01

    Lipoprotein(a), plasma lipoproteins, dietary proteins, soy protein, casein, liquid-formula, coronary artery disease, men, Denmark......Lipoprotein(a), plasma lipoproteins, dietary proteins, soy protein, casein, liquid-formula, coronary artery disease, men, Denmark...

  5. Determining the risk of cardiovascular disease using ion mobility of lipoproteins

    Science.gov (United States)

    Benner, W. Henry; Krauss, Ronald M.; Blanche, Patricia J.

    2010-05-11

    A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

  6. Method of assessing a lipid-related health risk based on ion mobility analysis of lipoproteins

    Science.gov (United States)

    Benner, W. Henry; Krauss, Ronald M.; Blanche, Patricia J.

    2010-12-14

    A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

  7. Native and Reconstituted Plasma Lipoproteins in Nanomedicine: Physicochemical Determinants of Nanoparticle Structure, Stability, and Metabolism

    OpenAIRE

    Pownall, Henry J.; Rosales, Corina; Gillard, Baiba K.; Ferrari, Mauro

    2016-01-01

    Although many acute and chronic diseases are managed via pharmacological means, challenges remain regarding appropriate drug targeting and maintenance of therapeutic levels within target tissues. Advances in nanotechnology will overcome these challenges through the development of lipidic particles, including liposomes, lipoproteins, and reconstituted high-density lipoproteins (rHDL) that are potential carriers of water-soluble, hydrophobic, and amphiphilic molecules. Herein we summarize the p...

  8. Effects of hormones on lipids and lipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, R.M.

    1991-12-01

    Levels of plasma lipids and lipoproteins are strong predictors for the development of atherosclerotic cardiovascular disease in postmenopausal women. In women, as in men, numerous factors contribute to variations in plasma lipoproteins that may affect cardiovascular disease risk. These include age, dietary components, adiposity, genetic traits, and hormonal changes. Each of these factors may operate to varying degrees in determining changes in plasma lipoprotein profiles accompanying menopause- Cross-sectional and longitudinal studies have suggested increases in levels of cholesterol, low density lipoproteins (LDL) and triglyceride-rich lipoproteins associated with menopause. High density lipoproteins (HDL), which are higher in women than men and are thought to contribute to relative protection of premenopausal women from cardiovascular disease, remain relatively constant in the years following menopause, although small, and perhaps transient reductions in the HDL{sub 2} subfraction have been reported in relation to reduced estradiol level following menopause. Despite these associations, it has been difficult to determine the role of endogenous hormones in influencing the plasma lipoproteins of postmenopausal women. In principle, the effects of hormone replacement should act to reverse any alterations in lipoprotein metabolism that are due to postmenopausal hormone changes. While there may be beneficial effects on lipoproteins, hormone treatment does not restore a premenopausal lipoprotein profile. Furthermore, it is not dear to what extent exogenous hormone-induced lipoprotein changes contribute to the reduced incidence of cardiovascular disease with hormone replacement therapy.

  9. A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain

    Directory of Open Access Journals (Sweden)

    Yang Qi

    2009-12-01

    Full Text Available Abstract The midbrain periaqueductal grey (PAG is a structure known for its roles in pain transmission and modulation. Noxious stimuli potentiate the glutamate synaptic transmission and enhance glutamate NMDA receptor expression in the PAG. However, little is known about roles of NMDA receptor subunits in the PAG in processing the persistent inflammatory pain. The present study was undertaken to investigate NR2A- and NR2B-containing NMDA receptors in the PAG and their modulation to the peripheral painful inflammation. Noxious stimuli induced by hind-paw injection of complete Freund's adjuvant (CFA caused up-regulation of NR2B-containing NMDA receptors in the PAG, while NR2A-containing NMDA receptors were not altered. Whole-cell patch-clamp recordings revealed that NMDA receptor mediated mEPSCs were increased significantly in the PAG synapse during the chronic phases of inflammatory pain in mice. PAG local infusion of Ro 25-6981, an NR2B antagonist, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in rats. Hyperoside (Hyp, one of the flavonoids compound isolated from Rhododendron ponticum L., significantly reversed up-regulation of NR2B-containing NMDA receptors in the PAG and exhibited analgesic activities against persistent inflammatory stimuli in mice. Our findings provide strong evidence that up-regulation of NR2B-containing NMDA receptors in the PAG involves in the modulation to the peripheral persistent inflammatory pain.

  10. Biogenesis and Membrane Targeting of Lipoproteins.

    Science.gov (United States)

    Narita, Shin-Ichiro; Tokuda, Hajime

    2010-09-01

    Bacterial lipoproteins represent a unique class of membrane proteins, which are anchored to membranes through triacyl chains attached to the amino-terminal cysteine. They are involved in various functions localized in cell envelope. Escherichia coli possesses more than 90 species of lipoproteins, most of which are localized in the outer membrane, with others being in the inner membrane. All lipoproteins are synthesized in the cytoplasm with an N-terminal signal peptide, translocated across the inner membrane by the Sec translocon to the periplasmic surface of the inner membrane, and converted to mature lipoproteins through sequential reactions catalyzed by three lipoprotein-processing enzymes: Lgt, LspA, and Lnt. The sorting of lipoproteins to the outer membrane requires a system comprising five Lol proteins. An ATP-binding cassette transporter, LolCDE, initiates the sorting by mediating the detachment of lipoproteins from the inner membrane. Formation of the LolA-lipoprotein complex is coupled to this LolCDE-dependent release reaction. LolA accommodates the amino-terminal acyl chain of lipoproteins in its hydrophobic cavity, thereby generating a hydrophilic complex that can traverse the periplasmic space by diffusion. Lipoproteins are then transferred to LolB on the outer membrane and anchored to the inner leaflet of the outer membrane by the action of LolB. In contrast, since LolCDE does not recognize lipoproteins possessing Asp at position +2, these lipoproteins remain anchored to the inner membrane. Genes for Lol proteins are widely conserved among gram-negative bacteria, and Lol-mediated outer membrane targeting of lipoproteins is considered to be the general lipoprotein localization mechanism.

  11. Lipoprotein (a: Structure, Pathophysiology and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Raul Cavalcante Maranhão

    2014-07-01

    Full Text Available The chemical structure of lipoprotein (a is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a bound to apo B100 via one disulfide bridge. Lipoprotein (a is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from 1,000 mg/dL. Lipoprotein (a levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a levels. Lipoprotein (a homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a on arterial wall is also a possible mechanism, lipoprotein (a being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a, although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.

  12. Dietary fatty acids were not independently associated with lipoprotein subclasses in elderly women.

    Science.gov (United States)

    Alaghehband, Fatemeh Ramezan; Lankinen, Maria; Värri, Miika; Sirola, Joonas; Kröger, Heikki; Erkkilä, Arja T

    2017-07-01

    Dietary fatty acids are known to affect serum lipoproteins; however, little is known about the associations between consumption of dietary fatty acids and lipoprotein subclasses. In this study, we hypothesized that there is an association between dietary fatty acids and lipoprotein subclasses and investigated the cross-sectional association of dietary fat intake with subclasses of lipoproteins in elderly women. Altogether, 547 women (aged ≥65 years) who were part of OSTPRE cohort participated. Dietary intake was assessed by 3-day food records, lifestyle, and health information obtained through self-administrated questionnaires, and lipoprotein subclasses were determined by nuclear magnetic resonance spectroscopy. To analyze the associations between fatty acids and lipoprotein subclasses, we used Pearson and Spearman correlation coefficients and the analysis of covariance (ANCOVA) test with, adjustment for physical activity, body mass index, age, smoking status, and intake of lipid-lowering drugs. There were significant correlations between saturated fatty acids (SFA; % of energy) and concentrations of large, medium, and small low-density lipoproteins (LDL); total cholesterol in large, medium, and small LDL; and phospholipids in large, medium, and small LDL, after correction for multiple testing. After adjustment for covariates, the higher intake of SFA was associated with smaller size of LDL particles (P = .04, ANCOVA) and lower amount of triglycerides in small very low-density lipoproteins (P = .046, ANCOVA). However, these associations did not remain significant after correction for multiple testing. In conclusion, high intake of SFA may be associated with the size of LDL particles, but the results do not support significant, independent associations between dietary fatty acids and lipoprotein subclasses. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Coconut oil affects lipoprotein composition and structure of neonatal chicks.

    Science.gov (United States)

    Castillo, M; Hortal, J H; García-Fuentes, E; Zafra, M F; García-Peregrín, E

    1996-04-01

    Supplementation of 10 or 20% coconut oil in the diet for 1-2 weeks produced a significant hypercholesterolemia in neonatal chicks. Plasma triacylglycerol concentration significantly increased after the addition of 20% coconut oil for 2 weeks. These results show that newborn chicks are more sensitive to saturated fatty acids from coconut oil than adult animals. The effects of this saturated fat on lipoprotein composition were studied for the first 1-2 weeks of neonatal chick life. Coconut oil supplementation in the diet (20%) for 2 weeks increased cholesterol concentration in all the lipoprotein fractions, while 10% coconut oil only increased cholesterol in low-density and very-low-density lipoproteins, an increase that was significant after 1 week of treatment. Similar results were obtained for triacylglycerol concentration after 2 weeks of treatment. Changes in phospholipid and total protein levels were less profound. Coconut oil decreased low-density and very-low-density lipoprotein fluidity, measured as total cholesterol/phospholipid ratio. Changes in esterified cholesterol/phospholipid and triacylglycerol/phospholipid ratios suggest that coconut oil affects the distribution of lipid components in the core of very-low-density particles. Likewise, the esterified cholesterol/triacylglycerol ratio was clearly increased in the low-density, and especially in the very-low-density, fraction after the first week of coconut oil feeding. Our results show that neonatal chick provides a suitable model in which to study the role of very-low-density lipoproteins in atherogenesis and the rapid response to saturated fatty acids with 12-14 carbons.

  14. Lipoprotein genotype and conserved pathway for exceptional longevity in humans.

    Directory of Open Access Journals (Sweden)

    Gil Atzmon

    2006-04-01

    Full Text Available Alteration of single genes involved in nutrient and lipoprotein metabolism increases longevity in several animal models. Because exceptional longevity in humans is familial, it is likely that polymorphisms in genes favorably influence certain phenotypes and increase the likelihood of exceptional longevity. A group of Ashkenazi Jewish centenarians (n = 213, their offspring (n = 216, and an age-matched Ashkenazi control group (n = 258 were genotyped for 66 polymorphisms in 36 candidate genes related to cardiovascular disease (CVD. These genes were tested for association with serum lipoprotein levels and particle sizes, apolipoprotein A1, B, and C-3 levels and with outcomes of hypertension, insulin resistance, and mortality. The prevalence of homozygosity for the -641C allele in the APOC3 promoter (rs2542052 was higher in centenarians (25% and their offspring (20% than in controls (10% (p = 0.0001 and p = 0.001, respectively. This genotype was associated with significantly lower serum levels of APOC3 and a favorable pattern of lipoprotein levels and sizes. We found a lower prevalence of hypertension and greater insulin sensitivity in the -641C homozygotes, suggesting a protective effect against CVD and the metabolic syndrome. Finally, in a prospectively studied cohort, a significant survival advantage was demonstrated in those with the favorable -641C homozygote (p < 0.0001. Homozygosity for the APOC3 -641C allele is associated with a favorable lipoprotein profile, cardiovascular health, insulin sensitivity, and longevity. Because modulation of lipoproteins is also seen in genetically altered longevity models, it may be a common pathway influencing lifespan from nematodes to humans.

  15. Elevated Lipoprotein(A Impairs Platelet Radiolabeling Yield

    Directory of Open Access Journals (Sweden)

    Susanne Granegger

    2015-02-01

    Full Text Available Objectives: Platelet radiolabeling in clinical routine usually results in labeling efficiencies (LE above 80%. A variety of risk factors and clinical conditions are known to impair platelet labeling yield, among them elevated triglycerides and low-density lipoproteins. The potential influence of lipoprotein(a (Lp(a, an atherogenic lipoprotein particle containing a kringle subunit, which is widely found in the proteins of fibrinolysis pathway, has never been studied. Normal Lp(a levels range below 30 mg/ dl. The exact prevalence of elevated Lp(a is unknown, most likely ranging below 10%. Even more rare is an isolated elevation despite an otherwise normal lipoprotein profile. Methods: We examined the role of isolated elevated Lp(a (> 50 mg/dl, ranging up to 440 mg/dl compared to patients with normal lipid profile. Platelets were radiolabeled with in-111-oxine at 37 °C for 5 minutes using ISORBE-consensus methodology. Results: The findings indicate that already at levels below 100 mg/dl Lp(a decreases LE. LE assessment after cross-incubation of hyper-Lp(a platelets with normal Lp(a plasma and vice versa reveals that platelets rather than the plasmatic environment are responsible for the deterioration of labeling yield. This behavior already has been reported for elevated low-density lipoproteins. Apparently, the quantitative influence of LDL and Lp(a/mg is comparable. Plotting the sum of LDL and Lp(a versus LE reveals a clear significant negative correlation. Conclusion: As extremely elevated Lp(a, particularly above 150 mg/dl, may significantly impair labeling results. We therefore recommend to include extremely elevated Lp(a into the list of parameters, which should be known before performing radiolabeling of human platelets.

  16. A More Flexible Lipoprotein Sorting Pathway

    Science.gov (United States)

    Chahales, Peter

    2015-01-01

    Lipoprotein biogenesis in Gram-negative bacteria occurs by a conserved pathway, each step of which is considered essential. In contrast to this model, LoVullo and colleagues demonstrate that the N-acyl transferase Lnt is not required in Francisella tularensis or Neisseria gonorrhoeae. This suggests the existence of a more flexible lipoprotein pathway, likely due to a modified Lol transporter complex, and raises the possibility that pathogens may regulate lipoprotein processing to modulate interactions with the host. PMID:25755190

  17. Relationship of pericardial fat with lipoprotein distribution: The Multi-Ethnic study of atherosclerosis.

    Science.gov (United States)

    Ong, Kwok-Leung; Ding, Jingzhong; McClelland, Robyn L; Cheung, Bernard M Y; Criqui, Michael H; Barter, Philip J; Rye, Kerry-Anne; Allison, Matthew A

    2015-08-01

    Pericardial fat and lipoprotein abnormalities contribute to increased risk of cardiovascular disease (CVD). We investigated the relationship between pericardial fat volume and lipoprotein distribution, and whether the association of pericardial fat volume with subclinical atherosclerosis and incident CVD events differs according to lipoprotein distribution. We analyzed data from 5407 participants from the Multi-Ethnic Study of Atherosclerosis who had measurements of pericardial fat volume, lipoprotein distribution, carotid intima-media thickness (IMT), and coronary artery calcium (CAC). All participants were free of clinically apparent CVD at baseline. Incident CVD was defined as any adjudicated CVD event. After adjusting for demographic factors, traditional risk factors, and biomarkers of inflammation and hemostasis, a larger pericardial fat volume was associated with higher large VLDL particle (VLDL-P) concentration and small HDL particle (HDL-P) concentration, and smaller HDL-P size (regression coefficients = 0.585 nmol/L, 0.366 μmol/L, and -0.025 nm per SD increase in pericardial fat volume respectively, all P 0.05). Pericardial fat is associated with atherogenic lipoprotein abnormalities. However, its relationship with subclinical atherosclerosis and incident CVD events does not differ according to lipoprotein distribution. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Raman Spectroscopic Analysis of Biochemical Changes in Individual Triglyceride-Rich Lipoproteins in the Pre- and Postprandial State

    Energy Technology Data Exchange (ETDEWEB)

    Chan, J; Motton, D; Rutledge, J; Keim, N; Huser, T

    2004-09-13

    Individual triglyceride-rich lipoprotein (TGRL) particles derived from human volunteers are non-destructively analyzed by laser tweezers Raman microspectroscopy and information on their composition and distribution is obtained. The Raman signature of single optically trapped very low-density lipoproteins (VLDL), a subclass of TGRL, which play an important role in cardiovascular disease, exhibits distinct peaks associated with molecular vibrations of fatty acids, proteins, lipids, and structural rearrangements of lipids. Our analysis of pre- and postprandial VLDL exhibits the signature of biochemical changes in individual lipoprotein particles following the consumption of meals. Interaction of VLDL with endothelium leads to the breakdown of complex triacylglycerols and the formation of a highly ordered core of free saturated fatty acids in the particle. A particle distribution analysis reveals trends in the degree to which this process has occurred in particles at different times during the postprandial period. Differences in particle distributions based on the different ratios of polyunsaturated to saturated fats in the consumed meals are also easily discerned. Individual lipoprotein particles hydrolyzed in-vitro through addition of lipoprotein lipase (LpL) exhibit strikingly similar changes in their Raman spectra. These results demonstrate the feasibility of monitoring the dynamics of lipid metabolism of individual TGRL particles as they interact with LpL in the endothelial cell wall using Raman spectroscopy.

  19. The role of phospholipid transfer protein in lipoprotein-mediated neutralization of the procoagulant effect of anionic liposomes.

    Science.gov (United States)

    Oslakovic, C; Jauhiainen, M; Ehnholm, C; Dahlbäck, B

    2010-04-01

    Serum has the ability to neutralize the procoagulant properties of anionic liposomes, with transfer of phospholipids (PLs) to both high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles. Phospholipid transfer protein (PLTP) mediates transfer of PLs between HDL and other lipoproteins and conversion of HDL into larger and smaller particles. To examine the role of PLTP in the neutralization of procoagulant liposomes. Procoagulant liposomes were incubated with different lipoproteins in the presence or absence of PLTP, and then tested for their ability to stimulate thrombin formation. In the absence of added PLTP, the lipoprotein-enriched fraction, total HDL, HDL(3) and very high-density lipoprotein (VHDL) were all able to neutralize the procoagulant properties of the liposomes. In these samples, endogenous PLTP was present, as judged by Western blotting. In contrast, no PLTP was present in LDL, HDL(2) and lipoprotein-deficient serum, all of which displayed no ability to neutralize the procoagulant liposomes. The phospholipid (PL) transfer activity was dependent on both enzyme (PLTP) and PL acceptor (lipoproteins). After treatment of the VHDL fraction with antiserum against PLTP, the neutralization of procoagulant activity was reduced, but could be regained by the addition of active PLTP. The neutralizing activity was dependent on a catalytically active form of PLTP, and addition of a low activity form of PLTP had no effect. In conclusion, PLTP was found to mediate transfer of anionic PLs to HDL and LDL, thereby neutralizing the effect of procoagulant liposomes, resulting in a reduction of procoagulant activity.

  20. Lipoprotein Nanoplatform for Targeted Delivery of Diagnostic and Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Jerry D. Glickson

    2008-03-01

    Full Text Available Low-density lipoprotein (LDL provides a highly versatile natural nanoplatform for delivery of visible or near-infrared fluorescent optical and magnetic resonance imaging (MRI contrast agents and photodynamic therapy and chemotherapeutic agents to normal and neoplastic cells that overexpress low-density lipoprotein receptors (LDLRs. Extension to other lipoproteins ranging in diameter from about 10 nm (high-density lipoprotein [HDL] to over a micron (chylomicrons is feasible. Loading of contrast or therapeutic agents onto or into these particles has been achieved by protein loading (covalent attachment to protein side chains, surface loading (intercalation into the phospholipid monolayer, and core loading (extraction and reconstitution of the triglyceride/cholesterol ester core. Core and surface loading of LDL have been used for delivery of optical imaging agents to tumor cells in vivo and in culture. Surface loading was used for delivery of gadolinium-bis-stearylamide contrast agents for in vivo MRI detection in tumor-bearing mice. Chlorin and phthalocyanine near-infrared photodynamic therapy agents (≤ 400/LDL have been attached by core loading. Protein loading was used to reroute the LDL from its natural receptor (LDLR to folate receptors and could be used to target other receptors. A semisynthetic nanoparticle has been constructed by coating magnetite iron oxide nanoparticles with carboxylated cholesterol and overlaying a monolayer of phospholipid to which apolipoprotein A1 or E was adsorbed for targeting HDL or adsorbing synthetic amphipathic helical peptides ltargeting LDL or folate receptors. These particles can be used for in situ loading of magnetite into cells for MRI-monitored cell tracking or gene expression.

  1. NR2B-containing NMDA receptors promote neural progenitor cell proliferation through CaMKIV/CREB pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mei, E-mail: limeihit@163.com [Department of Anatomy and Neurobiology, Xuzhou Medical College, Xuzhou (China); Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing (China); Zhang, Dong-Qing; Wang, Xiang-Zhen [Department of Anatomy and Neurobiology, Xuzhou Medical College, Xuzhou (China); Xu, Tie-Jun, E-mail: xztjxu@163.com [Department of Anatomy and Neurobiology, Xuzhou Medical College, Xuzhou (China); Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing (China)

    2011-08-12

    Highlights: {yields} The NR2B component of the NMDARs is important for the NSPC proliferation. {yields} pCaMKIV and pCREB exist in NSPCs. {yields} The CaMKIV/CREB pathway mediates NSPC proliferation. -- Abstract: Accumulating evidence indicates the involvement of N-methyl-D-aspartate receptors (NMDARs) in regulating neural stem/progenitor cell (NSPC) proliferation. Functional properties of NMDARs can be markedly influenced by incorporating the regulatory subunit NR2B. Here, we aim to analyze the effect of NR2B-containing NMDARs on the proliferation of hippocampal NSPCs and to explore the mechanism responsible for this effect. NSPCs were shown to express NMDAR subunits NR1 and NR2B. The NR2B selective antagonist, Ro 25-6981, prevented the NMDA-induced increase in cell proliferation. Moreover, we demonstrated that the phosphorylation levels of calcium/calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein (CREB) were increased by NMDA treatment, whereas Ro 25-6981 decreased them. The role that NR2B-containing NMDARs plays in NSPC proliferation was abolished when CREB phosphorylation was attenuated by CaMKIV silencing. These results suggest that NR2B-containing NMDARs have a positive role in regulating NSPC proliferation, which may be mediated through CaMKIV phosphorylation and subsequent induction of CREB activation.

  2. Bio F1B hamster: a unique animal model with reduced lipoprotein lipase activity to investigate nutrient mediated regulation of lipoprotein metabolism

    Directory of Open Access Journals (Sweden)

    Cornish Marion L

    2007-12-01

    Full Text Available Abstract Background Bio F1B hamster is an inbred hybrid strain that is highly susceptible to diet-induced atherosclerosis. We previously reported that feeding a high fat fish oil diet to Bio F1B hamster caused severe hyperlipidaemia. In this study we compared the effects of various diets in the Bio F1B hamster and the Golden Syrian hamster, which is an outbred hamster strain to investigate whether genetic background plays an important role in dietary fat mediated regulation of lipoprotein metabolism. We further investigated the mechanisms behind diet-induced hyperlipidaemia in F1B hamster. Methods The Bio F1B and Golden Syrian hamsters, 8 weeks old, were fed high fat diets rich in either monounsaturated fatty acids, an n-6: n-3 ratio of 5 or a fish oil diet for 4 weeks. Animals were fasted overnight and blood and tissue samples were collected. Plasma was fractionated into various lipoprotein fractions and assayed for triacylglycerol and cholesterol concentrations. Plasma lipoprotein lipase activity was measured using radioisotope method. Microsomal triglyceride transfer protein activity was measured in the liver and intestine. Plasma apolipoproteinB48, -B100 and apolipoprotein E was measured using Western blots. Two-way ANOVA was used to determine the effect of diet type and animal strain. Results The fish oil fed F1B hamsters showed milky plasma after a 14-hour fast. Fish oil feeding caused accumulation of apolipoproteinB48 containing lipoprotein particles suggesting hindrance of triglyceride-rich lipoprotein clearance. There was no significant effect of diet or strain on hepatic or intestinal microsomal triglyceride transfer protein activity indicating that hyperlipidaemia is not due to an increase in the assembly or secretion of lipoprotein particles. F1B hamsters showed significantly reduced levels of lipoprotein lipase activity, which was inhibited by fish oil feeding. Conclusion Evidence is presented for the first time that alterations in

  3. Characterization of human high-density lipoprotein subclasses LP A-I and LP A-I/A-II and binding to HepG2 cells

    NARCIS (Netherlands)

    E.P.C. Kilsdonk (Liesbeth); T. van Gent (Teus); A. van Tol (Arie)

    1990-01-01

    markdownabstractAbstract Plasma HDL can be classified according to their apolipoprotein content into at least two types of lipoprotein particles: lipoproteins containing both apo A-I and apo A-II (LP A-I/A-II) and lipoproteins with apo A-I but without apo A-II (LP A-I). LP A-I and LP A-I/A-II

  4. Lipoprotein(a in Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Michele Malaguarnera

    2013-01-01

    Full Text Available Lipoprotein(a (Lp(a is an LDL-like molecule consisting of an apolipoprotein B-100 (apo(B-100 particle attached by a disulphide bridge to apo(a. Many observations have pointed out that Lp(a levels may be a risk factor for cardiovascular diseases. Lp(a inhibits the activation of transforming growth factor (TGF and contributes to the growth of arterial atherosclerotic lesions by promoting the proliferation of vascular smooth muscle cells and the migration of smooth muscle cells to endothelial cells. Moreover Lp(a inhibits plasminogen binding to the surfaces of endothelial cells and decreases the activity of fibrin-dependent tissue-type plasminogen activator. Lp(a may act as a proinflammatory mediator that augments the lesion formation in atherosclerotic plaques. Elevated serum Lp(a is an independent predictor of coronary artery disease and myocardial infarction. Furthermore, Lp(a levels should be a marker of restenosis after percutaneous transluminal coronary angioplasty, saphenous vein bypass graft atherosclerosis, and accelerated coronary atherosclerosis of cardiac transplantation. Finally, the possibility that Lp(a may be a risk factor for ischemic stroke has been assessed in several studies. Recent findings suggest that Lp(a-lowering therapy might be beneficial in patients with high Lp(a levels. A future therapeutic approach could include apheresis in high-risk patients in order to reduce major coronary events.

  5. Proteomic analysis of high-density lipoprotein

    NARCIS (Netherlands)

    Rezaee, Farhad; Casetta, Bruno; Levels, J. Han M.; Speijer, Dave; Meijers, Joost C. M.

    2006-01-01

    Plasma lipoproteins, such as high-density lipoprotein (HDL), can serve as carriers for a wide range of proteins that are involved in processes such as lipid metabolism, thrombosis, inflammation and atherosclerosis. The identification of HDL-associated proteins is essential with regards to

  6. Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism

    NARCIS (Netherlands)

    Kersten, A.H.

    2008-01-01

    Plasma lipoproteins are responsible for carrying triglycerides and cholesterol in the blood and ensuring their delivery to target organs. Regulation of lipoprotein metabolism takes place at numerous levels including via changes in gene transcription. An important group of transcription factors that

  7. Lipoprotein (a) Blood Test: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... https://medlineplus.gov/labtests/lipoproteinabloodtest.html Lipoprotein (a) Blood Test To use the sharing features on this page, please enable JavaScript. What is a Lipoprotein (a) Blood Test? A lipoprotein (a) test measures the level of ...

  8. [Blood serum lipoprotein spectrum in myocardial infarct].

    Science.gov (United States)

    Efremushkin, G G; Goriacheva, A V; Kolomenskaia, T I; Solomatina, L G; Ovcharenko, R P

    1979-11-01

    The lipoprotein spectrum was studied in polyacrylamide gel and by thin-layer chromatography on silica gel in 236 patients with myocardial infarction in different periods of the disease, in 45 patients with unstable angina pectoris, in 75 healthy persons and in 8 dogs with experimental myocardial infarction. Besides an increase in the concentration of cholesterol and triglycerides and a decrease in the level of diglycerides in blood serum, there is a disturbance in the ratio of phospholipid fractions, mainly in myocardial infarction. The level of pre-beta-lipoproteins was increased in the acute period of myocardial infarction, the level of beta-lipoproteins in the subacute period. Complications and concomitant inflammatory diseases were attended by a higher level of beta-lipoproteins. A connection was noted between the lipoprotein spectrum, predominantly of the pre-beta-fraction, and the ABO phenotype and the season.

  9. Lipoprotein nanoplatform for targeted delivery of diagnostic and therapeutic agents.

    Science.gov (United States)

    Glickson, Jerry D; Lund-Katz, Sissel; Zhou, Rong; Choi, Hoon; Chen, I-Wei; Li, Hui; Corbin, Ian; Popov, Anatoliy V; Cao, Weiguo; Song, Liping; Qi, Chenze; Marotta, Diane; Nelson, David S; Chen, Juan; Chance, Britton; Zheng, Gang

    2009-01-01

    Low-density lipoprotein (LDL) provides a highly versatile natural nanoplatform for delivery of optical and MRI contrast agents, photodynamic therapy agents and chemotherapeutic agents to normal and neoplastic cells that over express LDL receptors (LDLR). Extension to other lipoproteins ranging in diameter from approximately 5-10 nm (high density lipoprotein, HDL) to over a micron (chilomicrons) is feasible. Loading of contrast or therapeutic agents has been achieved by covalent attachment to protein side chains, intercalation into the phospholipid monolayer and extraction and reconstitution of the triglyceride/cholesterol ester core. Covalent attachment of folate to the lysine side chain amino groups was used to reroute the LDL from its natural receptor (LDLR) to folate receptors and could be utilized to target other receptors. A semi-synthetic nanoparticle has been constructed by coating magnetite iron oxide nanoparticles (MIONs) with carboxylated cholesterol and overlaying a monolayer ofphospholipid to which Apo A1, Apo E or synthetic amphoteric alpha-helical polypeptides were adsorbed for targeting HDL, LDL or folate receptors, respectively. These particles can be utilized for in situ loading of magnetite into cells for MRI monitored cell tracking or gene therapy.

  10. Acrolein consumption induces systemic dyslipidemia and lipoprotein modification

    International Nuclear Information System (INIS)

    Conklin, Daniel J.; Barski, Oleg A.; Lesgards, Jean-Francois; Juvan, Peter; Rezen, Tadeja; Rozman, Damjana; Prough, Russell A.; Vladykovskaya, Elena; Liu, SiQi; Srivastava, Sanjay; Bhatnagar, Aruni

    2010-01-01

    Aldehydes such as acrolein are ubiquitous pollutants present in automobile exhaust, cigarette, wood, and coal smoke. Such aldehydes are also constituents of several food substances and are present in drinking water, irrigation canals, and effluents from manufacturing plants. Oral intake represents the most significant source of exposure to acrolein and related aldehydes. To study the effects of short-term oral exposure to acrolein on lipoprotein levels and metabolism, adult mice were gavage-fed 0.1 to 5 mg acrolein/kg bwt and changes in plasma lipoproteins were assessed. Changes in hepatic gene expression related to lipid metabolism and cytokines were examined by qRT-PCR analysis. Acrolein feeding did not affect body weight, blood urea nitrogen, plasma creatinine, electrolytes, cytokines or liver enzymes, but increased plasma cholesterol and triglycerides. Similar results were obtained with apoE-null mice. Plasma lipoproteins from acrolein-fed mice showed altered electrophoretic mobility on agarose gels. Chromatographic analysis revealed elevated VLDL cholesterol, phospholipids, and triglycerides levels with little change in LDL or HDL. NMR analysis indicated shifts from small to large VLDL and from large to medium-small LDL with no change in the size of HDL particles. Increased plasma VLDL was associated with a significant decrease in post-heparin plasma hepatic lipase activity and a decrease in hepatic expression of hepatic lipase. These observations suggest that oral exposure to acrolein could induce or exacerbate systemic dyslipidemia and thereby contribute to cardiovascular disease risk.

  11. Synaptic NR2A- but not NR2B-containing NMDA receptors increase with blockade of ionotropic glutamate receptors

    Directory of Open Access Journals (Sweden)

    Jakob Von Engelhardt

    2009-10-01

    Full Text Available NMDA receptors are key molecules involved in physiological and pathophysiological brain processes such as plasticity and excitotoxicity. Neuronal activity regulates NMDA receptor levels in the cell membrane. However, little is known on which time scale this regulation occurs and whether the two main diheteromeric NMDA receptor subtypes in forebrain, NR1/NR2A and NR1/NR2B, are regulated in a similar fashion. As these differ considerably in their electrophysiological properties, the NR2A/NR2B ratio affects the neurons’ reaction to NMDA receptor activation. Here we provide evidence that the basal turnover rate in the cell membrane of NR2A- and NR2B-containing receptors is comparable. However, the level of the NR2A subtype in the cell membrane is highly regulated by NMDA receptor activity, resulting in a several-fold increased insertion of new receptors after blocking NMDA receptors for 8 hours. Blocking AMPA receptors also increases the delivery of NR2A-containing receptors to the cell membrane. In contrast, the amount of NR2B-containing receptors in the cell membrane is not affected by ionotropic glutamate receptor block. Moreover, electrophysiological analysis of synaptic currents in hippocampal cultures and CA1 neurons of hippocampal slices revealed that after 8 hours of NMDA receptor blockade the NMDA EPSCs increase as a result of augmented NMDA receptor-mediated currents. In conclusion, synaptic NR2A- but not NR2B-containing receptors are dynamically regulated, enabling neurons to change their NR2A/NR2B ratio within a time scale of hours.

  12. Oral administration of policosanol inhibits in vitro copper ion-induced rat lipoprotein peroxidation.

    Science.gov (United States)

    Menéndez, R; Fraga, V; Amor, A M; González, R M; Más, R

    1999-08-01

    Policosanol, a new cholesterol-lowering agent, is a mixture of higher aliphatic primary alcohols isolated from sugar cane (Saccharum officinarum L.) wax, which prevents the onset of espontaneously and experimentally induced atherosclerotic lesions in experimental models. Because the oxidation of low-density lipoprotein (LDL) may play a role in the pathogenesis of atherosclerosis, we investigate the effect of policosanol on copper oxidative susceptibility of rat lipoprotein fractions (VLDL + LDL). Rats fed normal diet were treated with policosanol (250-500 mg/kg/day) for up to 4 weeks. EDTA-free lipoprotein particles were oxidized in a cell-free system by the addition of copper ions, and conjugated dienes generation was monitored by changes of optical density at 234 nm. Thiobarbituric acid-reactive substances (TBARS) content and lysine-amino group reactivity were investigated. After administration, there was no change in cholesterol, triglycerides, and phospholipid content of lipoprotein fractions; however, policosanol significantly prolongs the lag time and reduces the propagation rate of diene generation. Also, policosanol reduces TBARS content and increases lysine reactivity in lipoprotein fractions treated with Cu2+. In conclusion, policosanol, in addition to its cholesterol-lowering effect, has other properties that enables it to reduce the potential of lipoprotein to undergo lipid peroxidation. Such effect can be considered of promissory value in the management of atherosclerosis.

  13. Bacterial lipoproteins; biogenesis, sorting and quality control.

    Science.gov (United States)

    Narita, Shin-Ichiro; Tokuda, Hajime

    2017-11-01

    Bacterial lipoproteins are a subset of membrane proteins localized on either leaflet of the lipid bilayer. These proteins are anchored to membranes through their N-terminal lipid moiety attached to a conserved Cys. Since the protein moiety of most lipoproteins is hydrophilic, they are expected to play various roles in a hydrophilic environment outside the cytoplasmic membrane. Gram-negative bacteria such as Escherichia coli possess an outer membrane, to which most lipoproteins are sorted. The Lol pathway plays a central role in the sorting of lipoproteins to the outer membrane after lipoprotein precursors are processed to mature forms in the cytoplasmic membrane. Most lipoproteins are anchored to the inner leaflet of the outer membrane with their protein moiety in the periplasm. However, recent studies indicated that some lipoproteins further undergo topology change in the outer membrane, and play critical roles in the biogenesis and quality control of the outer membrane. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Comparison of human plasma low- and high-density lipoproteins as substrates for lecithin: cholesterol acyltransferase.

    Science.gov (United States)

    Barter, P J; Hopkins, G J; Gorjatschko, L

    1984-01-17

    A recent observation that lecithin: cholesterol acyltransferase (EC 2.3.1.43) interacts with both low-density lipoproteins (LDL) and high-density lipoproteins (HDL) in human plasma is in apparent conflict with an earlier finding that the purified enzyme, while highly reactive with isolated HDL, was only minimally reactive with LDL. There is evidence, however, that lecithin: cholesterol acyltransferase may exist physiologically as a component of a complex with other proteins and that studies with the isolated enzyme may therefore provide misleading results. Consequently, interactions of the enzyme with isolated human lipoproteins have been re-examined in incubations containing lecithin: cholesterol acyltransferase as a component of human lipoprotein-free plasma in which a physiologically active complex of the enzyme with other proteins may have been preserved. In this system there was a ready esterification of the free cholesterol associated with both LDL and HDL-subfraction 3 (HDL3) in reactions that obeyed typical enzyme-saturation kinetics. For a given preparation of lipoprotein-free plasma the Vmax values with LDL and with HDL3 were virtually identical. The apparent Km for free cholesterol associated with HDL3 was 5.6 X 10(-5) M, while for that associated with LDL it was 4.1 X 10(-4) M. This implied that, in terms of free cholesterol concentration, the affinity of HDL3 for lecithin: cholesterol acyltransferase was about 7-times greater than that of LDL. When expressed in terms of lipoprotein particle concentration, however, it was apparent that the affinity of LDL for the enzyme was considerably greater than that of HDL3. When the lipoprotein fractions were equated in terms of lipoprotein surface area, the apparent affinities of the two fractions for the enzyme were found to be comparable.

  15. Effects of plant sterols and olive oil phenols on serum lipoproteins in humans

    NARCIS (Netherlands)

    Vissers, M.N.

    2001-01-01

    The studies described in this thesis investigated whether minor components from vegetable oils can improve health by decreasing cholesterol concentrations or oxidative modification of low-density-lipoprotein (LDL) particles.

    The plant sterolsβ-sitosterol and sitostanol are

  16. A more flexible lipoprotein sorting pathway.

    Science.gov (United States)

    Chahales, Peter; Thanassi, David G

    2015-05-01

    Lipoprotein biogenesis in Gram-negative bacteria occurs by a conserved pathway, each step of which is considered essential. In contrast to this model, LoVullo and colleagues demonstrate that the N-acyl transferase Lnt is not required in Francisella tularensis or Neisseria gonorrhoeae. This suggests the existence of a more flexible lipoprotein pathway, likely due to a modified Lol transporter complex, and raises the possibility that pathogens may regulate lipoprotein processing to modulate interactions with the host. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. The lipid- and lipoprotein- [LDL-Lp(a)] apheresis techniques. Updating.

    Science.gov (United States)

    Stefanutti, C; Morozzi, C; Perrone, G; Di Giacomo, S; Vivenzio, A; D'Alessandri, G

    2012-01-01

    Therapeutic plasmapheresis allows the extracorporeal removal of plasmatic lipoproteins (Lipid-apheresis) (LA). It can be non selective (non specific), semi - selective or selective low density lipoprotein-lipoprotein(a) (specific [LDL- Lp(a)] apheresis) (Lipoprotein apheresis, LDLa). The LDL removal rate is a perfect parameter to assess the system efficiency. Plasma-Exchange (PEX) cannot be considered either specific nor, selective. In PEX the whole blood is separated into plasma and its corpuscular components usually through centrifugation or rather filtration. The corpuscular components mixed with albumin solution plus saline (NaCl 0.9%) solution at 20%-25%, are then reinfused to the patient, to substitute the plasma formerly removed. PEX eliminates atherogenic lipoproteins, but also other essential plasma proteins, such as albumin, immunoglobulins, and hemocoagulatory mediators. Cascade filtration (CF) is a method based on plasma separation and removal of plasma proteins through double filtration. During the CF two hollow-fiber filters with pores of different diameter are used to eliminate the plasma components of different weight and molecular diameter. A CF system uses a first polypropylene filter with 0.55 µm diameter pores and a second one of diacetate of cellulose with 0.02 µm pores. The first filter separates the whole blood, and the plasma is then perfused through a second filter which allows the recovery of molecules with a diameter lower than 0.02 µm, and the removal of molecules larger in diameter as apoB100-containing lipoproteins. Since both albumin and immunoglobulins are not removed, or to a negligible extent, plasma-expanders, substitution fluids, and in particular albumin, as occurs in PEX are not needed. CF however, is characterized by lower selectivity since removes also high density lipoprotein (HDL) particles which have an antiatherogenic activity. In the 80's, a variation of Lipid-apheresis has been developed which allows the LDL

  18. Effects of dietary coconut oil, butter and safflower oil on plasma lipids, lipoproteins and lathosterol levels.

    Science.gov (United States)

    Cox, C; Sutherland, W; Mann, J; de Jong, S; Chisholm, A; Skeaff, M

    1998-09-01

    The aim of this present study was to determine plasma levels of lathosterol, lipids, lipoproteins and apolipoproteins during diets rich in butter, coconut fat and safflower oil. The study consisted of sequential six week periods of diets rich in butter, coconut fat then safflower oil and measurements were made at baseline and at week 4 in each diet period. Forty-one healthy Pacific island polynesians living in New Zealand participated in the trial. Subjects were supplied with some foods rich in the test fats and were given detailed dietary advice which was reinforced regularly. Plasma lathosterol concentration (P cholesterol (P=0.04), low density lipoprotein (LDL) cholesterol (Pcoconut and safflower oil diets compared with butter diets. Plasma total cholesterol, HDL cholesterol and apoA-levels were also significantly (Pcoconut diets. These data suggest that cholesterol synthesis is lower during diets rich in coconut fat and safflower oil compared with diets rich in butter and might be associated with lower production rates of apoB-containing lipoproteins.

  19. Estradiol-induced increase in novel object recognition requires hippocampal NR2B-containing NMDA receptors.

    Science.gov (United States)

    Vedder, Lindsey C; Smith, Caroline C; Flannigan, Alaina E; McMahon, Lori L

    2013-01-01

    17β-estradiol (E2), at high circulating levels, enhances learning and memory in many women, making it a clinical treatment for hormone-related cognitive decline in aging. However, the mechanisms stimulated by E2, which are responsible for its cognitive enhancing effects, remain incompletely defined. Using an ovariectomized rat model, we previously reported that increasing plasma E2 enhances the magnitude of long-term potentiation (LTP) at hippocampal CA3-CA1 synapses, which is caused by a selective increase in current mediated by NR2B-containing NMDARs, leading to an increase in the NMDAR/AMPAR ratio. Whether the increase in NR2B current is causally related to the ability of E2 to enhance hippocampal dependent learning and memory has yet to be tested. Here, we find that E2 enhances performance in the novel object recognition (NOR) task with the same time course we previously showed E2 enhances the LTP magnitude, temporally linking the increase in LTP to enhanced learning and memory. Furthermore, using the selective NR2B subunit antagonist Ro25-6981, we find that the E2-enhanced NOR, like the enhanced LTP, requires hippocampal NR2B-containing NMDARs, specifically in area CA1. Finally, using whole-cell recordings and the phosphatase inhibitor orthovanadate, we investigated whether the E2-induced increase in NMDAR current is caused by an increase in the density of synaptic NMDARs and/or an increase in NMDAR subunit phosphorylation. We find that both mechanisms are responsible for the enhanced NMDAR current in E2-treated rats. Our results show that the E2-enhanced NOR requires a functional increase in NR2B-containing NMDARs, a requirement shared with the E2-enhanced LTP magnitude at CA3-CA1 synapses, supporting the hypothesis that the increase in LTP likely contributes to the enhanced learning and memory following an increase in plasma E2 levels. Copyright © 2012 Wiley Periodicals, Inc.

  20. Relationships between the responses of triglyceride-rich lipoproteins in blood plasma containing apolipoproteins B-48 and B-100 to a fat-containing meal in normolipidemic humans.

    Science.gov (United States)

    Schneeman, B O; Kotite, L; Todd, K M; Havel, R J

    1993-01-01

    The concentration of triglyceride-rich lipoproteins containing apolipoprotein (apo) B-48 (chylomicrons) and apo B-100 (very low density lipoproteins) was measured in blood plasma of healthy young men after an ordinary meal containing one-third of daily energy and fat. Plasma obtained in the postabsorptive state and at intervals up to 12 hr after the meal was subjected to immunoaffinity chromatography against a monoclonal antibody to apo B-100 that does not bind apo B-48 and a minor fraction of apo B-100 rich in apo E. Measurements of the concentrations of components of the total and unbound triglyceride-rich lipoproteins separated from plasma by ultracentrifugation showed that about 80% of the increase in lipoprotein particle number was in very low density lipoproteins containing apo B-100 and only 20% was in chylomicrons containing apo B-48 that carry dietary fat from the intestine. The maximal increments and the average concentrations of apo B-48 and B-100 during the 12 hr were highly correlated (r2 = 0.80), suggesting that preferential clearance of chylomicron triglycerides by lipoprotein lipase leads to accumulation of hepatogenous very low density lipoproteins during the alimentary period. The composition of the bulk of very low density lipoproteins that were bound to the monoclonal antibody changed little and these particles contained about 90% of the cholesterol and most of the apo E that accumulated in triglyceride-rich lipoproteins. The predominant accumulation of very low density lipoprotein rather than chylomicron particles after ingestion of ordinary meals is relevant to the potential atherogenicity of postprandial lipoproteins. PMID:8446630

  1. Aspects on lipoprotein lipase and atherosclerosis

    OpenAIRE

    Neuger, Lucyna

    2005-01-01

    Lipoprotein lipase (LPL) hydrolyses blood lipids at the vascular endothelium. This action makes fatty acids available for tissue metabolic requirements. LPL is anchored to the endothelium by electrostatic forces and may act as a bridge connecting lipoproteins to cell surfaces. Clusters of positively charged amino acid residues in LPL interact with anionic groups on oligosaccharides covering the cell surfaces. Heparin competes with cell surface oligosaccharides for binding to LPL. Interaction ...

  2. Involvement of spinal NR2B-containing NMDA receptors in oxaliplatin-induced mechanical allodynia in rats

    Directory of Open Access Journals (Sweden)

    Yano Takahisa

    2011-01-01

    Full Text Available Abstract Background Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. The chronic neuropathy is a dose-limiting toxicity. We previously reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and mechanical allodynia in the late phase in rats. In the present study, we investigated the involvement of NR2B-containing N-methyl-D-aspartate (NMDA receptors in oxaliplatin-induced mechanical allodynia in rats. Results Repeated administration of oxaliplatin (4 mg/kg, i.p., twice a week caused mechanical allodynia in the fourth week, which was reversed by intrathecal injection of MK-801 (10 nmol and memantine (1 μmol, NMDA receptor antagonists. Similarly, selective NR2B antagonists Ro25-6981 (300 nmol, i.t. and ifenprodil (50 mg/kg, p.o. significantly attenuated the oxaliplatin-induced pain behavior. In addition, the expression of NR2B protein and mRNA in the rat spinal cord was increased by oxaliplatin on Day 25 (late phase but not on Day 5 (early phase. Moreover, we examined the involvement of nitric oxide synthase (NOS as a downstream target of NMDA receptor. L-NAME, a non-selective NOS inhibitor, and 7-nitroindazole, a neuronal NOS (nNOS inhibitor, significantly suppressed the oxaliplatin-induced pain behavior. The intensity of NADPH diaphorase staining, a histochemical marker for NOS, in the superficial layer of spinal dorsal horn was obviously increased by oxaliplatin, and this increased intensity was reversed by intrathecal injection of Ro25-6981. Conclusion These results indicated that spinal NR2B-containing NMDA receptors are involved in the oxaliplatin-induced mechanical allodynia.

  3. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality

    DEFF Research Database (Denmark)

    Collaboration, Emerging Risk Factors; Erqou, Sebhat; Kaptoge, Stephen

    2009-01-01

    CONTEXT: Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationship of Lp(a) concentration with risk of major vascular...... and nonvascular outcomes. STUDY SELECTION: Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual...

  4. Lipoprotein particle subclasses, cardiovascular disease and HIV infection

    DEFF Research Database (Denmark)

    Duprez, Daniel A; Kuller, Lewis H; Tracy, Russell

    2009-01-01

    using conditional logistic models. RESULTS: Total, large and small HDL-p, but not VLDL-p nor LDL-p, were significantly and inversely associated with CVD and its major component, non-fatal coronary heart disease. The HDL-p associations with CVD were reduced after adjustment for high sensitive C...

  5. Combined analysis of six lipoprotein lipase genetic variants on triglycerides, high-density lipoprotein, and ischemic heart disease

    DEFF Research Database (Denmark)

    Wittrup, Hans H; Andersen, Rolf V; Tybjaerg-Hansen, Anne

    2006-01-01

    Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD).......Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD)....

  6. Revisiting the Gram-negative lipoprotein paradigm.

    Science.gov (United States)

    LoVullo, Eric D; Wright, Lori F; Isabella, Vincent; Huntley, Jason F; Pavelka, Martin S

    2015-05-01

    The processing of lipoproteins (Lpps) in Gram-negative bacteria is generally considered an essential pathway. Mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by Lnt, an apolipoprotein N-acyltransferase. The mature lipoproteins are then sorted by the Lol system, with most Lpps inserted into the outer membrane (OM). We demonstrate here that the lnt gene is not essential to the Gram-negative pathogen Francisella tularensis subsp. tularensis strain Schu or to the live vaccine strain LVS. An LVS Δlnt mutant has a small-colony phenotype on sucrose medium and increased susceptibility to globomycin and rifampin. We provide data indicating that the OM lipoprotein Tul4A (LpnA) is diacylated but that it, and its paralog Tul4B (LpnB), still sort to the OM in the Δlnt mutant. We present a model in which the Lol sorting pathway of Francisella has a modified ABC transporter system that is capable of recognizing and sorting both triacylated and diacylated lipoproteins, and we show that this modified system is present in many other Gram-negative bacteria. We examined this model using Neisseria gonorrhoeae, which has the same Lol architecture as that of Francisella, and found that the lnt gene is not essential in this organism. This work suggests that Gram-negative bacteria fall into two groups, one in which full lipoprotein processing is essential and one in which the final acylation step is not essential, potentially due to the ability of the Lol sorting pathway in these bacteria to sort immature apolipoproteins to the OM. This paper describes the novel finding that the final stage in lipoprotein processing (normally considered an essential process) is not required by Francisella tularensis or Neisseria gonorrhoeae. The paper provides a potential reason for this and shows that it may be widespread in other Gram-negative bacteria. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. The effects of exercise on the lipoprotein subclass profile: a meta-analysis of 10 interventions

    Science.gov (United States)

    Sarzynski, Mark A.; Burton, Jeffrey; Rankinen, Tuomo; Blair, Steven N.; Church, Timothy S.; Després, Jean-Pierre; Hagberg, James M.; Landers-Ramos, Rian; Leon, Arthur S.; Mikus, Catherine R.; Rao, D.C.; Seip, Richard L.; Skinner, James S.; Slentz, Cris A.; Thompson, Paul D.; Wilund, Kenneth R.; Kraus, William E.; Bouchard, Claude

    2015-01-01

    Objective The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts. Methods Nuclear magnetic resonance spectroscopy was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles (VLDL-P, LDL-P, and HDL-P, respectively) before and after an exercise intervention in 1,555 adults from six studies, encompassing 10 distinct exercise programs: APOE (N=106), DREW (N=385), GERS (N=79), HERITAGE (N=715), STRRIDE I (N=168) and II (N=102). Random-effects meta-analyses were performed to evaluate the overall estimate of mean change across the unadjusted and adjusted mean change values from each exercise group. Results Meta-analysis of unadjusted data showed that regular exercise induced significant decreases in the concentration of large VLDL-P, small LDL-P, and medium HDL-P and mean VLDL-P size, with significant increases in the concentration of large LDL-P and large HDL-P and mean LDL-P size. These changes remained significant in meta-analysis with adjustment for age, sex, race, baseline body mass index, and baseline trait value. Conclusions Despite differences in exercise programs and study populations, regular exercise produced putatively beneficial changes in the lipoprotein subclass profile across 10 exercise interventions. Further research is needed to examine how exercise-induced changes in lipoprotein subclasses may be associated with (concomitant changes in) cardiovascular disease risk. PMID:26520888

  8. Consumption of nonfat milk results in a less atherogenic lipoprotein profile: a pilot study.

    Science.gov (United States)

    Hidaka, Hiroya; Takiwaki, Masaki; Yamashita, Mine; Kawasaki, Kenji; Sugano, Mitsutoshi; Honda, Takayuki

    2012-01-01

    An increase in plasma low-density lipoprotein (LDL) is a well-known risk factor in the development of atherosclerosis. Dairy consumption may lower the risk of atherosclerosis; however, studies on the effects of milk on cardiovascular risk factors are still scarce. We were interested in investigating whether the intake of milk improves the atherogenic lipoprotein profile. We investigated the effects of consuming whole or nonfat milk on plasma lipoprotein composition in healthy Japanese subjects as a pilot study. Normolipidemic subjects consumed 500 ml of whole milk (whole milk group; n=7) or nonfat milk (nonfat milk group; n=7) every day for 2 weeks. The consumption of nonfat milk resulted in a lowering of plasma triglyceride (TG) and phospholipid levels and TG level in high-density lipoprotein (HDL) and increased the plasma apolipoprotein (apo) C-III level. In addition, the TG/cholesterol ratios in HDL and LDL were significantly decreased, and LDL particles became larger. In contrast, the only changes observed following whole milk consumption were increases in the plasma levels of apoC-III and apoE. These findings suggest that consumption of nonfat milk, but not whole milk, may result in a less atherogenic lipoprotein profile, and that the constituents of nonfat milk may improve lipid metabolism.

  9. Cultured human astrocytes secrete large cholesteryl ester- andtriglyceride-rich lipoproteins along with endothelial lipase

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Lin; Liu, Yanzhu; Forte, Trudy M.; Chisholm, Jeffrey W.; Parks, John S.; Shachter, Neil S.

    2003-12-01

    We cultured normal human astrocytes and characterized their secreted lipoproteins. Human astrocytes secreted lipoproteins in the size range of plasma VLDL (Peak 1), LDL (Peak 2), HDL (Peak 3) and a smaller peak (Peak 4), as determined by gel filtration chromatography, nondenaturing gradient gel electrophoresis and transmission electron microscopy. Cholesterol enrichment of astrocytes led to a particular increase in Peak 1. Almost all Peak 2, 3 and 4 cholesterol and most Peak 1 cholesterol was esterified (unlike mouse astrocyte lipoproteins, which exhibited similar peaks but where cholesterol was predominantly non-esterified). Triglycerides were present at about 2/3 the level of cholesterol. LCAT was detected along with two of its activators, apolipoprotein (apo) A-IV and apoC-I. ApoA-I and apoA-II mRNA and protein were absent. ApoJ was present equally in all peaks but apoE was present predominantly in peaks 3 and 4. ApoB was not detected. The electron microscopic appearance of Peak 1 lipoproteins suggested partial lipolysis leading to the detection of a heparin-releasable triglyceride lipase consistent with endothelial lipase. The increased neuronal delivery of lipids from large lipoprotein particles, for which apoE4 has greater affinity than does apoE3, may be a mechanism whereby the apoE {var_epsilon}4 allele contributes to neurodegenerative risk.

  10. Role of heparanase on hepatic uptake of intestinal derived lipoprotein and fatty streak formation in mice.

    Directory of Open Access Journals (Sweden)

    David Planer

    Full Text Available BACKGROUND: Heparanase modulates the level of heparan sulfate proteoglycans (HSPGs which have an important role in multiple cellular processes. Recent studies indicate that HSPGs have an important function in hepatic lipoprotein handling and processes involving removal of lipoprotein particles. PRINCIPAL FINDINGS: To determine the effects of decreased HSPGs chain length on lipoprotein metabolism and atherosclerosis, transgenic mice over-expressing the human heparanase gene were studied. Hepatic lipid uptake in hpa-Tg mice were evaluated by giving transgenic mice oral fat loads and labeled retinol. Sections of aorta from mice over-expressing heparanase (hpa-Tg and controls (C57/BL6 fed an atherogenic diet were examined for evidence of atherosclerosis. Heparanase over-expression results in reduced hepatic clearance of postprandial lipoproteins and higher levels of fasting and postprandial serum triglycerides. Heparanase over-expression also induces formation of fatty streaks in the aorta. The mean lesion cross-sectional area in heparanase over-expressing mice was almost 6 times higher when compared to control mice (23,984 µm(2±5,922 vs. 4,189 µm(2±1,130, p<0.001. CONCLUSIONS: Over-expression of heparanase demonstrates the importance of HSPGs for the uptake of intestinal derived lipoproteins and its role in the formation of fatty streaks.

  11. Current situation of lipoprotein apheresis in Saxony.

    Science.gov (United States)

    Julius, U; Taseva, K; Fischer, S; Passauer, J; Bornstein, S R

    2013-01-01

    This paper summarizes the situation pertinent to treatment via lipoprotein apheresis in the federal state of Saxony, Germany in 2010. In total, 119 predominately male patients were treated in 10 centers; the majority of the patients was older than the mean age of the general population. Several risk factors were present, particularly a familial predisposition and hypertension. All patients had experienced cardiovascular events and the majority was taking statins. Patient data from the University Hospital Carl Gustav Carus in Dresden concurred with data derived from patients treated at nephrological practices. In the mean, patients attended the centers for about 6 years, the majority weekly. LDL cholesterol concentrations prior to apheresis were clearly higher than target levels; apheresis sessions decreased LDL cholesterol by 69%. Lipoprotein(a) levels could be measured in 75 patients and were effectively reduced by lipoprotein apheresis. In Saxony, 29 patients per 1 million inhabitants received lipoprotein apheresis, which is higher than the proportion of patients treated in Germany as a whole. The need for this extracorporeal treatment seems to be much greater than its current utilization. Among the patients only one homozygous patient with familial hypercholesterolemia was observed. Physicians should be actively informed about this therapeutic possibility to reduce the cardiovascular risk efficiently. The introduction of new drugs may alter the position of lipoprotein apheresis within the therapeutic spectrum. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. Sortilins: new players in lipoprotein metabolism

    DEFF Research Database (Denmark)

    Willnow, Thomas; Kjølby, Mads Fuglsang; Nykjær, Anders

    2011-01-01

    of the nervous system. Recent data, including genome-wide association studies, now suggest equally important functions for sortilins in control of systemic lipoprotein metabolism and risk of cardiovascular disease. This review discusses the evidence implicating two members of this gene family, sortilin and SORLA......, in cardiovascular processes. RECENT FINDINGS: SORLA is a multifunctional receptor expressed in macrophages and vascular smooth muscle cells. It may act proatherogenic by promoting intimal SMC migration and by regulating apolipoprotein A-V dependent activation of lipoprotein lipase to modulate systemic triglyceride...... on the importance of sorting receptors in control of cellular and systemic lipoprotein metabolism and how altered trafficking pathways may represent a major risk factor for dyslipidemia and atherosclerosis in the human population....

  13. Lipoprotein heterogeneity in persons with Spinal Cord Injury: a model of prolonged sitting and restricted physical activity.

    Science.gov (United States)

    La Fountaine, Michael F; Cirnigliaro, Christopher M; Emmons, Racine R; Kirshblum, Steven C; Galea, Marinella; Spungen, Ann M; Bauman, William A

    2015-07-28

    Persons with spinal cord injury (SCI) often have low levels of physical activity, which predispose to increased adiposity and decreased high density lipoprotein cholesterol (HDL-C) concentrations, and, generally, normal low density lipoprotein cholesterol (LDL-C) concentrations. In spite of the mixed lipoprotein profile, the SCI population has been reported to have an elevated risk of cardiovascular-related morbidity and mortality. Nuclear magnetic resonance spectroscopy may permit a more precise quantification of lipoprotein particle (P) species, enabling a more accurate inference of risk for cardiovascular disease (CVD) in the SCI population. Fasting blood samples were obtained on 83 persons with chronic SCI and 62 able-bodied (AB) subjects. Fasting plasma insulin (FPI), triglycerides (TG), and P number and size of VLDL (very low density lipoprotein), LDL, and HDL subclasses were determined. AB and SCI subjects were stratified based on HDL-C (i.e., Low insulin resistance by the Lipoprotein-Insulin Resistance (LP-IR) score. In the SCI-Low group, the decreased number and reduced size of lipoprotein P were more prevalent and may be associated with increased waist circumference (i.e., abdominal adiposity), relatively elevated TG values (compared to the other subgroups), and an underlying subclinical state of insulin resistance. Prolonged sitting and restricted physical activity in individuals with SCI had the most profound effect on the HDL-C and its lipoprotein P subclasses, but not on LDL-C, however its P subclasses were also unfavorably affected but not to the same degree. The quantification of lipoprotein P characteristics may be a potent tool for the determination of risk for CVD in persons with SCI.

  14. Molecular Model of Plasma PAF Acetylhydrolase-Lipoprotein Association: Insights from the Structure.

    Science.gov (United States)

    Srinivasan, Prabhavathi; Bahnson, Brian J

    2010-03-08

    Plasma platelet-activating factor acetylhydrolase (PAF-AH), also called lipoprotein-associated phospholipase A₂ (Lp-PLA₂), is a group VIIA PLA₂ enzyme that catalyzes the hydrolysis of PAF and certain oxidized phospholipids. Although the role of PAF-AH as a pro- or anti-atherosclerotic enzyme is highly debated, several studies have shown it to be an independent marker of cardiovascular diseases. In humans the majority of plasma PAF-AH is bound to LDL and a smaller portion to HDL; the majority of the enzyme being associated with small dense LDL and VHDL-1 subclasses. Several studies suggest that the anti- or pro-atherosclerotic tendency of PAF-AH might be dependent on the type of lipoprotein it is associated with. Amino acid residues in PAF-AH necessary for binding to LDL and HDL have been identified. However our understanding of the interaction of PAF-AH with LDL and HDL is still incomplete. In this review we present an overview of what is already known about the interaction of PAF-AH with lipoprotein particles, and we pose questions that are yet to be answered. The recently solved crystal structure of PAF-AH, along with functional work done by others is used as a guide to develop a model of interaction of PAF-AH with lipoprotein particles.

  15. Molecular Model of Plasma PAF Acetylhydrolase-Lipoprotein Association: Insights from the Structure

    Directory of Open Access Journals (Sweden)

    Brian J. Bahnson

    2010-03-01

    Full Text Available Plasma platelet-activating factor acetylhydrolase (PAF-AH, also called lipoprotein-associated phospholipase A2 (Lp-PLA2, is a group VIIA PLA2 enzyme that catalyzes the hydrolysis of PAF and certain oxidized phospholipids. Although the role of PAF-AH as a pro- or anti-atherosclerotic enzyme is highly debated, several studies have shown it to be an independent marker of cardiovascular diseases. In humans the majority of plasma PAF-AH is bound to LDL and a smaller portion to HDL; the majority of the enzyme being associated with small dense LDL and VHDL-1 subclasses. Several studies suggest that the anti- or pro-atherosclerotic tendency of PAF-AH might be dependent on the type of lipoprotein it is associated with. Amino acid residues in PAF-AH necessary for binding to LDL and HDL have been identified. However our understanding of the interaction of PAF-AH with LDL and HDL is still incomplete. In this review we present an overview of what is already known about the interaction of PAF-AH with lipoprotein particles, and we pose questions that are yet to be answered. The recently solved crystal structure of PAF-AH, along with functional work done by others is used as a guide to develop a model of interaction of PAF-AH with lipoprotein particles.

  16. Analysis of individual lipoproteins and liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Robbins, D.L.; Keller, R.A.; Nolan, J.P. [and others

    1997-08-01

    We describe the application of single molecule detection (SMD) technologies for the analysis of natural (serum lipoproteins) and synthetic (liposomes) transport systems. The need for advanced analytical procedures of these complex and important systems is presented with the specific enhancements afforded by SMD with flowing sample streams. In contrast to bulk measurements which yield only average values, measurement of individual species allows creation of population histograms from heterogeneous samples. The data are acquired in minutes and the analysis requires relatively small sample quantities. Preliminary data are presented from the analysis of low density lipoprotein, and multilamellar and unilamellar vesicles.

  17. 21 CFR 862.1475 - Lipoprotein test system.

    Science.gov (United States)

    2010-04-01

    ... measure lipoprotein in serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases...

  18. Relationship among sera lipoprotein abnormalities in healthy ...

    African Journals Online (AJOL)

    Jane

    2011-08-29

    Aug 29, 2011 ... HOMA-IR (P = 0.03) in the case group as compared to the control group. We conclude that a family history of diabetic parents can lead to lipid parameters abnormalities and CVD risk factor via aggregation of inherited defected genes. Key words: Diabetes, oxidized-low density lipoprotein (LDL), Apo B100, ...

  19. Lipoprotein receptors in cultured bovine endothelial cells

    International Nuclear Information System (INIS)

    Struempfer, A.E.M.

    1983-07-01

    In this study, receptors that may be involved in the uptake of low density lipoproteins (LDL) and low density lipoproteins which have been modified by acetylation (AcLDL), were characterized. Aortic epithelial cells were used and a cell culture system which closely resembled the in vivo monolayer was established. Endothelial cell and lipoprotein interactions were examined by incubating the cells with 125 l-labelled lipoproteins under various conditions. The receptor affinity of bovine aortic endothelial cells was higher for AcLDL than that for LDL. Competition studies demonstrated that there were two distinct receptors for LDL and AcLDL on the endothelial cells. AcLDL did not compete with LDL for the LDL receptor, and conversely LDL did not compete with AcLDL for the AcLDL receptor. The receptor activities for LDL and AcLDL were examined as a function of culture age. Whereas the LDL receptor could be regulated, the AcLDL receptor was not as susceptible to regulation. Upon exposing endothelial cells for 72 h to either LDL or AcLDL, it was found that the total amount of cellular cholesterol increased by about 50%. However, the increase of total cholesterol was largely in the form of free cholesterol. This is in contrast to macrophages, where the increase in total cholesterol upon exposure to AcLDL is largely in the form cholesteryl esters

  20. Lipophorin Receptor: The Insect Lipoprotein Receptor

    Indian Academy of Sciences (India)

    IAS Admin

    physiology and develop- mental biology of silkworms, and use of silk in industrial applications. The low-density lipoprotein receptor (LDLR), one of the best characterized cell-surface receptors, mediates cholesterol ho- meostasis and other functions in mammals. The members of the LDLR superfamily are structurally related ...

  1. Lipophorin Receptor: The Insect Lipoprotein Receptor

    Indian Academy of Sciences (India)

    Permanent link: http://www.ias.ac.in/article/fulltext/reso/018/08/0748-0755. Keywords. Low-density lipoprotein receptor; lipophorin; lipophorin receptor; insects. Author Affiliations. G Ravikumar1 N B Vijayaprakash1. Seri-biotech Research Laboratory Central Silk Board Kodathi, Carmelaram Post Bangalore 560 035, India.

  2. Inactivation of Tm6sf2, a Gene Defective in Fatty Liver Disease, Impairs Lipidation but Not Secretion of Very Low Density Lipoproteins.

    Science.gov (United States)

    Smagris, Eriks; Gilyard, Shenise; BasuRay, Soumik; Cohen, Jonathan C; Hobbs, Helen H

    2016-05-13

    A missense mutation (E167K) in TM6SF2 (transmembrane 6 superfamily member 2), a polytopic protein of unknown function, is associated with the full spectrum of fatty liver disease. To investigate the role of TM6SF2 in hepatic triglyceride (TG) metabolism, we inactivated the gene in mice. Chronic inactivation of Tm6sf2 in mice is associated with hepatic steatosis, hypocholesterolemia, and transaminitis, thus recapitulating the phenotype observed in humans. No dietary challenge was required to elicit the phenotype. Immunocytochemical and cell fractionation studies revealed that TM6SF2 was present in the endoplasmic reticulum and Golgi complex, whereas the excess neutral lipids in the Tm6sf2(-/-) mice were located in lipid droplets. Plasma VLDL-TG levels were reduced in the KO animals due to a 3-fold decrease in VLDL-TG secretion rate without any associated reduction in hepatic apoB secretion. Both VLDL particle size and plasma cholesterol levels were significantly reduced in KO mice. Despite levels of TM6SF2 protein being 10-fold higher in the small intestine than in the liver, dietary lipid absorption was only modestly reduced in the KO mice. Our data, taken together, reveal that TM6SF2 is required to mobilize neutral lipids for VLDL assembly but is not required for secretion of apoB-containing lipoproteins. Despite TM6SF2 being located in the endoplasmic reticulum and Golgi complex, the lipids that accumulate in its absence reside in lipid droplets. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Role of the spinal cord NR2B-containing NMDA receptors in the development of neuropathic pain.

    Science.gov (United States)

    Qu, Xiao-Xiu; Cai, Jie; Li, Ming-Jia; Chi, Ye-Nan; Liao, Fei-Fei; Liu, Feng-Yu; Wan, You; Han, Ji-Sheng; Xing, Guo-Gang

    2009-02-01

    Activation of N-methyl-d-aspartate (NMDA) receptors in the spinal dorsal horn has been shown to be essential for the initiation of central sensitization and the hyperexcitability of dorsal horn neurons in chronic pain. However, whether the spinal NR2B-containing NMDA (NMDA-2B) receptors are involved still remains largely unclear. Using behavioral test and in vivo extracellular electrophysiological recording in L5 spinal nerve-ligated (SNL) neuropathic rats, we investigate the roles of spinal cord NMDA-2B receptors in the development of neuropathic pain. Our study showed that intrathecal (i.t.) injection of Ro 25-6981, a selective NMDA-2B receptor antagonist, had a dose-dependent anti-allodynic effect without causing motor dysfunction. Furthermore, i.t. application of another NMDA-2B receptor antagonist ifenprodil prior to SNL also significantly inhibited the mechanical allodynia but not the thermal hyperalgesia. These data suggest that NMDA-2B receptors at the spinal cord level play an important role in the development of neuropathic pain, especially at the early stage following nerve injury. In addition, spinal administration of Ro 25-6981 not only had a dose-dependent inhibitory effect on the C-fiber responses of dorsal horn wide dynamic range (WDR) neurons in both normal and SNL rats, but also significantly inhibited the long-term potentiation (LTP) in the C-fiber responses of WDR neurons induced by high-frequency stimulation (HFS) applied to the sciatic nerve. These results indicate that activation of the dorsal horn NMDA-2B receptors may be crucial for the spinal nociceptive synaptic transmission and for the development of long-lasting spinal hyperexcitability following nerve injury. In conclusion, the spinal cord NMDA-2B receptors play a role in the development of central sensitization and neuropathic pain via the induction of LTP in dorsal horn nociceptive synaptic transmission. Therefore, the spinal cord NMDA-2B receptor is likely to be a target for

  4. Genetic determinants of LDL, lipoprotein(a), triglyceride-rich lipoproteins and HDL: concordance and discordance with cardiovascular disease risk

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2011-01-01

    To evaluate whether new and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), triglyceride-rich lipoproteins, and HDL cholesterol associate with the risk of cardiovascular disease expected from the effect on lipoprotein levels. Concordance or discordance...

  5. Carotid intima media thickness is related positively to plasma pre beta-high density lipoproteins in non-diabetic subjects

    NARCIS (Netherlands)

    de Vries, Rindert; Perton, Frank G.; van Tol, Arie; Dullaart, Robin P. F.

    2012-01-01

    Background: Lipid-poor or lipid-free high density lipoprotein (HDL) particles, designated pre beta-HDL, stimulate removal of cell-derived cholesterol to the extracellular compartment, which is an initial step in the reverse cholesterol transport pathway. Pre beta-HDL levels may be elevated in

  6. Association of height and pubertal timing with lipoprotein subclass profile: exploring the role of genetic and environmental effects.

    Science.gov (United States)

    Jelenkovic, Aline; Bogl, Leonie H; Rose, Richard J; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Kaprio, Jaakko; Silventoinen, Karri

    2013-01-01

    Little is known about the relationship between growth and lipoprotein profile. We aimed to analyze common genetic and environmental factors in the association of height from late childhood to adulthood and pubertal timing with serum lipid and lipoprotein subclass profile. A longitudinal cohort of Finnish twin pairs (FinnTwin12) was analyzed using self-reported height at 11-12, 14, 17 years and measured stature at adult age (21-24 years). Data were available for 719 individual twins including 298 complete pairs. Serum lipids and lipoprotein subclasses were measured by proton nuclear magnetic resonance spectroscopy. Multivariate variance component models for twin data were fitted. Cholesky decomposition was used to partition the phenotypic covariation among traits into additive genetic and unique environmental correlations. In men, the strongest associations for both adult height and puberty were observed with total cholesterol, low-density lipoprotein cholesterol, intermediate-density lipoprotein cholesterol, and low-density lipoprotein particle subclasses (max. r = -0.19). In women, the magnitude of the correlations was weaker (max. r = -0.13). Few associations were detected between height during adolescence and adult lipid profile. Early onset of puberty was related to an adverse lipid profile, but delayed pubertal development in girls was associated with an unfavorable profile, as well. All associations were mediated mainly by additive genetic factors, but unique environmental effects cannot be disregarded. Early puberty and shorter adult height relate to higher concentrations of atherogenic lipids and lipoprotein particles in early adulthood. Common genetic effects behind these phenotypes substantially contribute to the observed associations. Copyright © 2013 Wiley Periodicals, Inc.

  7. Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Manfredi Rizzo

    2013-03-01

    Full Text Available Small, dense low density lipoprotein (sdLDL represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG, very low density lipoprotein (VLDL and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk.

  8. Fractionation of human serum lipoproteins and simultaneous enzymatic determination of cholesterol and triglycerides

    Energy Technology Data Exchange (ETDEWEB)

    Qureshi, Rashid Nazir [Polymer-Analysis Group, van' t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018WV Amsterdam (Netherlands); Kok, Wim Th., E-mail: W.Th.Kok@uva.nl [Polymer-Analysis Group, van' t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018WV Amsterdam (Netherlands); Schoenmakers, Peter J. [Polymer-Analysis Group, van' t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018WV Amsterdam (Netherlands)

    2009-11-03

    A method based on Asymmetric Flow Field-Flow Fractionation (AF4) was developed to separate different types of lipoproteins from human serum. The emphasis in the method optimization was on the possibilities to characterize the largest lipoprotein fractions (LDL and VLDL), which is usually not possible with the size-exclusion chromatography methods applied in routine analysis. Different channel geometries and flow programs were tested and compared. The use of a short fractionation channel was shown to give less sample dilution at the same fractionation power compared to a conventional, long channel. Different size selectivities were obtained with an exponential decay and a linear cross flow program. The ratio of the UV absorption signal to the light scattering signal was used to validate the relation between retention time and size of the fractionated particles. An experimental setup was developed for the simultaneous determination of the cholesterol and triglycerides distribution over the lipoprotein fractions, based on enzymatic reactions followed by UV detection at 500 nm. Coiled and knitted PTFE tubing reactors were compared. An improved peak sharpness and sensitivity were observed with the knitted tubing reactor. After optimization of the experimental conditions a satisfactory linearity and precision (2-3% rsd for cholesterol and 5-6% rsd for triglycerides) were obtained. Finally, serum samples, a pooled sample from healthy volunteers and samples of sepsis patients, were analyzed with the method developed. Lipoprotein fractionation and cholesterol and triglyceride distributions could be correlated with the clinical background of the samples.

  9. Increased transvascular lipoprotein transport in diabetes

    DEFF Research Database (Denmark)

    Jensen, Jan Skov; Feldt-Rasmussen, Bo; Borch-Johnsen, Knut

    2005-01-01

    with type 2 diabetes) and 42 healthy controls. All were randomly recruited. MAIN OUTCOME MEASURE: We used an in vivo method for measurement of transvascular transport of low-density lipoprotein (LDL). Autologous 131I-LDL was reinjected iv, and the 1-h fractional escape rate was taken as an index...... of transvascular transport. RESULTS: Transvascular LDL transport was 1.8 (1.6-2.0), 2.3 (2.0-2.6), and 2.6 (1.3-4.0)%/[h x (liter/m2)] in healthy controls, diabetic controls, and diabetes patients with systolic hypertension or albuminuria, respectively (P = 0.013; F = 4.5; df =2; ANOVA). These differences most......CONTEXT: Diabetes is associated with a highly increased risk of atherosclerosis, especially if hypertension or albuminuria is present. OBJECTIVE: We hypothesized that the increased transvascular lipoprotein transport in diabetes may be further accelerated if hypertension or albuminuria is present...

  10. Lipoprotein (a) Management: Lifestyle and Hormones.

    Science.gov (United States)

    Garcia-Rios, Antonio; Leon-Acuna, Ana; Lopez-Miranda, Jose; Perez-Martinez, Pablo

    2017-01-01

    Cardiovascular disease (CVD) continues to be the first cause of mortality in developed countries. Moreover, far from diminishing, the cardiovascular risk factors leading towards the development of CVD are on the rise. Therefore, the preventive and therapeutic management which is currently in place is clearly not enough to stop this pandemic. In this context, a major resurgence in interest in lipoprotein (a) [Lp(a)] has occurred in light of its association with CVD. This series aims to review the basic and clinical aspects of Lp(a) biology. Specifically, the present review considers the current situation regarding the influence of lifestyle, hormones and other physiological or pathological conditions on Lp(a) plasma concentrations which might mitigate the harmful effects of this lipoprotein. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Lipoprotein lipase deficiency with visceral xanthomas

    Energy Technology Data Exchange (ETDEWEB)

    Servaes, Sabah; Bellah, Richard [Department of Radiology, Philadelphia, PA (United States); Verma, Ritu [Department of Gastroenterology, Philadelphia, PA (United States); Pawel, Bruce [Department of Pathology, Philadelphia, PA (United States)

    2010-08-15

    Lipoprotein lipase deficiency (LLD) is a rare metabolic disorder that typically presents with skin xanthomas and pancreatitis in childhood. We report a case of LLD in an infant who presented with jaundice caused by a pancreatic head mass. Abdominal imaging also incidentally revealed hyperechoic renal masses caused by renal xanthomas. This appearance of the multiple abdominal masses makes this a unique infantile presentation of LLD. (orig.)

  12. Analyzing the molecular mechanism of lipoprotein localization in Brucella

    Science.gov (United States)

    Goolab, Shivani; Roth, Robyn L.; van Heerden, Henriette; Crampton, Michael C.

    2015-01-01

    Bacterial lipoproteins possess diverse structure and functionality, ranging from bacterial physiology to pathogenic processes. As such many lipoproteins, originating from Brucella are exploited as potential vaccines to countermeasure brucellosis infection in the host. These membrane proteins are translocated from the cytoplasm to the cell membrane where they are anchored peripherally by a multifaceted targeting mechanism. Although much research has focused on the identification and classification of Brucella lipoproteins and their potential use as vaccine candidates for the treatment of Brucellosis, the underlying route for the translocation of these lipoproteins to the outer surface of the Brucella (and other pathogens) outer membrane (OM) remains mostly unknown. This is partly due to the complexity of the organism and evasive tactics used to escape the host immune system, the variation in biological structure and activity of lipoproteins, combined with the complex nature of the translocation machinery. The biosynthetic pathway of Brucella lipoproteins involves a distinct secretion system aiding translocation from the cytoplasm, where they are modified by lipidation, sorted by the lipoprotein localization machinery pathway and thereafter equipped for export to the OM. Surface localized lipoproteins in Brucella may employ a lipoprotein flippase or the β-barrel assembly complex for translocation. This review provides an overview of the characterized Brucella OM proteins that form part of the OM, including a handful of other characterized bacterial lipoproteins and their mechanisms of translocation. Lipoprotein localization pathways in gram negative bacteria will be used as a model to identify gaps in Brucella lipoprotein localization and infer a potential pathway. Of particular interest are the dual topology lipoproteins identified in Escherichia coli and Haemophilus influenza. The localization and topology of these lipoproteins from other gram negative bacteria

  13. Analyzing the molecular mechanism of lipoprotein localization in Brucella.

    Science.gov (United States)

    Goolab, Shivani; Roth, Robyn L; van Heerden, Henriette; Crampton, Michael C

    2015-01-01

    Bacterial lipoproteins possess diverse structure and functionality, ranging from bacterial physiology to pathogenic processes. As such many lipoproteins, originating from Brucella are exploited as potential vaccines to countermeasure brucellosis infection in the host. These membrane proteins are translocated from the cytoplasm to the cell membrane where they are anchored peripherally by a multifaceted targeting mechanism. Although much research has focused on the identification and classification of Brucella lipoproteins and their potential use as vaccine candidates for the treatment of Brucellosis, the underlying route for the translocation of these lipoproteins to the outer surface of the Brucella (and other pathogens) outer membrane (OM) remains mostly unknown. This is partly due to the complexity of the organism and evasive tactics used to escape the host immune system, the variation in biological structure and activity of lipoproteins, combined with the complex nature of the translocation machinery. The biosynthetic pathway of Brucella lipoproteins involves a distinct secretion system aiding translocation from the cytoplasm, where they are modified by lipidation, sorted by the lipoprotein localization machinery pathway and thereafter equipped for export to the OM. Surface localized lipoproteins in Brucella may employ a lipoprotein flippase or the β-barrel assembly complex for translocation. This review provides an overview of the characterized Brucella OM proteins that form part of the OM, including a handful of other characterized bacterial lipoproteins and their mechanisms of translocation. Lipoprotein localization pathways in gram negative bacteria will be used as a model to identify gaps in Brucella lipoprotein localization and infer a potential pathway. Of particular interest are the dual topology lipoproteins identified in Escherichia coli and Haemophilus influenza. The localization and topology of these lipoproteins from other gram negative bacteria

  14. Immune Response to Lipoproteins in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Sonia Samson

    2012-01-01

    Full Text Available Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.

  15. Synthetic Nano-Low Density Lipoprotein as Targeted Drug DeliveryVehicle for Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Nikanjam, Mina; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Shu,Xiao; Budinger, Thomas F.; Forte, Trudy M.

    2006-06-14

    This paper discribes a synthetic low density lipoprotein(LDL) made by complexing a 29 amino acid that consists of a lipid bindingdomain and the LDL receptor binding domain with a lipid microemulsion.The nano-LDL particles were intermdiate in size between LDL and HDL andbound to LDL receptors on GBM brain tumor cells. Synthetic nano-LDLuptake by GBM cells was LDL receptor specific and dependent on cellreceptor number. It is suggested that these synthetic particles can serveas a delivery vehicle for hydophobic anti-tumor drugs by targeting theLDL receptor.

  16. Serum and urinary lipoproteins in the human nephrotic syndrome: evidence for renal catabolism of lipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Shore, V.G.; Forte, T.; Licht, H.; Lewis, S.B.

    1982-03-01

    The urinary excretion of lipoproteins and the possibility of catabolic alterations on glomerular filtration were investigated in four nephrotic subjects difering in etiology, serum lipoprotein profile, and 24 hr urinary output of protein and lipids. The apolipoproteins and lipoproteins of urine were compared with those of serum with respect to distribution profile, physical properties, and composition. As expected from molecular sieving effects during glomerular filtration, the urinary HDL were more abundant than the lower density lipoproteins even when the plasma LDL was elevated markedly. Intact apolipoproteins were not found in the concentrated urinary fraction isolated by ultrafiltration between the limits of 10/sup 4/ and 5 x 10/sup 4/ daltons. On the basis of immunoreactivity, gel electrophoresis, and amino acid composition, apolipoproteins B and AI are the major and minor proteins, respectively, of urinary LDL, and apo B is the major protein of the urinary IDL and VLDL. Apolipoproteins AI, AII, CI, CIII, and possibly AIV were isolated from the urinary HDL. As much as 20% of the protein moiety of the urinary HDL appeared to be large apolipoprotien fragments with molecular weights and isoelectric points similar to those of apo CII and apo CIII. The lower density classes of urinary lipoproteins also appeared to have lost apo E and apo C's and to have undergone partial proteolysis.

  17. Insulin Resistance Predicts Atherogenic Lipoprotein Profile in Nondiabetic Subjects

    Directory of Open Access Journals (Sweden)

    Flávia De C. Cartolano

    2017-01-01

    Full Text Available Background. Atherogenic diabetes is associated with an increased cardiovascular risk and mortality in diabetic individuals; however, the impact of insulin resistance (IR in lipid metabolism in preclinical stages is generally underreported. For that, we evaluated the capacity of IR to predict an atherogenic lipid subfraction profile. Methods. Complete clinical evaluation and biochemical analysis (lipid, glucose profile, LDL, and HDL subfractions and LDL phenotype and size were performed in 181 patients. The impact of IR as a predictor of atherogenic lipoproteins was tested by logistic regression analysis in raw and adjusted models. Results. HDL-C and Apo AI were significantly lower in individuals with IR. Individuals with IR had a higher percentage of small HDL particles, lower percentage in the larger ones, and reduced frequency of phenotype A (IR = 62%; non-IR = 83%. IR individuals had reduced probability to have large HDL (OR = 0.213; CI = 0.999–0.457 and had twice more chances to show increased small HDL (OR = 2.486; CI = 1.341–7.051. IR was a significant predictor of small LDL (OR = 3.075; CI = 1.341–7.051 and atherogenic phenotype (OR = 3.176; CI = 1.469–6.867. Conclusion. IR, previously DM2 diagnosis, is a strong predictor of quantitative and qualitative features of lipoproteins directly associated with an increased atherogenic risk.

  18. Correlation between the High Density Lipoprotein and its Subtypes in Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Fen Gao

    2016-05-01

    Full Text Available Background/Aims: To detect the changes of high density lipoprotein (HDL and its subtypes in serum of patients with coronary heart disease (CHD. Methods: 337 hospitalized patients were selected from our hospital during August, 2014 - January, 2015, and divided into CHD group (n = 190 and control group (n = 127. Lipoprint lipoprotein analyzer was used to classify low density lipoprotein (LDL particle size and its sub-components, as well as HDL particle size and its sub-components. The changes of the subtypes in patients with CHD were statistically analyzed. The possible mechanism was explored. Results: (1 Compared with the control group, the concentration of HDL in CHD patients reduced, HDLL significantly decreased (P S increased (P L had the most significant decreased; (3 HDL and all HDL subtypes were positively correlated with apolipoprotein A-I (apoA-I, of which, HDLL had the biggest correlation with apoA-I (P M had a maximum correlation with HDL (P Conclusion: HDL maturation disorders existed in the serum of CHD patients, HDLL may be protected factor for CHD, whose decrease was closely related wit the risk increase of CHD. The cardiovascular protection function of HDLL may be related with apoA-I content.

  19. Effect of apolipoprotein M on high density lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knock-out mice

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Jauhiainen, Matti; Moser, Markus

    2008-01-01

    To investigate the role of apoM in high density lipoprotein (HDL) metabolism and atherogenesis, we generated human apoM transgenic (apoM-Tg) and apoM-deficient (apoM(-/-)) mice. Plasma apoM was predominantly associated with 10-12-nm alpha-migrating HDL particles. Human apoM overexpression (11-fold......) increased plasma cholesterol concentration by 13-22%, whereas apoM deficiency decreased it by 17-21%. The size and charge of apoA-I-containing HDL in plasma were not changed in apoM-Tg or apoM(-/-) mice. However, in plasma incubated at 37 degrees C, lecithin:cholesterol acyltransferase-dependent conversion...... of alpha- to pre-alpha-migrating HDL was delayed in apoM-Tg mice. Moreover, lecithin: cholesterol acyltransferase-independent generation of pre-beta-migrating apoA-I-containing particles in plasma was increased in apoM-Tg mice (4.2 +/- 1.1%, p = 0.06) and decreased in apoM(-/-) mice (0.5 +/- 0.3%, p = 0...

  20. Nerve growth factor (NGF) and pro-NGF increase low-density lipoprotein (LDL) receptors in neuronal cells partly by different mechanisms: role of LDL in neurite outgrowth.

    Science.gov (United States)

    Do, Hai Thi; Bruelle, Céline; Pham, Dan Duc; Jauhiainen, Matti; Eriksson, Ove; Korhonen, Laura T; Lindholm, Dan

    2016-01-01

    Low-density lipoprotein receptors (LDLRs) mediate the uptake of lipoprotein particles into cells, as studied mainly in peripheral tissues. Here, we show that nerve growth factor (NGF) increases LDLR levels in PC6.3 cells and in cultured septal neurons from embryonic rat brain. Study of the mechanisms showed that NGF enhanced transcription of the LDLR gene, acting mainly via Tropomyosin receptor kinase A receptors. Simvastatin, a cholesterol-lowering drug, also increased the LDLR expression in PC6.3 cells. In addition, pro-NGF and pro-brain-derived neurotrophic factor, acting via the p75 neurotrophin receptor (p75NTR) also increased LDLRs. We further observed that Myosin Regulatory Light Chain-Interacting Protein/Inducible Degrader of the LDLR (Mylip/Idol) was down-regulated by pro-NGF, whereas the other LDLR regulator, proprotein convertase subtilisin kexin 9 (PCSK9) was not significantly changed. On the functional side, NGF and pro-NGF increased lipoprotein uptake by neuronal cells as shown using diacetyl-labeled LDL. The addition of serum-derived lipoprotein particles in conjunction with NGF or simvastatin enhanced neurite outgrowth. Collectively, these results show that NGF and simvastatin are able to stimulate lipoprotein uptake by neurons with a positive effect on neurite outgrowth. Increases in LDLRs and lipoprotein particles in neurons could play a functional role during brain development, in neuroregeneration and after brain injuries. Nerve growth factor (NGF) and pro-NGF induce the expression of low-density lipoprotein receptors (LDLRs) in neuronal cells leading to increased LDLR levels. Pro-NGF also down-regulated myosin regulatory light chain-interacting protein/inducible degrader of the LDLR (Mylip/Idol) that is involved in the degradation of LDLRs. NGF acts mainly via Tropomyosin receptor kinase A (TrkA) receptors, whereas pro-NGF stimulates p75 neurotrophin receptor (p75NTR). Elevated LDLRs upon NGF and pro-NGF treatments enhanced lipoprotein uptake

  1. Estradiol-induced increase in the magnitude of long-term potentiation is prevented by blocking NR2B-containing receptors.

    Science.gov (United States)

    Smith, Caroline C; McMahon, Lori L

    2006-08-16

    Estradiol, through activation of genomic estrogen receptors, induces changes in synaptic morphology and function in hippocampus, a brain region important for memory acquisition. Specifically, this hormone increases CA1 pyramidal cell dendritic spine density, NMDA receptor (NMDAR)-mediated transmission, and the magnitude of long-term potentiation (LTP) at CA3-CA1 synapses. We recently reported that the estradiol-induced increase in LTP magnitude occurs only when there is a simultaneous increase in the fractional contribution of NMDAR-mediated transmission relative to AMPA receptor transmission, suggesting a direct role for the increase in NMDAR transmission to the heightened LTP magnitude. Estradiol has been shown to increase expression of the NMDAR subunit NR2B, but whether this translates into an increase in function of NR2B-containing receptors remains to be determined. Here we show that not only is the estradiol-induced increase in NMDAR transmission mediated by NR2B-containing receptors, but blocking these receptors using RO25-6981 [R-(R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine propranol] (0.5 microM), an NR2B selective antagonist, prevents the estradiol-induced increase in LTP magnitude. Thus, our data show a causal link between the estradiol-induced increase in transmission mediated by NR2B-containing NMDARs and the increase in LTP magnitude.

  2. Exploring neuroprotective potential of Withania somnifera phytochemicals by inhibition of GluN2B-containing NMDA receptors: An in silico study.

    Science.gov (United States)

    Kumar, Gaurav; Patnaik, Ranjana

    2016-07-01

    N-methyl-d-aspartate receptors (NMDARs) mediated excitotoxicity has been implicated in multi-neurodegenerative diseases. Due to lack of efficacy and adverse effects of NMDA receptor antagonists, search for herbal remedies that may act as therapeutic agents is an active area of research to combat these diseases. Withania somnifera (WS) is being used for centuries as a nerve tonic and Nootropic agents. The present study targets the in silico evaluation of the neuroprotective efficacy of W. somnifera phytochemicals by inhibition of NMDA receptor-mediated excitotoxicity through allosteric inhibition of the GluN2B containing NMDARs. We predict Blood Brain Barrier (BBB) penetration, mutagenicity, drug-likeness and Human Intestinal Absorption properties of 25 WS phytochemicals. Further, molecular docking was performed to know whether these phytochemicals inhibit the GluN2B containing NMDARs or not. The results suggest that Anaferine, Beta-Sitosterol, Withaferin A, Withanolide A, Withanolide B and Withanolide D inhibit GluN2B containing NMDARs through allosteric mode similar to the well-known selective antagonist Ifenprodil. These phytochemicals have potential as an essentially useful oral drug to counter NMDARs mediated excitotoxicity and to treat multi-neurodegenerative diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Intercorrelations of lipoprotein subfractions and their covariation with lifestyle factors in healthy men

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Eckoldt, Joachim; Winkler, Karl

    2014-01-01

    So far, little is known about the effect of nutrition and lifestyle on the composition of circulating lipoprotein subfractions. In the current study, we measured the correlations among physical activity, nutrient intake, smoking, body-mass index (BMI), and age with the concentration of triglyceri......So far, little is known about the effect of nutrition and lifestyle on the composition of circulating lipoprotein subfractions. In the current study, we measured the correlations among physical activity, nutrient intake, smoking, body-mass index (BMI), and age with the concentration...... of triglycerides, cholesterol, phospholipids, and apolipoproteins (ApoA1, ApoA2 and ApoB) in subfractions of LDL and HDL in 265 healthy working men. Concentrations of cholesterol, phospholipids, and ApoB in small, dense atherogenic LDL particles (sdLDL) correlated negatively (p

  4. Apolipoprotein(a) phenotypes and lipoprotein(a) concentrations in patients with hyperthyroidism

    DEFF Research Database (Denmark)

    Klausen, I C; Hegedüs, L; Hansen, P S

    1995-01-01

    Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle in which apolipoprotein B-100 (apoB) is attached to a glycoprotein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma...... and determined apo(a) phenotypes in 31 patients with hyperthyroidism, before and after the patients had become euthyroid by treatment. The mean concentration of LDL cholesterol rose from 2.67 to 3.88 mmol/l (P ....01) and in patients with low molecular weight apo(a) phenotypes (n = 16; P LDL cholesterol and apoB in untreated hyperthyroidism may result from increased LDL receptor activity. The increase in Lp(a) levels were not correlated...

  5. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality

    DEFF Research Database (Denmark)

    (Tybjaerg-Hansen, A.) The Fibrinogen Studies Collaboration.The Copenhagen City Heart Study; Tybjærg-Hansen, Anne

    2009-01-01

    CONTEXT: Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationship of Lp(a) concentration with risk of major vascular...... searches of reference lists, and discussion with collaborators. DATA EXTRACTION: Individual records were provided for each of 126,634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22,076 first-ever fatal or nonfatal vascular disease outcomes or nonvascular deaths...... were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta...

  6. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality

    DEFF Research Database (Denmark)

    (Tybjaerg-Hansen, A.) The Fibrinogen Studies Collaboration.The Copenhagen City Heart Study; Tybjærg-Hansen, Anne

    2009-01-01

    CONTEXT: Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationship of Lp(a) concentration with risk of major vascular...... were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis...... broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95% confidence interval [CI], 5.4-5.9) per 1000 person-years and 4.4 (95% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted...

  7. High Density Lipoprotein and it's Dysfunction.

    Science.gov (United States)

    Eren, Esin; Yilmaz, Necat; Aydin, Ozgur

    2012-01-01

    Plasma high-density lipoprotein cholesterol(HDL-C) levels do not predict functionality and composition of high-density lipoprotein(HDL). Traditionally, keeping levels of low-density lipoprotein cholesterol(LDL-C) down and HDL-C up have been the goal of patients to prevent atherosclerosis that can lead to coronary vascular disease(CVD). People think about the HDL present in their cholesterol test, but not about its functional capability. Up to 65% of cardiovascular death cannot be prevented by putative LDL-C lowering agents. It well explains the strong interest in HDL increasing strategies. However, recent studies have questioned the good in using drugs to increase level of HDL. While raising HDL is a theoretically attractive target, the optimal approach remains uncertain. The attention has turned to the quality, rather than the quantity, of HDL-C. An alternative to elevations in HDL involves strategies to enhance HDL functionality. The situation poses an opportunity for clinical chemists to take the lead in the development and validation of such biomarkers. The best known function of HDL is the capacity to promote cellular cholesterol efflux from peripheral cells and deliver cholesterol to the liver for excretion, thereby playing a key role in reverse cholesterol transport (RCT). The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High antioxidant and anti-inflammatory activities of HDL are associated with protection from CVD.This review addresses the current state of knowledge regarding assays of HDL functions and their relationship to CVD. HDL as a therapeutic target is the new frontier with huge potential for positive public health implications.

  8. Lipids and lipoprotein subfractions in women with PCOS: relationship to metabolic and endocrine parameters.

    Science.gov (United States)

    Pirwany, I R; Fleming, R; Greer, I A; Packard, C J; Sattar, N

    2001-04-01

    Women with polycystic ovary syndrome (PCOS) exhibit an abnormal lipoprotein profile, characterized by raised concentrations of plasma triglyceride, marginally elevated low density lipoprotein (LDL)-cholesterol, and reduced high density lipoprotein (HDL)-cholesterol. However, a normal LDL-cholesterol level may be misleading since LDL exists as subpopulations of particles differing in size and atherogenic potential. Smaller LDL particles are more atherogenic and high concentrations often occur in association with elevated circulating triglyceride concentrations (but frequently normal total LDL-cholesterol), increased hepatic lipase activity (HL) and insulin resistance. Information on LDL subclasses and HL activity in women with PCOS is sparse. The aim of this study was to determine the concentrations of small, dense LDL (LDL-III) in women with PCOS relative to body mass index (BMI)-matched controls. We also examined the association of lipoprotein subfraction concentrations with endogenous sex hormone concentrations, since existing literature suggested that androgens up-regulate and oestrogens down-regulate HL activity, a key determinant of LDL subfraction distribution. Cross sectional study. Fifty-two women with oligomenorrhoea and polycystic ovaries determined by ultrasound and BMI matched women with normal menstrual rhythm (NMR) and normal ovarian appearances (n = 14) were recruited from gynaecology clinics. Anthropometric data and fasting blood samples were obtained for metabolic, hormonal and LDL subfraction estimation and a heparin provocation test was used to estimate HL activity. Subjects with PCOS demonstrated higher waist:hip ratio (WHR), testosterone, triglyceride, VLDL-cholesterol concentrations, and HL activity (P fat distribution (waist circumference or WHR) and fasting insulin concentration. Serum testosterone concentration was not associated either in univariate or multivariate analysis with any of the measured lipid, lipoprotein or subfraction

  9. Serum Lipoprotein Changes in Dogs with Renal Disease

    OpenAIRE

    Behling?Kelly, E.

    2014-01-01

    Background People with renal disease develop a dyslipidemia that contributes to progression of renal injury and development of cardiovascular disease. Lipoproteins in dogs with renal disease have not been investigated. Hypothesis Dogs with chronic kidney disease (CKD) have dyslipidemia characterized by increased lower density lipoproteins and decreased high?density lipoproteins (HDLs). The degree of dyslipidemia is positively correlated with severity of disease, as reflected by serum creatini...

  10. Sex differences in the associations of visceral adiposity, HOMA-IR, and BMI with lipoprotein subclass analysis in obese adolescents

    Science.gov (United States)

    Hatch-Stein, Jacquelyn A; Kelly, Andrea; Gidding, Samuel S; Zemel, Babette S; Magge, Sheela N

    2016-01-01

    Background The relationship of lipoprotein particle subclasses to visceral adipose tissue area (VAT-area) in obese children has not been examined previously. Objectives The study aims were to compare the relationships of VAT-area, homeostatic model assessment of insulin resistance (HOMA-IR), and body mass index (BMI) with lipids and lipoprotein subclasses in obese adolescents, and to determine if these relationships vary by sex. Methods This cross-sectional study of obese adolescents (BMI≥95th percentile), ages 12-18y, measured VAT-area by dual energy x-ray absorptiometry (DXA), BMI, fasting lipids, lipoprotein subclasses, and HOMA-IR. Linear regression models evaluated the associations of VAT-area, HOMA-IR, and BMI with lipid cardiometabolic risk factors. Sex-stratified analyses further explored these associations. Results Included were 127 adolescents (age=14.4±1.5 years; 53.5% female; 88.2% African-American), mean BMI=34.0±5.1 kg/m2. VAT-area was negatively associated with LDL particle (−P) size (β=−0.28, p=0.0001), HDL-P size (β=−0.33, pHOMA-IR, and BMI associations were compared, VAT-area had the strongest associations with most of the lipoprotein subclasses. After sex-stratification, the associations of VAT-area with HDL cholesterol, LDL-P size, and large LDL-P concentration were significant only for females (all pHOMA-IR and BMI, VAT-area had the strongest associations with most lipoprotein subclasses. The relationships between VAT-area and certain lipoprotein subclasses are significantly different in males versus females. PMID:27578105

  11. The causal effects of alcohol on lipoprotein subfraction and triglyceride levels using a Mendelian randomization analysis: The Nagahama study.

    Science.gov (United States)

    Tabara, Yasuharu; Arai, Hidenori; Hirao, Yuhko; Takahashi, Yoshimitsu; Setoh, Kazuya; Kawaguchi, Takahisa; Kosugi, Shinji; Ito, Yasuki; Nakayama, Takeo; Matsuda, Fumihiko

    2017-02-01

    Light-to-moderate alcohol consumption may increase circulating high-density lipoprotein cholesterol (HDL-C) levels and decrease low-density lipoprotein cholesterol (LDL-C) levels. However, the effect of alcohol on biologically important lipoprotein subfractions remains largely unknown. Here we aimed to clarify the effects of alcohol on lipoprotein subfractions using a Mendelian randomization analysis. The study subjects consisted of 8364 general Japanese individuals. The rs671 polymorphism in aldehyde dehydrogenase 2 gene, a rate-controlling enzyme of alcohol metabolism, was used as an instrumental variable. Lipoprotein subfractions were measured by a homogeneous assay. The biologically active *1 allele of the ALDH2 genotype was strongly associated with alcohol consumption in men (p Alcohol may increase HDL-C levels irrespective of the particle size. Moreover, alcohol may decrease the total LDL-C, although the proportion of atherogenic small-dense LDL-C increased partially due to a potential inter-relationship with decreased triglyceride levels. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Outer membrane lipoprotein biogenesis: Lol is not the end.

    Science.gov (United States)

    Konovalova, Anna; Silhavy, Thomas J

    2015-10-05

    Bacterial lipoproteins are lipid-anchored proteins that contain acyl groups covalently attached to the N-terminal cysteine residue of the mature protein. Lipoproteins are synthesized in precursor form with an N-terminal signal sequence (SS) that targets translocation across the cytoplasmic or inner membrane (IM). Lipid modification and SS processing take place at the periplasmic face of the IM. Outer membrane (OM) lipoproteins take the localization of lipoproteins (Lol) export pathway, which ends with the insertion of the N-terminal lipid moiety into the inner leaflet of the OM. For many lipoproteins, the biogenesis pathway ends here. We provide examples of lipoproteins that adopt complex topologies in the OM that include transmembrane and surface-exposed domains. Biogenesis of such lipoproteins requires additional steps beyond the Lol pathway. In at least one case, lipoprotein sequences reach the cell surface by being threaded through the lumen of a beta-barrel protein in an assembly reaction that requires the heteropentomeric Bam complex. The inability to predict surface exposure reinforces the importance of experimental verification of lipoprotein topology and we will discuss some of the methods used to study OM protein topology. © 2015 The Author(s).

  13. Vitamin D is associated with atheroprotective high-density lipoprotein profile in postmenopausal women

    Science.gov (United States)

    Kazlauskaite, Rasa; Powell, Lynda H.; Mandapakala, Chaitanya; Cursio, John F.; Avery, Elizabeth F.; Calvin, James

    2012-01-01

    BACKGROUND Low vitamin D has been associated with low levels of high-density lipoprotein (HDL) cholesterol, a marker of coronary risk. Whether atheroprotective HDL particle composition accounts for this association and whether fat affects this association is not known. OBJECTIVE To explore the association between HDL particle composition and 25-hydroxy vitamin D (25[OH]D) in post-menopausal women. METHODS Vitamin D levels and lipoprotein composition were assessed in fasting blood samples of apparently healthy women from a diverse Chicago community. Visceral (VAT) and subcutaneous (SAT) abdominal fat area were assessed using computed tomography. Total body fat mass was measured by dual-energy X-ray absorptiometry. RESULTS We enrolled 78 women (50% black; 50% white), age 48 to 64 years, all of whom were participants in a longitudinal study of fat patterning. They had a mean 25[OH]D of 31 ± 15 µg/L, HDL cholesterol 57 ± 11 mg/dL, and large HDL particle subclass 8.6 ± 3.4 µmol/L. In a multivariable-adjusted regression model, each 5 µg/L higher 25[OH]D predicted 0.57 µmol/L (95%CI 0.20–0.95) higher large HDL particles, independent of race, season, and total HDL particle concentration. This association was only partially confounded by total body fat mass (0.49, 95%CI 0.10–0.89), SAT (0.50, 95%CI 0.11–0.90), or VAT (0.37, 95%CI 0.01–0.74). Age did not significantly influence the strength of associations. CONCLUSIONS Higher 25[OH]D levels are associated with large HDL particles. This association is stronger than that of HDL cholesterol and only partially confounded by body fat. Theoretically, vitamin D may protect against cardiovascular risk by promoting formation of large HDL particles, affecting reverse cholesterol transport. PMID:21122638

  14. Acrolein impairs the cholesterol transport functions of high density lipoproteins.

    Science.gov (United States)

    Chadwick, Alexandra C; Holme, Rebecca L; Chen, Yiliang; Thomas, Michael J; Sorci-Thomas, Mary G; Silverstein, Roy L; Pritchard, Kirkwood A; Sahoo, Daisy

    2015-01-01

    High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway.

  15. Olive oil phenolic compounds and high-density lipoprotein function.

    Science.gov (United States)

    Hernáez, Alvaro; Farràs, Marta; Fitó, Montserrat

    2016-02-01

    The functional capacities of high-density lipoproteins (HDLs) reflect the physiological role of the particle better than the quantity of HDL cholesterol. Owing to its phenolic compounds, the consumption of virgin olive oil has emerged as a promising therapy to promote these capacities. This review highlights the human studies that explain these benefits and explores some possible mechanisms. The consumption of olive oil phenolic compounds increased the ability of HDLs to pick up cholesterol excess in peripheral cells (the cholesterol efflux capacity). Olive oil phenolic compounds have also been shown to improve HDL antioxidant capacities and some anti-inflammatory traits. These changes respond to an improvement of HDL oxidative status and composition. Novel strategies to increase HDL functional capacities are in demand from clinicians. The attainment of a fully-functional HDL through dietary or lifestyle changes is a priority in cardiovascular research. Within this context, the consumption of virgin olive oil, because of its phenolic compounds, may be a relevant protective approach. Further studies in large-scale, randomized controlled trials are, however, required to confirm these effects in HDL functionality.

  16. The usefulness of total cholesterol and high density lipoprotein ...

    African Journals Online (AJOL)

    Objective: To determine the usefulness of total cholesterol/high-density lipoprotein cholesterol and/or highdensity lipoprotein cholesterol/total cholesterol ratios in the interpretation of lipid profile result in clinical practice. Methods: This is a prospective case-control study involving 109 diabetics, 98 diabetic hypertensives, 102 ...

  17. Redefining the essential trafficking pathway for outer membrane lipoproteins

    Science.gov (United States)

    Grabowicz, Marcin; Silhavy, Thomas J.

    2017-01-01

    The outer membrane (OM) of Gram-negative bacteria is a permeability barrier and an intrinsic antibiotic resistance factor. Lipoproteins are OM components that function in cell wall synthesis, diverse secretion systems, and antibiotic efflux pumps. Moreover, each of the essential OM machines that assemble the barrier requires one or more lipoproteins. This dependence is thought to explain the essentiality of the periplasmic chaperone LolA and its OM receptor LolB that traffic lipoproteins to the OM. However, we show that in strains lacking substrates that are toxic when mislocalized, both LolA and LolB can be completely bypassed by activating an envelope stress response without compromising trafficking of essential lipoproteins. We identify the Cpx stress response as a monitor of lipoprotein trafficking tasked with protecting the cell from mislocalized lipoproteins. Moreover, our findings reveal that an alternate trafficking pathway exists that can, under certain conditions, bypass the functions of LolA and LolB, implying that these proteins do not perform any truly essential mechanistic steps in lipoprotein trafficking. Instead, these proteins’ key function is to prevent lethal accumulation of mislocalized lipoproteins. PMID:28416660

  18. Redefining the essential trafficking pathway for outer membrane lipoproteins.

    Science.gov (United States)

    Grabowicz, Marcin; Silhavy, Thomas J

    2017-05-02

    The outer membrane (OM) of Gram-negative bacteria is a permeability barrier and an intrinsic antibiotic resistance factor. Lipoproteins are OM components that function in cell wall synthesis, diverse secretion systems, and antibiotic efflux pumps. Moreover, each of the essential OM machines that assemble the barrier requires one or more lipoproteins. This dependence is thought to explain the essentiality of the periplasmic chaperone LolA and its OM receptor LolB that traffic lipoproteins to the OM. However, we show that in strains lacking substrates that are toxic when mislocalized, both LolA and LolB can be completely bypassed by activating an envelope stress response without compromising trafficking of essential lipoproteins. We identify the Cpx stress response as a monitor of lipoprotein trafficking tasked with protecting the cell from mislocalized lipoproteins. Moreover, our findings reveal that an alternate trafficking pathway exists that can, under certain conditions, bypass the functions of LolA and LolB, implying that these proteins do not perform any truly essential mechanistic steps in lipoprotein trafficking. Instead, these proteins' key function is to prevent lethal accumulation of mislocalized lipoproteins.

  19. Extreme lipoprotein(a) levels and improved cardiovascular risk prediction

    DEFF Research Database (Denmark)

    Kamstrup, Pia R; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2013-01-01

    The study tested whether extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes improve myocardial infarction (MI) and coronary heart disease (CHD) risk prediction beyond conventional risk factors.......The study tested whether extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes improve myocardial infarction (MI) and coronary heart disease (CHD) risk prediction beyond conventional risk factors....

  20. Lipoprotein lipase gene variants: Association with acute myocardial ...

    African Journals Online (AJOL)

    Background: Studies showed that lipid metabolism disorders are significant risk factors for myocardial infarction and coronary artery disease (CAD). Therefore, genes involved in lipid and lipoprotein metabolism pathways such as lipoprotein lipase (LPL), are proper candidates for susceptibility to CAD. Aim: To investigate the ...

  1. Effect of Ascorbic Acid on Lipoprotein Lipase Activity | Kotze | South ...

    African Journals Online (AJOL)

    Baboons kept on hypovitaminotic C diets, but without clinical signs of scurvy, had significantly higher heart muscle lipoprotein lipase activity than baboons on vitamin C 34 mg/kg body mass/day. When the serum vitamin C levels were above 0,35 mg/100 ml the heart muscle lipoprotein lipase was repressed. Serum vitamin C ...

  2. Mendelian Disorders of High-Density Lipoprotein Metabolism

    NARCIS (Netherlands)

    Oldoni, Federico; Sinke, Richard J.; Kuivenhoven, Jan Albert

    2014-01-01

    High-density lipoproteins (HDLs) are a highly heterogeneous and dynamic group of the smallest and densest lipoproteins present in the circulation. This review provides the current molecular insight into HDL metabolism led by articles describing mutations in genes that have a large affect on HDL

  3. DMPD: Lipoprotein trafficking in vascular cells. Molecular Trojan horses and cellularsaboteurs. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 9287290 Lipoprotein trafficking in vascular cells. Molecular Trojan horses and cell...ml) Show Lipoprotein trafficking in vascular cells. Molecular Trojan horses and cellularsaboteurs. PubmedID ...9287290 Title Lipoprotein trafficking in vascular cells. Molecular Trojan horses

  4. Prediction of lipoprotein signal peptides in Gram-negative bacteria

    DEFF Research Database (Denmark)

    Juncker, Agnieszka; Willenbrock, Hanni; Von Heijne, G.

    2003-01-01

    A method to predict lipoprotein signal peptides in Gram-negative Eubacteria, LipoP, has been developed. The hidden Markov model (HMM) was able to distinguish between lipoproteins (SPaseII-cleaved proteins), SPaseI-cleaved proteins, cytoplasmic proteins, and transmembrane proteins. This predictor...... was able to predict 96.8% of the lipoproteins correctly with only 0.3% false positives in a set of SPaseI-cleaved, cytoplasmic, and transmembrane proteins. The results obtained were significantly better than those of previously developed methods. Even though Gram-positive lipoprotein signal peptides differ...... from Gram-negatives, the HMM was able to identify 92.9% of the lipoproteins included in a Gram-positive test set. A genome search was carried out for 12 Gram-negative genomes and one Gram-positive genome. The results for Escherichia coli K12 were compared with new experimental data, and the predictions...

  5. Nanotechnology for Synthetic High Density Lipoproteins

    Science.gov (United States)

    Luthi, Andrea J.; Patel, Pinal C.; Ko, Caroline H.; Mutharasan, R. Kannan; Mirkin, Chad A.; Thaxton, C. Shad

    2014-01-01

    Atherosclerosis is the disease mechanism responsible for coronary heart disease (CHD), the leading cause of death worldwide. One strategy to combat atherosclerosis is to increase the amount of circulating high density lipoproteins (HDL), which transport cholesterol from peripheral tissues to the liver for excretion. The process, known as reverse cholesterol transport, is thought to be one of the main reasons for the significant inverse correlation observed between HDL blood levels and the development of CHD. This article highlights the most common strategies for treating atherosclerosis using HDL. We further detail potential treatment opportunities that utilize nanotechnology to increase the amount of HDL in circulation. The synthesis of biomimetic HDL nanostructures that replicate the chemical and physical properties of natural HDL provides novel materials for investigating the structure-function relationships of HDL and for potential new therapeutics to combat CHD. PMID:21087901

  6. Effect of high density lipoproteins on permeability of rabbit aorta to low density lipoproteins

    International Nuclear Information System (INIS)

    Klimov, A.N.; Popov, V.A.; Nagornev, V.A.; Pleskov, V.M.

    1985-01-01

    A study was made on the effect of high density lipoproteins (HDL) on the permeability of rabbit aorta to low density lipoproteins (LDL) after intravenous administration of human HDL and human ( 125 I)LDL to normal and hypercholesterolemic rabbits. Evaluation of radioactivity in plasma and aorta has shown that the administration of a large dose of HDL decreased the aorta permeability rate for ( 125 I)LDL on an average by 19% in normal rabbits, and by 45% in rabbits with moderate hypercholesterolemia. A historadiographic study showed that HDL also decreased the vessel wall permeability to ( 125 I)LDL in normal and particularly in hypercholesterolemic animals. The suggestion was made that HDL at very high molar concentration can hamper LDL transportation through the intact endothelial layer into the intima due to the ability of HDL to compete with LDL in sites of low affinity on the surface of endothelial cells. (author)

  7. Comparison of assessment techniques: plasma lipid and lipoproteins related to the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Davy Kevin P

    2006-01-01

    Full Text Available Abstract Background The purpose of this investigation was to determine the influence of analytical method on reported concentrations of plasma lipids and lipoproteins, and to determine if there are clinical implications of any potential differences on identification of the metabolic syndrome dyslipidemia, CVD risk stratification and classification of LDL subclass phenotype. Results Plasma triglyceride (TG concentrations were 1.09 ± 0.06 and 1.17 ± 0.06 mmol/L and plasma high density lipoprotein cholesterol (HDL-C concentrations were 1.09 ± 0.03 vs 1.19 ± 0.03 mmol/L (both p Conclusion Different plasma lipid and lipoprotein analytical techniques yield results which are highly correlated, yet significantly different, which suggests a consistent measurement difference. This difference has clinical implications, in that the proportion of individuals identified as meeting the metabolic syndrome dyslipidemia criteria, "at risk" based upon apo B or LDL particle number, and the LDL pattern B phenotype will differ based upon choice of analytical method.

  8. PLTP activity in premenopausal women. Relationship with lipoprotein lipase, HDL, LDL, body fat, and insulin resistance.

    Science.gov (United States)

    Murdoch, S J; Carr, M C; Hokanson, J E; Brunzell, J D; Albers, J J

    2000-02-01

    Plasma phospholipid transfer protein (PLTP) is thought to play a major role in the facilitated transfer of phospholipids between lipoproteins and in the modulation of high density lipoprotein (HDL) particle size and composition. However, little has been reported concerning the relationships of PLTP with plasma lipoprotein parameters, lipolytic enzymes, body fat distribution, insulin, and glucose in normolipidemic individuals, particularly females. In the present study, 50 normolipidemic healthy premenopausal females were investigated. The relationships between the plasma PLTP activity and selected variables were assessed. PLTP activity was significantly and positively correlated with low density lipoprotein (LDL) cholesterol (r(s) = 0.53), apoB (r(s) = 0.44), glucose (r(s) = 0.40), HDL cholesterol (r(s) = 0.38), HDL(3) cholesterol (r(s) = 0.37), lipoprotein lipase activity (r(s) = 0.36), insulin (r(s) = 0.33), subcutaneous abdominal fat (r(s) = 0.36), intra-abdominal fat (r(s) = 0.29), and body mass index (r(s) = 0.29). HDL(2) cholesterol, triglyceride, and hepatic lipase were not significantly related to PLTP activity. As HDL(2) can be decreased by hepatic lipase and hepatic lipase is increased in obesity with increasing intra-abdominal fat, the participants were divided into sub-groups of non-obese (n = 35) and obese (n = 15) individuals and the correlation of PLTP with HDL(2) cholesterol was re-examined. In the non-obese subjects, HDL(2) cholesterol was found to be significantly and positively related to PLTP activity (r(s) = 0.44). Adjustment of the HDL(2) values for the effect of hepatic lipase activity resulted in a significant positive correlation between PLTP and HDL(2) (r(s) = 0.41), indicating that the strength of the relationship between PLTP activity and HDL(2) can be reduced by the opposing effect of hepatic lipase on HDL(2) concentrations. We conclude that PLTP-facilitated lipid transfer activity is related to HDL and LDL metabolism, as well as

  9. The fibrate drug gemfibrozil disrupts lipoprotein metabolism in rainbow trout

    International Nuclear Information System (INIS)

    Prindiville, John S.; Mennigen, Jan A.; Zamora, Jake M.; Moon, Thomas W.; Weber, Jean-Michel

    2011-01-01

    Gemfibrozil (GEM) is a fibrate drug consistently found in effluents from sewage treatment plants. This study characterizes the pharmacological effects of GEM on the plasma lipoproteins of rainbow trout (Oncorhynchus mykiss). Our goals were to quantify the impact of the drug on: 1) lipid constituents of lipoproteins (phospholipids (PL), triacylglycerol (TAG), and cholesterol), 2) lipoprotein classes (high, low and very low density lipoproteins), and 3) fatty acid composition of lipoproteins. Potential mechanisms of GEM action were investigated by measuring lipoprotein lipase activity (LPL) and the hepatic gene expression of LPL and of the peroxisome proliferator-activated receptor (PPAR) α, β, and γ isoforms. GEM treatment resulted in decreased plasma lipoprotein levels (- 29%) and a reduced size of all lipoprotein classes (lower PL:TAG ratios). However, the increase in HDL-cholesterol elicited by GEM in humans failed to be observed in trout. Therefore, HDL-cholesterol cannot be used to assess the impact of the drug on fish. GEM also modified lipoprotein composition by reducing the abundance of long-chain n-3 fatty acids, thereby potentially reducing the nutritional quality of exposed fish. The relative gene expression of LPL was increased, but the activity of the enzyme was not, and we found no evidence for the activation of PPAR pathways. The depressing effects of GEM on fish lipoproteins demonstrated here may be a concern in view of the widespread presence of fibrates in aquatic environments. Work is needed to test whether exposure to environmental concentrations of these drugs jeopardizes the capacity of fish for reproduction, temperature acclimation or migratory behaviors.

  10. [Lipoprotein (a) in an urban population of Venezuela: Evidence that estrogenic deprivation increase in lipoprotein (a) levels is transitory].

    Science.gov (United States)

    Bermúdez Pirela, V; Cabrera de Bravo, M; Mengual Moreno, E; Cano Ponce, C; Leal González, E; Lemus Antepaz, M; Amell de Díaz, A; Sorell Gómez, L

    2007-07-01

    Lipoprotein (a) [Lp (a)] is an independent risk factor for coronary artery disease and normal serum levels of this particle is not known in our country. Thus, the aim of this study was to determine plasma Lp (a) concentration in a population sample of Maracaibo. Fifth hundred out-patients, consulting at Centro de Investigaciones Endocrino-Metabólicas "Dr. Félix Gómez" were randomly underwent to venipunction to obtain a fasting blood simple to assess Lp (a) by a ELISA assay. No significantly differences were found when compared by sex or age separately, higher levels in Lp (a) was found in female 40-44 year group (median: 20,9 mg/dl). Thus, female population was divided in two sub-groups: < 40 years (median: 13 mg/dl) 40 yr and more (median: 16 mg/dl), finding higher Lp (a) levels in the second group (p < 0,02). Hormonal replace therapy was assessed by age, resulting that women subjected this approach shows lower levels of Lp (a) (p < 0,01), except in 60-64 year group. Lp (a) in a Maracaibo was within normal levels. Hormonal replace therapy diminishes Lp (a) concentration in menopausal women, but in menopausal women without hormonal therapy Lp (a) levels experienced a sustained decrease to normal levels in a age-depended manner.

  11. Alterations of serum cholesterol and serum lipoprotein in breast cancer of women

    OpenAIRE

    Hasija, Kiran; Bagga, Hardeep K.

    2005-01-01

    Fasting blood sample of 50 normal subjects (control) and 100 patients of breast cancer were investigated for serum total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein, high density lipoprotein cholesterol:low density lipoprotein cholesterol ratio and total cholesterol:high density lipoprotein cholesterol ratio during breast cancer of women. Five cancer stages, types, age groups, parity and menopausal status were undertaken...

  12. Role of adipocyte-derived lipoprotein lipase in adipocyte hypertrophy

    Directory of Open Access Journals (Sweden)

    Orlando Robert A

    2007-10-01

    Full Text Available Abstract Background A major portion of available fatty acids for adipocyte uptake is derived from lipoprotein lipase (LPL-mediated hydrolysis of circulating lipoprotein particles. In vivo studies aimed at identifying the precise role of adipocyte-derived LPL in fat storage function of adipose tissue have been unable to provide conclusive evidence due to compensatory mechanisms that activate endogenous fatty acid synthesis. To address this gap in knowledge, we have measured the effect of reducing adipocyte LPL expression on intracellular lipid accumulation using a well-established cultured model of adipocyte differentiation. Methods siRNA specific for mouse LPL was transfected into 3T3-L1 adipocytes. Expression of LPL was measured by quantitative real-time PCR and cell surface-associated LPL enzymatic activity was measured by colorimetric detection following substrate (p-nitrophenyl butyrate hydrolysis. Apolipoprotein CII and CIII expression ratios were also measured by qRT-PCR. Intracellular lipid accumulation was quantified by Nile Red staining. Results During differentiation of 3T3-L1 pre-adipocytes, LPL mRNA expression increases 6-fold resulting in a 2-fold increase in cell surface-associated LPL enzymatic activity. Parallel to this increase in LPL expression, we found that intracellular lipids increased ~10-fold demonstrating a direct correlation between adipocyte-derived LPL expression and lipid storage. We next reduced LPL expression in adipocytes using siRNA transfections to directly quantify the contributions of adipocyte-derived LPL to lipid storage, This treatment reduced LPL mRNA expression and cell surface-associated LPL enzymatic activity to ~50% of non-treated controls while intracellular lipid levels were reduced by 80%. Exogenous addition of purified LPL (to restore extracellular lipolytic activity or palmitate (as a source of free fatty acids to siRNA-treated cells restored intracellular lipid levels to those measured for non

  13. Modulation of low-density lipoprotein-induced inhibition of intercellular communication by antioxidants and high-density lipoproteins

    NARCIS (Netherlands)

    Zwijsen, R. M.; de Haan, L. H.; Kuivenhoven, J. A.; Nusselder, I. C.

    1991-01-01

    In order to study the capacity of antioxidants and high-density lipoproteins (HDL) to modulate the effects of low-density lipoprotein (LDL) on intercellular communication, arterial smooth muscle cells and a dye transfer method were used. LDL, in contrast to HDL, inhibited the communication between

  14. Modulation of low-density lipoprotein-induced inhibition of intercellular communication by antioxidants and high-density lipoproteins

    NARCIS (Netherlands)

    Zwijsen, R M; de Haan, L. H. J.; Kuivenhoven, J A; Nusselder, I C

    In order to study the capacity of antioxidants and high-density lipoproteins (HDL) to modulate the effects of low-density lipoprotein (LDL) on intercellular communication, arterial smooth muscle cells and a dye transfer method were used. LDL, in contrast to HDL, inhibited the communication between

  15. Cholesterol esterification and atherogenic index of plasma correlate with lipoprotein size and findings on coronary angiography

    Czech Academy of Sciences Publication Activity Database

    Dobiášová, Milada; Frohlich, J.; Šedová, Michaela; Cheung, M. C.; Brown, B.G.

    2011-01-01

    Roč. 52, č. 3 (2011), s. 566-571 ISSN 0022-2275 R&D Projects: GA MZd(CZ) NR8328; GA MŠk(CZ) 1M06014 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z10300504 Keywords : fractional esterification rate (FERHDL). * log(TG/HDL-Cholesterol) * AIP * biomarkers of cardiovascular risk * lipoprotein particle size * HDL- Atherosclerosis Treatment Study (HATS) Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 5.559, year: 2011

  16. Effect of classic ketogenic diet treatment on lipoprotein subfractions in children and adolescents with refractory epilepsy.

    Science.gov (United States)

    Azevedo de Lima, Patricia; Baldini Prudêncio, Mariana; Murakami, Daniela Kawamoto; Pereira de Brito Sampaio, Leticia; Figueiredo Neto, Antônio Martins; Teixeira Damasceno, Nágila Raquel

    2017-01-01

    The aim of this study was to evaluate the effects of the classic ketogenic diet (KD) on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions in children and adolescents with refractory epilepsy. This prospective study recruited children and adolescents of either sex, whose epilepsy was refractory to treatment with multiple drugs. To be included, the patient had to have an indication for treatment with the KD and be treated as an outpatient. At baseline and after 3 and 6 mo of the KD, lipid profile (total cholesterol [TC], triacylglycerols [TG], LDL cholesterol [LDL-C], and HDL cholesterol [HDL-C]), apolipoproteins (apoA-I and apoB), 10 subfractions of HDL, 7 subfractions of LDL, LDL phenotype, and LDL size were analyzed using the Lipoprint system. The lipid profile components (TC, TG, LDL-C, HDL-C, apoA-I, and apoB) increased during the 3-mo follow-up, and remained consistent after 6 mo of treatment. Similarly, non-HDL-C, TC/HDL-C, LDL-C/HDL-C, and apoB/apoA-I ratios, representing atherogenic particles, significantly increased. In contrast, qualitative lipoprotein characteristics progressively changed during the follow-up period. Small LDL subfractions increased, and this profile was related with reduced LDL size (27.3 nm to 26.7 nm). The LDL phenotype became worse; 52.1% of the patients had a non-A phenotype after 6 mo of the KD. Small HDL subfractions decreased only after 6 mo of the KD. KD treatment promotes negative changes in lipoprotein size and phenotype, contributing to atherogenic risk in these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Anion exchange HPLC isolation of high-density lipoprotein (HDL and on-line estimation of proinflammatory HDL.

    Directory of Open Access Journals (Sweden)

    Xiang Ji

    Full Text Available Proinflammatory high-density lipoprotein (p-HDL is a biomarker of cardiovascular disease. Sickle cell disease (SCD is characterized by chronic states of oxidative stress that many consider to play a role in forming p-HDL. To measure p-HDL, apolipoprotein (apo B containing lipoproteins are precipitated. Supernatant HDL is incubated with an oxidant/LDL or an oxidant alone and rates of HDL oxidation monitored with dichlorofluorescein (DCFH. Although apoB precipitation is convenient for isolating HDL, the resulting supernatant matrix likely influences HDL oxidation. To determine effects of supernatants on p-HDL measurements we purified HDL from plasma from SCD subjects by anion exchange (AE chromatography, determined its rate of oxidation relative to supernatant HDL. SCD decreased total cholesterol but not triglycerides or HDL and increased cell-free (cf hemoglobin (Hb and xanthine oxidase (XO. HDL isolated by AE-HPLC had lower p-HDL levels than HDL in supernatants after apoB precipitation. XO+xanthine (X and cf Hb accelerated purified HDL oxidation. Although the plate and AE-HPLC assays both showed p-HDL directly correlated with cf-Hb in SCD plasma, the plate assay yielded p-HDL data that was influenced more by cf-Hb than AE-HPLC generated p-HDL data. The AE-HPLC p-HDL assay reduces the influence of the supernatants and shows that SCD increases p-HDL.

  18. Comparison of the DASH (Dietary Approaches to Stop Hypertension) diet and a higher-fat DASH diet on blood pressure and lipids and lipoproteins: a randomized controlled trial.

    Science.gov (United States)

    Chiu, Sally; Bergeron, Nathalie; Williams, Paul T; Bray, George A; Sutherland, Barbara; Krauss, Ronald M

    2016-02-01

    The DASH (Dietary Approaches to Stop Hypertension) dietary pattern, which is high in fruit, vegetables, and low-fat dairy foods, significantly lowers blood pressure as well as low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. The study was designed to test the effects of substituting full-fat for low-fat dairy foods in the DASH diet, with a corresponding increase in fat and a reduction in sugar intake, on blood pressure and plasma lipids and lipoproteins. This was a 3-period randomized crossover trial in free-living healthy individuals who consumed in random order a control diet, a standard DASH diet, and a higher-fat, lower-carbohydrate modification of the DASH diet (HF-DASH diet) for 3 wk each, separated by 2-wk washout periods. Laboratory measurements, which included lipoprotein particle concentrations determined by ion mobility, were made at the end of each experimental diet. Thirty-six participants completed all 3 dietary periods. Blood pressure was reduced similarly with the DASH and HF-DASH diets compared with the control diet. The HF-DASH diet significantly reduced triglycerides and large and medium very-low-density lipoprotein (VLDL) particle concentrations and increased LDL peak particle diameter compared with the DASH diet. The DASH diet, but not the HF-DASH diet, significantly reduced LDL cholesterol, HDL cholesterol, apolipoprotein A-I, intermediate-density lipoprotein and large LDL particles, and LDL peak diameter compared with the control diet. The HF-DASH diet lowered blood pressure to the same extent as the DASH diet but also reduced plasma triglyceride and VLDL concentrations without significantly increasing LDL cholesterol. This trial was registered at clinicaltrials.gov as NCT01404897. © 2016 American Society for Nutrition.

  19. Triglycerides, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol in rats exposed to premium motor spirit fumes.

    Science.gov (United States)

    Aberare, Ogbevire L; Okuonghae, Patrick; Mukoro, Nathaniel; Dirisu, John O; Osazuwa, Favour; Odigie, Elvis; Omoregie, Richard

    2011-06-01

    Deliberate and regular exposure to premium motor spirit fumes is common and could be a risk factor for liver disease in those who are occupationally exposed. A possible association between premium motor spirit fumes and plasma levels of triglyceride, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol using a rodent model could provide new insights in the pathology of diseases where cellular dysfunction is an established risk factor. The aim of this study was to evaluate the possible effect of premium motor spirit fumes on lipids and lipoproteins in workers occupationally exposed to premium motor spirit fumes using rodent model. Twenty-five Wister albino rats (of both sexes) were used for this study between the 4(th) of August and 7(th) of September, 2010. The rats were divided into five groups of five rats each. Group 1 rats were not exposed to premium motor spirit fumes (control group), group 2 rats were exposed for 1 hour daily, group 3 for 3 hours daily, group 4 for 5 hours daily and group 5 for 7 hours daily. The experiment lasted for a period of 4 weeks. Blood samples obtained from all the groups after 4 weeks of exposure were used for the estimation of plasma levels of triglyceride, total cholesterol, high density lipoprotein- cholesterol and low density lipoprotein- cholesterol. Results showed significant increase in means of plasma total cholesterol and low density lipoprotein levels (Plevel of high density lipoprotein, the ratio of low density lipoprotein to high density lipoprotein and the ratio of total cholesterol to high density lipoprotein did not differ significantly in exposed subjects when compared with the control group. These results showed that frequent exposure to petrol fumes may be highly deleterious to the liver cells.

  20. Factors affecting particle retention in thermal field-flow fractionation

    African Journals Online (AJOL)

    ABSTRACT. In this paper, we report a range of factors which affect the retention of colloidal particles in thermal field-flow fractionation (ThFFF). These results are observed among different sizes of polystyrene (PS) latex particles suspended in both aqueous and nonaqueous liquid carriers and very low density lipoproteins in ...

  1. factors affecting particle retention in thermal field-flow fractionation

    African Journals Online (AJOL)

    In this paper, we report a range of factors which affect the retention of colloidal particles in thermal field-flow fractionation (ThFFF). These results are observed among different sizes of polystyrene (PS) latex particles suspended in both aqueous and nonaqueous liquid carriers and very low density lipoproteins in a phosphate ...

  2. Cholesterol synthesis by human fetal hepatocytes: effect of lipoproteins

    International Nuclear Information System (INIS)

    Carr, B.R.; Simpson, E.R.

    1984-01-01

    The purpose of the present investigation was to determine the effect of various lipoproteins on the rate of cholesterol synthesis of human fetal liver cells maintained in culture. This was accomplished by measuring the rate of incorporation of tritium from tritiated water or carbon 14-labeled acetate into cholesterol in human fetal liver cells. Optimal conditions for each assay were determined. When human fetal liver cells were maintained in the presence of low-density lipoprotein, cholesterol synthesis was inhibited in a concentration-dependent fashion. Intermediate--density lipoprotein and very-low-density lipoprotein also suppressed cholesterol synthesis in human fetal liver cells. In contrast, high-density lipoprotein stimulated cholesterol synthesis in human fetal liver cells. The results of the present as well as our previous investigations suggest that multiple interrelationships exist between fetal liver cholesterol synthesis and lipoprotein-cholesterol utilization by the human fetal adrenal gland and that these processes serve to regulate the lipoprotein-cholesterol levels in fetal plasma

  3. Genetics of Lipid and Lipoprotein Disorders and Traits.

    Science.gov (United States)

    Dron, Jacqueline S; Hegele, Robert A

    2016-01-01

    Plasma lipids, namely cholesterol and triglyceride, and lipoproteins, such as low-density lipoprotein (LDL) and high-density lipoprotein, serve numerous physiological roles. Perturbed levels of these traits underlie monogenic dyslipidemias, a diverse group of multisystem disorders. We are on the verge of having a relatively complete picture of the human dyslipidemias and their components. Recent advances in genetics of plasma lipids and lipoproteins include the following: (1) expanding the range of genes causing monogenic dyslipidemias, particularly elevated LDL cholesterol; (2) appreciating the role of polygenic effects in such traits as familial hypercholesterolemia and combined hyperlipidemia; (3) accumulating a list of common variants that determine plasma lipids and lipoproteins; (4) applying exome sequencing to identify collections of rare variants determining plasma lipids and lipoproteins that via Mendelian randomization have also implicated gene products such as NPC1L1 , APOC3 , LDLR , APOA5 , and ANGPTL4 as causal for atherosclerotic cardiovascular disease; and (5) using naturally occurring genetic variation to identify new drug targets, including inhibitors of apolipoprotein (apo) C-III, apo(a), ANGPTL3, and ANGPTL4. Here, we compile this disparate range of data linking human genetic variation to plasma lipids and lipoproteins, providing a "one stop shop" for the interested reader.

  4. Lipoprotein-specific transport of circulating lipid peroxides.

    Science.gov (United States)

    Ahotupa, Markku; Suomela, Jukka-Pekka; Vuorimaa, Timo; Vasankari, Tommi

    2010-10-01

    Serum lipoproteins, the carriers of cholesterol and other lipophilic substances in blood, are known to contain variable amounts of lipid peroxides. We investigated the transport of food-derived and endogenously formed lipid peroxides by serum lipoproteins under physiological conditions. Five independent trials were conducted in which different groups of healthy volunteers either consumed a test meal (a standard hamburger meal rich in lipid peroxides) or underwent strenuous physical exercise. The transport function was characterized by analyzing the kinetics of lipid peroxides in lipoprotein fractions. For evaluation of their potential involvement, indicators of oxidative stress (8-isoprostanes, malondialdehyde, 8-oxo-deoxyguanosine), antioxidant functions (total antioxidant potential, paraoxonase activity), and serum lipids were also analyzed. We found that food lipid peroxides are incorporated into serum triglyceride-rich lipoproteins and low-density lipoprotein, directing the flow of lipid peroxides towards peripheral tissues. High-density lipoprotein appears to have an opposite and protective function, and is able to respond to oxidative stress by substantially increasing the reverse transport of lipid peroxides. We propose that the specific atherosclerosis-related effects of serum lipoproteins are not explained by cholesterol transport alone and may rather result from the transport of the more directly atherogenic lipid peroxides.

  5. Redefining the essential trafficking pathway for outer membrane lipoproteins

    OpenAIRE

    Grabowicz, Marcin; Silhavy, Thomas J.

    2017-01-01

    In Gram-negative bacteria, most lipoproteins synthesized in the inner membrane (IM) are trafficked to the outer membrane (OM). The Lol pathway is the trafficking paradigm: LolCDE releases lipoproteins from the IM; LolA shuttles them between membranes to LolB in the OM. Several OM lipoproteins are essential for viability. In apparent concordance, the Lol proteins are each essential in wild-type cells. However, we show that Escherichia coli grows well without LolA and LolB in the absence of one...

  6. Lipoprotein X Causes Renal Disease in LCAT Deficiency.

    Directory of Open Access Journals (Sweden)

    Alice Ossoli

    Full Text Available Human familial lecithin:cholesterol acyltransferase (LCAT deficiency (FLD is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX in plasma, and renal disease. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, chemical and biologic characteristics, to wild-type and Lcat-/- mice. Our in vitro and in vivo studies demonstrated an apoA-I and LCAT-dependent pathway for LpX conversion to HDL-like particles, which likely mediates normal plasma clearance of LpX. Plasma clearance of exogenous LpX was markedly delayed in Lcat-/- mice, which have low HDL, but only minimal amounts of endogenous LpX and do not spontaneously develop renal disease. Chronically administered exogenous LpX deposited in all renal glomerular cellular and matrical compartments of Lcat-/- mice, and induced proteinuria and nephrotoxic gene changes, as well as all of the hallmarks of FLD renal disease as assessed by histological, TEM, and SEM analyses. Extensive in vivo EM studies revealed LpX uptake by macropinocytosis into mouse glomerular endothelial cells, podocytes, and mesangial cells and delivery to lysosomes where it was degraded. Endocytosed LpX appeared to be degraded by both human podocyte and mesangial cell lysosomal PLA2 and induced podocyte secretion of pro-inflammatory IL-6 in vitro and renal Cxl10 expression in Lcat-/- mice. In conclusion, LpX is a nephrotoxic particle that in the absence of Lcat induces all of the histological and functional hallmarks of FLD and hence may serve as a biomarker for monitoring recombinant LCAT therapy. In addition, our studies suggest that LpX-induced loss of endothelial barrier function and release of cytokines by renal glomerular cells likely plays a role in the initiation and progression of FLD nephrosis.

  7. Particle Pollution

    Science.gov (United States)

    ... Your Health Particle Pollution Public Health Issues Particle Pollution Recommend on Facebook Tweet Share Compartir Particle pollution — ... see them in the air. Where does particle pollution come from? Particle pollution can come from two ...

  8. Hepatic trans-Golgi action coordinated by the GTPase ARFRP1 is crucial for lipoprotein lipidation and assembly[S

    Science.gov (United States)

    Hesse, Deike; Radloff, Katrin; Jaschke, Alexander; Lagerpusch, Merit; Chung, Bomee; Tailleux, Anne; Staels, Bart; Schürmann, Annette

    2014-01-01

    The liver is a major organ in whole body lipid metabolism and malfunctioning can lead to various diseases including dyslipidemia, fatty liver disease, and type 2 diabetes. Triglycerides and cholesteryl esters are packed in the liver as very low density lipoproteins (VLDLs). Generation of these lipoproteins is initiated in the endoplasmic reticulum and further maturation likely occurs in the Golgi. ADP-ribosylation factor-related protein 1 (ARFRP1) is a small trans-Golgi-associated guanosine triphosphatase (GTPase) that regulates protein sorting and is required for chylomicron lipidation and assembly in the intestine. Here we show that the hepatocyte-specific deletion of Arfrp1 (Arfrp1liv−/−) results in impaired VLDL lipidation leading to reduced plasma triglyceride levels in the fasted state as well as after inhibition of lipoprotein lipase activity by Triton WR-1339. In addition, the concentration of ApoC3 that comprises 40% of protein mass of secreted VLDLs is markedly reduced in the plasma of Arfrp1liv−/− mice but accumulates in the liver accompanied by elevated triglycerides. Fractionation of Arfrp1liv−/− liver homogenates reveals more ApoB48 and a lower concentration of triglycerides in the Golgi compartments than in the corresponding fractions from control livers. In conclusion, ARFRP1 and the Golgi apparatus play an important role in lipoprotein maturation in the liver by influencing lipidation and assembly of proteins to the lipid particles. PMID:24186947

  9. Low-Density Lipoproteins Oxidation and Endometriosis

    Directory of Open Access Journals (Sweden)

    Grzegorz Polak

    2013-01-01

    Full Text Available The etiopathogenesis of endometriosis still remains unknown. Recent data provide new valuable information concerning the role of oxidative stress in the pathophysiology of the disease. It has been proved that levels of different lipid peroxidation end products are increased in both peritoneal fluid (PF and serum of endometriotic patients. We assessed the concentration of oxidized low-density lipoproteins (oxLDL in PF of 110 women with different stages of endometriosis and 119 women with serous ( or dermoid ( ovarian cysts, as the reference groups. PF oxLDL levels were evaluated by ELISA. We found that concentrations of oxLDL in PF of endometriotic women were significantly higher compared to women with serous but not dermoid ovarian cysts. Interestingly, by analyzing concentrations of oxLDL in women with different stages of the disease, it was noted that they are significantly higher only in the subgroup of patients with stage IV endometriosis as compared to women with ovarian serous cysts. In case of minimal, mild, and moderate disease, PF oxLDL levels were similar to those noted in reference groups. Our results indicate that disrupted oxidative status in the peritoneal cavity of women with endometriosis may play a role in the pathogenesis of advanced stages of the disease.

  10. High-density lipoprotein cholesterol: How High

    Directory of Open Access Journals (Sweden)

    G Rajagopal

    2012-01-01

    Full Text Available The high-density lipoprotein cholesterol (HDL-C is considered anti-atherogenic good cholesterol. It is involved in reverse transport of lipids. Epidemiological studies have found inverse relationship of HDL-C and coronary heart disease (CHD risk. When grouped according to HDL-C, subjects having HDL-C more than 60 mg/dL had lesser risk of CHD than those having HDL-C of 40-60 mg/dL, who in turn had lesser risk than those who had HDL-C less than 40 mg/dL. No upper limit for beneficial effect of HDL-C on CHD risk has been identified. The goals of treating patients with low HDL-C have not been firmly established. Though many drugs are known to improve HDL-C concentration, statins are proven to improve CHD risk and mortality. Cholesteryl ester transfer protein (CETP is involved in metabolism of HDL-C and its inhibitors are actively being screened for clinical utility. However, final answer is still awaited on CETP-inhibitors.

  11. Effect of lithocholic acid feeding on plasma lipoproteins and binding of radioiodinated human lipoproteins to hepatic membranes in rats.

    Science.gov (United States)

    Loo, G; Kessie, G; Berlin, E; Nair, P P

    1992-06-01

    1. Male Sprague-Dawley rats fed diets containing 0.25% lithocholic acid for 6 weeks exhibited elevated serum cholesterol. 2. The rats were fed diets containing 5 or 20% fat with and without the lithocholate and/or oxytetracycline-HCl. 3. The cholesterol elevation was associated with high density lipoprotein (HDL) and not very low density lipoprotein (VLDL) or low density lipoprotein (LDL). 4. Specific binding of human [125I]HDL to hepatic membranes was lowered in lithocholate-fed rats, but binding of human [125I]LDL to these membranes was not affected.

  12. Distribution of perfluorooctanesulfonate and perfluorooctanoate into human plasma lipoprotein fractions

    NARCIS (Netherlands)

    Butenhoff, J.L.; Pieterman, E.; Ehresman, D.J.; Gorman, G.S.; Olsen, G.W.; Chang, S.C.; Princen, H.M.

    2012-01-01

    Some cross-sectional epidemiological studies have reported positive associations of serum concentrations of non-high density lipoprotein cholesterol with serum perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA). However, the strength of the reported associations is inconsistent for

  13. Sex, plasma lipoproteins, and atherosclerosis: prevailing assumptions and outstanding questions.

    Science.gov (United States)

    Godsland, I F; Wynn, V; Crook, D; Miller, N E

    1987-12-01

    We review the hypothesis that the incidence of coronary heart disease (CHD) is higher in men than in women due to differences in plasma lipoprotein risk factors between the sexes. Men and women appear to be equally susceptible to the effects of lipoprotein risk factors for CHD, and the difference between the sexes in lipoprotein risk factors for CHD appears to be consistent with their being, at least in part, responsible for the sex difference in CHD. This is apparent both when men and women of equal age are compared, and when age-related variations in the sex differences in plasma lipoproteins and CHD are considered. Differences between the sexes in lipoprotein concentrations are still present when sex differences in adiposity, cigarette smoking, physical activity, and diet are taken into account. Evidence relating these sex differences in CHD and lipoproteins to the effects of sex hormones is critically examined. It is commonly accepted that androgens induce changes in lipoprotein concentrations that would predispose towards CHD, whereas estrogens are held to have opposite effects. However, much of the evidence for this comes from studies of changes associated with administration of synthetic gonadal steroids or with changes in gonadal function. Studies of differences in lipoprotein metabolism in normal men and women are extremely limited. In males high-density lipoprotein (HDL) cholesterol levels fall at puberty, correlating with the rise in plasma testosterone concentrations. In females, HDL levels do not change at puberty, despite the rise in estrogen concentrations. Evidence for lipoprotein changes during the menopause, when estrogen levels decline, is equivocal. Similarly, the evidence for an increase in CHD incidence at the menopause is inconclusive. National mortality data indicate that the decreasing sex difference in CHD after 50 years of age is due to a declining rate of increase in men rather than to an acceleration in CHD incidence in women. In men

  14. Preferential enrichment of large-sized very low density lipoprotein populations with transferred cholesteryl esters

    International Nuclear Information System (INIS)

    Eisenberg, S.

    1985-01-01

    The effect of lipid transfer proteins on the exchange and transfer of cholesteryl esters from rat plasma HDL2 to human very low (VLDL) and low density (LDL) lipoprotein populations was studied. The use of a combination of radiochemical and chemical methods allowed separate assessment of [ 3 H]cholesteryl ester exchange and of cholesteryl ester transfer. VLDL-I was the preferred acceptor for transferred cholesteryl esters, followed by VLDL-II and VLDL-III. LDL did not acquire cholesteryl esters. The contribution of exchange of [ 3 H]cholesteryl esters to total transfer was highest for LDL and decreased in reverse order along the VLDL density range. Inactivation of lecithin: cholesterol acyltransferase (LCAT) and heating the HDL2 for 60 min at 56 degrees C accelerated transfer and exchange of [ 3 H]cholesteryl esters. Addition of lipid transfer proteins increased cholesterol esterification in all systems. The data demonstrate that large-sized, triglyceride-rich VLDL particles are preferred acceptors for transferred cholesteryl esters. It is suggested that enrichment of very low density lipoproteins with cholesteryl esters reflects the triglyceride content of the particles

  15. Association of intima-media thickness of carotid arteries with remnant lipoproteins in men and women.

    Science.gov (United States)

    Piťha, J; Kovář, J; Škodová, Z; Cífková, R; Stávek, P; Červenka, L; Šejda, T; Lánská, V; Poledne, R

    2015-01-01

    The subclass of triglyceride-rich lipoproteins - remnant-like particles (RLP) seems to be strong and independent risk factor for cardiovascular disease. We evaluated the role of RLP and other risk factors (RF) with sonographically measured intima-media thickness of carotid arteries (IMT CCA) in a cohort of Czech population including women defined according to the time after menopause. We investigated relation of IMT CCA to age, weight, central obesity, plasma lipids including remnant-like particles cholesterol (RLP-C) and triglycerides (RLP-TG) in 136 men and 160 women. Using multiple linear regression analysis, significant association between IMT CCA and RLP-C was found in women 1-7 years after menopause. In the whole group of women, only age and fasting blood glucose were independently associated with IMT CCA. In men only age significantly correlated with IMT CCA. Significant decrease of all plasma lipids between 1988 and 1996 in men was detected, while in women significant increase in triglycerides and no change in non-HDL cholesterol was observed. RLP-C was the strongest independent RF for atherosclerosis in postmenopausal women but its association with IMT CCA was limited to several years after menopause. In conclusion, women changing reproductive status could be more sensitive to atherogenic impact of remnant lipoproteins.

  16. Lipoprotein(a) as a cardiovascular risk factor: current status

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Chapman, M John; Ray, Kausik

    2010-01-01

    The aims of the study were, first, to critically evaluate lipoprotein(a) [Lp(a)] as a cardiovascular risk factor and, second, to advise on screening for elevated plasma Lp(a), on desirable levels, and on therapeutic strategies.......The aims of the study were, first, to critically evaluate lipoprotein(a) [Lp(a)] as a cardiovascular risk factor and, second, to advise on screening for elevated plasma Lp(a), on desirable levels, and on therapeutic strategies....

  17. The use of transgenic animals to study lipoprotein metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, E.M.; Plump, A.S.

    1993-12-01

    The application of transgenic technology to lipoprotein metabolism and atherosclerosis was first reported in 1988. Today, a large percentage of the genes involved in lipoprotein metabolism have been overexpressed in mice, and a substantial number of these same genes have been disrupted by homologous recombination in embryonic stem (ES) cells. The utility of animal models of lipoprotein metabolism and atherosclerosis is far-reaching given the complex nature of these systems. There are at least 17 known genes directly involved in lipoprotein metabolism and likely dozens more may be involved. This massive network of interacting factors has necessitated the development of in vivo systems which can be subject to genetic manipulation. The power of overexpression is obvious: elucidating function in a relatively controlled genetic environment in which the whole system is present and operational. The not-so-obvious problem with transgenics is ``background,`` or for purposes of the current discussion, the mouse`s own lipoprotein system. With the advent of gene knockout, we have been given the ability to overcome ``background.`` By recreating the genetic complement of the mouse we can alter a system in essentially any manner desired. As unique tools, and in combination with one another, the overexpression of foreign genes and the targeted disruption or alteration of endogenous genes has already and will continue to offer a wealth of information on the biology of lipoprotein metabolism and its effect on atherosclerosis susceptibility.

  18. Recent advances in lipoprotein and atherosclerosis: nutrigenomic approach

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, S.; Ortega, A.; Varela, L.; Bermudez, B.; Muriana, F. J. G.; Abaia, R.

    2009-07-01

    Atherosclerosis is a disease in which multiple factors contribute to the degeneration of the vascular wall. Many risk factors have been identified as having influence on the progression of atherosclerosis among them, the type of diet. Multifactorial interaction among lipoproteins, vascular wall cells, and inflammatory mediators has been recognised as the basis of atherogenesis. Dietary intake affects lipoprotein concentration and composition providing risk or protection at several stages of atherosclerosis. More intriguingly, it has been demonstrated that the extent to which each lipid or lipoprotein is associated with cardiovascular disease depends on the time to last meal; thus, postprandial lipoproteins, main lipoproteins in blood after a high-fat meal, have been shown to strongly influence atherogenesis. As a complex biological process, the full cellular and molecular characterization of atherosclerosis derived by diet, calls for application of the newly developing omics techniques of analysis. This review will considered recent studies using high-throughput technologies and a nutrigenomic approach to reveal the patho-physiological effects that the fasting and postprandial lipoproteins may exert on the vascular wall. (Author) 55 refs.

  19. Moderate dyslipoproteinemia induced inflammation and remodeling HDL and VLDL particles in post-renal transplant patients

    Directory of Open Access Journals (Sweden)

    Kimak Elzbieta

    2017-06-01

    Full Text Available The aim of this paper was to examine whether moderate dyslipoproteinemia can cause an increase of hsCRP and LPO levels in Tx patients who had received immunosuppressive therapy and were without acute inflammatory diseases. Herein, the lipid levels, hsCRP, LPO, apolipoprotein (apoB, AI, AII, AIInonB, apoB-containing AII (apoB:AII, apoCIII, apoCIIInonB, apoB:CIII, LCAT level, as well as CETP and PON1 activity were determined. All examined Tx patients had moderate dyslipidemia and slightly increased hsCRP, LPO, apoB:AII and apoCIII levels, but decreased LCAT mass, PON1 activity and lipoprotein ratios. Tx patients with apoAI150mg/dl (n=39, but no difference in CETP activity was indicated. Multiple ridge forward regression and Spearman’s correlation test were used. The results of the presented study, show for the first time that higher apoAI/apoB and apoAI/apoCIII ratios induced a decrease of the hsCRP concentration. Moreover, the composition of apoCIIInonB, LDL-C and apoAI brought about an increase of LCAT mass and PON1 activity. In Tx patients with lower concentration of apoAI, an increase of concentration of apoB:AII in VLDL generated a mild oxidation of lipoprotein and an elevated concentration of LPO. However, lower ApoAI/apoB ratio resulted in an increase of PON1 activity and apoB, as well as nonHDL-C levels, and in turn, PON1 activity increased LCAT mass. These disorders rearranged the HDL particle, and, simultaneously, remodeled the VLDL particle. This may prevent antioxidant activity, reverse cholesterol transport and accelerate the rejection of the transplant, as well as bringing about cardiovascular diseases in Tx patients with lower apoAI. Such metabolic pathways can be used as potentially novel targets for pharmacological intervention.

  20. Impaired lipoprotein processing in HIV patients on antiretroviral therapy: aberrant high-density lipoprotein lipids, stability, and function.

    Science.gov (United States)

    Gillard, Baiba K; Raya, Joe L; Ruiz-Esponda, Raul; Iyer, Dinakar; Coraza, Ivonne; Balasubramanyam, Ashok; Pownall, Henry J

    2013-07-01

    HIV patients on antiretroviral therapy (HIV/ART) exhibit a unique atherogenic dyslipidemic profile with hypertriglyceridemia (HTG) and low plasma concentrations of high-density lipoprotein (HDL) cholesterol. In the Heart Positive Study of HIV/ART patients, a hypolipidemic therapy of fenofibrate, niacin, diet, and exercise reduced HTG and plasma non-HDL cholesterol concentrations and raised plasma HDL cholesterol and adiponectin concentrations. We tested the hypothesis that HIV/ART HDL have abnormal structures and properties and are dysfunctional. Hypolipidemic therapy reduced the TG contents of low-density lipoprotein and HDL. At baseline, HIV/ART low-density lipoproteins were more triglyceride (TG)-rich and HDL were more TG- and cholesteryl ester-rich than the corresponding lipoproteins from normolipidemic (NL) subjects. Very-low-density lipoproteins, low-density lipoprotein, and HDL were larger than the corresponding lipoproteins from NL subjects; HIV/ART HDL were less stable than NL HDL. HDL-[(3)H]cholesteryl ester uptake by Huh7 hepatocytes was used to assess HDL functionality. HIV/ART plasma were found to contain significantly less competitive inhibition activity for hepatocyte HDL-cholesteryl ester uptake than NL plasma were found to contain (PART patients are larger and more neutral lipid-rich, and their HDL are less stable and less receptor-competent. On the basis of this work and previous studies of lipase activity in HIV, we present a model in which plasma lipolytic activities or hepatic cholesteryl ester uptake are impaired in HIV/ART patients. These findings provide a rationale to determine whether the distinctive lipoprotein structure, properties, and function of HIV/ART HDL predict atherosclerosis as assessed by carotid artery intimal medial thickness.

  1. Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M.; Brown, Robert J., E-mail: rbrown@mun.ca

    2014-09-05

    Highlights: • Lipoprotein hydrolysis products were produced by lipoprotein lipase. • Hydrolysis products lowers expression of macrophage cholesterol transporters. • Hydrolysis products reduces expression of select nuclear receptors. • Fatty acid products lowers cholesterol transporters and select nuclear receptors. • Fatty acid products reduces cholesterol efflux from macrophages. - Abstract: Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL.

  2. Non-leaky vesiculation of large unilamellar vesicles (LUV) induced by plasma high density lipoproteins (HDL): Detection by HPLC

    International Nuclear Information System (INIS)

    Tischler, U.; Rueckert, D.S.; Schubert, R.; Jaroni, H.W.; Schmidt, K.H.

    1989-01-01

    Interaction of large unilamellar phosphatidylcholine vesicles (LUV, 75nm) and plasma high density lipoproteins (HDL) resulted in a non-leaky vesiculation of LUV. This vesiculation was detected by a HPLC-system consisting of a combination of three TSK-gel columns (6000PW, 5000PW, 3000SW). With increasing incubation time liposomal [ 14 C]PC, entrapped [ 3 H]inulin, and apoprotein of HDL origin decreased. The decrease was accompanied by a formation of new particles, consisting of liposomal PC and apoprotein. These particles also enclosed [3H]inulin, reflecting a hydrophilic inner space. The formation of the particles reached a maximum after one day of incubation. Retention time was 21 minutes for LUV, 28 minutes for the new particles, and 36 minutes for HDL. In vesicles with membranes consisting of phosphatidylcholine and 30% cholesterol no interactions were observed

  3. Aminoacylation of the N-terminal cysteine is essential for Lol-dependent release of lipoproteins from membranes but does not depend on lipoprotein sorting signals.

    Science.gov (United States)

    Fukuda, Ayumu; Matsuyama, Shin-Ichi; Hara, Takashi; Nakayama, Jiro; Nagasawa, Hiromichi; Tokuda, Hajime

    2002-11-08

    Lipoproteins are present in a wide variety of bacteria and are anchored to membranes through lipids attached to the N-terminal cysteine. The Lol system of Escherichia coli mediates the membrane-specific localization of lipoproteins. Aspartate at position 2 functions as a Lol avoidance signal and causes the retention of lipoproteins in the inner membrane, whereas lipoproteins having residues other than aspartate at position 2 are released from the inner membrane and localized to the outer membrane by the Lol system. Phospholipid:apolipoprotein transacylase, Lnt, catalyzes the last step of lipoprotein modification, converting apolipoprotein into mature lipoprotein. To reveal the importance of this aminoacylation for the Lol-dependent membrane localization, apolipoproteins were prepared by inhibiting lipoprotein maturation. Lnt was also purified and used to convert apolipoprotein into mature lipoprotein in vitro. The release of these lipoproteins was examined in proteoliposomes. We show here that the aminoacylation is essential for the Lol-dependent release of lipoproteins from membranes. Furthermore, lipoproteins with aspartate at position 2 were found to be aminoacylated both in vivo and in vitro, indicating that the lipoprotein-sorting signal does not affect lipid modification.

  4. Activated platelets contribute to oxidized low-density lipoproteins and dysfunctional high-density lipoproteins through a phospholipase A2-dependent mechanism

    NARCIS (Netherlands)

    Blache, Denis; Gautier, Thomas; Tietge, Uwe J. F.; Lagrost, Laurent

    Plasma activity of secretory phospholipase A2 (sPLA2) increases in patients with cardiovascular disease. The present study investigated whether platelet-released sPLA2 induces low-density lipoprotein (LDL) and high-density lipoprotein (HDL) modifications that translate into changes in lipoprotein

  5. Proteome of human plasma very low-density lipoprotein and low-density lipoprotein exhibits a link with coagulation and lipid metabolism

    NARCIS (Netherlands)

    Dashty Rahmatabady, Monireh; Motazacker, Mohammad M.; Levels, Johannes; de Vries, Marcel; Mahmoudi, Morteza; Peppelenbosch, Maikel; Rezaee, Farhad

    Apart from transporting lipids through the body, the human plasma lipoproteins very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) are also thought to serve as a modality for intra-organismal protein transfer, shipping proteins with important roles in inflammation and thrombosis

  6. Structures of discoidal high density lipoproteins: a combined computational-experimental approach.

    Science.gov (United States)

    Gu, Feifei; Jones, Martin K; Chen, Jianguo; Patterson, James C; Catte, Andrea; Jerome, W Gray; Li, Ling; Segrest, Jere P

    2010-02-12

    Conversion of discoidal phospholipid (PL)-rich high density lipoprotein (HDL) to spheroidal cholesteryl ester-rich HDL is a central step in reverse cholesterol transport. A detailed understanding of this process and the atheroprotective role of apolipoprotein A-I (apoA-I) requires knowledge of the structure and dynamics of these various particles. This study, combining computation with experimentation, illuminates structural features of apoA-I allowing it to incorporate varying amounts of PL. Molecular dynamics simulated annealing of PL-rich HDL models containing unesterified cholesterol results in double belt structures with the same general saddle-shaped conformation of both our previous molecular dynamics simulations at 310 K and the x-ray structure of lipid-free apoA-I. Conversion from a discoidal to a saddle-shaped particle involves loss of helicity and formation of loops in opposing antiparallel parts of the double belt. During surface expansion caused by the temperature-jump step, the curved palmitoyloleoylphosphatidylcholine bilayer surfaces approach planarity. Relaxation back into saddle-shaped structures after cool down and equilibration further supports the saddle-shaped particle model. Our kinetic analyses of reconstituted particles demonstrate that PL-rich particles exist in discrete sizes corresponding to local energetic minima. Agreement of experimental and computational determinations of particle size/shape and apoA-I helicity provide additional support for the saddle-shaped particle model. Truncation experiments combined with simulations suggest that the N-terminal proline-rich domain of apoA-I influences the stability of PL-rich HDL particles. We propose that apoA-I incorporates increasing PL in the form of minimal surface bilayers through the incremental unwinding of an initially twisted saddle-shaped apoA-I double belt structure.

  7. Pharmacological isolation of postsynaptic currents mediated by NR2A- and NR2B-containing NMDA receptors in the anterior cingulate cortex

    Directory of Open Access Journals (Sweden)

    Cao Xiaoyan

    2007-04-01

    Full Text Available Abstract NMDA receptors (NMDARs are involved in excitatory synaptic transmission and plasticity associated with a variety of brain functions, from memory formation to chronic pain. Subunit-selective antagonists for NMDARs provide powerful tools to dissect NMDAR functions in neuronal activities. Recently developed antagonist for NR2A-containing receptors, NVP-AAM007, triggered debates on its selectivity and involvement of the NMDAR subunits in bi-directional synaptic plasticity. Here, we re-examined the pharmacological properties of NMDARs in the anterior cingulate cortex (ACC using NVP-AAM007 as well as ifenprodil, a selective antagonist for NR2B-containing NMDARs. By alternating sequence of drug application and examining different concentrations of NVP-AAM007, we found that the presence of NVP-AAM007 did not significantly affect the effect of ifenprodil on NMDAR-mediated EPSCs. These results suggest that NVP-AAM007 shows great preference for NR2A subunit and could be used as a selective antagonist for NR2A-containing NMDARs in the ACC.

  8. Association between serum fatty acids and lipoprotein subclass profile in healthy young adults: exploring common genetic and environmental factors.

    Science.gov (United States)

    Jelenkovic, Aline; Bogl, Leonie H; Rose, Richard J; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Kaprio, Jaakko; Silventoinen, Karri

    2014-04-01

    Little is known about the associations of serum fatty acids with lipoprotein profile and the underlying genetic and environmental etiology of these relationships. We aimed to analyze the phenotypic association of serum n-6 and n-3 polyunsaturated (PUFAs), monounsaturated (MUFAs) and saturated (SFAs) fatty acids (relative proportion to total fatty acids) with lipids and lipoproteins, and to quantify common genetic and environmental factors determining their covariation. Two cohorts of healthy Finnish twins were assessed in young adulthood. Data were available for 1269 individual twins including 561 complete pairs. Serum metabolites were measured by nuclear magnetic resonance spectroscopy. Bivariate quantitative genetic models were used to decompose the phenotypic covariance between the pairs of traits into genetic and environmental components. Among the strongest correlations observed, serum total n-6 PUFAs and linoleic acid were inversely (max. r=-0.65) and MUFAs positively (max. r=0.63) correlated with triglycerides and very low-density lipoprotein (VLDL) particle concentration, particularly with large VLDL (for n-6 PUFAs) and medium VLDL (for MUFAs). Genetic factors significantly contributed to their covariance with bivariate heritability estimates ranging from 44% to 56% for n-6 PUFAs and 58% to 66% for MUFAs. Genetic correlations with lipid traits were moderate to high (max. rA=-0.59 and 0.70 for n-6 PUFAs and MUFAs, respectively). Statistically significant, but substantially weaker phenotypic correlations of total n-3 PUFAs, docosahexaenoic acid (DHA) and SFAs with lipoprotein profile were not decomposed into their genetic and environmental components. Shared genetic factors are important in explaining why higher concentrations of serum n-6 PUFAs and lower concentrations of serum MUFAs strongly associate with lower triglyceride and VLDL particle concentrations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Measurement of plasma protein and lipoprotein binding of pyrethroids.

    Science.gov (United States)

    Sethi, Pankaj K; Muralidhara, S; Bruckner, James V; White, Catherine A

    2014-01-01

    A simple, reliable procedure was developed to measure binding of pyrethroid insecticides to total proteins and lipoproteins of rat and human plasma. The extent of binding of (14)C-labeled deltamethrin (DLM), cis-permethrin (CIS) and trans-permethrin (TRANS) was quantified by a 3-step organic solvent extraction technique. Rat and human plasma samples, containing NaF to inhibit esterases, were spiked with a range of concentrations of each radiolabeled pyrethroid. Protein binding reached equilibrium within ~1h of incubation at 37°C. The samples were extracted in turn with: isooctane to collect the unbound fraction; 2-octanol to extract the lipoprotein-bound fraction; and acetonitrile to obtain the protein-bound fraction. Absolute recoveries of DLM, CIS and TRANS ranged from 86 to 95%. Adherence of these very lipophilic chemicals to glass and plastic was minimized by using silanized glass vials and LoBind® plastic pipettes. The method's ability to distinguish lipoprotein from protein binding was confirmed by experiments with diazepam and cyclosporine, drugs that bind selectively to albumin and lipoproteins, respectively. This procedure was effectively utilized for studies of the species-dependence of plasma protein and lipoprotein binding of three pyrethroids for inclusion in physiologically-based pharmacokinetic models of pyrethroids for use in health risk assessments of the insecticides in children and adults. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Lipoproteins tethered dendrimeric nanoconstructs for effective targeting to cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Anupriya; Jain, Keerti, E-mail: keertijain02@gmail.com; Mehra, Neelesh Kumar, E-mail: neelesh81mph@gmail.com; Jain, N. K., E-mail: dr.jnarendr@gmail.com [Dr. H. S. Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India)

    2013-10-15

    In the present investigation, poly (propylene imine) dendrimers up to fifth generation (PPI G5.0) were synthesized using ethylene diamine and acrylonitrile. Lipoproteins (high-density lipoprotein; HDL and low-density lipoprotein; LDL) were isolated from human plasma by discontinuous density gradient ultracentrifugation, characterized and tethered to G5.0 PPI dendrimers to construct LDL- and HDL-conjugated dendrimeric nanoconstructs for tumor-specific delivery of docetaxel. Developed formulations showed sustained release characteristics in in vitro drug release and in vivo pharmacokinetic studies. The cancer targeting potential of lipoprotein coupled dendrimers was investigated by ex vivo cytotoxicity and cell uptake studies using human hepatocellular carcinoma cell lines (HepG2 cells) and biodistribution studies in albino rats of Sprague-Dawley strain. Lipoprotein anchored dendrimeric nanoconstructs showed significant uptake by cancer cells as well as higher biodistribution of docetaxel to liver and spleen. It is concluded that these precisely synthesized engineered dendrimeric nanoconstructs could serve as promising drug carrier for fighting with the fatal disease, i.e., cancer, attributed to their defined targeting and therapeutic potential.

  11. Low density lipoproteins mediated nanoplatforms for cancer targeting

    International Nuclear Information System (INIS)

    Jain, Anupriya; Jain, Keerti; Kesharwani, Prashant; Jain, Narendra K.

    2013-01-01

    Chemotherapy is a foremost remedial approach for the treatment of localized and metastasized tumors. In order to explore new treatment modalities for cancer, it is important to identify qualitative or quantitative differences in metabolic processes between normal and malignant cells. One such difference may be that of increased receptor-mediated cellular uptake of low density lipoproteins (LDLs) by cancer cells. Lipoproteins in general and specifically LDL are ideal candidates for loading and delivering cancer therapeutic and diagnostic agents due to their biocompatibility. By mimicking the endogenous shape and structure of lipoproteins, the reconstituted lipoproteins can remain in circulation for an extended period of time, while largely evading the reticuloendothelial cells in the body’s defenses. In this account, we review the field of low density inspired nanoparticles in relation to the delivery of cancer imaging and therapeutic agents. LDL has instinctive cancer targeting potential and has been used to incorporate various lipophillic molecules to transport them to tumors. Nature’s method of rerouting LDL provides a strategy to extend the cancer targeting potential of lipoproteins far off its constricted purview. In this review, we have discussed the various aspects of LDL including its role in cancer imaging and chemotherapy in retrospect and prospect and current efforts aimed to further improve the delivery efficacy of LDL–drug complexes with reduced chances of drug resistance leading to optimal drug delivery. This review provides a strong support for the concept of using LDL as a drug carrier

  12. Structural insights into high density lipoprotein: Old models and new facts

    Directory of Open Access Journals (Sweden)

    Valentin eGogonea

    2016-01-01

    Full Text Available The physiological link between circulating high density lipoprotein (HDL levels and cardiovascular disease is well documented, albeit its intricacies are not well understood. An improved appreciation of HDL function and overall role in vascular health and disease requires at its foundation a better understanding of the lipoprotein's molecular structure, its formation, and its process of maturation through interactions with various plasma enzymes and cell receptors that intervene along the pathway of reverse cholesterol transport. This review focuses on summarizing recent developments in the field of lipid free apoA-I and HDL structure, with emphasis on new insights revealed by newly published nascent and spherical HDL models constructed by combining low resolution structures obtained from small angle neutron scattering (SANS with contrast variation and geometrical constraints derived from hydrogen-deuterium exchange (HDX, crosslinking mass spectrometry, electron microscopy, Förster resonance energy transfer, and electron spin resonance. Recently published low resolution structures of nascent and spherical HDL obtained from SANS with contrast variation and isotopic labeling of apolipoprotein A-I (apoA-I will be critically reviewed and discussed in terms of how they accommodate existing biophysical structural data from alternative approaches. The new low resolution structures revealed and also provided some answers to long standing questions concerning lipid organization and particle maturation of lipoproteins. The review will discuss the merits of newly proposed SANS based all atom models for nascent and spherical HDL, and compare them with accepted models. Finally, naturally occurring and bioengineered mutations in apoA-I, and their impact on HDL phenotype, are reviewed and discuss together with new therapeutics employed for restoring HDL function.

  13. Experimental hypothyroidism modulates the expression of the low density lipoprotein receptor by the liver

    International Nuclear Information System (INIS)

    Scarabottolo, Lia; Trezzi, Ermanno; Roma, Paola; Catapano, A.L.

    1986-01-01

    The effect of exprimental hypothyroidism of the catabolism of plasma lipoproteins and on the expression of low density lipoprotein receptors by the liver was investigated in rats made hypothyroid by surgery. The animals developed mild hypercholesterolemia, mainly due to an increase of plasma low density lipoprotein, while other lipoprotein classes were only marginally affected. Kinetic studies using ( 125 I)LDL indicated that a decreased fractional catabolic rate of the lipoprotein was responsible for this finding in agreement with the in vitro observation of a reduced binding of lipoproteins to liver membranes from hyperthyroid rats and with the demonstrations, by ligand blotting analysis, of a decreasd expression of lipoprotein receptors in liver membranes. These data suggest that hypothyroidism affects lipoprotein distribution also by decreasing the catabolism of low density lipoproteins by the liver (author)

  14. Macrophage cholesterol efflux correlates with lipoprotein subclass distribution and risk of obstructive coronary artery disease in patients undergoing coronary angiography

    Directory of Open Access Journals (Sweden)

    Kremer Werner

    2009-04-01

    Full Text Available Abstract Background Studies in patients with low HDL have suggested that impaired cellular cholesterol efflux is a heritable phenotype increasing atherosclerosis risk. Less is known about the association of macrophage cholesterol efflux with lipid profiles and CAD risk in normolipidemic subjects. We have therefore measured macrophage cholesterol efflux in142 normolipidemic subjects undergoing coronary angiography. Methods Monocytes isolated from blood samples of patients scheduled for cardiac catheterization were differentiated into macrophages over seven days. Isotopic cholesterol efflux to exogenously added apolipoprotein A-I and HDL2 was measured. Quantitative cholesterol efflux from macrophages was correlated with lipoprotein subclass distribution in plasma from the same individuals measured by NMR-spectroscopy of lipids and with the extent of coronary artery disease seen on coronary angiography. Results Macrophage cholesterol efflux was positively correlated with particle concentration of smaller HDL and LDL particles but not with total plasma concentrations of HDL or LDL-cholesterol. We observed an inverse relationship between macrophage cholesterol efflux and the concntration of larger and triglyceride rich particles (VLDL, chylomicrons. Subjects with significant stenosis on coronary angiography had lower cholesterol efflux from macrophages compared to individuals without significant stenosis (adjusted p = 0.02. Conclusion Macrophage cholesterol efflux is inversely correlated with lipoprotein particle size and risk of CAD.

  15. Auto antibodies against oxidized low density lipoprotein in severe preeclampsia.

    Science.gov (United States)

    Jain, Meenakshi; Sawhney, Harjeet; Aggarwal, Neelam; Vashistha, Kala; Majumdhar, Siddarth

    2004-06-01

    To study autoantibody titres against oxidized low density lipoprotein in preeclamsia. Ten millimeters of heparinized blood samples were collected from 20 primigravidae with severe preeclamsia (study group) and 20 gestation-matched normotensive primigravidae (control group). Concentration of malondialdehyde, metabolite of lipid peroxidation were measured in sera by HPLC and autoantibodies against oxidized low density lipoproteins (obtained after oxidation with 2 mm CuSO(4)) were determined by ELISA. Statistical analysis was performed by Student's t-test and chi(2) test. Mean triglyceride levels were significantly (P /=1.32). In preeclamptic women, diastolic blood pressure, the amount of urinary protein excretion and the plasma level of urea were significantly higher (P < 0.05) in patients with higher auto antibody titre. Titres of autoantibodies to oxidized low density lipoprotein were similar in normotensive and preeclamptic women. In preeclamptic women, titres correlated positively with the severity of preeclampsia.

  16. Transvascular lipoprotein transport in patients with chronic renal disease

    DEFF Research Database (Denmark)

    Jensen, Trine Krogsgaard; Nordestgaard, Børge Grønne; Feldt-Rasmussen, Bo

    2004-01-01

    BACKGROUND: While increased plasma cholesterol is a well-established cardiovascular risk factor in the general population, this is not so among patients with chronic renal disease. We hypothesized that the transvascular lipoprotein transport, in addition to the lipoprotein concentration in plasma......, determines the degree of atherosclerosis among patients with chronic renal disease. METHODS: We used an in vivo method for measurement of transvascular transport of low-density lipoprotein (LDL) in 21 patients with chronic renal disease and in 42 healthy control patients. Autologous 131-iodinated LDL...... was reinjected intravenously, and the 1-hour fractional escape rate was taken as index of transvascular transport. RESULTS: Transvascular LDL transport tended to be lower in patients with chronic renal disease than in healthy control patients [3.3 (95% CI 2.4-4.2) vs. 4.2 (3.7-4.2)%/hour; NS]. However...

  17. Oxidized low-density lipoprotein in postmenopausal women

    DEFF Research Database (Denmark)

    Jankowski, Vera; Just, Alexander R; Pfeilschifter, Johannes

    2014-01-01

    BACKGROUND: Oxidized low-density lipoprotein (oxLDL) leads to atherosclerosis and cardiovascular disease, the most frequent causes of death worldwide. After menopause, lipid and lipoprotein metabolism changes and women are at greater risk of cardiovascular disease compared to fertile women. The aim...... arteries was conducted and blood was drawn from 533 postmenopausal women. oxLDL concentration was determined using proton NMR spectroscopy. RESULTS: Oxidized LDL was detected in 12.4% (95% confidence interval 9.7-15.5) of postmenopausal women with a median of 0.18 mg/dl (interquartile range 0.......10-0.43). Although intima-media thickness did not differ, postmenopausal women with serous oxLDL had more often atherosclerotic plaques compared to women without oxLDL (6/66 vs. 0/467; P lipoprotein, impaired glucose intolerance, and DBP were independently associated...

  18. Lipids, Lipoproteins, and Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Katayoon B. Ebrahimi

    2011-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness among the elderly. While excellent treatment has emerged for neovascular disease, treatment for early AMD is lacking due to an incomplete understanding of the early molecular events. A prominent age-related change is the accumulation of neutral lipid in normal Bruch's membrane (BrM throughout adulthood and also disease-related BrM accumulations called basal deposits and drusen. AMD lesion formation has thus been conceptualized as sharing mechanisms with atherosclerotic plaque formation, where low-density lipoprotein (LDL retention within the arterial wall initiates a cascade of pathologic events. However, we do not yet understand how lipoproteins contribute to AMD. This paper explores how systemic and local production of lipoproteins might contribute to the pathogenesis of AMD.

  19. [Nicotinic acid increases cellular transport of high density lipoprotein cholesterol in patients with hypoalphalipoproteinemia].

    Science.gov (United States)

    Figueroa, Catalina; Droppelmann, Katherine; Quiñones, Verónica; Amigo, Ludwig; Mendoza, Camila; Serrano, Valentina; Véjar, Margarita; Maiz, Alberto; Rigotti, Attilio

    2015-09-01

    Plasma high density lipoproteins (HDL) are involved in reverse cholesterol transport mediated by the scavenger receptor class B type I (SR-BI). Nicotinic acid increases HDL cholesterol levels, even though its specific impact on SR-BI dependent-cellular cholesterol transport remains unknown. To determine the effect of nicotinic acid on HDL particle functionality in cholesterol efflux and uptake mediated by SR-BI in cultured cells in hypoalphalipoproteinemic patients. In a pilot study, eight patients with low HDL (≤ 40 mg/dL) were treated with extended release nicotinic acid. HDL cholesterol and phospholipid levels, HDL2 and HDL3 fractions and HDL particle sizes were measured at baseline and post-therapy. Before and after nicotinic acid treatment, HDL particles were used for cholesterol transport studies in cells transfected with SR-BI. Nicotinic acid treatment raised total HDL cholesterol and phospholipids, HDL2 levels as well as HDL particle size. Nicotinic acid significantly increased HDL cholesterol efflux and uptake capacity mediated by SR-BI in cultured cells. Nicotinic acid therapy increases SR-BI-dependent HDL cholesterol transport in cultured cells, establishing a new cellular mechanism by which this lipid-lowering drug appears to modulate HDL metabolism in patients with hypoalphalipoproteinemia.

  20. Human endothelial progenitor cells internalize high-density lipoprotein.

    Directory of Open Access Journals (Sweden)

    Kaemisa Srisen

    Full Text Available Endothelial progenitor cells (EPCs originate either directly from hematopoietic stem cells or from a subpopulation of monocytes. Controversial views about intracellular lipid traffic prompted us to analyze the uptake of human high density lipoprotein (HDL, and HDL-cholesterol in human monocytic EPCs. Fluorescence and electron microscopy were used to investigate distribution and intracellular trafficking of HDL and its associated cholesterol using fluorescent surrogates (bodipy-cholesterol and bodipy-cholesteryl oleate, cytochemical labels and fluorochromes including horseradish peroxidase and Alexa Fluor® 568. Uptake and intracellular transport of HDL were demonstrated after internalization periods from 0.5 to 4 hours. In case of HDL-Alexa Fluor® 568, bodipy-cholesterol and bodipy-cholesteryl oleate, a photooxidation method was carried out. HDL-specific reaction products were present in invaginations of the plasma membrane at each time of treatment within endocytic vesicles, in multivesicular bodies and at longer periods of uptake, also in lysosomes. Some HDL-positive endosomes were arranged in form of "strings of pearl"- like structures. HDL-positive multivesicular bodies exhibited intensive staining of limiting and vesicular membranes. Multivesicular bodies of HDL-Alexa Fluor® 568-treated EPCs showed multilamellar intra-vacuolar membranes. At all periods of treatment, labeled endocytic vesicles and organelles were apparent close to the cell surface and in perinuclear areas around the Golgi apparatus. No HDL-related particles could be demonstrated close to its cisterns. Electron tomographic reconstructions showed an accumulation of HDL-containing endosomes close to the trans-Golgi-network. HDL-derived bodipy-cholesterol was localized in endosomal vesicles, multivesicular bodies, lysosomes and in many of the stacked Golgi cisternae and the trans-Golgi-network Internalized HDL-derived bodipy-cholesteryl oleate was channeled into the lysosomal

  1. Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G

    2016-01-01

    Scientific interest in triglyceride-rich lipoproteins has fluctuated over the past many years, ranging from beliefs that these lipoproteins cause atherosclerotic cardiovascular disease (ASCVD) to being innocent bystanders. Correspondingly, clinical recommendations have fluctuated from a need.......1-fold for myocardial infarction, 3.2-fold for ischemic heart disease, 3.2-fold for ischemic stroke, and 2.2-fold for all-cause mortality. Also, genetic studies using the Mendelian randomization design, an approach that minimizes problems with confounding and reverse causation, now demonstrate...

  2. Lipoprotein(a) accelerates atherosclerosis in uremic mice

    DEFF Research Database (Denmark)

    Pedersen, Tanja X; McCormick, Sally P; Tsimikas, Sotirios

    2010-01-01

    Uremic patients have increased plasma lipoprotein(a) [Lp(a)] levels and elevated risk of cardiovascular disease. Lp(a) is a subfraction of LDL, where apolipoprotein(a) [apo(a)] is disulfide bound to apolipoprotein B-100 (apoB). Lp(a) binds oxidized phospholipids (OxPL), and uremia increases...... lipoprotein-associated OxPL. Thus, Lp(a) may be particularly atherogenic in a uremic setting. We therefore investigated whether transgenic (Tg) expression of human Lp(a) increases atherosclerosis in uremic mice. Moderate uremia was induced by 5/6 nephrectomy (NX) in Tg mice with expression of human apo(a) (n...

  3. IDOL stimulates clathrin-independent endocytosis and multivesicular body-mediated lysosomal degradation of the low-density lipoprotein receptor.

    Science.gov (United States)

    Scotti, Elena; Calamai, Martino; Goulbourne, Chris N; Zhang, Li; Hong, Cynthia; Lin, Ron R; Choi, Jinkuk; Pilch, Paul F; Fong, Loren G; Zou, Peng; Ting, Alice Y; Pavone, Francesco S; Young, Stephen G; Tontonoz, Peter

    2013-04-01

    The low-density lipoprotein receptor (LDLR) is a critical determinant of plasma cholesterol levels that internalizes lipoprotein cargo via clathrin-mediated endocytosis. Here, we show that the E3 ubiquitin ligase IDOL stimulates a previously unrecognized, clathrin-independent pathway for LDLR internalization. Real-time single-particle tracking and electron microscopy reveal that IDOL is recruited to the plasma membrane by LDLR, promotes LDLR internalization in the absence of clathrin or caveolae, and facilitates LDLR degradation by shuttling it into the multivesicular body (MVB) protein-sorting pathway. The IDOL-dependent degradation pathway is distinct from that mediated by PCSK9 as only IDOL employs ESCRT (endosomal-sorting complex required for transport) complexes to recognize and traffic LDLR to lysosomes. Small interfering RNA (siRNA)-mediated knockdown of ESCRT-0 (HGS) or ESCRT-I (TSG101) components prevents IDOL-mediated LDLR degradation. We further show that USP8 acts downstream of IDOL to deubiquitinate LDLR and that USP8 is required for LDLR entry into the MVB pathway. These results provide key mechanistic insights into an evolutionarily conserved pathway for the control of lipoprotein receptor expression and cellular lipid uptake.

  4. High-density lipoproteins and adrenal steroidogenesis : A population-based study

    NARCIS (Netherlands)

    Buitenwerf, Edward; Kerstens, Michiel N.; Links, Thera P.; Kema, Ido P.; Dullaart, Robin P. F.

    BACKGROUND: Cholesterol trafficked within plasma lipoproteins, in particular high-density lipoproteins (HDL), may represent an important source of cholesterol that is required for adrenal steroidogenesis. Based on a urinary gas chromatography method, compromised adrenal function has been suggested

  5. DMPD: Low density lipoprotein oxidation and its pathobiological significance. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 9261091 Low density lipoprotein oxidation and its pathobiological significance. Ste...in oxidation and its pathobiological significance. PubmedID 9261091 Title Low density lipoprotein oxidation and its pathobiol

  6. Single step reconstitution of multifunctional high-density lipoprotein-derived nanomaterials using microfluidics

    NARCIS (Netherlands)

    Kim, Yongtae; Fay, Francois; Cormode, David P.; Sanchez-Gaytan, Brenda L.; Tang, Jun; Hennessy, Elizabeth J.; Ma, Mingming; Moore, Kathryn; Farokhzad, Omid C.; Fisher, Edward Allen; Mulder, Willem J. M.; Langer, Robert; Fayad, Zahi A.

    2013-01-01

    High-density lipoprotein (HDL) is a natural nanoparticle that transports peripheral cholesterol to the liver. Reconstituted high-density lipoprotein (rHDL) exhibits antiatherothrombotic properties and is being considered as a natural treatment for cardiovascular diseases. Furthermore, HDL

  7. Lifecycle of a Lipoprotein from a Biophysical Perspective

    Science.gov (United States)

    Rutledge, John C.; Huser, Thomas; Voss, John; Chan, James; Parikh, Atul

    The goal of our project was to understand how lipids and lipoproteins interact with cell membranes. This chapter will present the five major areas in which we have focused our attention on understanding how lipids and lipoproteins interact with cell membranes (Fig. 11.1): (1) triglycerides and vascular injury, (2) single lipoprotein analysis, (3) apolipoprotein E (apoE) conformation changes in the postprandial state, (4) triglyceride-rich lipoproteins (TGRLs) and endothelial cell inflammation, and (5) TGRL lipolysis products and monocyte activation. For over a hundred years, Western civilization has questioned how the food we eat translates into disease, and specifically atherosclerotic cardiovascular disease. Although most information indicates that this basic pathophysiological process is mediated through consumption of excess saturated fats, much remains unknown. After humans eat a meal, there is an elevation of triglycerides in the blood in the postprandial state. In normal individuals, triglycerides can rise after a meal by 50 to 100%. This has been documented many times in the past, including a paper by Hyson et al, (1998) [1]. In that study, normal healthy individuals were given a 40%-fat meal. Plasma triglycerides, which were modestly elevated initially, rose about 60% higher three to four hours after ingestion of the meal. Subsequently plasma triglycerides fell to baseline levels six hours after the meal. Even in these healthy individuals, a significant elevation of triglycerides was noted after ingestion of a moder ately high-fat meal.

  8. Human Low Density Lipoprotein as a Vehicle of Atherosclerosis ...

    African Journals Online (AJOL)

    Low-density lipoproteins have been sufficiently established as an important precursor of atherosclerosis. The actual mechanism is still unclear, and the current technique of using radioisotopes has clinical limitation. However, the current study techniques or methods excellently elucidate the functional aspects of ...

  9. Interaction of low density lipoproteins with rat liver cells

    NARCIS (Netherlands)

    L. Harkes (Leendert)

    1985-01-01

    textabstractThe most marked conclusion is the establishment of the important role of non-parenchymal cells in the catabolism of the low density lipoproteins by the rat liver. Because the liver is responsible for 70-80% of the removal of LDL from blood this conclusion can be extended to total

  10. Low-density lipoprotein cholesterol and risk of gallstone disease

    DEFF Research Database (Denmark)

    Stender, Stefan; Frikke-Schmidt, Ruth; Benn, Marianne

    2013-01-01

    Drugs which reduce plasma low-density lipoprotein cholesterol (LDL-C) may protect against gallstone disease. Whether plasma levels of LDL-C per se predict risk of gallstone disease remains unclear. We tested the hypothesis that elevated LDL-C is a causal risk factor for symptomatic gallstone...

  11. Serum lipid and lipoprotein patterns of Iranian horses.

    Science.gov (United States)

    Asadi, F; Asadian, P; Shahriari, A; Pourkabir, M; Kazemi, A

    2011-12-01

    Patterns of serum biochemical parameters vary among horse breeds. The objective of the present study was to compare serum lipoproteins of Iranian Caspian ponies with those of other horses (Arabs and Thoroughbreds) in the Iranian region. Serum lipoprotein values were determined by agar-agarose gel electrophoresis and measured by scan densitometry. Moreover, serum triglyceride and cholesterol concentrations were determined and the results were analysed by one-way analysis of variance. Serum triglyceride and cholesterol values were 1.13 +/- 0.23 and 2.38 +/- 0.18 mmol/l in Caspian ponies, 1.96 +/- 0.49 and 1.92 +/- 0.25 mmol/l in Arab horses and 1.38 +/- 0.26 and 2.17 +/- 0.53 mmol/l in Thoroughbred horses. The relative percentages of alpha- (72.63 +/- 17.76%) and beta-lipoproteins (29.10 +/- 5.49%) in serum electrophoretic tracings from Caspian ponies were not significantly different from those of other horses (p > 0.05). The lipoprotein phenotype in Caspian ponies may be useful for evaluating metabolic diseases.

  12. Evaluation of Homocysteine, Lipoprotein(a) and Endothelin as ...

    African Journals Online (AJOL)

    Indians have been reported to have high prevalence rates of coronary artery disease (CAD) even in the absence of traditional risk factors. The objective of this study was to assess the role of endothelin, lipoprotein(a), homocysteine and lipid profile as markers of CAD in Indian population. It was a hospital based ...

  13. High density lipoproteins, dyslipidemia, and coronary heart disease

    National Research Council Canada - National Science Library

    2010-01-01

    ... with premature coronary heart disease (CHD). These familial disorders include lipoprotein(a) excess, dyslipidemia (high triglycerides and low HDL), combined hyperlipidemia (high cholesterol and high triglycerides often with low HDL), hypoalphalipoproteinemia (low HDL), and hypercholesterolemia. We discuss the management of these disorders. W...

  14. Role of oxidized low-density lipoprotein in renal disease

    NARCIS (Netherlands)

    Heeringa, P; Tervaert, JWC

    Accelerated atherosclerosis is often observed in patients with chronic renal failure. In the present review we summarize and discuss the recent literature on the pathogenic role of low-density lipoproteins modified by oxidative processes in atherosclerosis and the possible role in renal diseases.

  15. Antioxidant activity of high-density lipoprotein (HDL) using different ...

    African Journals Online (AJOL)

    HDL is a potent antioxidant in terms of inhibition of lipid peroxidation, ROS production and LDL oxidation. These may to some extent add to the antiatherogenic beyond reverse-cholesterol transport properties of HDL. Keywords: high-density lipoprotein; reverse cholesterol transport; apolipoprotein A1; antioxidant; in vitro.

  16. Unfavorable apoAI-containing lipoproteins profile in Tunisian obese ...

    African Journals Online (AJOL)

    hope&shola

    HDL-Chol and an excess of small dense LDL fractions. We have no information concerning the profile of. apoAI-containing lipoproteins. The investigation of the impact of obesity on this profile is the principal objective of our study. MATERIALS AND METHODS. Subjects. On the basis of the body weight excess, two volunteer ...

  17. Evaluation of plasma lipids and lipoproteins in nigerians suffering ...

    African Journals Online (AJOL)

    There are conflicting reports on the role of plasma lipids in depressive illness. Very little is known about the lipid and lipoprotein status in Nigerian adults suffering from depression. One hundred subjects consisting of sixty (60) depressed patients with mean age (40.3±12.3 yrs) and forty (40) apparently healthy controls ...

  18. Lipoprotein metabolism in hypothyroidism : the contribution of growth hormone

    NARCIS (Netherlands)

    N. Hoogerbrugge (Nicoline)

    1992-01-01

    textabstractCurrent data suggest a role for GH in the regulation of lipoprotein metabolism. In hypothyroidism not only the secretion of thyroid hormone, but also of GH is decreased. Generally the effects on plasma lipids seen in hypothyroid individuals are considered to be a consequence of

  19. Lipoprotein Lipase Maintains Microglial Innate Immunity in Obesity

    NARCIS (Netherlands)

    Gao, Yuanqing; Vidal-Itriago, Andrés; Kalsbeek, Martin J; Layritz, Clarita; García-Cáceres, Cristina; Tom, Robby Zachariah; Eichmann, Thomas O; Vaz, Frédéric M; Houtkooper, Riekelt H; van der Wel, Nicole; Verhoeven, Arthur J; Yan, Jie; Kalsbeek, A.; Eckel, Robert H; Hofmann, Susanna M; Yi, Chun-Xia

    2017-01-01

    Consumption of a hypercaloric diet upregulates microglial innate immune reactivity along with a higher expression of lipoprotein lipase (Lpl) within the reactive microglia in the mouse brain. Here, we show that knockdown of the Lpl gene specifically in microglia resulted in deficient microglial

  20. Serological response to the outer membrane lipoprotein in animal brucellosis.

    OpenAIRE

    Gómez-Miguel, M J; Moriyón, I; Alonso-Urmeneta, B; Riezu-Boj, J I; Díaz, R

    1988-01-01

    The presence of antibodies to Brucella outer membrane lipoprotein was investigated in cattle and rams. Low but significant amounts of antibody were detected in sera from B. abortus-infected cattle and from B. ovis-infected rams which had developed epididymitis. Strain-19-vaccinated cattle also showed a weak albeit transient antibody response.

  1. High density lipoproteins (HDLs) and atherosclerosis; the unanswered questions

    NARCIS (Netherlands)

    Barter, Philip; Kastelein, John; Nunn, Alistair; Hobbs, Richard

    2003-01-01

    The concentration of high density lipoprotein-cholesterol (HDL-C) has been found consistently to be a powerful negative predictor of premature coronary heart disease (CHD) in human prospective population studies. There is also circumstantial evidence from human intervention studies and direct

  2. Analyzing the molecular mechanism of lipoprotein localization in Brucella

    CSIR Research Space (South Africa)

    Goolab, S

    2015-10-01

    Full Text Available . This is partly due to the complexity of the organism and evasive tactics used to escape the host immune system, the variation in biological structure and activity of lipoproteins, combined with the complex nature of the translocation machinery. The biosynthetic...

  3. Efficacy of lovastatin on learning and memory deficits caused by chronic intermittent hypoxia-hypercapnia: through regulation of NR2B-containing NMDA receptor-ERK pathway.

    Directory of Open Access Journals (Sweden)

    Xin-long Huo

    Full Text Available BACKGROUND: Chronic intermittent hypoxia-hypercapnia (CIHH exposure leads to learnning and memory deficits in rats. Overactivation of N-methyl-D-aspartate receptors(NMDARs can lead to the death of neurons through a process termed excitotoxicity, which is involved in CIHH-induced cognitive deficits. Excessively activated NR2B (GluN2B-containing NMDARs was reported as the main cause of excitotoxicity. The ERK1/2 (extracellular signal-regulated kinase 1/2 signaling cascade acts as a key component in NMDARs-dependent neuronal plasticity and survival. Ca2+/calmodulin-dependent protein kinase II (CaMKII, synapse-associated protein 102 (SAP102 and Ras GTPase-activating protein (SynGAP have been shown to be involved in the regulation of NMDAR-ERK signalling cascade. Recent studies revealed statins (the HMG-CoA reductase inhibitor have effect on the expression of NMDARs. The present study intends to explore the potential effect of lovastatin on CIHH-induced cognitive deficits and the NR2B-ERK signaling pathway. METHODS AND FINDINGS: Eighty male Sprague Dawley rats were randomly divided into five groups. Except for those in the control group, the rats were exposed to chronic intermittent hypoxia-hypercapnia (CIHH (9 ∼ 11%O2, 5.5 ∼ 6.5%CO2 for 4 weeks. After lovastatin administration, the rats performed better in the Morris water maze test. Electron microscopy showed alleviated hippocampal neuronal synaptic damage. Further observation suggested that either lovastatin or ifenprodil (a selective NR2B antagonist administration similarly downregulated NR2B subunit expression leading to a suppression of CaMKII/SAP102/SynGAP signaling cascade, which in turn enhanced the phosphorylation of ERK1/2. The phosphorylated ERK1/2 induced signaling cascade involving cAMP-response element-binding protein (CREB phosphorylation and brain-derived neurotrophic factor (BDNF activation, which is responsible for neuroprotection. CONCLUSIONS: These findings suggest that the

  4. Efficacy of lovastatin on learning and memory deficits caused by chronic intermittent hypoxia-hypercapnia: through regulation of NR2B-containing NMDA receptor-ERK pathway.

    Science.gov (United States)

    Huo, Xin-long; Min, Jing-jing; Pan, Cai-yu; Zhao, Cui-cui; Pan, Lu-lu; Gui, Fei-fei; Jin, Lu; Wang, Xiao-tong

    2014-01-01

    Chronic intermittent hypoxia-hypercapnia (CIHH) exposure leads to learnning and memory deficits in rats. Overactivation of N-methyl-D-aspartate receptors(NMDARs) can lead to the death of neurons through a process termed excitotoxicity, which is involved in CIHH-induced cognitive deficits. Excessively activated NR2B (GluN2B)-containing NMDARs was reported as the main cause of excitotoxicity. The ERK1/2 (extracellular signal-regulated kinase 1/2) signaling cascade acts as a key component in NMDARs-dependent neuronal plasticity and survival. Ca2+/calmodulin-dependent protein kinase II (CaMKII), synapse-associated protein 102 (SAP102) and Ras GTPase-activating protein (SynGAP) have been shown to be involved in the regulation of NMDAR-ERK signalling cascade. Recent studies revealed statins (the HMG-CoA reductase inhibitor) have effect on the expression of NMDARs. The present study intends to explore the potential effect of lovastatin on CIHH-induced cognitive deficits and the NR2B-ERK signaling pathway. Eighty male Sprague Dawley rats were randomly divided into five groups. Except for those in the control group, the rats were exposed to chronic intermittent hypoxia-hypercapnia (CIHH) (9 ∼ 11%O2, 5.5 ∼ 6.5%CO2) for 4 weeks. After lovastatin administration, the rats performed better in the Morris water maze test. Electron microscopy showed alleviated hippocampal neuronal synaptic damage. Further observation suggested that either lovastatin or ifenprodil (a selective NR2B antagonist) administration similarly downregulated NR2B subunit expression leading to a suppression of CaMKII/SAP102/SynGAP signaling cascade, which in turn enhanced the phosphorylation of ERK1/2. The phosphorylated ERK1/2 induced signaling cascade involving cAMP-response element-binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) activation, which is responsible for neuroprotection. These findings suggest that the ameliorative cognitive deficits caused by lovastatin

  5. Effect of Theobromine Consumption on Serum Lipoprotein Profiles in Apparently Healthy Humans with Low HDL-Cholesterol Concentrations.

    Science.gov (United States)

    Jacobs, Doris M; Smolders, Lotte; Lin, Yuguang; de Roo, Niels; Trautwein, Elke A; van Duynhoven, John; Mensink, Ronald P; Plat, Jogchum; Mihaleva, Velitchka V

    2017-01-01

    Scope: Theobromine is a major active compound in cocoa with allegedly beneficial effect on high-density-lipoprotein-cholesterol (HDL-CH). We have investigated the effect of theobromine (TB) consumption on the concentrations of triglyceride (TG) and cholesterol (CH) in various lipoprotein (LP) subclasses. Methods: In a randomized, double-blind, placebo-controlled, cross-over study, 44 apparently healthy women and men (age: 60 ± 6 years, BMI: 29 ± 3 kg/m 2 ) with low baseline HDL-CH concentrations consumed a drink supplemented with 500 mg/d theobromine for 4 weeks. TG and CH concentrations in 15 LP subclasses were predicted from diffusion-edited 1 H NMR spectra of fasting serum. Results: The LP phenotype of the subjects was characterized by low CH concentrations in the large HDL particles and high TG concentrations in large VLDL and chylomicron (CM) particles, which clearly differed from a LP phenotype of subjects with normal HDL-CH. TB only reduced CH concentrations in the LDL particles by 3.64 and 6.79%, but had no effect on TG and CH in any of the HDL, VLDL and CM subclasses. Conclusion: TB was not effective on HDL-CH in subjects with a LP phenotype characterized by low HDL-CH and high TG in VLDL.

  6. Effect of Theobromine Consumption on Serum Lipoprotein Profiles in Apparently Healthy Humans with Low HDL-Cholesterol Concentrations

    Directory of Open Access Journals (Sweden)

    Doris M. Jacobs

    2017-08-01

    Full Text Available Scope: Theobromine is a major active compound in cocoa with allegedly beneficial effect on high-density-lipoprotein-cholesterol (HDL-CH. We have investigated the effect of theobromine (TB consumption on the concentrations of triglyceride (TG and cholesterol (CH in various lipoprotein (LP subclasses.Methods: In a randomized, double-blind, placebo-controlled, cross-over study, 44 apparently healthy women and men (age: 60 ± 6 years, BMI: 29 ± 3 kg/m2 with low baseline HDL-CH concentrations consumed a drink supplemented with 500 mg/d theobromine for 4 weeks. TG and CH concentrations in 15 LP subclasses were predicted from diffusion-edited 1H NMR spectra of fasting serum.Results: The LP phenotype of the subjects was characterized by low CH concentrations in the large HDL particles and high TG concentrations in large VLDL and chylomicron (CM particles, which clearly differed from a LP phenotype of subjects with normal HDL-CH. TB only reduced CH concentrations in the LDL particles by 3.64 and 6.79%, but had no effect on TG and CH in any of the HDL, VLDL and CM subclasses.Conclusion: TB was not effective on HDL-CH in subjects with a LP phenotype characterized by low HDL-CH and high TG in VLDL.

  7. Receptor-mediated endocytosis of insect lipoprotein : insight into LDL receptor functioning

    NARCIS (Netherlands)

    Hoof, Dennis van

    2004-01-01

    The extracellular transport of water-insoluble lipids through the aqueous circulatory system of animals is mediated by lipoproteins. The lipoprotein of insects, lipophorin (Lp), is homologous to that of mammalian low-density lipoprotein (LDL). Moreover, an endocytic receptor for Lp has been

  8. Hindiii and S447x polymorphisms of lipoprotein lipase gene and ...

    African Journals Online (AJOL)

    Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Lipoprotein lipase is a key enzyme in lipoprotein metabolism and its gene is a major candidate gene for coronary heart disease. The aim of the present work was to study the association of HindIII and S447X polymorphisms in lipoprotein ...

  9. 21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

    Science.gov (United States)

    2010-04-01

    ... device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a high-density lipoprotein) in serum and other body fluids. Measurement of lipoprotein X aids in the diagnosis of obstructive liver disease. (b) Classification. Class I (general controls). The device is exempt from the...

  10. Comparison of the DASH (Dietary Approaches to Stop Hypertension) diet and a higher-fat DASH diet on blood pressure and lipids and lipoproteins: a randomized controlled trial123

    Science.gov (United States)

    Chiu, Sally; Bergeron, Nathalie; Williams, Paul T; Bray, George A; Sutherland, Barbara; Krauss, Ronald M

    2016-01-01

    Background: The DASH (Dietary Approaches to Stop Hypertension) dietary pattern, which is high in fruit, vegetables, and low-fat dairy foods, significantly lowers blood pressure as well as low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. Objective: The study was designed to test the effects of substituting full-fat for low-fat dairy foods in the DASH diet, with a corresponding increase in fat and a reduction in sugar intake, on blood pressure and plasma lipids and lipoproteins. Design: This was a 3-period randomized crossover trial in free-living healthy individuals who consumed in random order a control diet, a standard DASH diet, and a higher-fat, lower-carbohydrate modification of the DASH diet (HF-DASH diet) for 3 wk each, separated by 2-wk washout periods. Laboratory measurements, which included lipoprotein particle concentrations determined by ion mobility, were made at the end of each experimental diet. Results: Thirty-six participants completed all 3 dietary periods. Blood pressure was reduced similarly with the DASH and HF-DASH diets compared with the control diet. The HF-DASH diet significantly reduced triglycerides and large and medium very-low-density lipoprotein (VLDL) particle concentrations and increased LDL peak particle diameter compared with the DASH diet. The DASH diet, but not the HF-DASH diet, significantly reduced LDL cholesterol, HDL cholesterol, apolipoprotein A-I, intermediate-density lipoprotein and large LDL particles, and LDL peak diameter compared with the control diet. Conclusions: The HF-DASH diet lowered blood pressure to the same extent as the DASH diet but also reduced plasma triglyceride and VLDL concentrations without significantly increasing LDL cholesterol. This trial was registered at clinicaltrials.gov as NCT01404897. PMID:26718414

  11. Alteration in lipoprotein lipase activity bound to triglyceride-rich lipoproteins in the postprandial state in type 2 diabetes

    NARCIS (Netherlands)

    Pruneta-Deloche, Valérie; Sassolas, Agnès; Dallinga-Thie, Geesje M.; Berthezène, François; Ponsin, Gabriel; Moulin, Philippe

    2004-01-01

    Postprandial lipid metabolism is largely dependent upon lipoprotein lipase (LPL), which hydrolyses triglycerides (TGs). The time course of LPL activity in the postprandial state following a single meal has never been studied, because its determination required heparin injection. Recently, we have

  12. Native High Density Lipoproteins (HDL Interfere with Platelet Activation Induced by Oxidized Low Density Lipoproteins (OxLDL

    Directory of Open Access Journals (Sweden)

    Ivo Volf

    2013-05-01

    Full Text Available Platelets and lipoproteins play a crucial role in atherogenesis, in part by their ability to modulate inflammation and oxidative stress. While oxidized low density lipoproteins (OxLDL play a central role in the development of this disease, high density lipoproteins (HDL represent an atheroprotective factor of utmost importance. As platelet function is remarkably sensitive to the influence of plasma lipoproteins, it was the aim of this study to clarify if HDL are able to counteract the stimulating effects of OxLDL with special emphasis on aspects of platelet function that are relevant to inflammation. Therefore, HDL were tested for their ability to interfere with pro-thrombotic and pro-inflammatory aspects of platelet function. We are able to show that HDL significantly impaired OxLDL-induced platelet aggregation and adhesion. In gel-filtered platelets, HDL decreased both the formation of reactive oxygen species and CD40L expression. Furthermore, HDL strongly interfered with OxLDL-induced formation of platelet-neutrophil aggregates in whole blood, suggesting that platelets represent a relevant and sensitive target for HDL. The finding that HDL effectively competed with the binding of OxLDL to the platelet surface might contribute to their atheroprotective and antithrombotic properties.

  13. Alterations in plasma lipoproteins and apolipoproteins before the age of 40 in heterozygotes for lipoprotein lipase deficiency

    NARCIS (Netherlands)

    Bijvoet, S.; Gagné, S. E.; Moorjani, S.; Gagné, C.; Henderson, H. E.; Fruchart, J. C.; Dallongeville, J.; Alaupovic, P.; Prins, M. [=Martin H.; Kastelein, J. J.; Hayden, M. R.

    1996-01-01

    We have assessed the expression of heterozygosity for lipoprotein lipase (LPL) deficiency by studying a single large French Canadian family comprising 92 persons including 21 carriers of the catalytically defective P207L mutation. Phenotypic changes distinguishing heterozygotes from controls were

  14. Testosterone increases the muscle protein synthesis rate but does not affect very-low-density lipoprotein metabolism in obese premenopausal women.

    Science.gov (United States)

    Wang, Xuewen; Smith, Gordon I; Patterson, Bruce W; Reeds, Dominic N; Kampelman, Janine; Magkos, Faidon; Mittendorfer, Bettina

    2012-03-15

    Men and women with hyperandrogenemia have a more proatherogenic plasma lipid profile [e.g., greater triglyceride (TG) and total and low-density lipoprotein-cholesterol and lower high-density lipoprotein-cholesterol concentrations] than healthy premenopausal women. Furthermore, castration of male rats markedly reduces testosterone availability below normal and decreases plasma TG concentration, and testosterone replacement reverses this effect. Testosterone is, therefore, thought to be an important regulator of plasma lipid homeostasis. However, little is known about the effect of testosterone on plasma TG concentration and kinetics. Furthermore, testosterone is a potent skeletal muscle protein anabolic agent in men, but its effect on muscle protein turnover in women is unknown. We measured plasma lipid concentrations, hepatic very low density lipoprotein (VLDL)-TG and VLDL-apolipoprotein B-100 secretion rates, and the muscle protein fractional synthesis rate in 10 obese women before and after trandermal testosterone (1.25 g of 1% AndroGel daily) treatment for 3 wk. Serum total and free testosterone concentrations increased (P testosterone treatment, reaching concentrations that are comparable to those in women with hyperandrogenemia, but lower than the normal range for eugonadal men. Except for a small (∼10%) decrease in plasma high-density lipoprotein particle and cholesterol concentrations (P testosterone therapy had no effect on plasma lipid concentrations, lipoprotein particle sizes, and hepatic VLDL-TG and VLDL-apolipoprotein B-100 secretion rates (all P > 0.05); the muscle protein fractional synthesis rate, however, increased by ∼45% (P testosterone is a potent skeletal muscle protein anabolic agent, but not an important regulator of plasma lipid homeostasis in obese women.

  15. Low-density lipoprotein apheresis: an evidence-based analysis.

    Science.gov (United States)

    2007-01-01

    To assess the effectiveness and safety of low-density lipoprotein (LDL) apheresis performed with the heparin-induced extracorporeal LDL precipitation (HELP) system for the treatment of patients with refractory homozygous (HMZ) and heterozygous (HTZ) familial hypercholesterolemia (FH). BACKGROUND ON FAMILIAL HYPERCHOLESTEROLEMIA: Familial hypercholesterolemia is a genetic autosomal dominant disorder that is caused by several mutations in the LDL-receptor gene. The reduced number or absence of functional LDL receptors results in impaired hepatic clearance of circulating low-density lipoprotein cholesterol (LDL-C) particles, which results in extremely high levels of LDL-C in the bloodstream. Familial hypercholesterolemia is characterized by excess LDL-C deposits in tendons and arterial walls, early onset of atherosclerotic disease, and premature cardiac death. Familial hypercholesterolemia occurs in both HTZ and HMZ forms. Heterozygous FH is one of the most common monogenic metabolic disorders in the general population, occurring in approximately 1 in 500 individuals. Nevertheless, HTZ FH is largely undiagnosed and an accurate diagnosis occurs in only about 15% of affected patients in Canada. Thus, it is estimated that there are approximately 3,800 diagnosed and 21,680 undiagnosed cases of HTZ FH in Ontario. In HTZ FH patients, half of the LDL receptors do not work properly or are absent, resulting in plasma LDL-C levels 2- to 3-fold higher than normal (range 7-15mmol/L or 300-500mg/dL). Most HTZ FH patients are not diagnosed until middle age when either they or one of their siblings present with symptomatic coronary artery disease (CAD). Without lipid-lowering treatment, 50% of males die before the age of 50 and 25% of females die before the age of 60, from myocardial infarction or sudden death. In contrast to the HTZ form, HMZ FH is rare (occurring in 1 case per million persons) and more severe, with a 6- to 8-fold elevation in plasma LDL-C levels (range 15-25mmol

  16. Sorting of bacterial lipoproteins to the outer membrane by the Lol system.

    Science.gov (United States)

    Narita, Shin-ichiro; Tokuda, Hajime

    2010-01-01

    Bacterial lipoproteins comprise a subset of membrane proteins with a lipid-modified cysteine residue at their amino termini through which they are anchored to the membrane. In Gram-negative bacteria, lipoproteins are localized on either the inner or the outer membrane. The Lol system is responsible for the transport of lipoproteins to the outer membrane.The Lol system comprises an inner-membrane ABC transporter LolCDE complex, a periplasmic carrier protein, LolA, and an outer membrane receptor protein, LolB. Lipoproteins are synthesized as precursors in the cytosol and then translocated across the inner membrane by the Sec translocon to the outer leaflet of the inner membrane, where lipoprotein precursors are processed to mature lipoproteins. The LolCDE complex then mediates the release of outer membrane-specific lipoproteins from the inner membrane while the inner membrane-specific lipoproteins possessing Asp at position 2 are not released by LolCDE because it functions as a LolCDE avoidance signal, causing the retention of these lipoproteins in the inner membrane. A water-soluble lipoprotein-LolA complex is formed as a result of the release reaction mediated by LolCDE. This complex traverses the hydrophilic periplasm to reach the outer membrane, where LolB accepts a lipoprotein from LolA and then catalyzes its incorporation into the inner leaflet of the outer membrane.

  17. High-Density Lipoproteins and the Immune System

    Directory of Open Access Journals (Sweden)

    Hidesuke Kaji

    2013-01-01

    Full Text Available High-density lipoprotein (HDL plays a major role in vasodilation and in the reduction of low-density lipoprotein (LDL oxidation, inflammation, apoptosis, thrombosis, and infection; however, HDL is now less functional in these roles under certain conditions. This paper focuses on HDL, its anti-inflammation behavior, and the mechanisms by which HDL interacts with components of the innate and adaptive immune systems. Genome-wide association studies (GWAS and proteomic studies have elucidated important molecules involved in the interaction between HDL and the immune system. An understanding of these mechanisms is expected to be useful for the prevention and treatment of chronic inflammation due to metabolic syndrome, atherosclerosis, or various autoimmune diseases.

  18. Nonalcoholic Fatty Liver Disease: Focus on Lipoprotein and Lipid Deregulation

    Directory of Open Access Journals (Sweden)

    Klementina Fon Tacer

    2011-01-01

    Full Text Available Obesity with associated comorbidities is currently a worldwide epidemic and among the most challenging health conditions in the 21st century. A major metabolic consequence of obesity is insulin resistance which underlies the pathogenesis of the metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD is the hepatic manifestation of obesity and metabolic syndrome. It comprises a disease spectrum ranging from simple steatosis (fatty liver, through nonalcoholic steatohepatitis (NASH to fibrosis, and ultimately liver cirrhosis. Abnormality in lipid and lipoprotein metabolism accompanied by chronic inflammation is the central pathway for the development of metabolic syndrome-related diseases, such as atherosclerosis, cardiovascular disease (CVD, and NAFLD. This paper focuses on pathogenic aspect of lipid and lipoprotein metabolism in NAFLD and the relevant mouse models of this complex multifactorial disease.

  19. Lipoprotein (a) as a cause of cardiovascular disease

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Langsted, Anne

    2016-01-01

    Human epidemiologic and genetic evidence using the Mendelian randomization approach in large-scale studies now strongly supports that elevated lipoprotein (a) [Lp(a)] is a causal risk factor for cardiovascular disease, that is, for myocardial infarction, atherosclerotic stenosis, and aortic valve...... with very high concentrations to reduce cardiovascular disease are awaited. Recent genetic evidence documents elevated Lp(a) as a cause of myocardial infarction, atherosclerotic stenosis, and aortic valve stenosis....

  20. Lipoprotein metabolism in hypothyroidism : the contribution of growth hormone

    OpenAIRE

    Hoogerbrugge, Nicoline

    1992-01-01

    textabstractCurrent data suggest a role for GH in the regulation of lipoprotein metabolism. In hypothyroidism not only the secretion of thyroid hormone, but also of GH is decreased. Generally the effects on plasma lipids seen in hypothyroid individuals are considered to be a consequence of decreased thyroid hormone levels. More then twenty years ago evidence was found that treatment of hypothyroid rats with GH in supraphysiologic doses affects plasma lipid concentrations, but whether a lack o...

  1. Apolipoprotein (A) Isoform Distribution and Plasma Lipoprotein (a ...

    African Journals Online (AJOL)

    Plasma lipoprotein (a) Concentrations and apo(a) isoforms were determined in 101 healthy Nigerian subjects (M=63), F=38; age range 17-68 years), and coronary heart disease (CHD) patients (M=19, F=17, age range 30-79 years). Median Lp(a) level was 24.4 mg/di in the CHD patients and 22.1 mg/di in the controls.

  2. Atherogenic Lipoprotein Subfractions Determined by Ion Mobility and First Cardiovascular Events After Random Allocation to High-Intensity Statin or Placebo: The Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) Trial.

    Science.gov (United States)

    Mora, Samia; Caulfield, Michael P; Wohlgemuth, Jay; Chen, Zhihong; Superko, H Robert; Rowland, Charles M; Glynn, Robert J; Ridker, Paul M; Krauss, Ronald M

    2015-12-08

    Cardiovascular disease (CVD) can occur in individuals with low low-density lipoprotein (LDL) cholesterol (LDL-C). We investigated whether detailed measures of LDL subfractions and other lipoproteins can be used to assess CVD risk in a population with both low LDL-C and high C-reactive protein who were randomized to high-intensity statin or placebo. In 11 186 Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) participants, we tested whether lipids, apolipoproteins, and ion mobility-measured particle concentrations at baseline and after random allocation to rosuvastatin 20 mg/d or placebo were associated with first CVD events (n=307) or CVD/all-cause death (n=522). In placebo-allocated participants, baseline LDL-C was not associated with CVD (adjusted hazard ratio [HR] per SD, 1.03; 95% confidence interval [CI], 0.88-1.21). In contrast, associations with CVD events were observed for baseline non-high-density lipoprotein (HDL) cholesterol (HR, 1.18; 95% CI, 1.01-1.38), apolipoprotein B (HR, 1.28; 95% CI, 1.11-1.48), and ion mobility-measured non-HDL particles (HR, 1.19; 95% CI, 1.05-1.35) and LDL particles (HR, 1.21; 95% CI, 1.07-1.37). Association with CVD events was also observed for several LDL and very-low-density lipoprotein subfractions but not for ion mobility-measured HDL subfractions. In statin-allocated participants, CVD events were associated with on-treatment LDL-C, non-HDL cholesterol, and apolipoprotein B; these were also associated with CVD/all-cause death, as were several LDL and very-low-density lipoprotein subfractions, albeit with a pattern of association that differed from the baseline risk. In JUPITER, baseline LDL-C was not associated with CVD events, in contrast with significant associations for non-HDL cholesterol and atherogenic particles: apolipoprotein B and ion mobility-measured non-HDL particles, LDL particles, and select subfractions of very-low-density lipoprotein particles and

  3. Correlation studies between serum concentrations of zinc and lipoproteins

    International Nuclear Information System (INIS)

    Saiki, Mitiko; Alves, Edson R.; Vasconcellos, M.B.A.; Sumita, Nairo M.; Jaluul, Omar; Jacob-Filho, Wilson

    2009-01-01

    In this study, serum zinc and lipoprotein concentrations were determined in order to assess the health status of an elderly population residing in Sao Paulo city, SP, Brazil. This population consisted of elderly considered healthy and participating of a 'Successful Ageing' program of the Sao Paulo University Medical School. Fasting blood samples were collected from 87 elderly individuals (63 females and 24 males) aged 60-91 and mean age of 72 +- 7 years. Zn concentrations were determined by neutron activation analysis at the IPEN/CNEN/ SP and, the lipoprotein (HDL, LDL and total cholesterol) concentrations were determined using routine analysis methods of the Central Laboratory Division, Hospital das Clinicas, FMUSP. Results obtained for Zn indicated that all the individuals presented this element within the recommended value. For total cholesterol and HDL-cholesterol concentrations, 96 % of elderly presented levels within the desired range but for LDL cholesterol concentrations only about 70.0 % of individuals were in the desired range. Serum concentration of Zn were positively correlated to LDL-cholesterol levels (correlation coefficient r = 0.21, p < 0.06). Furthermore, the ratios of [HDL-cholesterol] / [LDL-cholesterol] were negatively correlated with Zn concentrations (r = - 0.234, p < 0.04). The positive correlation found between the serum concentrations of Zn and LDL-cholesterol indicates the possible effect of this element in serum lipoprotein profiles. Thus ,these findings suggest that more investigations should be conducted on Zn supplementation in elderly subjects with cardiovascular diseases. (author)

  4. Comparison of a direct enzymatic assay and polyacrylamide tube gel electrophoresis for measurement of small, dense low-density lipoprotein cholesterol.

    Science.gov (United States)

    Vanavanan, Somlak; Srisawasdi, Pornpen; Rochanawutanon, Mana; Kerdmongkol, Jirapa; Kroll, Martin H

    2015-01-01

    Small, dense low-density lipoprotein cholesterol (sdLDL-C) has been linked to the progression of cardiovascular disease. We compared two methods for determination of sdLDL-C, a direct enzymatic (ENZ) method and a polyacrylamide tube gel electrophoresis (PGE) assay, and investigated the associations of both sdLDL-C measurements with metabolic syndrome. We analyzed 242 patient sera for sdLDL and atherosclerosis-related markers. The PGE method separates the intermediate-density lipoprotein particles into three midbands (MID-A to MID-C) and the LDL particles into seven subfractions (LDL1 to LDL7); the sdLDL-PGE result is calculated as the sum of cholesterol concentrations from LDL3 to LDL7. The regression equation for sdLDL-C was [ENZmmol/L]=0.779[PGE]+0.67, r=0.713. ENZ showed higher sdLDL-C concentrations than PGE (0.86±0.33 vs. 0.24±0.32 mmol/L); however, the difference was not associated with sdLDL-C concentration (p=0.290). sdLDL-C, as measured with the enzymatic assay, exhibited significant positive correlations with very-low-density lipoprotein, MID-C, MID-B, and LDL2 (all p0.600). The ENZ and PGE methods yielded similar patterns of correlation between sdLDL-C, and atherosclerosis-related markers. Using logistic regression, sdLDL-ENZ and apolipoprotein B were identified as significant predictors of metabolic syndrome (p<0.03). The ENZ assay for sdLDL-C correlated well with the PGE method. The ENZ method measures a broader range of atherogenic lipoprotein particles than PGE and has the potential to identify subjects with vascular risk, thus contributing in directing specific interventions for cardiovascular prevention.

  5. Assessment of anti-atherogenic drugs in vivo and reconstitution of lipoproteins using radioiodinated cholesteryl iopanoate

    International Nuclear Information System (INIS)

    DeGalan, M.R.

    1987-01-01

    A nonhydrolyzable radioiodinated cholesteryl ester, 125I-cholesteryl iopanoate (125I-Cl), was found to accumulate in high concentrations in atherosclerotic aortas of cholesterol-fed rabbits after intravenous administration. Aortas from normal chow-fed rabbits did not exhibit significant 125I-Cl accumulation. When cholesterol-fed rabbits were intravenously administered Tween-solubilized 125I-Cl and simultaneously treated with either of two anti-atherogenic compounds, estradiol 17β-cypionate or colestipol, the extent of aortic atherosclerosis was found to dramatically decrease. Measurement of aortic radioactivity was found to strongly correlate with the severity of atherosclerosis. Although the specificity of 125I-Cl for atheromatous lesions was very good, gamma-camera scintigraphy of the abdomens of these rabbits 6 days after cessation of 125I-Cl administration was not able to consistently predict the severity of atherosclerosis. Tissue distribution studies suggested that high blood and spinal column bone marrow radioactivity produced aorta:nontarget radioactivity ratios unfavorable with respect to imaging. To improve this ratio so as to permit noninvasive imaging, attempts were made to incorporate 125I-Cl into serum lipoproteins. Labelling of either rabbit LDL by in vivo incorporation or human LDL by transfer of 125I-Cl from liposomes using cholesteryl ester transfer protein resulted in lipoproteins with low specific activity. Higher specific activity was achieved by reconstituting delipidated human LDL with a mixture of 125I-Cl and unlabeled cholesteryl oleate. These particles were taken up in high amounts by monolayers of human fibroblasts but not by fibroblasts deficient in LDL receptors or by normal fibroblasts during competition with unlabeled native LDL

  6. Cosmic particles

    International Nuclear Information System (INIS)

    Fritszh, Harald; Max-Planck-Institut fuer Physik und Astrophysik, Muenchen

    1986-01-01

    The paper on 'Cosmic particles' was presented at the conference on 'The early universe and its evolution', Erice, Italy 1986. The link between ideas in cosmology and in elementary particle physics is examined. The subject is discussed under the following topic headings: cosmic kinetics, cosmic dynamics and general relativity, dynamics of the dust universe, particle physics, unity of quarks and leptons, the hot universe and standard particle physics, creation of matter, and the inflation of the universe. (U.K.)

  7. Strange particles

    International Nuclear Information System (INIS)

    Chinowsky, W.

    1989-01-01

    Work done in the mid 1950s at Brookhaven National Laboratory on strange particles is described. Experiments were done on the Cosmotron. The author describes his own and others' work on neutral kaons, lambda and theta particles and points out the theoretical gap between predictions and experimental findings. By the end of the decade, the theory of strange particles was better understood. (UK)

  8. [ANTIOXIDANT DYSFUNCTIONALITY OF HIGH-DENSITY LIPOPROTEINS (HDL) IN DECOMPENSATED DIABETIC PATIENTS].

    Science.gov (United States)

    Awad, Fernanda; Contreras-Duarte, Susana; Molina, Patricia; Quiñones, Verónica; Serrano, Valentina; Abbott, Eduardo; Maiz, Alberto; Busso, Dolores; Rigotti, Attilio

    2015-09-01

    high density lipoproteins (HDL) have important cardiovascular protective effects mediated by their role in reverse cholesterol transport as well as other functional activities, including significant anti-inflammatory and antioxidant properties. It has been shown that HDL anti-inflammatory and antioxidant functions are defective in metabolically stable diabetic patients; however they have not been evaluated during a hyperglycemic crisis. to determine the antioxidant activity of HDL during a severe diabetic decompensation and to analyze whether this function is restored after resolution of the acute event. the antioxidant activity of HDL was measured in vitro by a fluorescent assay in plasma samples obtained from diabetic patients with acute metabolic decompensation at admission, recovery within the hospital and follow-up in ambulatory care. As a comparison, HDL particles from some healthy subjects were used as controls. the HDL antioxidant function was significantly reduced in patients during an acute diabetic decompensation compared with the control group, and was gradually restored reaching normal values during the ambulatory follow-up. Hyperglycemic crisis also showed low plasma paraoxonase-1 activity, which increased significantly during at follow-up. HDL particles isolated from acute diabetic descompensated patients exhibit a significantly and reversibly low antioxidant capacity, which is probably due to a reduced paraoxonase-1 activity. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  9. Low density lipoprotein subclasses and response to a low-fat diet in healthy men

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, R.M.; Dreon, D.M. [Lawrence Berkeley Lab., CA (United States). Life Sciences Div.

    1994-11-01

    Lipid and lipoprotein response to reduced dietary fat intake was investigated in relation to differences in distribution of LDL subclasses among 105 healthy men consuming high-fat (46%) and low-fat (24%) diets in random order for six weeks each. On high-fat, 87 subjects had predominantly large, buoyant LDL as measured by gradient gel electrophoresis and confirmed by analytic ultracentrifugation (pattern A), while the remainder had primarily smaller, denser LDL (pattern B). On low-fat, 36 men changed from pattern A to B. Compared with the 51 men in the stable A group, men in the stable B group (n = 18) had a three-fold greater reduction in LDL cholesterol and significantly greater reductions in plasma apoB and mass of intermediate (LDL II) and small (LDL III) LDL subtractions measured by analytic ultracentrifugation. In both stable A and change groups, reductions in LDL-cholesterol were not accompanied by reduced plasma apoB, consistent with the observation of a shift in LDL particle mass from larger, lipid-enriched (LDL I and II) to smaller, lipid-depleted (LDL III and IV) subfractions, without significant change in particle number. Genetic and environmental factors influencing LDL subclass distributions thus may also contribute substantially to interindividual variation in response to a low-fat diet.

  10. Sorting of an integral outer membrane protein via the lipoprotein-specific Lol pathway and a dedicated lipoprotein pilotin.

    Science.gov (United States)

    Collin, Séverine; Guilvout, Ingrid; Nickerson, Nicholas N; Pugsley, Anthony P

    2011-05-01

    The lipoprotein PulS is a dedicated chaperone that is required to target the secretin PulD to the outer membrane in Klebsiella or Escherichia coli, and to protect it from proteolysis. Here, we present indirect evidence that PulD protomers do not assemble into the secretin dodecamer before they reach the outer membrane, and that PulS reaches the outer membrane in a soluble heterodimer with the general lipoprotein chaperone LolA. However, we could not find any direct evidence for PulD protomer association with the PulS-LolA heterodimer. Instead, in cells producing PulD and a permanently locked PulS-LolA dimer (in which LolA carries an R43L substitution that prevents lipoprotein transfer to LolB in the outer membrane), LolAR43L was found in the inner membrane, probably still associated with PulS bound to PulD that had been incorrectly targeted because of the LolAR43L substitution. It is speculated that PulD protomers normally cross the periplasm together with PulS bound to LolA but when the latter cannot be separated (due to the mutation in lolA), the PulD protomers form dodecamers that insert into the inner membrane. © 2011 Blackwell Publishing Ltd.

  11. Lipoprotein distribution and serum concentrations of 7α-hydroxy-4-cholesten-3-one and bile acids: effects of monogenic disturbances in high-density lipoprotein metabolism

    DEFF Research Database (Denmark)

    Steiner, Carine; Holleboom, Adriaan G; Karuna, Ratna

    2012-01-01

    distributions of the major 15 BA species and their precursor C4 (7a-hydroxy-4-cholesten-3-one). In normolipidaemic plasma, approximately 84%, 11% and 5% of BAs were recovered in the LPDS (lipoprotein-depleted serum), HDL and the combined LDL (low-density lipoprotein)/VLDL (very-low-density lipoproteins......) fraction respectively. Conjugated BAs were slightly over-represented in HDL. For C4, the respective percentages were 23%, 21% and 56% (41% in LDL and 15% in VLDL) respectively. Compared with unaffected family members, neither HDL-C (HDL-cholesterol)-decreasing mutations in the genes APOA1 [encoding Apo......BA (bile acid) formation is considered an important final step in RCT (reverse cholesterol transport). HDL (high-density lipoprotein) has been reported to transport BAs. We therefore investigated the effects of monogenic disturbances in human HDL metabolism on serum concentrations and lipoprotein...

  12. Associations between smoking, components of metabolic syndrome and lipoprotein particle size

    NARCIS (Netherlands)

    Slagter, Sandra N.; van Vliet-Ostaptchouk, Jana V.; Vonk, Judith M.; Boezen, H. Marike; Dullaart, Robin P. F.; Kobold, Anneke C. Muller; Feskens, Edith J.; van Beek, Andre P.; van der Klauw, Melanie M.; Wolffenbuttel, Bruce H. R.

    2013-01-01

    BACKGROUND: The clustering of metabolic and cardiovascular risk factors is known as metabolic syndrome (MetS). The risk of having MetS is strongly associated with increased adiposity and can be further modified by smoking behavior. Apolipoproteins (apo) associated with low-density

  13. Associations between smoking, components of metabolic syndrome and lipoprotein particle size

    NARCIS (Netherlands)

    Slagter, S.N.; Vliet-Ostaptchouk, J.V.; Vonk, J.M.; Boezen, H.M.; Dullaart, R.P.F.; Muller Kobold, A.C.; Feskens, E.J.M.; Beek, van A.P.; Klauw, van der M.M.; Wolffenbuttel, B.H.R.

    2013-01-01

    Background: The clustering of metabolic and cardiovascular risk factors is known as metabolic syndrome (MetS). The risk of having MetS is strongly associated with increased adiposity and can be further modified by smoking behavior. Apolipoproteins (apo) associated with low-density

  14. Oxidation of Cholesterol Does Not Alter Significantly Its Uptake into High-Density Lipoprotein Particles

    Czech Academy of Sciences Publication Activity Database

    Karilainen, T.; Timr, Štěpán; Vattulainen, I.; Jungwirth, Pavel

    2015-01-01

    Roč. 119, č. 13 (2015), s. 4594-4600 ISSN 1520-6106 R&D Projects: GA ČR GBP208/12/G016 Institutional support: RVO:61388963 Keywords : molecular dynamics * free energy profiles * cholesterol Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.187, year: 2015

  15. Proteinuria increases oxylipid concentrations in VLDL and HDL but not LDL particles in the rat.

    Science.gov (United States)

    Newman, John W; Kaysen, George A; Hammock, Bruce D; Shearer, Gregory C

    2007-08-01

    We previously established that proteinuria alters the apolipoprotein content of lipoproteins. This study was conducted to establish whether proteinuria also alters the concentrations of oxidized lipids within lipoprotein density fractions. To this end, we induced passive Heymann nephritis in Sprague Dawley rats and measured an array of alkaline-stable oxylipids in VLDL, LDL, and HDL particles. Proteinuria increased the total oxylipid amounts in the HDL and VLDL fractions. More importantly, these levels were increased when expressed per unit lipoprotein protein, indicating that the oxidized lipid load per particle was increased. Epoxides and diols increased approximately 2-fold in HDL and approximately 5-fold in VLDL, whereas LDL showed approximately 2-fold decreases. The hydroxyeicosatetraenoic acids and hydroxyoctadecadienoic acids (HODEs) increased >4-fold in HDL and >20-fold in VLDL, whereas LDL showed approximately 2-fold decreases in the HODEs. Therefore, nephrotic syndrome alters the lipoprotein oxylipid composition independently of an increase in total lipoprotein levels. These proteinuria-induced changes may be associated with the cardiovascular risk of lipoprotein oxidation.

  16. Recent advances in lipoprotein and atherosclerosis: A nutrigenomic approach

    Directory of Open Access Journals (Sweden)

    López, Sergio

    2009-03-01

    Full Text Available Atherosclerosis is a disease in which multiple factors contribute to the degeneration of the vascular wall. Many risk factors have been identified as having influence on the progression of atherosclerosis among them, the type of diet. Multifactorial interaction among lipoproteins, vascular wall cells, and inflammatory mediators has been recognised as the basis of atherogenesis. Dietary intake affects lipoprotein concentration and composition providing risk or protection at several stages of atherosclerosis. More intriguingly, it has been demonstrated that the extent to which each lipid or lipoprotein is associated with cardiovascular disease depends on the time to last meal; thus, postprandial lipoproteins, main lipoproteins in blood after a high-fat meal, have been shown to strongly influence atherogenesis. As a complex biological process, the full cellular and molecular characterization of atherosclerosis derived by diet, calls for application of the newly developing “omics” techniques of analysis. This review will considered recent studies using high-throughput technologies and a nutrigenomic approach to reveal the patho-physiological effects that the fasting and postprandial lipoproteins may exert on the vascular wall.La aterosclerosis es una enfermedad en la que múltiples factores, entre los que se encuentra la dieta, contribuyen a la degradación de la pared vascular. En la etiología de la aterogénesis son determinantes las lipoproteínas plasmáticas y los distintos tipos celulares de la pared vascular, incluyendo una respuesta inflamatoria. La ingesta de alimentos afecta la concentración y composición de las lipoproteínas, ejerciendo un papel de riesgo o protector durante las diferentes etapas del proceso aterosclerótico. Es importante destacar que la naturaleza de las lipoproteínas y por lo tanto su papel en la enfermedad cardiovascular, también depende del tiempo transcurrido entre comidas. Por ejemplo, las lipoprote

  17. Correlation studies between serum concentrations of zinc and lipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Saiki, Mitiko; Alves, Edson R.; Vasconcellos, M.B.A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], e-mail: mitiko@ipen.br, e-mail: eralves@ipen.br, e-mail: mbvascon@ipen.br; Sumita, Nairo M. [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas.Central Lab. Division and Laboratories of Medical Investigation (LIM-03)], e-mail: dlc.bioquimica@hcnet.usp.br; Jaluul, Omar; Jacob-Filho, Wilson [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina], e-mail: jaluul@uol.com.br, wiljac@usp.br

    2009-07-01

    In this study, serum zinc and lipoprotein concentrations were determined in order to assess the health status of an elderly population residing in Sao Paulo city, SP, Brazil. This population consisted of elderly considered healthy and participating of a 'Successful Ageing' program of the Sao Paulo University Medical School. Fasting blood samples were collected from 87 elderly individuals (63 females and 24 males) aged 60-91 and mean age of 72 +- 7 years. Zn concentrations were determined by neutron activation analysis at the IPEN/CNEN/ SP and, the lipoprotein (HDL, LDL and total cholesterol) concentrations were determined using routine analysis methods of the Central Laboratory Division, Hospital das Clinicas, FMUSP. Results obtained for Zn indicated that all the individuals presented this element within the recommended value. For total cholesterol and HDL-cholesterol concentrations, 96 % of elderly presented levels within the desired range but for LDL cholesterol concentrations only about 70.0 % of individuals were in the desired range. Serum concentration of Zn were positively correlated to LDL-cholesterol levels (correlation coefficient r = 0.21, p < 0.06). Furthermore, the ratios of [HDL-cholesterol] / [LDL-cholesterol] were negatively correlated with Zn concentrations (r = - 0.234, p < 0.04). The positive correlation found between the serum concentrations of Zn and LDL-cholesterol indicates the possible effect of this element in serum lipoprotein profiles. Thus ,these findings suggest that more investigations should be conducted on Zn supplementation in elderly subjects with cardiovascular diseases. (author)

  18. Increased transvascular low density lipoprotein transport in insulin dependent diabetes

    DEFF Research Database (Denmark)

    Kornerup, Karen; Nordestgaard, Børge Grønne; Feldt-Rasmussen, Bo

    2003-01-01

    for albumin were 6.8+/-2.5 and 5.4+/-2.0%/h (Paltered hepatic LDL receptor expression, glycosylation of LDL, small LDL size, nephropathy, statin use, or different plasma insulin levels in diabetes patients. CONCLUSION: Transvascular LDL transport may...... accumulation and thus atherosclerosis. METHODS: We used an in vivo method for measurement of transvascular transport of low density lipoprotein (LDL) and applied it in 24 patients with insulin dependent diabetes mellitus (type 1) and in 30 healthy controls. LDL was individually sampled and autologous 131...

  19. Low-density lipoproteins cause atherosclerotic cardiovascular disease

    DEFF Research Database (Denmark)

    Ference, Brian A.; Ginsberg, Henry N.; Graham, Ian

    2017-01-01

    Aims To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD). Methods and results We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from......, and randomized trials including more than 2 million participants with over 20 million person-years of follow-up and over 150 000 cardiovascular events demonstrate a remarkably consistent dose-dependent log-linear association between the absolute magnitude of exposure of the vasculature to LDL-C and the risk...

  20. Biomimetic High Density Lipoprotein Nanoparticles For Nucleic Acid Delivery

    Science.gov (United States)

    McMahon, Kaylin M.; Mutharasan, R. Kannan; Tripathy, Sushant; Veliceasa, Dorina; Bobeica, Mariana; Shumaker, Dale K.; Luthi, Andrea J.; Helfand, Brian T.; Ardehali, Hossein; Mirkin, Chad A.; Volpert, Olga; Thaxton, C. Shad

    2014-01-01

    We report a gold nanoparticle-templated high density lipoprotein (HDL AuNP) platform for gene therapy which combines lipid-based nucleic acid transfection strategies with HDL biomimicry. For proof-of-concept, HDL AuNPs are shown to adsorb antisense cholesterylated DNA. The conjugates are internalized by human cells, can be tracked within cells using transmission electron microscopy (TEM), and regulate target gene expression. Overall, the ability to directly image the AuNP core within cells, the chemical tailorability of the HDL AuNP platform, and the potential for cell-specific targeting afforded by HDL biomimicry make this platform appealing for nucleic acid delivery. PMID:21319839

  1. Lipoprotein glomerulopathy may provide a key to unlock the puzzles of renal lipidosis.

    Science.gov (United States)

    Saito, Takao; Matsunaga, Akira

    2014-02-01

    Lipoprotein glomerulopathy is an inherited renal disease characterized by unique lipoprotein thrombi in the glomerulus and is associated with the APOE mutation. Hu and colleagues investigated the genetic and clinical features of a large group of patients with lipoprotein glomerulopathy who carried APOE Kyoto, a major APOE variant. Their findings suggest its descent through a founder effect. Fibrate therapy in this group showed favorable results in the patient and renal survival rates.

  2. Characterization of the Pseudomonas aeruginosa Lol system as a lipoprotein sorting mechanism.

    Science.gov (United States)

    Tanaka, Shin-Ya; Narita, Shin-Ichiro; Tokuda, Hajime

    2007-05-04

    Escherichia coli lipoproteins are localized to either the inner or the outer membrane depending on the residue that is present next to the N-terminal acylated Cys. Asp at position 2 causes the retention of lipoproteins in the inner membrane. In contrast, the accompanying study (9) revealed that the residues at positions 3 and 4 determine the membrane specificity of lipoproteins in Pseudomonas aeruginosa. Since the five Lol proteins involved in the sorting of E. coli lipoproteins are conserved in P. aeruginosa, we examined whether or not the Lol proteins of P. aeruginosa are also involved in lipoprotein sorting but utilize different signals. The genes encoding LolCDE, LolA, and LolB homologues were cloned and expressed. The LolCDE homologue thus purified was reconstituted into proteoliposomes with lipoproteins. When incubated in the presence of ATP and a LolA homologue, the reconstituted LolCDE homologue released lipoproteins, leading to the formation of a LolA-lipoprotein complex. Lipoproteins were then incorporated into the outer membrane depending on a LolB homologue. As revealed in vivo, lipoproteins with Lys and Ser at positions 3 and 4, respectively, remained in proteoliposomes. On the other hand, E. coli LolCDE released lipoproteins with this signal and transferred them to LolA of not only E. coli but also P. aeruginosa. These results indicate that Lol proteins are responsible for the sorting of lipoproteins to the outer membrane of P. aeruginosa, as in the case of E. coli, but respond differently to inner membrane retention signals.

  3. Secretion of Bacterial Lipoproteins: Through the Cytoplasmic Membrane, the Periplasm and Beyond

    Science.gov (United States)

    Zückert, Wolfram R.

    2014-01-01

    Bacterial lipoproteins are peripherally anchored membrane proteins that play a variety of roles in bacterial physiology and virulence in monoderm (single membrane-enveloped, e.g., grampositive) and diderm (double membrane-enveloped, e.g., gram-negative) bacteria. After export of prolipoproteins through the cytoplasmic membrane, which occurs predominantly but not exclusively via the general secretory or Sec pathway, the proteins are lipid-modified at the cytoplasmic membrane in a multistep process that involves sequential modification of a cysteine residue and cleavage of the signal peptide by the signal II peptidase Lsp. In both monoderms and diderms, signal peptide processing is preceded by acylation with a diacylglycerol through preprolipoprotein diacylglycerol transferase (Lgt). In diderms but also some monoderms, lipoproteins are further modified with a third acyl chain through lipoprotein N-acyl transferase (Lnt). Fully modified lipoproteins that are destined to be anchored in the inner leaflet of the outer membrane (OM) are selected, transported and inserted by the Lol (lipoprotein outer membrane localization) pathway machinery, which consists of the inner-membrane (IM) ABC transporterlike LolCDE complex, the periplasmic LolA chaperone and the OM LolB lipoprotein receptor. Retention of lipoproteins in the cytoplasmic membrane results from Lol avoidance signals that were originally described as the “+2 rule”. Surface localization of lipoproteins in diderms is rare in most bacteria, with the exception of several spirochetal species. Type 2 (T2SS) and type 5 (T5SS) secretion systems are involved in secretion of specific surface lipoproteins of γ-proteobacteria. In the model spirochete Borrelia burgdorferi, surface lipoprotein secretion does not follow established sorting rules, but remains dependent on N-terminal peptide sequences. Secretion through the outer membrane requires maintenance of lipoproteins in a translocation-competent unfolded conformation

  4. Obtention of scintillography images by low density lipoproteins labelled with technetium 99

    International Nuclear Information System (INIS)

    Silva, S.; Coelho, I.; Zanardo, E.; Pileggi, F.; Meneguethi, C.; Maranhao, R.C.

    1992-01-01

    The low density lipoproteins carry the most part of the cholesterol in the blood plasma. These lipoproteins are labelled with technetium-99-m and have been used for obtaining images in nuclear medicine. The introduction of this technique is presented, aiming futures clinical uses. Scintillographic images are obtained 25 minutes and 24 hours after the injection of 3 m Ci of low density lipoproteins - technetium-99 m in rabbits. (C.G.C.)

  5. Ultrafine particles

    DEFF Research Database (Denmark)

    Bekö, Gabriel; Weschler, Charles J.; Wierzbicka, Aneta

    2013-01-01

    Particle number (PN) concentrations (10-300 nm in size) were continuously measured over a period of ∼45 h in 56 residences of nonsmokers in Copenhagen, Denmark. The highest concentrations were measured when occupants were present and awake (geometric mean, GM: 22.3 × 103 cm-3), the lowest when...... the homes were vacant (GM: 6.1 × 103 cm-3) or the occupants were asleep (GM: 5.1 × 103 cm-3). Diary entries regarding occupancy and particle related activities were used to identify source events and apportion the daily integrated exposure among sources. Source events clearly resulted in increased PN...... concentrations and decreased average particle diameter. For a given event, elevated particle concentrations persisted for several hours after the emission of fresh particles ceased. The residential daily integrated PN exposure in the 56 homes ranged between 37 × 103 and 6.0 × 106 particles per cm3·h/day (GM: 3...

  6. Particle cosmology

    CERN Multimedia

    CERN. Geneva

    2007-01-01

    The understanding of the Universe at the largest and smallest scales traditionally has been the subject of cosmology and particle physics, respectively. Studying the evolution of the Universe connects today's large scales with the tiny scales in the very early Universe and provides the link between the physics of particles and of the cosmos. This series of five lectures aims at a modern and critical presentation of the basic ideas, methods, models and observations in today's particle cosmology.

  7. Impact of postprandial lipaemia on low-density lipoprotein (LDL) size and oxidized LDL in patients with coronary artery disease.

    Science.gov (United States)

    Granér, M; Kahri, J; Nakano, T; Sarna, S J; Nieminen, M S; Syvänne, M; Taskinen, M R

    2006-11-01

    Remnant lipoprotein particles (RLPs) and oxidative stress are components of postprandial state. We investigated the concentrations of triglyceride-rich lipoproteins (TRLs), RLPs, low-density lipoprotein (LDL) size, and oxidized LDL (oxLDL) during alimentary lipaemia, and evaluated whether changes among these variables could be associated with the severity and extent of coronary artery disease (CAD). Eighty men and 27 women with clinically suspected CAD underwent quantitative coronary angiography (QCA). TRLs were isolated by density gradient ultracentrifugation before and 6 h after an oral fat load. RLPs were measured by an immunoseparation method, oxLDL by ELISA, and LDL size by gradient gel electrophoresis. Triglycerides, apolipoprotein (apo) B-48, and apoB-100 concentration in Swedberg flotation units (Sf) > 400 and in Sf 12-400 fractions were markedly increased at 6 h. Postprandial cholesterol content of RLPs (RLP-C) correlated with respective triglycerides in Sf > 400 (r = 0.737) and Sf 12-400 (r = 0.857), apoB-48 in Sf > 400 (r = 0.710) and Sf 12-400 (r = 0.664), apoB-100 in Sf > 400 (r = 0.812) and Sf 12-400 (r = 0.533). RLP-C correlated with oxLDL both in fasting and in fed state (r = 0.482 and r = 0.543, respectively) and inversely with LDL size (r = -0.459 and r = -0.442, respectively). (P postprandially (P Postprandial state is associated with oxidative stress. The magnitude of oxLDL increases during alimentary lipaemia and is associated with coronary atherosclerosis.

  8. In vitro studies on the distribution of probucol among human plasma lipoproteins

    International Nuclear Information System (INIS)

    Urien, S.; Riant, P.; Albengres, E.; Brioude, R.; Tillement, J.P.

    1984-01-01

    The role of human plasma lipoproteins as carriers in the blood transport of the cholesterol-lowering and water-insoluble drug, probucol, was investigated in in vitro studies. [ 14 C]Probucol was incubated in whole human blood, a serum pool, individual diluted sera, and isolated protein and lipoprotein fractions. In whole blood, about 90% partitioned in plasma. Following ultracentrifugal fractionation of the serum, it was found that less than 5% distributed in the d greater than 1.20 protein fraction (albumin-rich fraction) and more than 95% in the lipoprotein fractions. The distribution of probucol in the lipoprotein fractions correlated with the lipoprotein total lipid volume under saturation conditions (incubation of isolated lipoprotein fractions) as well as nonsaturation conditions (fractionation of serum exposed to [ 14 C]probucol). Incubation of the albumin-rich fraction and of apolipoproteins originating from the isolated lipoprotein fractions showed that they account for a negligible part in the interaction of probucol with blood components. The probucol uptake of individual sera was shown to be correlated to the lipid content of the serum. When probucol was incubated in erythrocyte suspensions containing variable amounts of lipoproteins, probucol partitioned less in erythrocytes as the lipoprotein concentration increased in the suspension

  9. Defective Lipoprotein Sorting Induces lolA Expression through the Rcs Stress Response Phosphorelay System

    OpenAIRE

    Tao, Kazuyuki; Narita, Shin-ichiro; Tokuda, Hajime

    2012-01-01

    The Escherichia coli LolA protein is a lipoprotein-specific chaperone that carries lipoproteins from the inner to the outer membrane. A dominant negative LolA mutant, LolA(I93C/F140C), in which both 93Ile and 140Phe are replaced by Cys, binds tightly to the lipoprotein-dedicated ABC transporter LolCDE complex on the inner membrane and therefore inhibits the detachment of outer membrane-specific lipoproteins from the inner membrane. We found that the expression of this mutant strongly induced ...

  10. In vitro lipid transfer between lipoproteins and midgut-diverticula in the spider Polybetes pythagoricus.

    Science.gov (United States)

    Laino, Aldana; Cunningham, Mónica L; Heras, Horacio; Garcia, Fernando

    2011-12-01

    It has been already reported that most hemolymphatic lipids in the spider Polybetes pythagoricus are transported by HDL1 and VHDL lipoproteins. We studied in vitro the lipid transfer among midgut-diverticula (M-diverticula), and either hemolymph or purified lipoproteins as well as between hemolymphatic lipoproteins. M-diverticula and hemolymph were labeled by in vivo (14)C-palmitic acid injection. In vitro incubations were performed between M-diverticula and either hemolymph or isolated lipoproteins. Hemolymph lipid uptake was associated to HDL1 (67%) and VHDL (32%). Release from hemolymph towards M-diverticula showed the opposite trend, VHDL 75% and HDL1 45%. Isolated lipoproteins showed a similar behavior to that observed with whole hemolymph. Lipid transfer between lipoproteins showed that HDL1 transfer more (14)C-lipids to VHDL than vice versa. Only 38% FFA and 18% TAG were transferred from M-diverticula to lipoproteins, while on the contrary 75% and 73% of these lipids, respectively, were taken up from hemolymph. A similar trend was observed regarding lipoprotein phospholipids. This study supports the hypothesis that HDL1 and hemocyanin-containing VHDL are involved in the uptake and release of FFA, phospholipids and triacylglycerols in the spider P. pythagoricus. The data support a directional flow of lipids from HDL1 and VHDL suggesting a mode of lipid transport between lipoproteins and M-diverticula. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. A large discoidal lipoprotein present in only one of two closely related crayfish.

    Science.gov (United States)

    Stieb, Stefanie; Hoeger, Ulrich; Schenk, Sven

    2008-08-01

    The hemolymph lipoproteins of two European freshwater crayfish, Astacus astacus and Astacus leptodactylus, were isolated and characterized. The former species possesses two sex-independent lipoproteins, which can be related to the formerly described high-density lipoprotein (HDL)/beta-glucan binding protein and very high-density lipoprotein/clotting protein from other crustaceans. The latter species, however, contains an additional third lipoprotein with a unique structure. It is a large discoidal HDL with a diameter of 42 nm, a thickness of 7 nm and a density of 1.1 g/ml. SDS-PAGE revealed two different apolipoproteins with molecular masses of 240 and 85 kDa, respectively, arranged in a 1:1 stoichiometry as judged from cross linking experiments. The lipid content of this lipoprotein was 67%, far higher than in every other crustacean lipoprotein described so far. The native molecular mass of this HDL-type lipoprotein was estimated to be about 930 kDa. The lipid content of the other lipoproteins ranged between 25 and 30% for the HDL/beta-glucan binding protein and 6-8% for the VHDL/clotting protein.

  12. Characterization of Lipoprotein Lipases interactions with Sortilin and SorLA

    DEFF Research Database (Denmark)

    Klinger, Stine Christensen

    . The present study describes their trafficking of two ligands, lipoprotein lipase and apolipoprotein A-V, which are integral parts of the lipid metabolism. Lipoprotein lipase is found at the luminal side of capillary endothelial cells, where it is involved in the conversion of circulating triglycerides to free...... direct endosomal trafficking of a ligand, and it represents a possible mechanism of posttranslational regulation of lipoprotein lipase expression. Furthermore, it was demonstrated that SorLA affects the distribution of lipoprotein lipase in hippocampal neurons and glia cells, which indicates that Sor...

  13. Metabolic factors clustering, lipoprotein cholesterol, apolipoprotein B, lipoprotein (a) and apolipoprotein E phenotypes in premature coronary artery disease in French Canadians.

    Science.gov (United States)

    Weber, M; McNicoll, S; Marcil, M; Connelly, P; Lussier-Cacan, S; Davignon, J; Latour, Y; Genest, J

    1997-03-01

    Plasma lipoprotein cholesterol abnormalities, diabetes, hypertension and smoking have all been identified as independent predictors of cardiovascular events. Clustering of multiple risk factors suggests a common metabolic link among high blood pressure, insulin resistance, plasma lipoprotein abnormalities and obesity. New guidelines for the management of dyslipidemias target patients with established coronary artery disease (CAD), and high risk patients with multiple risk factors and severe genetic lipoprotein disorders, such as familial hypercholesterolemia. To determine the prevalence of lipoprotein, apolipoprotein and metabolic disorders in premature CAD, 243 men and 61 women with premature CAD (occurring before age 60 years) and 203 age- and sex-matched controls (152 men, 61 women) were studied. After correcting for beta-blocker use (40% of men and 54% of women), hypertension and diabetes were seen more frequently in CAD patients than in controls. In men and women, cholesterol, triglycerides, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein (a) were significantly higher, and high density lipoprotein (HDL) cholesterol was lower, in CAD patients than in controls. By stratifying patients according to LDL cholesterol: HDL cholesterol ratio (5 or less, or greater than 5) and by triglyceride levels (less than 2.3 mmol/L, or 2.3 mmol/L or greater), significantly more men and women with CAD were found to have an elevated LDL cholesterol:HDL cholesterol ratio and elevated triglycerides (13.8% versus 1.9%, men and women combined, CAD versus controls, P women versus 11.7% in controls (P women, low HDL cholesterol, lipoprotein (a), the presence of diabetes, smoking and apolipoprotein B levels were all predictors of risk (P < 0.05). However, the clustering of risk factors may be the best predictor of risk. In this selected population, HDL and lipoprotein (a) are the best metabolic markers of premature CAD; metabolic factor clustering is common in

  14. Particle physics

    International Nuclear Information System (INIS)

    Kamal, Anwar

    2014-01-01

    Provides step-by-step derivations. Contains numerous tables and diagrams. Supports learning and teaching with numerous worked examples, questions and problems with answers. Sketches also the historical development of the subject. This textbook teaches particle physics very didactically. It supports learning and teaching with numerous worked examples, questions and problems with answers. Numerous tables and diagrams lead to a better understanding of the explanations. The content of the book covers all important topics of particle physics: Elementary particles are classified from the point of view of the four fundamental interactions. The nomenclature used in particle physics is explained. The discoveries and properties of known elementary particles and resonances are given. The particles considered are positrons, muon, pions, anti-protons, strange particles, neutrino and hadrons. The conservation laws governing the interactions of elementary particles are given. The concepts of parity, spin, charge conjugation, time reversal and gauge invariance are explained. The quark theory is introduced to explain the hadron structure and strong interactions. The solar neutrino problem is considered. Weak interactions are classified into various types, and the selection rules are stated. Non-conservation of parity and the universality of the weak interactions are discussed. Neutral and charged currents, discovery of W and Z bosons and the early universe form important topics of the electroweak interactions. The principles of high energy accelerators including colliders are elaborately explained. Additionally, in the book detectors used in nuclear and particle physics are described. This book is on the upper undergraduate level.

  15. Particle Physics

    CERN Document Server

    Martin, B R

    2008-01-01

    An essential introduction to particle physics, with coverage ranging from the basics through to the very latest developments, in an accessible and carefully structured text. Particle Physics: Third Edition is a revision of a highly regarded introduction to particle physics. In its two previous editions this book has proved to be an accessible and balanced introduction to modern particle physics, suitable for those students needed a more comprehensive introduction to the subject than provided by the 'compendium' style physics books. In the Third Edition the standard mod

  16. Comparison of 2 electrophoretic methods and a wet-chemistry method in the analysis of canine lipoproteins.

    Science.gov (United States)

    Behling-Kelly, Erica

    2016-03-01

    The evaluation of lipoprotein metabolism in small animal medicine is hindered by the lack of a gold standard method and paucity of validation data to support the use of automated chemistry methods available in the typical veterinary clinical pathology laboratory. The physical and chemical differences between canine and human lipoproteins draw into question whether the transference of some of these human methodologies for the study of canine lipoproteins is valid. Validation of methodology must go hand in hand with exploratory studies into the diagnostic or prognostic utility of measuring specific lipoproteins in veterinary medicine. The goal of this study was to compare one commercially available wet-chemistry method to manual and automated lipoprotein electrophoresis in the analysis of canine lipoproteins. Canine lipoproteins from 50 dogs were prospectively analyzed by 2 electrophoretic methods, one automated and one manual method, and one wet-chemistry method. Electrophoretic methods identified a higher proportion of low-density lipoproteins than the wet-chemistry method. Automated electrophoresis occasionally failed to identify very low-density lipoproteins. Wet-chemistry methods designed for evaluation of human lipoproteins are insensitive to canine low-density lipoproteins and may not be applicable to the study of canine lipoproteins. Automated electrophoretic methods will likely require significant modifications if they are to be used in the analysis of canine lipoproteins. Studies aimed at determining the impact of a disease state on lipoproteins should thoroughly investigate the selected methodology prior to the onset of the study. © 2016 American Society for Veterinary Clinical Pathology.

  17. MicroRNAs and lipoproteins: a connection beyond atherosclerosis?

    Science.gov (United States)

    Norata, Giuseppe Danilo; Sala, Federica; Catapano, Alberico Luigi; Fernández-Hernando, Carlos

    2014-01-01

    MicroRNAs (miRNAs) are involved in the pathogenesis of a number of cardiovascular diseases. In this review article, we have summarized the role of miRNAs in regulating lipid metabolism and how their therapeutical inhibition may lead to new approaches to treat cardiometabolic diseases, including atherosclerosis and metabolic syndrome. Specific miRNAs, such as miR-33a and -33b, represent one of the most interesting and attractive targets for metabolic-related disorders and anti-miR33 approaches are under intensive investigation. In addition to miR-33, other miRNAs, including miR-122, are also emerging as key players in lipid metabolism. More recently miRNAs were shown to exert their activities in a paracrine manner and also systemically. The latter is possible due to lipid-carriers, including lipoproteins, that transport and protect miRNAs from degradation. The emerging strong connection between miRNAs, lipoproteins and lipid metabolism indicates the existence of a reciprocal modulation that might go beyond atherosclerosis. PMID:23260873

  18. Transport of cholesterol autoxidation products in rabbit lipoproteins

    International Nuclear Information System (INIS)

    Peng, Shi-Kaung; Phillips, G.A.; Xia, Guang-Zhi; Morin, R.J.

    1987-01-01

    Radiolabeled pure [4- 14 C] cholesterol was kept at 60 0 C under air to autoxidize for 5 weeks, after which approximately 12% cholesterol oxidation products were formed. The mixture, suspended in gelatin, was given to rabbits by gastric gavage. Rabbits were killed 4, 24 and 48 h after treatment. Cholesterol and its autoxidation products were separated by thin-layer chromatography into 5 fractions and radioactivities of each fraction were measured. Percentages of each fraction of cholesterol oxidation products and cholesterol in the original mixture before administration and in the rabbit sera after administration were similar, suggesting that the rates of absorption of cholesterol oxidation products are not significantly different from that of cholesterol. Lipoproteins were fractioned by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each fraction in lipoproteins separated by thin layer chromatography showed that fractions containing cholestane-3β, 5α, 6β-triol, 7α- and 7β-hydroxycholesterol and 7-ketocholesterol were more selectively transported in VLDL, whereas most of the 25-hydroxycholesterol was present in LDL. HDL contained only minute amounts of cholesterol oxidation products. 22 refs

  19. [Effect of biliary obstruction on lipoprotein(a) concentration].

    Science.gov (United States)

    Calmarza, Pilar; Bajador, Eduardo; Lapresta, Carlos; García Castañón, Sandra; de Castro, Isabel; Civeira, Fernando

    2014-01-01

    This study was appointed to determine the correlation between the concentration of lipoprotein(a) [Lp(a)], apolipoproteins and lipids with biochemical parameters of liver function in a group of patients with reversible cholestasis. We have also determined the concentration of these parameters once solved the biliary obstruction process. Eighteen adults over 17 years with extrahepatic cholestasis were included in the study on a prospective basis, and we determined in them biochemical liver function parameters and lipoprotein metabolism parameters, particularly Lp(a) before and after unblocking. The concentration of Lp(a) prior to desobstruction was inverse and statistically significantly correlated with the concentration of gamma glutamyl transpeptidase (correlation coefficient [r] = -0.757, P = .018). The concentration of Lp(a) (median = 2.66 mg/dL, interquartile range = 5,62) showed a statistically significant increase (median = 9.72 mg/dL, interquartile range = 28.76, P acids exert a controlling effect on the synthesis of Lp(a) and open a mechanism for the treatment of hyper Lp(a). Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  20. Lipoprotein (a and cardiovascular risk factors in children and adolescents

    Directory of Open Access Journals (Sweden)

    Ástrid Camêlo Palmeira

    2013-12-01

    Full Text Available OBJECTIVE: To review the relationship between lipoprotein (a [Lp(a] and other risk factors for cardiovascular disease (CVD in children and adolescents. DATA SOURCES: This systematic review included studies from 2001 to 2011, a ten-year time period. Epidemiological studies with children and/or adolescents published in English, Portuguese or Spanish and fully available online were included. The searches were performed in Science Direct, PubMed/Medline, BVS (Biblioteca Virtual em Saúde and Cochrane Library databases, using the following combination of key-words: "lipoprotein a" and "cardiovascular diseases" and "obesity". DATA SYNTHESIS: Overall, 672 studies were obtained but only seven were included. Some studies assessed the family history for CVD. In all of them, Lp(a levels were increased in patients with family history for CVD. There was also a positive correlation between Lp(a and LDL-cholesterol, total cholesterol, and apolipoprotein B levels, suggesting an association between Lp(a levels and the lipid profile. CONCLUSIONS: The evidence that CVD may originate in childhood and adolescence leads to the need for investigating the risk factors during this period in order to propose earlier and possibly more effective interventions to reduce morbidity and mortality rates.

  1. Hunting particles

    International Nuclear Information System (INIS)

    Southworth, B.; Boixader, G.

    1978-09-01

    The authors provide a general introduction to elementary particle physics and the work of CERN. This introduction is aimed at the young reader and uses cartoons to explain how elementary particles behave and how they are studied in the CERN accelerators. The purpose and administration of CERN is also briefly summarized. (W.D.L.)

  2. Mediterranean Diet Improves High-Density Lipoprotein Function in High-Cardiovascular-Risk Individuals: A Randomized Controlled Trial.

    Science.gov (United States)

    Hernáez, Álvaro; Castañer, Olga; Elosua, Roberto; Pintó, Xavier; Estruch, Ramón; Salas-Salvadó, Jordi; Corella, Dolores; Arós, Fernando; Serra-Majem, Lluis; Fiol, Miquel; Ortega-Calvo, Manuel; Ros, Emilio; Martínez-González, Miguel Ángel; de la Torre, Rafael; López-Sabater, M Carmen; Fitó, Montserrat

    2017-02-14

    The biological functions of high-density lipoproteins (HDLs) contribute to explaining the cardioprotective role of the lipoprotein beyond quantitative HDL cholesterol levels. A few small-scale interventions with a single antioxidant have improved some HDL functions. However, to date, no long-term, large-scale, randomized controlled trial has been conducted to assess the effects of an antioxidant-rich dietary pattern (such as a traditional Mediterranean diet [TMD]) on HDL function in humans. This study was performed in a random subsample of volunteers from the PREDIMED Study (Prevención con Dieta Mediterránea; n=296) after a 1-year intervention. We compared the effects of 2 TMDs, one enriched with virgin olive oil (TMD-VOO; n=100) and the other enriched with nuts (TMD-Nuts; n=100), with respect to a low-fat control diet (n=96). We assessed the effects of both TMDs on the role of HDL particles on reverse cholesterol transport (cholesterol efflux capacity, HDL ability to esterify cholesterol, and cholesteryl ester transfer protein activity), HDL antioxidant properties (paraoxonase-1 arylesterase activity and total HDL antioxidant capacity on low-density lipoproteins), and HDL vasodilatory capacity (HDL ability to induce the release of nitric oxide in endothelial cells). We also studied the effects of a TMD on several HDL quality-related characteristics (HDL particle oxidation, resistance against oxidative modification, main lipid and protein composition, and size distribution). Both TMDs increased cholesterol efflux capacity relative to baseline ( P =0.018 and P =0.013 for TMD-VOO and TMD-Nuts, respectively). The TMD-VOO intervention decreased cholesteryl ester transfer protein activity (relative to baseline, P =0.028) and increased HDL ability to esterify cholesterol, paraoxonase-1 arylesterase activity, and HDL vasodilatory capacity (relative to control, P =0.039, P =0.012, and P =0.026, respectively). Adherence to a TMD induced these beneficial changes by

  3. Particle accelerator

    International Nuclear Information System (INIS)

    Ress, R.I.

    1976-01-01

    Charged particles are entrained in a predetermined direction, independent of their polarity, in a circular orbit by a magnetic field rotating at high speed about an axis in a closed cylindrical or toroidal vessel. The field may be generated by a cylindrical laser structure, whose beam is polygonally reflected from the walls of an excited cavity centered on the axis, or by high-frequency energization of a set of electromagnets perpendicular to the axis. In the latter case, a separate magnetostatic axial field limits the orbital radius of the particles. These rotating and stationary magnetic fields may be generated centrally or by individual magnets peripherally spaced along its circular orbit. Chemical or nuclear reactions can be induced by collisions between the orbiting particles and an injected reactant, or by diverting high-speed particles from one doughnut into the path of counterrotating particles in an adjoining doughnut

  4. Glucagon-like peptide-1 as a key regulator of lipid and lipoprotein metabolism in fasting and postprandial states.

    Science.gov (United States)

    Farr, Sarah; Taher, Jennifer; Adeli, Khosrow

    2014-01-01

    Insulin resistance and the metabolic syndrome are associated with fasting and postprandial dyslipidemia. This involves the hepatic and intestinal overproduction of very low density lipoproteins (VLDL) and chylomicron particles, respectively, which give rise to atherogenic remnants upon lipolysis in the circulation. Recently, the insulin secretagogue glucagon-like peptide-1 (GLP-1) has received attention not only as an anti-diabetic therapy for regulating glycaemia, but also as a regulator of lipid and lipoprotein metabolism. In fact, agents that raise endogenous bioactive levels of GLP-1 (dipeptidyl peptidase 4 inhibitors) and agents that directly stimulate GLP-1 receptors (GLP-1 receptor agonists) have been assessed in both preclinical and clinical trials for their ability to modulate plasma lipid parameters. Here we describe current evidence supporting a role for GLP-1 in preventing elevated intestinal chylomicron output and postprandial hypertriglyceridemia--an independent predictor of cardiovascular risk. Furthermore, we examine a role for GLP-1 in regulating fasting hepatic VLDL production and hindering the development of a potentially devastating comorbidity, hepatic steatosis. Possible mechanisms of action of GLP-1 are discussed including a reduction in intestinal absorption of dietary lipid and enhanced hepatic fatty acid oxidation or autophagy. Finally, we discuss the current controversy over whether these effects could occur via direct receptor stimulation or alternative, indirect pathways. We conclude that GLP- 1-based therapies appear promising in the management of diabetic dyslipidemia, and further studies are warranted to elucidate their mechanisms of action in both the intestine and liver.

  5. Hepatic lipogenesis and a marker of hepatic lipid oxidation, predict postprandial responses of triglyceride-rich lipoproteins.

    Science.gov (United States)

    Matikainen, Niina; Adiels, Martin; Söderlund, Sanni; Stennabb, Sanna; Ahola, Tytti; Hakkarainen, Antti; Borén, Jan; Taskinen, Marja-Riitta

    2014-08-01

    Postprandial hypertriglyceridemia is an important risk factor for cardiovascular disease. The mechanisms are still unclear. Here it was tested if hepatic de novo lipogenesis (DNL) and lipid oxidation influence the postprandial responses of triglyceride-rich lipoproteins (TRL) in humans. The contribution of hepatic DNL to hepatic TRL production was analyzed in 67 men and women with a moderate range of BMI after a fat-rich meal. Also, lipase activities, liver fat, and 3-OH-butyrate were quantitated as an indicator of β-oxidation. Lipoproteins and metabolic markers were measured in fasting and postprandial blood samples. Postprandial DNL correlates with postprandial TG and apolipoprotein (apo) C-III responses in plasma and with TG, apoB48 and apoB100 responses in TRLs and their larger remnant particles. Fasting and 8-h postprandial DNL was inversely related to 3-OH-butyrate but not to liver fat content. Fasting apoC-III and 3-OH-butyrate, but not liver fat, independently predicted fasting DNL. The fasting and 8-h postprandial rate of DNL was inversely associated with the hepatic lipid oxidation in humans. DNL contributes significantly to the TG content in TRLs but not to the amount of liver fat, suggesting that an imbalance between DNL and fat oxidation contributes to postprandial atherogenic dyslipidemia. Copyright © 2014 The Obesity Society.

  6. Lipoprotein Transport: Greasing the Machines of Outer Membrane Biogenesis: Re-Examining Lipoprotein Transport Mechanisms Among Diverse Gram-Negative Bacteria While Exploring New Discoveries and Questions.

    Science.gov (United States)

    Grabowicz, Marcin

    2018-04-01

    The Gram-negative outer membrane (OM) is a potent permeability barrier against antibiotics, limiting clinical options amid mounting rates of resistance. The Lol transport pathway delivers lipoproteins to the OM. All the OM assembly machines require one or more OM lipoprotein to function, making the Lol pathway central for all aspects of OM biogenesis. The Lol pathways of many medically important species clearly deviate from the Escherichia coli paradigm, perhaps with implications for efforts to develop novel antibiotics. Moreover, recent work reveals the existence of an undiscovered alternate route for bringing lipoproteins to the OM. Here, lipoprotein transport mechanisms, and the quality control systems that underpin them, is re-examined in context of their diversity. © 2018 WILEY Periodicals, Inc.

  7. SCARB1 Gene Variants Are Associated With the Phenotype of Combined High High-Density Lipoprotein Cholesterol and High Lipoprotein (a)

    DEFF Research Database (Denmark)

    Yang, Xiaoping; Sethi, Amar A; Yanek, Lisa R

    2016-01-01

    BACKGROUND: SR-B1 (scavenger receptor class B type 1), encoded by the gene SCARB1, is a lipoprotein receptor that binds both high-density lipoprotein (HDL) and low-density lipoprotein. We reported that SR-B1 is also a receptor for lipoprotein (a) (Lp(a)), mediating cellular uptake of Lp(a) in vitro...... variants in 6. Functional studies with 4 of the SCARB1 variants (c.386C>T, c.631-14T>G, c.4G>A, and c.631-53(m)C>T & c.726+55(m)CG>CA) showed decreased receptor function in vitro. CONCLUSIONS: Human SCARB1 gene variants are associated with a new lipid phenotype, characterized by high levels of both HDL...... cholesterol and Lp(a). SCARB1 exonic variants often result in diminished function of translated SR-B1 via reduced binding/intracellular transport of Lp(a)....

  8. Utilization of Cow Milk Enriched with Conjugated Linoleic Acid to Decrease Body Weight, Cholesterol, Low Density Lipoprotein and to Increase Blood High Density Lipoprotein

    OpenAIRE

    Suhartati, FM; Suryapratama, W; Rahayu, S

    2012-01-01

    An experiment to investigate the ability of cow milk enriched with conjugated linoleic acid to decrease body weight, total cholesterol, blood Low Density Lipoprotein (LDL), and to increase blood High Density Lipoprotein (HDL) has been conducted using in vivo experimental method. Research material consisted of 40 8-week-old white female rats (Rattus norvegicus) of Wistar strain (as an animal model). The method used was an experimental method with a Completely Randomized Design. The treatments ...

  9. Uptake of low density lipoproteins by the hamster lung. Interactions with capillary endothelium

    International Nuclear Information System (INIS)

    Nistor, A.; Simionescu, M.

    1986-01-01

    The mechanism by which the circulating low density lipoproteins (LDL) contribute to the lung surfactant cholesterol was investigated by perfusing the hamster lung in situ with LDL either radiolabeled or coupled to gold, or both. Part of [ 125 I]-LDL and [ 3 H]-cholesterol LDL were taken up by a specific process which was time- and concentration-dependent and reached saturation within 20 to 30 min of perfusion. Competition experiments and removal of receptor-bound LDL by heparin suggested that about 50% of LDL uptake is receptor-independent. Experiments using double labeled LDL showed a preferential uptake of 3 H-cholesterol versus 125 I by the lung both in situ and in vivo. LDL-gold particles (LDL-Au), recirculated through the isolated lung, bound to the endothelial luminal plasma membrane and to features potentially involved in receptor-mediated endocytosis (coated pits, coated vesicles, lysosomelike structures) and in transcytosis (plasmalemmal vesicles). The results suggest that LDL uptake by the lung takes place by both receptor-mediated and receptor-independent mechanisms. Cholesterol may be in part transferred to the lung without the apoprotein moiety; the alveolar capillary endothelium appears to be the first monitor of this complex process

  10. Isolation of low density lipoprotein (LDL with its modification by Copper ion and Malondialdehyde (MDA

    Directory of Open Access Journals (Sweden)

    Doosty M

    1999-06-01

    Full Text Available Oxidation of low density lipoproteins (LDLs is belived to be an important step in the pathogenesis of atherosclerosis. During oxidation, LDL particle undergoes a large number of structural changes that alters its biological properties, so it becomes atherogenic. To study atherogenic proteins, usually two forms of modified LDLs, including Cu2+-oxidized LDL (ox-LDL and malondialdehyde (MDA modified LDL (mal-LDL are used. In this study, LDL was isolated from 72 ml freshly prepared plasma by sequential Floatation Ultracentrifugation (SFU, which resulted in separation of 12.5 mg LDL protein. LDL oxidation was accomplished in Phosphate Buffered Saline (PBS with 2µM cupric sulfate, and mal-LDL was prepared by incubating LDL in PBS with 0.5 M solution of freshly prepared MDA. These modifications were evaluated by measuring optical density at 234 nm, Thiobarbitoric Acid Reactive Substances (TBARS, and electrophoretic mobility at pH 8.6. The increase of 234 nm absorption reflected initiation of LDL oxidation. TBARS of ox-LDL and mal-LDL was 80 Nm MAD/mg LDL protein and 400 nm MDA/mg LDL protein, respectively. Electrophoretic mobility of ox-LDL and mal-LDL, in respect to native LDL (n-LDL, were increased.

  11. Structural changes of low density lipoproteins with Cu2+ and glucose induced oxidation.

    Science.gov (United States)

    Gallego-Nicasio, J; López-Rodríguez, G; Martínez, R; Tarancón, M J; Fraile, M V; Carmona, P

    2003-01-01

    The compositional and structural changes of lipids and apolipoproteins during in vitro oxidation of low density lipoprotein (LDL) are investigated in this study by IR spectroscopy. For comparison, LDL samples containing either copper or glucose at physiological or pathological concentrations are considered in order to know the separate affects of these chemical factors on LDL oxidation. The results show that the initial steps of lipid oxidation proceed through hydrogen atom loss from methylene groups, as well as loss of cholesteryl ester molecules, and later a recovering of carbonyl compounds resulting from aldehyde formation that generally occurs in autooxidation processes. Lipid oxidation is induced by copper ions, and glucose enhances metal ion induced LDL oxidation as determined by conjugated diene formation. As to the protein conformational changes, IR spectroscopy reveals for the first time that LDL oxidation involves formation of beta-sheet structures, these being more abundant in LDL samples with pathological concentrations of glucose or copper. Consequently, the LDL structural changes may contribute to the recognition of oxidized LDL particles by scavenger receptors. Copyright 2003 Wiley Periodicals, Inc.

  12. Low-density lipoproteins investigated under high hydrostatic pressure by elastic incoherent neutron scattering.

    Science.gov (United States)

    Peters, J; Martinez, N; Lehofer, B; Prassl, R

    2017-07-01

    Human low-density lipoprotein (LDL) is a highly complex nano-particle built up of various lipid classes and a single large protein moiety (apoB-100) owning essential physiological functions in the human body. Besides its vital role as a supplier of cholesterol and fat for peripheral tissues and cells, it is also a known key player in the formation of atherosclerosis. Due to these important roles in physiology and pathology the elucidation of structural and dynamical details is of great interest. In the current study we drew a broader picture of LDL dynamics using elastic incoherent neutron scattering (EINS) as a function of specified temperature and pressure points. We not only investigated a normolipidemic LDL sample, but also a triglyceride-rich and an oxidized one to mimic pathologic conditions as found under hyperlipidemic conditions or in atherosclerotic plaques, respectively. We could show that pressure has a significant effect on atomic motions in modified forms of LDL, whereas the normolipidemic sample seems to cope much better with high-pressure conditions irrespective of temperature. These findings might be explained by the altered lipid composition, which is either caused through elevated triglyceride content or modifications through lipid peroxidation.

  13. Sphingomyelin in High-Density Lipoproteins: Structural Role and Biological Function

    Directory of Open Access Journals (Sweden)

    Jesús Osada

    2013-04-01

    Full Text Available High-density lipoprotein (HDL levels are an inverse risk factor for cardiovascular diseases, and sphingomyelin (SM is the second most abundant phospholipid component and the major sphingolipid in HDL. Considering the marked presence of SM, the present review has focused on the current knowledge about this phospholipid by addressing its variable distribution among HDL lipoparticles, how they acquire this phospholipid, and the important role that SM plays in regulating their fluidity and cholesterol efflux from different cells. In addition, plasma enzymes involved in HDL metabolism such as lecithin–cholesterol acyltransferase or phospholipid transfer protein are inhibited by HDL SM content. Likewise, HDL SM levels are influenced by dietary maneuvers (source of protein or fat, drugs (statins or diuretics and modified in diseases such as diabetes, renal failure or Niemann–Pick disease. Furthermore, increased levels of HDL SM have been shown to be an inverse risk factor for coronary heart disease. The complexity of SM species, described using new lipidomic methodologies, and their distribution in different HDL particles under many experimental conditions are promising avenues for further research in the future.

  14. Biomedicinal implications of high-density lipoprotein: its composition, structure, functions, and clinical applications.

    Science.gov (United States)

    Cho, Kyung-Hyun

    2009-07-31

    High-density lipoprotein (HDL) is a proven biomarker for the monitoring of changes in antioxidant and anti-inflammation capability of body fluids. The beneficial virtues of HDL are highly dependent on its lipids and protein compositions, and their ratios. In normal state, the HDL particle is enriched with lipids and several HDL-associated enzymes, which are responsible for its antioxidant activity. Lower HDL-cholesterol levels (40 mg/dL) have been recognized as an independent risk factor for coronary artery disease, as well as being a known component of metabolic syndrome. Functional and structural changes of HDL have been recognized as factors pivotal to the evaluation of HDL-quality. In this review, I have elected to focus on the functional and structural correlations of HDL and the roles of HDL-associated apolipoproteins and enzymes. Recent clinical applications of HDL have also been reviewed, particularly the therapeutic targeting of HDL metabolism and reconstituted HDL; these techniques represent promising emerging strategies for the treatment of cardiovascular disease, for drug or gene therapy.

  15. Increased fluidity and oxidation of malarial lipoproteins: relation with severity and induction of endothelial expression of adhesion molecules

    Directory of Open Access Journals (Sweden)

    Looareesuwan Sornchai

    2004-06-01

    Full Text Available Abstract Introduction Oxidative stress has been demonstrated in malaria. The potential oxidative modification of lipoproteins derived from malaria patients was studied. These oxidized lipids may have role in pathogenesis of malaria. Method The plasma lipid profile and existence of oxidized forms of very low density lipoprotein (VLDL, low density lipoprotein (LDL and high density lipoprotein (HDL were investigated in malaria (17 mild and 24 severe patients and 37 control subjects. Thiobarbituric acid reactive substances (TBARs, conjugated dienes, tryptophan fluorescence and fluidity of lipoproteins were determined as markers of oxidation. The biological effect of malarial lipoproteins was assessed by the expression of adhesion molecules on endothelial cells. Results Malarial lipoproteins had decreased cholesterol (except in VLDL and phospholipid. The triglyceride levels were unchanged. The cholesterol/phospholipid ratio of LDL was decreased in malaria, but increased in VLDL and HDL. TBARs and conjugate dienes were increased in malarial lipoproteins, while the tryptophan fluorescence was decreased. The fluidity of lipoproteins was increased in malaria. These indicated the presence of oxidized lipoproteins in malaria by which the degree of oxidation was correlated with severity. Of three lipoproteins from malarial patients, LDL displayed the most pronounced oxidative modification. In addition, oxidized LDL from malaria patients increased endothelial expression of adhesion molecules. Conclusion In malaria, the lipoproteins are oxidatively modified, and the degree of oxidation is related with severity. Oxidized LDL from malarial patients increases the endothelial expression of adhesion molecules. These suggest the role of oxidized lipoproteins, especially LDL, on the pathogenesis of disease.

  16. In vivo transfer of lipoprotein(a) into human atherosclerotic carotid arterial intima

    DEFF Research Database (Denmark)

    Nielsen, Lars Bo; Grønholdt, Marie-Louise; Schroeder, T V

    1997-01-01

    The aim of this study was to compare the atherogenic potential of lipoprotein(a) [Lp(a)] and LDL by measuring the intimal clearance of these two plasma lipoproteins in the atherosclerotic intima of the human carotid artery in vivo. Autologous 131I-Lp(a) and 125I-LDL were mixed and reinjected intr...

  17. Subunit II of Bacillus subtilis cytochrome c oxidase is a lipoprotein

    NARCIS (Netherlands)

    Bengtsson, J; Tjalsma, H; Rivolta, C; Hederstedt, L

    The sequence of the N-terminal end of the deduced ctaC gene product of Bacillus species has the features of a bacterial lipoprotein. CtaC is the subunit II of cytochrome caa(3), which is a cytochrome c oxidase. Using Bacillus subtilis mutants blocked in lipoprotein synthesis, we show that CtaC is a

  18. PLASMA-LIPOPROTEIN ABNORMALITIES IN TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS

    NARCIS (Netherlands)

    DULLAART, RPF

    Lipoprotein abnormalities may well contribute to the increased risk of coronary heart disease, cerebrovascular disease and peripheral vascular disease observed in type 1 (insulin-dependent) diabetes mellitus. The spectrum of diabetes-associated changes in lipoprotein metabolism is discussed. The

  19. Effects of Anabolic Steroids on Lipoprotein Profiles of Female Weight Lifters.

    Science.gov (United States)

    Moffatt, Robert J.; And Others

    1990-01-01

    This study examined the effects of resistance exercise and anabolic steroids on lipoprotein profiles of female weightlifters. The study found that women who participate in resistance training have better lipoprotein profiles than their sedentary counterparts, but these changes do not offset the deleterious effects of steroid use. (SM)

  20. The effect of interaction between Lipoprotein Lipase and ApoVLDL-II ...

    African Journals Online (AJOL)

    Body weight, abdominal fat weight and serum biochemical levels were determined from lean and fat chicken breeds at 12 weeks of age. Single nucleotide polymorphism (SNP) in apoVLDL-II and lipoprotein lipase genes was screened by PCR-SSCP and detected by direct sequencing. Lipoprotein lipase gene frequency ...

  1. Analysis of lipoproteins by capillary zone electrophoresis in microfluidic devices: Assay development and surface roughness measurements

    NARCIS (Netherlands)

    Weiller, Bruce H.; Ceriotti, Laura; Shibata, Takayuki; Rein, Dietrich; Roberts, Matthew A.; Lichtenberg, Jan; German, J. Bruce; De Rooij, Nico F.; Verpoorte, Elisabeth

    2002-01-01

    The development of a new assay for lipoproteins by capillary electrophoresis in fused-silica capillaries and in glass microdevices is described in this paper. The separation of low-density (LDL) and high-density (HDL) lipoproteins by capillary zone electrophoresis is demonstrated in fused-silica

  2. Quantification of lipoprotein profiles by nuclear magnetic resonance spectroscopy and multivariate data analysis

    DEFF Research Database (Denmark)

    Aru, Violetta; Lam, Chloie; Khakimov, Bekzod

    2017-01-01

    Lipoproteins and their subfraction profiles have been associated to diverse diseases including Cardio Vascular Disease (CVD). There is thus a great demand for measuring and quantifying the lipoprotein profile in an efficient and accurate manner. Nuclear Magnetic Resonance (NMR) spectroscopy is un...

  3. The effect of interaction between Lipoprotein Lipase and ApoVLDL-II ...

    African Journals Online (AJOL)

    GREGO

    2007-04-02

    Apr 2, 2007 ... Body weight, abdominal fat weight and serum biochemical levels were determined from lean and fat chicken breeds at 12 weeks of age. Single nucleotide polymorphism (SNP) in apoVLDL-II and lipoprotein lipase genes was screened by PCR-SSCP and detected by direct sequencing. Lipoprotein.

  4. Apolipoprotein M affecting lipid metabolism or just catching a ride with lipoproteins in the circulation?

    DEFF Research Database (Denmark)

    Dahlbäck, B; Nielsen, Lars Bo

    2009-01-01

    M retains its signal peptide, which serves as a hydrophobic anchor to the lipoproteins. This prevents apoM from being lost in the urine. Approximately 5% of HDL carries an apoM molecule. ApoM in plasma (1 microM) correlates strongly with both low-density lipoprotein (LDL) and HDL cholesterol, suggesting...

  5. Particle separation

    International Nuclear Information System (INIS)

    Baker, C.A.

    1990-01-01

    Solid particles are separated from a liquid which also contains ferric hydroxide by subjecting the liquid to ultrasonic agitation from a transducer in order to break up the flocs so that they will pass with the liquid through a filter belt. The belt thus retains the solid particles without interference from the flocs. As shown the woven nylon belt collects rare radioactive solid particles from liquid and carries them under sensors. The belt is washed clean, with further ultrasonic agitation in a trough on its return run. (author)

  6. NMR and interval PLS as reliable methods for determination of cholesterol in rodent lipoprotein fractions

    DEFF Research Database (Denmark)

    Kristensen, Mette; Savorani, Francesco; Ravn-Haren, Gitte

    2010-01-01

    Risk of cardiovascular disease is related to cholesterol distribution in different lipoprotein fractions. Lipoproteins in rodent model studies can only reliably be measured by time- and plasma-consuming fractionation. An alternative method to measure cholesterol distribution in the lipoprotein...... fractions in rat plasma is presented in this paper. Plasma from two rat studies (n = 68) was used in determining the lipoprotein profile by an established ultracentrifugation method and proton nuclear magnetic resonance (NMR) spectra of replicate samples was obtained. From the ultracentrifugation reference...... data and the NMR spectra, an interval partial least-square (iPLS) regression model to predict the amount of cholesterol in the different lipoprotein fractions was developed. The relative errors of the prediction models were between 12 and 33% and had correlation coefficients (r) between 0.96 and 0...

  7. Lipoprotein(a) and ischemic heart disease-A causal association? A review

    DEFF Research Database (Denmark)

    Kamstrup, P.R.

    2010-01-01

    and animal studies in support of pathophysiological effects of the risk factor, and preferably evidence from randomized clinical trials documenting reduced morbidity in response to interventions targeting the risk factor. Elevated and in particular extreme lipoprotein(a) levels have in prospective studies...... atherosclerosis and thrombosis, including accumulation of lipoprotein(a) in atherosclerotic plaques and attenuation of t-PA mediated plasminogen activation. No randomized clinical trial of the effect of lowering lipoprotein(a) levels on IHD prevention has ever been conducted. Lacking evidence from randomized...... clinical trials, genetic studies, such as Mendelian randomization studies, can also support claims of causality. Levels of lipoprotein(a) are primarily determined by variation in the LPA gene coding for the apolipoprotein(a) moiety of lipoprotein(a), and genetic epidemiologic studies have documented...

  8. Elementary Particles

    Science.gov (United States)

    Parham, R.

    1974-01-01

    Presents the text of a speech given to a conference of physics teachers in which the full spectrum of elementary particles is given, along with their classification. Also includes some teaching materials available on this topic. (PEB)

  9. Low density lipoprotein receptors: preliminary results on 'in vivo' study

    International Nuclear Information System (INIS)

    Lupattelli, G.; Virgolini, I.; Li, S.R.; Sinzinger, H.

    1991-01-01

    Plasmatic levels of low density lipoproteins (LDL) are regulated by the receptor pathway and most LDL receptor are located in the liver. A receptor defect due to genetic mutations of the LDL receptor gene is the cause of familial hypercholesterolemia (F.H.), a disease characterized by high cholesterol levels and premature atherosclerosis. Injections of autologous radiolabelled LDL, followed by hepatic scintiscanning, can be used to obtain 'in vivo' quantification of hepatic receptor activity, both in normal and hypercholesterolemic patients. In this study we observe no hepatic increase of radioactivity in patients affected by F.H., confirming the liver receptor defect. Scintigraphy is a non-invasive technique which can be used to diagnose this disease and to monitor the efficiacy of hypolipidemic therapy. (Authors)

  10. Lipoprotein Lipase Maintains Microglial Innate Immunity in Obesity

    Directory of Open Access Journals (Sweden)

    Yuanqing Gao

    2017-09-01

    Full Text Available Consumption of a hypercaloric diet upregulates microglial innate immune reactivity along with a higher expression of lipoprotein lipase (Lpl within the reactive microglia in the mouse brain. Here, we show that knockdown of the Lpl gene specifically in microglia resulted in deficient microglial uptake of lipid, mitochondrial fuel utilization shifting to glutamine, and significantly decreased immune reactivity. Mice with knockdown of the Lpl gene in microglia gained more body weight than control mice on a high-carbohydrate high-fat (HCHF diet. In these mice, microglial reactivity was significantly decreased in the mediobasal hypothalamus, accompanied by downregulation of phagocytic capacity and increased mitochondrial dysmorphologies. Furthermore, HCHF-diet-induced POMC neuronal loss was accelerated. These results show that LPL-governed microglial immunometabolism is essential to maintain microglial function upon exposure to an HCHF diet. In a hypercaloric environment, lack of such an adaptive immunometabolic response has detrimental effects on CNS regulation of energy metabolism.

  11. Lipoprotein(a Induces Human Aortic Valve Interstitial Cell Calcification

    Directory of Open Access Journals (Sweden)

    Bin Yu, PhD

    2017-08-01

    Full Text Available Lipoprotein(a, or Lp(a, significantly increased alkaline phosphatase activity, release of phosphate, calcium deposition, hydroxyapatite, cell apoptosis, matrix vesicle formation, and phosphorylation of signal transduction proteins; increased expression of chondro-osteogenic mediators; and decreased SOX9 and matrix Gla protein (p < 0.001. Inhibition of MAPK38 and GSK3β significantly reduced Lp(a-induced calcification of human aortic valve interstitial cells (p < 0.001. There was abundant presence of Lp(a and E06 immunoreactivity in diseased human aortic valves. The present study demonstrates a causal effect for Lp(a in aortic valve calcification and suggests that interfering with the Lp(apathway could provide a novel therapeutic approach in the management of this debilitating disease.

  12. Particle detectors

    CERN Multimedia

    CERN. Geneva

    2001-01-01

    The lecture series will present an overview of the basic techniques and underlying physical principles of particle detectors, applied to current and future high energy physics experiments. Illustrating examples, mainly from the field of collider experiments, will demonstrate the performance and limitations of the various techniques. After an introduction the following topics will be covered: Tracking (gas, solid state based) - Scintillation and light detection Calorimetry - Particle Identification - Electronics and Data Acquisition - Detector Systems

  13. Degradation of high density lipoprotein in cultured rat luteal cells

    International Nuclear Information System (INIS)

    Rajan, V.P.; Menon, K.M.J.

    1986-01-01

    In rat ovary luteal cells, degradation of high density lipoprotein (HDL) to tricholoracetic acid (TCA)-soluble products accounts for only a fraction of the HDL-derived cholesterol used for steroidogenesis. In this study the authors have investigated the fate of 125 I]HDL bound to cultured luteal cells using pulse-chase technique. Luteal cell cultures were pulse labeled with [ 125 I]HDL 3 and reincubated in the absence of HDL. By 24 h about 50% of the initallay bound radioactivity was released into the medium, of which 60-65% could be precipitated with 10% TCA. Gel filtration of the chase incubation medium on 10% agarose showed that the amount of TCA-soluble radioactivity was nearly completely accounted for by a sharp peak in the low molecular weight region which was identified as 96% monoiodotyrosine by paper chromatography. The TCA-precipitable radioactivity was nearly completely accounted for by a sharp peak in the low molecular weight region which was identified as 96% monoiodotyrosine by paper chromatography. The TCA-precipitable radioactivity eluted over a wide range of molecular weights (15,000-80,000), and there was very little intact HDL present. Electrophoresis of the chase medium showed that component of the TCA-precipitable portion had mobility similar to apo AI. Lysosomal inhibitors of receptor-mediated endocytosis had no effect on the composition or quantity of radioactivity released during chase incubation. The results show that HDL 3 binding to luteal cells is followed by complete degradation of the lipoprotein, although the TCA-soluble part does not reflect the extent of degradation

  14. Biominetic High Density Lipoproteins for the Delivery of Therapeutic Oligonucleotides

    Science.gov (United States)

    Tripathy, Sushant

    Advances in nanotechnology have brought about novel inorganic and hybrid nanoparticles with unique physico-chemical properties that make them suitable for a broad range of applications---from nano-circuitry to drug delivery. A significant part of those advancements have led to ground-breaking discoveries that have changed the approaches to formulation of therapeutics against diseases, such as cancer. Now-a-days the focus does not lie solely on finding a candidate small-molecule therapeutic with minimal adverse effects, but researchers are looking up to nanoparticles to improve biodistribution and biocompatibility profile of clinically proven therapeutics. The plethora of conjugation chemistries offered by currently extant inorganic nanoparticles have, in recent years, led to great leaps in the field of biomimicry---a modality that promises high biocompatibility. Further, in the pursuit of highly specific therapeutic molecules, researchers have turned to silencing oligonucleotides and some have already brought together the strengths of nanoparticles and silencing oligonucleotides in search of an efficacious therapy for cancer with minimal adverse effects. This dissertation work focuses on such a biomimetic platform---a gold nanoparticle based high density lipoprotein biomimetic (HDL NP), for the delivery of therapeutic oligonucleotides. The first chapter of this body of work introduces the molecular target of the silencing oligonucleotides---VEGFR2, and its role in the progression of solid tumor cancers. The background information also covers important aspects of natural high density lipoproteins (HDL), especially their innate capacity to bind and deliver exogenous and endogenous silencing oligonucleotides to tissues that express their high affinity receptor SRB1. We subsequently describe the synthesis of the biomimetic HDL NP and its oligonucleotide conjugates, and establish their biocompatibility. Further on, experimental data demonstrate the efficacy of silencing

  15. Effect of omega-3 fatty acids on the oxylipin composition of lipoproteins in hypertriglyceridemic, statin-treated subjects

    Science.gov (United States)

    Background: Oxylipins mediate many physiological processes, including inflammation and vascular function. Generally considered local and transient, we suggest their presence in lipoproteins indicates they also mediate the effects lipoproteins have on inflammation and vascular biology. To support th...

  16. The ppm operon is essential for acylation and glycosylation of lipoproteins in Corynebacterium glutamicum.

    Directory of Open Access Journals (Sweden)

    Niloofar Mohiman

    Full Text Available BACKGROUND: Due to their contribution to bacterial virulence, lipoproteins and members of the lipoprotein biogenesis pathway represent potent drug targets. Following translocation across the inner membrane, lipoprotein precursors are acylated by lipoprotein diacylglycerol transferase (Lgt, cleaved off their signal peptides by lipoprotein signal peptidase (Lsp and, in Gram-negative bacteria, further triacylated by lipoprotein N-acyl transferase (Lnt. The existence of an active apolipoprotein N-acyltransferase (Ms-Ppm2 involved in the N-acylation of LppX was recently reported in M. smegmatis. Ms-Ppm2 is part of the ppm operon in which Ppm1, a polyprenol-monophosphomannose synthase, has been shown to be essential in lipoglycans synthesis but whose function in lipoprotein biosynthesis is completely unknown. RESULTS: In order to clarify the role of the ppm operon in lipoprotein biosynthesis, we investigated the post-translational modifications of two model lipoproteins (AmyE and LppX in C. glutamicum Δppm1 and Δppm2 mutants. Our results show that both proteins are anchored into the membrane and that their N-termini are N-acylated by Cg-Ppm2. The acylated N-terminal peptide of LppX was also found to be modified by hexose moieties. This O-glycosylation is localized in the N-terminal peptide of LppX and disappeared in the Δppm1 mutant. While compromised in the absence of Cg-Ppm2, LppX O-glycosylation could be restored when Cg-Ppm1, Cg-Ppm2 or the homologous Mt-Ppm1 of M. tuberculosis was overexpressed. CONCLUSION: Together, these results show for the first time that Cg-Ppm1 (Ppm synthase and Cg-Ppm2 (Lnt operate in a common biosynthetic pathway in which lipoprotein N-acylation and glycosylation are tightly coupled.

  17. Auroral particles

    Science.gov (United States)

    Evans, David S.

    1987-01-01

    The problems concerning the aurora posed prior to the war are now either solved in principle or were restated in a more fundamental form. The pre-war hypothesis concerning the nature of the auroral particles and their energies was fully confirmed, with the exception that helium and oxygen ions were identified as participating in the auroral particle precipitation in addition to the protons. The nature of the near-Earth energization processes affecting auroral particles was clarified. Charged particle trajectories in various electric field geometries were modeled. The physical problems have now moved from determining the nature and geometry of the electric fields, which accelerate charged particles near the Earth, to accounting for the existence of these electric fields as a natural consequence of the solar wind's interaction with Earth. Ultimately the reward in continuing the work in auroral and magnetospheric particle dynamics will be a deeper understanding of the subtleties of classical electricity and magnetism as applied to situations not blessed with well-defined and invariant geometries.

  18. Analysis of Hepatitis C Virus Particle Heterogeneity in Immunodeficient Human Liver Chimeric fah-/- MiceSummary

    Directory of Open Access Journals (Sweden)

    Ursula Andreo

    2017-11-01

    Full Text Available Background & Aims: Hepatitis C virus (HCV is a leading cause of chronic liver diseases and the most common indication for liver transplantation in the United States. HCV particles in the blood of infected patients are characterized by heterogeneous buoyant densities, likely owing to HCV association with lipoproteins. However, clinical isolates are not infectious in vitro and the relative infectivity of the particles with respect to their buoyant density therefore cannot be determined, pointing to the need for better in vivo model systems. Methods: To analyze the evolution of the buoyant density of in vivo–derived infectious HCV particles over time, we infected immunodeficient human liver chimeric fumaryl acetoacetate hydrolase-/- mice with J6/JFH1 and performed ultracentrifugation of infectious mouse sera on isopicnic iodixanol gradients. We also evaluated the impact of a high sucrose diet, which has been shown to increase very-low-density lipoprotein secretion by the liver in rodents, on lipoprotein and HCV particle characteristics. Results: Similar to the severe combined immunodeficiency disease/Albumin-urokinase plasminogen activator human liver chimeric mouse model, density fractionation of infectious mouse serum showed higher infectivity in the low-density fractions early after infection. However, over the course of the infection, viral particle heterogeneity increased and the overall in vitro infectivity diminished without loss of the human liver graft over time. In mice provided with a sucrose-rich diet we observed a minor shift in HCV infectivity toward lower density that correlated with a redistribution of triglycerides and cholesterol among lipoproteins. Conclusions: Our work indicates that the heterogeneity in buoyant density of infectious HCV particles evolves over the course of infection and can be influenced by diet. Keywords: HCV, Lipoprotein, Mouse Model, Human Liver Chimeric Mice

  19. Association of lipoprotein(a) level with short- and long-term outcomes after CABG: The role of lipoprotein apheresis.

    Science.gov (United States)

    Ezhov, Marat V; Afanasieva, Olga I; Il'ina, Larisa N; Safarova, Maya S; Adamova, Irina Yu; Matchin, Yuri G; Konovalov, Gennady A; Akchurin, Renat S; Pokrovsky, Sergei N

    2017-11-01

    To evaluate the association of lipoprotein(a) [Lp(a)] level with short- and long-term outcomes after coronary artery bypass grafting (CABG) and to assess the effect of a 12 month course of weekly lipoprotein apheresis on vein graft patency and coronary atherosclerosis course in post-CABG patients with hyperlipidemia. This study was performed in patients after successful CABG and consisted of three parts: a) a retrospective part with computed tomography assessment of vein graft patency in patients with first-year recurrence of chest pain after CABG (n = 102); b) a prospective trial with evaluation of cardiovascular outcomes during follow up time up to 15 years in relation to baseline Lp(a) levels (n = 356); c) an 12-months interventional controlled study in 50 patients with low-density lipoprotein cholesterol (LDL-C) levels >2.6 mmol/L prior to the operation despite statin treatment that allocated into 2 groups: active (n = 25, weekly apheresis by cascade plasma filtration (CPF) plus atorvastatin), and control (n = 25, atorvastatin alone). Patients subjected to computed tomography were divided in two groups: 66 (65%) with at least one vein graft occlusion and 36 (35%) without occlusions. Lp(a) levels were significantly higher in patients with occluded grafts with a median (95% confidence intervals (CI)) of 24 (17-42) mg/dL vs. 12 (6-24) mg/dL in patients with patent grafts, p < 0.01. Over a mean of 8.5 ± 3.5 years (range 0.9-15.0 years), the primary and secondary endpoints were registered in 46 (13%) and 107 (30%) patients, respectively. Patients with Lp(a) ≥30 mg/dL were at significantly greater risk for the primary endpoint (hazard ratio (HR) 2.98, 95% confidence interval (CI) 1.76-5.03, p < 0.001) and secondary endpoint (HR 3.47, 95%CI 2.48-4.85, p < 0.001) than patients with Lp(a) values <30 mg/dL. During the CPF procedure LDL-C levels decreased by 59 ± 14%, Lp(a) levels by 49 ± 15. The frequency of vein graft occlusions at study end

  20. Structure of spheroidal HDL particles revealed by combined atomistic and coarse-grained simulations

    NARCIS (Netherlands)

    Catte, Andrea; Patterson, James C.; Bashtovyy, Denys; Jones, Martin K.; Gu, Feifei; Li, Ling; Rampioni, Aldo; Sengupta, Durba; Vuorela, Timo; Niemela, Perttu; Karttunen, Mikko; Marrink, Siewert Jan; Vattulainen, Ilpo; Segrest, Jere P.

    2008-01-01

    Spheroidal high-density lipoprotein (HDL) particles circulating in the blood are formed through an enzymatic process activated by apoA-1, leading to the esterification of cholesterol, which creates a hydrophobic core of cholesteryl ester molecules in the middle of the discoidal phospholipid bilayer.

  1. Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export

    DEFF Research Database (Denmark)

    Kjølby, Mads Fuglsang; Andersen, Olav Michael; Breiderhoff, Tilman

    2010-01-01

    of lipoproteins from the liver and ameliorates hypercholesterolemia and atherosclerotic lesion formation in LDL receptor-deficient animals. In contrast, sortilin overexpression stimulates hepatic release of lipoproteins and increases plasma LDL levels. Our data have uncovered a regulatory pathway in hepatic...... lipoprotein export and suggest a molecular explanation for the cardiovascular risk being associated with 1p13.3. Udgivelsesdato: september 8...

  2. DMPD: The oxidation of lipoproteins by monocytes-macrophages. Biochemical andbiological mechanisms. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10473535 The oxidation of lipoproteins by monocytes-macrophages. Biochemical andbio.... (.png) (.svg) (.html) (.csml) Show The oxidation of lipoproteins by monocytes-macrophages. Biochemical and...biological mechanisms. PubmedID 10473535 Title The oxidation of lipoproteins by m

  3. Membrane receptors for very low density lipoprotein (VLDL) inhibitor of lymphocyte proliferation

    International Nuclear Information System (INIS)

    Yi, P.I.; Beck, G.; Zucker, S.

    1981-01-01

    Physiologic concentrations of human plasma very low density lipoproteins inhibit the DNA synthesis of lymphocytes stimulated by allogeneic cells or lectins. In this report reachers have compared the effects of isolated lipoproteins [very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL)] and lipoprotein-depleted plasma (LDP) on DNA synthesis by phytohemagglutinin-stimulated human lymphocytes. The relative potency for the inhibition of lymphocyte proliferation was VLDL greater than LDL greater than HDL greater than LDP. Fifty percent inhibition of DNA synthesis was observed at a VLDL protein concentration of 1.5--2.0 microgram/ml. Researchers have further demonstrated the presence of specific receptors for VLDL on human lymphocytes. Native VLDL was more effective than LDL in competing for 125I-VLDL binding sites. Subsequent to binding to lymphocytes, 125I-VLDL was internalized and degraded to acid-soluble products. Based on a Scatchard analysis of VLDL binding at 4 degrees C, the number of VLDL receptors per lymphocyte was estimated at 28,000 +/- 1300. Based on an estimated mean binding affinity for the VLDL receptor complex at half saturation of approximately 8.8 X 10(7) liter/mole, it is estimated that 91% of lymphocyte VLDL receptors are occupied at physiologic VLDL concentrations in blood. Although the immune regulatory role of plasma lipoproteins is uncertain, researchers suggest tha VLDL and LDL-In may maintain circulating blood lymphocytes in a nonproliferative state via their respective cell receptor mechanisms

  4. Particle detectors

    CERN Document Server

    AUTHOR|(CDS)2068232

    1998-01-01

    The lecture series will present and overview of the basic techniques and underlying physical principles of particle detectors, applied to current and future high energy physics experiments. Illustrating examples, mainly from the field of collider experiments, will demonstrate the performance and limitations of the various techniques. After and introduction we shall concentrate on particle tracking. Wire chambers, drift chambers, micro gaseous tracking devices and solid state trackers will be discussed. It follows and overview of scintillators, photon detection, fiber tracking and nuclear emulsions. One lecture will deal with the various techniques of calorimetry. Finally we shall focus on methods developed for particle identification. These comprise specific energy loss, time of flight Cherenkov and transition radiation detectors.

  5. Particle detectors

    CERN Document Server

    Hilke, Hans Jürgen; Joram, Christian; CERN. Geneva

    1991-01-01

    Lecture 5: Detector characteristics: ALEPH Experiment cut through the devices and events - Discuss the principles of the main techniques applied to particle detection ( including front-end electronics), the construction and performance of some of the devices presently in operartion and a few ideas on the future performance. Lecture 4-pt. b Following the Scintillators. Lecture 4-pt. a : Scintillators - Used for: -Timing (TOF, Trigger) - Energy Measurement (Calorimeters) - Tracking (Fibres) Basic scintillation processes- Inorganic Scintillators - Organic Scintil - Discuss the principles of the main techniques applied to particle detection ( including front-end electronics), the construction and performance of some of the devices presently in operation and a fiew ideas on future developpement session 3 - part. b Following Calorimeters lecture 3-pt. a Calorimeters - determine energy E by total absorption of charged or neutral particles - fraction of E is transformed into measurable quantities - try to acheive sig...

  6. Stable particles

    International Nuclear Information System (INIS)

    Samios, N.P.

    1994-01-01

    I have been asked to review the subject of stable particles, essentially the particles that eventually comprised the meson and baryon octets, with a few more additions - with an emphasis on the contributions made by experiments utilizing the bubble chamber technique. In this activity, much work had been done by the photographic emulsion technique and cloud chambers - exposed to cosmic rays as well as accelerator based beams. In fact, many if not most of the stable particles were found by these latter two techniques, however, the foree of the bubble chamber (coupled with the newer and more powerful accelerators) was to verify, and reinforce with large statistics, the existence of these states, to find some of the more difficult ones, mainly neutrals and further to elucidate their properties, i.e., spin, parity, lifetimes, decay parameters, etc. (orig.)

  7. Stable particles

    International Nuclear Information System (INIS)

    Samios, N.P.

    1993-01-01

    I have been asked to review the subject of stable particles, essentially the particles that eventually comprised the meson and baryon octets. with a few more additions -- with an emphasis on the contributions made by experiments utilizing the bubble chamber technique. In this activity, much work had been done by the photographic emulsion technique and cloud chambers-exposed to cosmic rays as well as accelerator based beams. In fact, many if not most of the stable particles were found by these latter two techniques, however, the forte of the bubble chamber (coupled with the newer and more powerful accelerators) was to verify, and reinforce with large statistics, the existence of these states, to find some of the more difficult ones, mainly neutrals and further to elucidate their properties, i.e., spin, parity, lifetimes, decay parameters, etc

  8. Structure of human low-density lipoprotein subfractions, determined by X-ray small-angle scattering.

    Science.gov (United States)

    Baumstark, M W; Kreutz, W; Berg, A; Frey, I; Keul, J

    1990-01-19

    The structure of low-density lipoprotein (LDL) particles from three different density ranges (LDL-1: d = 1.006-1.031 g/ml; LDL-3: d = 1.034-1.037 g/ml; LDL-6: d = 1.044-1.063 g/ml) was determined by X-ray small-angle scattering. By using a theoretical particle model, which accounted for the polydispersity of the samples, we were able to obtain fits of the scattering intensity that were inside the noise interval of the measured intensity. The assumption of deviations from radial symmetry is not supported by our data. This implies a spread-out conformation of the apolipoprotein B (apoB) molecule, which appears to be localized in the outer surface shell. A globular structure is not consistent with our data. Furthermore, different models exist concerning the structure of the cholesterol ester core below the phase transition temperature. The electron density data suggest an arrangement in which the steroid moieties are localized at average radii of 3.2 and 6.4 nm. Model calculations show that packing problems can only be avoided if approximately half of the acyl chains of each shell are pointing towards the center of the particle, the other half towards the surface. This arrangement of the acyl chains has never been proposed before. The LDL particles of different density classes differ mainly with respect to the size of the core but also with respect to the width of the surface shells. Model calculations show that the size of different LDL particles can be accurately predicted from the compositional data.

  9. Particle physics

    CERN Document Server

    Martin, Brian R

    2017-01-01

    An accessible and carefully structured introduction to Particle Physics, including important coverage of the Higgs Boson and recent progress in neutrino physics. Fourth edition of this successful title in the Manchester Physics series. Includes information on recent key discoveries including : An account of the discovery of exotic hadrons, beyond the simple quark model; Expanded treatments of neutrino physics and CP violation in B-decays; An updated account of ‘physics beyond the standard model’, including the interaction of particle physics with cosmology; Additional problems in all chapters, with solutions to selected problems available on the book’s website; Advanced material appears in optional starred sections.

  10. Characteristics of 2,4,5,2',4',5'-hexachlorobiphenyl distribution among lipoproteins in vitro

    International Nuclear Information System (INIS)

    Vomachka, M.S.; Vodicnik, M.J.; Lech, J.J.

    1983-01-01

    The uptake, distribution, and transfer of 2,4,5,2',4',5'-hexachlorobiphenyl (6-CB) were examined in vitro with human and rat whole blood, plasma, and lipoprotein fractions. 6-CB distribution between plasma and erythrocytes as well as among lipoproteins was determined following sedimentation of erythrocytes and ultracentrifugal fractionation of plasma. In both rat and human whole blood, 70 to 75% of 6-CB partitioned into plasma and 25 to 30% into erythrocytes. The uptake of 6-CB into plasma was extremely rapid and the rate of uptake was found to be dependent upon temperature. The distribution of 6-CB among lipoproteins was relatively homogeneous with 20 to 30% being distributed in very low-density lipoproteins (VLDL, d . 0.95-1.006 g/ml), 15 to 20% in low-density lipoproteins (LDL, d . 1.006-1.063 g/ml), and 15 to 25% in high-density lipoproteins (HDL, d . 1.063-1.21 g/ml). Over 25% of 6-CB was found in the remaining bottom fraction. In addition, each isolated fraction when incubated alone with 6-CB was shown capable of uptake. The relative proportion of 6-CB among the lipoproteins was independent of the level taken up by plasma. 6-CB was also found to transfer among lipoproteins. This exchange of 6-CB proved to be dependent upon the concentrations of both protein and triacylglycerol in the incubations. Two proteins in the bottom fraction (Bf), albumin and a steroid binding globulin, were capable of competing with the lipoproteins for 6-CB uptake

  11. [Lipoprotein (a)--a mysterious factor in atherogenesis].

    Science.gov (United States)

    Jelaković, Bojan; Laganović, Mario; Kuzmanić, Dusko

    2002-01-01

    Etiopathogenesis of arterial hypertension and coronary disease involves interaction of numerous exogenous factors which determine the clinical course and therapeutic response in genetically predisposed individuals. The role of numerous cardiovascular risk factors has been reevaluated during the past few years, yet some unresolved issues and gaps still remain. One of the still insufficiently studied factors is lipoprotein (a) [Lp (a)] which belongs to a subclass of LDL lipoproteins. Its important component is apolipoprotein (a) which is structurally similar to plasminogen. This characteristic can be followed through evolution and is probably crucial for its physiologic but also pathophysiologic role. Actually, through its competition with plasminogen, Lp (a) interferes with the process of fibrinolysis and may contribute to tissue healing and restoration but also support and accelerate atherothrombotic process. Lp (a) concentration is stable and genetically determined in an individual and the indication that persons with elevated levels are permanently exposed to increased risk is supported by the data on twofold incidence of myocardial infarction in mothers of children with highest Lp (a) concentrations. Apart from competing with plasminogen via apolipoprotein (a), Lp (a) increases the activity of inhibitors of plasminogen-I activator and reduces the activity of transforming growth factor-beta. This results both in the absence of fibrinolysis and promotion of migration and proliferation of media smooth muscle cells, which are important in the onset of atherosclerotic process. Lp (a) binds to elastin via apolipoprotein B, resulting in oxidation and facilitated entry into macrophages and their transition into the so-called foam cells, also an important sign of early atherosclerosis. Although many pathophysiologic processes by which Lp (a) contributes to atherosclerosis have also been confirmed by animal experiments as well as by the presence of histologic evidence

  12. Actual situation of lipoprotein apheresis in Saxony in 2013.

    Science.gov (United States)

    Emmrich, U; Hohenstein, B; Julius, U

    2015-05-01

    Lipoprotein apheresis (LA) is an officially accepted therapeutic approach in Germany. Reliable population-based data on the patients are scarce. It is of special interest to learn what are the main indications for this extracorporeal treatment and how many new patients started over the last years. This paper is a summary of the situation of the treatment of high-risk patients via LA in the federal state of Saxony, Germany. The documentation of all patients who agreed to be included into this study have been evaluated. Patients were treated at the University Hospital Dresden (UHD) and in private practices of nephrologists. This evaluation aimed at the characterization of patients treated with LA in Saxony with respect to age, gender, lipid pattern, to the number of new patients per year and the development of the ratio of patients to the Saxon population between 2010 and 2013. The obtained data were compared with the official statistics published by the National Association of Statutory Health Insurance Physicians for whole Germany. In 2013, 181 patients, primarily males, were treated in 15 LA centers by 32 doctors. Still, the number of apheresis doctors per 1 million inhabitants is under the average in Germany (Saxony: 7.7/1 million inhabitants, average: 12/1 million inhabitants). The usage of LA is 45 per 1 million inhabitants in Saxony; in comparison to 2010, this is an increase of 16 per 1 million inhabitants. The number of new patients in 2013 with an isolated elevation of Lipoprotein(a) (Lp(a)) is twice as high than it was in 2011. The mean duration of all patients being treated with LA, most on a weekly basis, was 5.75 years (UHD: 6.2 years, range: 1 month to 23.1 years; other centers: 5.3 years, range: 1 month to 19.2 years). About 19.3% of all patients suffered from elevated triglyceride (TG) levels (>5 mmol/L). Non-high- density lipoprotein cholesterol (Non-HDL-C) was calculated, which is also acutely reduced by LA sessions. The following data were

  13. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

    DEFF Research Database (Denmark)

    Chapman, M John; Ginsberg, Henry N; Amarenco, Pierre

    2011-01-01

    Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipop......Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high......-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic...... studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated...

  14. Relationships of plasma estradiol, testosterone, and sex hormone-binding globulin with lipoproteins, apolipoproteins, and high density lipoprotein subfractions in men.

    Science.gov (United States)

    Stefanick, M L; Williams, P T; Krauss, R M; Terry, R B; Vranizan, K M; Wood, P D

    1987-04-01

    Plasma estradiol, testosterone, and sex hormone-binding globulin (SHBG) were studied in relation to plasma lipoproteins, high density lipoprotein (HDL) subfractions, and apolipoproteins in 73 healthy but sedentary middle-aged men. Among potentially confounding variables, a strong positive association was found between estradiol levels and cigarette use, while testosterone and SHBG correlated negatively with percent body fat and alcohol intake. After adjustment for smoking, percent body fat, and alcohol, plasma estradiol levels correlated negatively with total cholesterol and low density lipoprotein cholesterol, and testosterone levels correlated positively with apolipoprotein B, while SHBG levels correlated positively with HDL2 mass and apolipoprotein A-I. SHBG was also strongly associated with the waist to hip girth ratio (WHR). Adjustment for WHR eliminated the significant associations of SHBG with triglycerides, HDL2 mass, and apolipoprotein A-I. SHBG levels and WHR may reflect tissue sensitivity and the impact of exposure to fluctuating levels of sex hormones for a period of days, or longer. These variables may provide more insight into the role of sex hormones in lipoprotein metabolism than do single samples of circulating hormones. It is also suggested that long term effects of sex hormones on adipose tissue distribution may at least partially underlie sex-related differences in lipoprotein metabolism.

  15. Secretion of bacterial lipoproteins: through the cytoplasmic membrane, the periplasm and beyond.

    Science.gov (United States)

    Zückert, Wolfram R

    2014-08-01

    Bacterial lipoproteins are peripherally anchored membrane proteins that play a variety of roles in bacterial physiology and virulence in monoderm (single membrane-enveloped, e.g., gram-positive) and diderm (double membrane-enveloped, e.g., gram-negative) bacteria. After export of prolipoproteins through the cytoplasmic membrane, which occurs predominantly but not exclusively via the general secretory or Sec pathway, the proteins are lipid-modified at the cytoplasmic membrane in a multistep process that involves sequential modification of a cysteine residue and cleavage of the signal peptide by the signal II peptidase Lsp. In both monoderms and diderms, signal peptide processing is preceded by acylation with a diacylglycerol through preprolipoprotein diacylglycerol transferase (Lgt). In diderms but also some monoderms, lipoproteins are further modified with a third acyl chain through lipoprotein N-acyl transferase (Lnt). Fully modified lipoproteins that are destined to be anchored in the inner leaflet of the outer membrane (OM) are selected, transported and inserted by the Lol (lipoprotein outer membrane localization) pathway machinery, which consists of the inner-membrane (IM) ABC transporter-like LolCDE complex, the periplasmic LolA chaperone and the OM LolB lipoprotein receptor. Retention of lipoproteins in the cytoplasmic membrane results from Lol avoidance signals that were originally described as the "+2 rule". Surface localization of lipoproteins in diderms is rare in most bacteria, with the exception of several spirochetal species. Type 2 (T2SS) and type 5 (T5SS) secretion systems are involved in secretion of specific surface lipoproteins of γ-proteobacteria. In the model spirochete Borrelia burgdorferi, surface lipoprotein secretion does not follow established sorting rules, but remains dependent on N-terminal peptide sequences. Secretion through the outer membrane requires maintenance of lipoproteins in a translocation-competent unfolded conformation

  16. [Lipoproteins HDL and coronary artery disease: a molecular mechanism of fibrate].

    Science.gov (United States)

    Kaletha, Krystian; Chodorowski, Zygmunt; Anand, Izabela Sein; Rybakowska, Iwona; Nagel-Starczynowska, Gabriela

    2003-01-01

    The importance of dyslipidemia in the development of cardiovascular disease is now recognized as a central factor of equal, if not greater significance than any other risk factor. Although correction of high level of low-density lipoproteins (LDL) has been regarded now as the main goal of therapy, it has now been reaffirmed that the contribution of low level of high-density lipoproteins (HDL) to the risk of ischaemic heart disease should also be considered. In the therapy of dislipidemias with hipertriglyceridemia and decreased level of HDL lipoprotein fibrates play an especially important role. In the article the molecular mechanism of fibrates action is presented.

  17. Recurrent Embolic Strokes of Undetermined Source in a Patient with Extreme Lipoprotein(a Levels

    Directory of Open Access Journals (Sweden)

    Zachary Bulwa

    2016-08-01

    Full Text Available Lipoprotein(a is a plasma lipoprotein and known cardiovascular risk factor most recently implicated in the development of high-risk carotid atherosclerotic plaques without significant carotid stenosis. We present a case of a young African-American female with recurrent embolic strokes of undetermined source. After our thorough investigation we identified the link between a small, irregular plaque in the right internal carotid artery and an extremely elevated plasma level of lipoprotein(a as the source of her embolic strokes.

  18. Application of directly coupled HPLC MMR to separation and characterization of lipoproteins from human serum

    DEFF Research Database (Denmark)

    Daykin, C. A.; Corcoran, O.; Hansen, S. H.

    2001-01-01

    Disorders in lipoprotein metabolism are critical in the etiology of several disease states such as coronary heart disease and atherosclerosis, Thus, there is considerable interest in the development of novel methods for the analysis of lipoprotein complexes. We report here a simple chromatographic...... with plasma proteins such as albumin occurred, and this clearly limits quantitation of that species by HPLC peak integration. We also show, for the first time, the application of directly coupled HPLC H-1 NMR spectroscopy to confirm the identification of the three major lipoproteins, The full chromatographic...

  19. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population

    DEFF Research Database (Denmark)

    Kamstrup, Pia R; Benn, Marianne; Tybjaerg-Hansen, Anne

    2008-01-01

    Elevated lipoprotein(a) levels are associated with myocardial infarction (MI) in some but not all studies. Limitations of previous studies include lack of risk estimates for extreme lipoprotein(a) levels, measurements in long-term frozen samples, no correction for regression dilution bias, and lack...... of absolute risk estimates in the general population. We tested the hypothesis that extreme lipoprotein(a) levels predict MI in the general population, measuring levels shortly after sampling, correcting for regression dilution bias, and calculating hazard ratios and absolute risk estimates....

  20. Analysis of receptor clustering on cell surfaces by imaging fluorescent particles

    OpenAIRE

    Morrison, I.E.; Anderson, C.M.; Georgiou, G.N.; Stevenson, G.V.; Cherry, R.J.

    1994-01-01

    Fluorescently labeled low density lipoproteins (LDL) and influenza virus particles were bound to the surface of human fibroblasts and imaged with a cooled slow-scan CCD camera attached to a fluorescence microscope. Particles were also imaged after attachment to polylysine-coated microscope slides. The digital images were analyzed by fitting data points in the region of fluorescent spots by a two-dimensional Gaussian function, thus obtaining a measure of spot intensity with correction for loca...

  1. Modification of low-density lipoprotein by different radioiodination methods

    International Nuclear Information System (INIS)

    Sobal, G.; Resch, U.; Sinzinger, H.

    2004-01-01

    Scintigraphic imaging of radiolabeled low-density lipoproteins (LDL) is an interesting tool for the understanding of its role in pathomechanism of atherosclerosis. Metabolism of native LDL shows quite different pattern and kinetics as compared to that of modified LDL which is not mediated by classical LDL-receptor and accumulates in atherosclerotic lesions to form lipid-laden foam cells. Therefore we were interested whether radiolabelling of LDL induces structural modifications. We performed the iodine labeling of LDL for scintigraphic imaging of atherosclerosis by three different methods: chloramine-T (A), iodine monochloride (B) and iodogen (C). The highest radiolabelling yield of 125 I was obtained by the iodogen method (75.44±13.52%) and the lowest (49.01±12.74%) by iodine monochloride. Chloramine T showed a labeling yield of 62.82±6.17%. The stability of the tracer was very high with all the methods, persisting up to 6 h (98.83±1.2% - 91.38±4.7%, 15 min vs 6 h after labeling). For the first time we not only investigated the influence of radiolabelling on relative electrophoretic mobility (REM), but also various oxidation parameters such as baseline dienes (BD), thiobarbituric acid reactive substances (TBARS), endogenous peroxides (POX) and oxidation resistance in the copper-mediated oxidation system (expressed as lag-time) were measured. Furthermore, oxidation- derived fragmentation of the lipoproteins was examined with SDS-PAGE electrophoresis. Data are expressed as % change compared to native LDL before radiolabeling. BD were reduced by 32% using the method (A), but increased by 33% and 47% with the monochloride (B) and iodogen method (C), respectively. The effect on lag-time was comparable for all the three methods, ranging from 25 to 36% reduction in lag-time. TBARS were strongly increased 5-7 fold by all the methods. REM was changed by all three methods. While by methods A and C we have found a moderate increase in REM by 1.75 and 2.0 fold

  2. Particle Physics

    CERN Multimedia

    2005-01-01

    While biomedicine and geoscience use grids to bring together many different sub-disciplines, particle physicists use grid computing to increase computing power and storage resources, and to access and analyze vast amounts of data collected from detectors at the world's most powerful accelerators (1 page)

  3. Pinpointing particles

    International Nuclear Information System (INIS)

    Miller, David J.

    1987-01-01

    The Conference on Position-Sensitive Detectors held at London's University College from 7-11 September highlighted the importance and the growing applications of these precision devices in many branches of science, underlining once again the high spinoff potential for techniques developed inside particle physics

  4. Observational study of lipid profile and LDL particle size in patients with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Martínez-Mernández Pedro

    2011-09-01

    Full Text Available Abstract Background The atherogenic lipoprotein phenotype is characterized by an increase in plasma triglycerides, a decrease in high-density lipoprotein cholesterol (HDLc, and the prevalence of small, dense-low density lipoprotein cholesterol (LDLc particles. The aim of this study was to establish the importance of LDL particle size measurement by gender in a group of patients with Metabolic Syndrome (MS attending at a Cardiovascular Risk Unit in Primary Care and their classification into phenotypes. Subjects and methods One hundred eighty-five patients (93 men and 92 women from several areas in the South of Spain, for a period of one year in a health centre were studied. Laboratory parameters included plasma lipids, lipoproteins, low-density lipoprotein size and several atherogenic rates were determinated. Results We found differences by gender between anthropometric parameters, blood pressure and glucose measures by MS status. Lipid profile was different in our two study groups, and gender differences in these parameters within each group were also remarkable, in HDLc and Apo A-I values. According to LDL particle size, we found males had smaller size than females, and patients with MS had also smaller than those without MS. We observed inverse relationship between LDL particle size and triglycerides in patients with and without MS, and the same relationship between all atherogenic rates in non-MS patients. When we considered our population in two classes of phenotypes, lipid profile was worse in phenotype B. Conclusion In conclusion, we consider worthy the measurement of LDL particle size due to its relationship with lipid profile and cardiovascular risk.

  5. First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay--Lp(a) SRM 2B.

    Science.gov (United States)

    Dati, Francesco; Tate, Jillian R; Marcovina, Santica M; Steinmetz, Armin

    2004-01-01

    Lipoprotein(a) is an important predictor of cardiovascular disease risk. The lack of internationally accepted standardization has impeded the broad application of this lipoprotein in laboratory medicine. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), through its Working Group on Lipoprotein(a) and together with research institutions and several diagnostic companies, have succeeded in developing an international reference material that is intended for the transfer of a lipoprotein(a) concentration to manufacturers' master calibrators. IFCC SRM 2B has recently been accepted by the WHO Expert Committee on Biological Standardization as the 'First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay'. The assigned unitage of 0.1071 nanomoles of lipoprotein(a) per vial is traceable to the consensus reference method for lipoprotein(a) and will enable conformity by diagnostic companies to the European Union's Directive on In vitro Diagnostic Medical Devices for the metrological traceability of calibrator materials.

  6. High Density Lipoprotein Cholesterol Increasing Therapy: The Unmet Cardiovascular Need

    Science.gov (United States)

    Cimmino, Giovanni; Ciccarelli, Giovanni; Morello, Alberto; Ciccarelli, Michele; Golino, Paolo

    2015-01-01

    Despite aggressive strategies are now available to reduce LDL-cholesterol, the risk of cardiovascular events in patients with coronary artery disease remains substantial. Several preclinical and clinical studies have shown that drug therapy ultimately leads to a regression of the angiographic lesions but also results in a reduction in cardiovascular events. The dramatic failure of clinical trials evaluating the cholesterol ester transfer protein (CEPT) inhibitors, torcetrapib and dalcetrapib, has led to considerable doubt about the value of the current strategy to raise high-density lipoprotein cholesterol (HDL-C) as a treatment for cardiovascular disease. These clinical results, as well as animal studies, have revealed the complexity of HDL metabolism, assessing a more important role of functional quality compared to circulating quantity of HDL. As a result, HDL-based therapeutic interventions that maintain or enhance HDL functionality, such as improving its main property, the reverse cholesterol transport, require closer investigation. In this review, we will discuss HDL metabolism and function, clinical-trial data available for HDL-raising agents, and potential strategies for future HDL-based therapies. PMID:26535185

  7. High Density Lipoprotein: A Therapeutic Target in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Philip J. Barter

    2013-09-01

    Full Text Available High density lipoproteins (HDLs have a number of properties that have the potential to inhibit the development of atherosclerosis and thus reduce the risk of having a cardiovascular event. These protective effects of HDLs may be reduced in patients with type 2 diabetes, a condition in which the concentration of HDL cholesterol is frequently low. In addition to their potential cardioprotective properties, HDLs also increase the uptake of glucose by skeletal muscle and stimulate the synthesis and secretion of insulin from pancreatic β cells and may thus have a beneficial effect on glycemic control. This raises the possibility that a low HDL concentration in type 2 diabetes may contribute to a worsening of diabetic control. Thus, there is a double case for targeting HDLs in patients with type 2 diabetes: to reduce cardiovascular risk and also to improve glycemic control. Approaches to raising HDL levels include lifestyle factors such as weight reduction, increased physical activity and stopping smoking. There is an ongoing search for HDL-raising drugs as agents to use in patients with type 2 diabetes in whom the HDL level remains low despite lifestyle interventions.

  8. Lipoprotein(a: Cellular Effects and Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Kirsten Riches

    2012-01-01

    Full Text Available Lipoprotein(a (Lp(a is an independent risk factor for the development of cardiovascular disease (CVD. Indeed, individuals with plasma concentrations >20 mg/dL carry a 2-fold increased risk of developing CVD, accounting for ~25% of the population. Circulating levels of Lp(a are remarkably resistant to common lipid lowering therapies, and there are currently no robust treatments available for reduction of Lp(a apart from plasma apheresis, which is costly and labour intensive. The Lp(a molecule is composed of two parts, an LDL/apoB-100 core and a unique glycoprotein, apolipoprotein(a (apo(a, both of which can interact with components of the coagulation cascade, inflammatory pathways, and cells of the blood vessel wall (smooth muscle cells (SMC and endothelial cells (EC. Therefore, it is of key importance to determine the molecular pathways by which Lp(a exerts its influence on the vascular system in order to design therapeutics to target its cellular effects. This paper will summarise the role of Lp(a in modulating cell behaviour in all aspects of the vascular system including platelets, monocytes, SMC, and EC.

  9. Escherichia coli lipoprotein binds human plasminogen via an intramolecular domain

    Directory of Open Access Journals (Sweden)

    Tammy eGonzalez

    2015-10-01

    Full Text Available Escherichia coli lipoprotein (Lpp is a major cellular component that exists in two distinct states, bound-form and free-form. Bound-form Lpp is known to interact with the periplasmic bacterial cell wall, while free-form Lpp is localized to the bacterial cell surface. A function for surface-exposed Lpp has yet to be determined. We hypothesized that the presence of C-terminal lysines in the surface-exposed region of Lpp would facilitate binding to the host zymogen plasminogen, a protease commandeered by a number of clinically important bacteria. Recombinant Lpp was synthesized and the binding of Lpp to plasminogen, the effect of various inhibitors on this binding, and the effects of various mutations of Lpp on Lpp-plasminogen interactions were examined. Additionally, the ability of Lpp-bound plasminogen to be converted to active plasmin was analyzed. We determined that Lpp binds plasminogen via an atypical domain located near the center of mature Lpp that may not be exposed on the surface of intact E. coli according to the current localization model. Finally, we found that plasminogen bound by Lpp can be converted to active plasmin. While the consequences of Lpp binding plasminogen are unclear, these results prompt further investigation of the ability of surface exposed Lpp to interact with host molecules such as extracellular matrix components and complement regulators, and the role of these interactions in infections caused by E. coli and other bacteria.

  10. Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages

    Directory of Open Access Journals (Sweden)

    Dana Atrahimovich

    2016-01-01

    Full Text Available High levels of circulating low-density lipoprotein (LDL are a primary initiating event in the development of atherosclerosis. Recently, the antiatherogenic effect of polyphenols has been shown to be exerted via a mechanism unrelated to their antioxidant capacity and to stem from their interaction with specific intracellular or plasma proteins. In this study, we investigated the interaction of the main polyphenol in pomegranate, punicalagin, with apolipoprotein B-100 (ApoB100 that surrounds LDL. Punicalagin bound to ApoB100 at low concentrations (0.25–4 μM. Upon binding, it induced LDL influx to macrophages in a concentration-dependent manner, up to 2.5-fold. In contrast, another polyphenol which binds to ApoB100, glabridin, did not affect LDL influx. We further showed that LDL influx occurs specifically through the LDL receptor, with LDL then accumulating in the cell cytoplasm. Taken together with the findings of Aviram et al., 2000, that pomegranate juice and punicalagin induce plasma LDL removal and inhibit macrophage cholesterol synthesis and accumulation, our results suggest that, upon binding, punicalagin stimulates LDL influx to macrophages, thus reducing circulating cholesterol levels.

  11. Adropin induction of lipoprotein lipase expression in tilapia hepatocytes.

    Science.gov (United States)

    Lian, Anji; Wu, Keqiang; Liu, Tianqiang; Jiang, Nan; Jiang, Quan

    2016-01-01

    The peptide hormone adropin plays a role in energy homeostasis. However, biological actions of adropin in non-mammalian species are still lacking. Using tilapia as a model, we examined the role of adropin in lipoprotein lipase (LPL) regulation in hepatocytes. To this end, the structural identity of tilapia adropin was established by 5'/3'-rapid amplification of cDNA ends (RACE). The transcripts of tilapia adropin were ubiquitously expressed in various tissues with the highest levels in the liver and hypothalamus. The prolonged fasting could elevate tilapia hepatic adropin gene expression, whereas no effect of fasting was observed on hypothalamic adropin gene levels. In primary cultures of tilapia hepatocytes, synthetic adropin was effective in stimulating LPL release, cellular LPL content, and total LPL production. The increase in LPL production also occurred with parallel rises in LPL gene levels. In parallel experiments, adropin could elevate cAMP production and up-regulate protein kinase A (PKA) and PKC activities. Using a pharmacological approach, cAMP/PKA and PLC/inositol trisphosphate (IP3)/PKC cascades were shown to be involved in adropin-stimulated LPL gene expression. Parallel inhibition of p38MAPK and Erk1/2, however, were not effective in these regards. Our findings provide, for the first time, evidence that adropin could stimulate LPL gene expression via direct actions in tilapia hepatocytes through the activation of multiple signaling mechanisms. © 2016 Society for Endocrinology.

  12. Hemorheological abnormalities in lipoprotein lipase deficient mice with severe hypertriglyceridemia

    International Nuclear Information System (INIS)

    Zhao Tieqiang; Guo Jun; Li Hui; Huang Wei; Xian Xunde; Ross, Colin J.D.; Hayden, Michael R.; Wen Zongyao; Liu George

    2006-01-01

    Severe hypertriglyceridemia (HTG) is a metabolic disturbance often seen in clinical practice. It is known to induce life-threatening acute pancreatitis, but its role in atherogenesis remains elusive. Hemorheological abnormality was thought to play an important role in pathogenesis of both pancreatitis and atherosclerosis. However, hemorheology in severe HTG was not well investigated. Recently, we established a severe HTG mouse model deficient in lipoprotein lipase (LPL) in which severe HTG was observed to cause a significant increase in plasma viscosity. Disturbances of erythrocytes were also documented, including decreased deformability, electrophoresis rate, and membrane fluidity, and increased osmotic fragility. Scanning electron microscopy demonstrated that most erythrocytes of LPL deficient mice deformed with protrusions, irregular appearances or indistinct concaves. Analysis of erythrocyte membrane lipids showed decreased cholesterol (Ch) and phospholipid (PL) contents but unaltered Ch/PL ratio. The changes of membrane lipids may be partially responsible for the hemorheological and morphologic abnormalities of erythrocytes. This study indicated that severe HTG could lead to significant impairment of hemorheology and this model may be useful in delineating the role of severe HTG in the pathogenesis of hyperlipidemic pancreatitis and atherosclerosis

  13. Lipoprotein(a) and risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Mora, Samia; Kamstrup, Pia R; Rifai, Nader

    2010-01-01

    BACKGROUND: Previous studies have demonstrated that cardiovascular risk is higher with increased lipoprotein (a) [Lp(a)]. Whether Lp(a) concentration is related to type 2 diabetes is unclear. METHODS: In 26 746 healthy US women (mean age 54.6 years), we prospectively examined baseline Lp......(a) concentrations and incident type 2 diabetes (n = 1670) for a follow-up period of 13 years. We confirmed our findings in 9652 Danish men and women with prevalent diabetes (n = 419). Analyses were adjusted for risk factors that included age, race, smoking, hormone use, family history, blood pressure, body mass...... index, hemoglobin A(1c) (Hb A(1c)), C-reactive protein, and lipids. RESULTS: Lp(a) was inversely associated with incident diabetes, with fully adjusted hazard ratios (HRs) and 95% CIs for quintiles 2-5 vs quintile 1 of 0.87 (0.75-1.01), 0.80 (0.68-0.93), 0.88 (0.76-1.02), and 0.78 (0.67-0.91); P...

  14. Lipoprotein(a) and risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Mora, S.; Kamstrup, Pia R; Rifai, N.

    2010-01-01

    (a) concentrations and incident type 2 diabetes (n = 1670) for a follow-up period of 13 years. We confirmed our findings in 9652 Danish men and women with prevalent diabetes (n = 419). Analyses were adjusted for risk factors that included age, race, smoking, hormone use, family history, blood pressure, body mass......BACKGROUND: Previous studies have demonstrated that cardiovascular risk is higher with increased lipoprotein (a) [Lp(a)]. Whether Lp(a) concentration is related to type 2 diabetes is unclear. METHODS: In 26 746 healthy US women (mean age 54.6 years), we prospectively examined baseline Lp...... index, hemoglobin A(1c) (Hb A(1c)), C-reactive protein, and lipids. RESULTS: Lp(a) was inversely associated with incident diabetes, with fully adjusted hazard ratios (HRs) and 95% CIs for quintiles 2-5 vs quintile 1 of 0.87 (0.75-1.01), 0.80 (0.68-0.93), 0.88 (0.76-1.02), and 0.78 (0.67-0.91); P...

  15. Effects of atorvastatin and simvastatin on low-density lipoprotein subfraction profile, low-density lipoprotein oxidizability, and antibodies to oxidized low-density lipoprotein in relation to carotid intima media thickness in familial hypercholesterolemia.

    NARCIS (Netherlands)

    Tits, L.J.H. van; Smilde, T.J.; Wissen, S. van; Graaf, J. de; Kastelein, J.J.P.; Stalenhoef, A.F.H.

    2004-01-01

    BACKGROUND: Little is known about the effects of statins on the quality of circulating low-density lipoprotein (LDL) in relation to atherosclerosis progression. METHODS: In a double-blind, randomized trial of 325 patients with familial hypercholesterolemia (FH), we assessed the effects of high-dose

  16. A brief history of lipid and lipoprotein measurements and their contribution to clinical chemistry.

    Science.gov (United States)

    McNamara, Judith R; Warnick, G Russell; Cooper, Gerald R

    2006-07-23

    The study of modern lipid chemistry began in the 17th and 18th centuries with early observations by Robert Boyle, Poulletier de la Salle, Antoine François de Fourcroy and others. The 19th century chemist, Chevreul, identified several fatty acids, suggested the name 'cholesterine' for the fatty substance in gallstones, coined the word 'glycerine', and showed that fats were comprised of glycerol and fatty acids. The 20th century brought many advances in the understanding of lipoprotein structure and function, and explored relationships between lipoproteins and disease states. The development of the ultracentrifuge and other lipoprotein separation techniques, and reagents for accurate, standardized quantitative measurement have steadily increased our understanding of the important role of lipoprotein metabolism in both healthy and disease states.

  17. Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family

    DEFF Research Database (Denmark)

    Nilsson, Stefan K; Lookene, Aivar; Beckstead, Jennifer A

    2007-01-01

    Apolipoprotein A-V is a potent modulator of plasma triacylglycerol levels. To investigate the molecular basis for this phenomenon we explored the ability of apolipoprotein A-V, in most experiments complexed to disks of dimyristoylphosphatidylcholine, to interact with two members of the low density...... lipoprotein receptor family, the low density lipoprotein receptor-related protein and the mosaic type-1 receptor, SorLA. Experiments using surface plasmon resonance showed specific binding of both free and lipid-bound apolipoprotein A-V to both receptors. The binding was calcium dependent and was inhibited......, apolipoprotein A-V (Arg210Glu/Lys211Gln), showed decreased binding to heparin and decreased ability to bind the low density lipoprotein receptor-related protein. Association of apolipoprotein A-V with the low density lipoprotein receptor-related protein or SorLA resulted in enhanced binding of human chylomicrons...

  18. Lipophilic antioxidants and polyunsaturated fatty acids in lipoprotein classes: distribution and interaction

    DEFF Research Database (Denmark)

    Sunesen, V.H.; Weber, Christine; Hølmer, Gunhild Kofoed

    2001-01-01

    (nine women, nine men), mean age 26 +/- 3 y, recruited among the university students; no dropouts. Interventions: Three supplementation periods of 10 days: 100 m/day CoQ(10), 350 mg/day D-alpha -tocopherol, and 2g/day concentrated fish oil. Fasting venous blood samples were collected twice before...... the first period and then after each period. Plasma and isolated lipoproteins were analysed for cholesterol, triacylglycerol, alpha- and gamma -tocopherol, CoQ(10), and fatty acid composition. Results: Significant (P tocopherol occurred in all lipoprotein classes after...... supplementation. CoQ(10) was primarily incorporated into low-density lipoprotein (LDL). alpha -tocopherol and fish oil n-3 PUFAs had similar patterns. They were equally distributed between LDL and high-density lipoprotein (HDL), with a smaller part in VLDL. The total sum of PUFA was unchanged following all...

  19. Behavioral versus genetic determination of lipoproteins andidentical twins discordant for exercise

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Paul T.; Blanche, Patricia J.; Krauss, Ronald M.

    2004-06-01

    Lipoprotein and weight differences between vigorously active and sedentary MZ twins are used to: (1) estimate the effects of training while controlling for genotype; (2) estimate genetic concordance in the presence of divergent lifestyles.

  20. Quantitative profiling of endocannabinoids in lipoproteins by LC-MS/MS.

    Science.gov (United States)

    Bilgin, Mesut; Bindila, Laura; Graessler, Juergen; Shevchenko, Andrej

    2015-07-01

    Endocannabinoids belong to a diverse family of endogenous lipid bioregulators acting as physiological ligands of cannabinoid receptor type 1 and cannabinoid receptor type 2 in the central and peripheral nervous system. They are also present in nmol L(-1) concentrations in human blood plasma; however, their association with possible molecular carriers remains poorly characterized. Here we report on the quantification of 46 endogenous molecular species from five major classes of endocannabinoids and endocannabinoid-related compounds in three lipoprotein fractions of human blood plasma: VLDL, LDL, HDL, and in the plasma lipoprotein-free fraction. Although sizable quantities of endocannabinoid-related molecules are associated with lipoproteins, we identified the lipoprotein-free fraction as a major carrier of endocannabinoids in blood circulation with the exception of 2-acylglycerols, which are markedly abundant in VLDL.

  1. Altered Serum Lipoprotein Profiles in Male and Female Power Lifters Ingesting Anabolic Steroids.

    Science.gov (United States)

    Cohen, Jonathan C.; And Others

    1986-01-01

    Serum lipoprotein profiles were measured in nine male and three female weightlifters who were taking anabolic steroids. The profiles suggest that steriod users may face an increased risk of coronary artery disease. (Author/MT)

  2. Assessing the functional properties of high-density lipoproteins : an emerging concept in cardiovascular research

    NARCIS (Netherlands)

    Triolo, Michela; Annema, Wijtske; Dullaart, Robin P. F.; Tietge, Uwe J. F.

    Although plasma concentrations of high-density lipoprotein (HDL) cholesterol correlate inversely with the incidence of atherosclerotic cardiovascular disease, results from recent epidemiological, genetic and pharmacological intervention studies resulted in a shift of concept. Rather than HDL

  3. Moderate doses of alcoholic beverages with dinner and postprandial high density lipoprotein composition

    NARCIS (Netherlands)

    Hendriks, H.F.J.; Veenstra, J.; Tol, A. van; Groener, J.E.M.; Schaafsma, G.

    1998-01-01

    Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. In this study, postprandial changes in plasma lipids, high-density lipoprotein (HDL) composition and cholesteryl ester transfer protein (CETP) and lecithin: cholesterol acyltransferase (LCAT) activity levels

  4. ABCA8 Regulates Cholesterol Efflux and High-Density Lipoprotein Cholesterol Levels

    NARCIS (Netherlands)

    Trigueros-Motos, Laia; van Capelleveen, Julian C.; Torta, Federico; Castaño, David; Zhang, Lin-Hua; Chai, Ee Chu; Kang, Martin; Dimova, Lidiya G.; Schimmel, Alinda W. M.; Tietjen, Ian; Radomski, Chris; Tan, Liang Juin; Thiam, Chung Hwee; Narayanaswamy, Pradeep; Wu, Daniel Heqing; Dorninger, Fabian; Yakala, Gopala Krishna; Barhdadi, Amina; Angeli, Veronique; Dubé, Marie-Pierre; Berger, Johannes; Dallinga-Thie, Geesje M.; Tietge, Uwe J. F.; Wenk, Markus R.; Hayden, Michael R.; Hovingh, G. Kees; Singaraja, Roshni R.

    2017-01-01

    Objective-High-density lipoproteins (HDL) are considered to protect against atherosclerosis in part by facilitating the removal of cholesterol from peripheral tissues. However, factors regulating lipid efflux are incompletely understood. We previously identified a variant in adenosine

  5. Multivariate DoE Optimization of Asymmetric Flow Field Flow Fractionation Coupled to Quantitative LC-MS/MS for Analysis of Lipoprotein Subclasses

    Directory of Open Access Journals (Sweden)

    Zsuzsanna Kuklenyik

    2015-02-01

    Full Text Available In this report we demonstrate a practical multivariate design of experiment (DoE approach for asymmetric flow field-flow fractionation (AF4 method optimization using separation of lipoprotein subclasses as an example. First, with the aid of commercially available software, we built a full factorial screening design where the theoretical outcomes were calculated by applying established formulas that govern AF4 channel performance for a 5–35 nm particle size range of interest for lipid particles. Second, using the desirable ranges of instrumental parameters established from theoretical optimization, we performed fractional factorial DoE for AF4 separation of pure albumin and ferritin with UV detection to narrow the range of instrumental parameters and allow optimum size resolution while minimizing losses from membrane immobilization. Third, the optimal range of conditions were tested using response surface DoE for sub-fractionation of high and low density lipoproteins (HDL and LDL in human serum, where the recovery of the analytes were monitored by fraction collection and isotope-dilution LC-MS/MS analysis of each individual fraction for cholesterol and apolipoproteins (ApoA-1 and ApoB-100. Our results show that DoE is an effective tool in combining AF4 theoretical knowledge and experimental data in finding the most optimal set of AF4 instrumental parameters for quantitative coupling with LC-MS/MS measurements.

  6. Active particles

    CERN Document Server

    Degond, Pierre; Tadmor, Eitan

    2017-01-01

    This volume collects ten surveys on the modeling, simulation, and applications of active particles using methods ranging from mathematical kinetic theory to nonequilibrium statistical mechanics. The contributing authors are leading experts working in this challenging field, and each of their chapters provides a review of the most recent results in their areas and looks ahead to future research directions. The approaches to studying active matter are presented here from many different perspectives, such as individual-based models, evolutionary games, Brownian motion, and continuum theories, as well as various combinations of these. Applications covered include biological network formation and network theory; opinion formation and social systems; control theory of sparse systems; theory and applications of mean field games; population learning; dynamics of flocking systems; vehicular traffic flow; and stochastic particles and mean field approximation. Mathematicians and other members of the scientific commu...

  7. Variability in lipoprotein concentrations in serum after prolonged storage at -20°C.

    OpenAIRE

    Tiedink, H.G.M.; Katan, M.B.

    1989-01-01

    The effects of freezing and storage at − 20° C of serum on the measurement of cholesterol and triglycerides concentrations in lipoprotein fractions separated by density gradient ultracentrifugation were investigated. Fresh, fasting, normolipidemic sera from 24 healthy individuals were divided into aliquots and stored, using different conditions. After storage, serum lipoproteins were separated by density gradient ultracentrifugation, and cholesterol and triglycerides assayed enzymatically. Fr...

  8. AUP1 (Ancient Ubiquitous Protein 1) Is a Key Determinant of Hepatic Very-Low-Density Lipoprotein Assembly and Secretion.

    Science.gov (United States)

    Zhang, Jing; Zamani, Mostafa; Thiele, Christoph; Taher, Jennifer; Amir Alipour, Mohsen; Yao, Zemin; Adeli, Khosrow

    2017-04-01

    AUP1 (ancient ubiquitous protein 1) is an endoplasmic reticulum-associated protein that also localizes to the surface of lipid droplets (LDs), with dual role in protein quality control and LD regulation. Here, we investigated the role of AUP1 in hepatic lipid mobilization and demonstrate critical roles in intracellular biogenesis of apoB100 (apolipoprotein B-100), LD mobilization, and very-low-density lipoprotein (VLDL) assembly and secretion. APPROACH AND RESULTS: siRNA (short/small interfering RNA) knockdown of AUP1 significantly increased secretion of VLDL-sized apoB100-containing particles from HepG2 cells, correcting a key metabolic defect in these cells that normally do not secrete much VLDL. Secreted particles contained higher levels of metabolically labeled triglyceride, and AUP1-deficient cells displayed a larger average size of LDs, suggesting a role for AUP1 in lipid mobilization. Importantly, AUP1 was also found to directly interact with apoB100, and this interaction was enhanced with proteasomal inhibition. Knockdown of AUP1 reduced apoB100 ubiquitination, decreased intracellular degradation of newly synthesized apoB100, and enhanced extracellular apoB100 secretion. Interestingly, the stimulatory effect of AUP1 knockdown on VLDL assembly was reminiscent of the effect previously observed after MEK-ERK (mitogen-activated protein kinase kinase-extracellular signal-regulated kinase) inhibition; however, further studies indicated that the AUP1 effect was independent of MEK-ERK signaling. In summary, our findings reveal an important role for AUP1 as a regulator of apoB100 stability, hepatic LD metabolism, and intracellular lipidation of VLDL particles. AUP1 may be a crucial factor in apoB100 quality control, determining the rate at which apoB100 is degraded or lipidated to enable VLDL particle assembly and secretion. © 2017 American Heart Association, Inc.

  9. A 90 minute soccer match decreases triglyceride and low density lipoprotein but not high-density lipoprotein and cholesterol levels

    Directory of Open Access Journals (Sweden)

    Nader - Rahnama

    2009-11-01

    Full Text Available

    • BACKGROUND: The association between the lipid profiles level and the incidence and severity of coronary heart disease (CHD is very pronounced in epidemiological studies, and an inverse relation between physical fitness and the incidence of coronary heart disease has been observed in many studies. The aim of this study was to investigate the impact of a soccer match on lipid parameters of professional soccer players.
    • METHODS: Twenty two professional soccer players participated in the study. Blood (10ml for determination of lipid profiles was obtained at rest and immediately after a 90 minute soccer match. Lipid parameters were measured using Boehringer Mannheim kits and Clinilab and BioMerieux analyser.
    • RESULTS: The results of this study showed that the triglyceride was significantly higher before the match than afterwards (159.09 ± 58.2 vs. 88.63 ± 34.1 mg/dl, p < 0.001, whereas the low-density lipoprotein (LDL was lower before the match than after it (98.04 ± 28.9 vs. 112.31 ± 30.5 mg/dl. Moreover, there were no significant differences in cholesterol concentration (171.4 ± 30.28 mg/dl vs. 173.18 ± 32.75 mg/dl and high-density lipoprotein (HDL concentration (34.04 ± 5.58 mg/dl vs. 34.4 ± 4.6 mg/dl between before and after the match.
    • CONCLUSIONS: Although the soccer competitive match has no favourable acute effect on lipid

    • Small-Molecule Inhibitors of Gram-Negative Lipoprotein Trafficking Discovered by Phenotypic Screening

      Science.gov (United States)

      Fleming, Paul R.; MacCormack, Kathleen; McLaughlin, Robert E.; Whiteaker, James D.; Narita, Shin-ichiro; Mori, Makiko; Tokuda, Hajime; Miller, Alita A.

      2015-01-01

      In Gram-negative bacteria, lipoproteins are transported to the outer membrane by the Lol system. In this process, lipoproteins are released from the inner membrane by the ABC transporter LolCDE and passed to LolA, a diffusible periplasmic molecular chaperone. Lipoproteins are then transferred to the outer membrane receptor protein, LolB, for insertion in the outer membrane. Here we describe the discovery and characterization of novel pyridineimidazole compounds that inhibit this process. Escherichia coli mutants resistant to the pyridineimidazoles show no cross-resistance to other classes of antibiotics and map to either the LolC or LolE protein of the LolCDE transporter complex. The pyridineimidazoles were shown to inhibit the LolA-dependent release of the lipoprotein Lpp from E. coli spheroplasts. These results combined with bacterial cytological profiling are consistent with LolCDE-mediated disruption of lipoprotein targeting to the outer membrane as the mode of action of these pyridineimidazoles. The pyridineimidazoles are the first reported inhibitors of the LolCDE complex, a target which has never been exploited for therapeutic intervention. These compounds open the door to further interrogation of the outer membrane lipoprotein transport pathway as a target for antimicrobial therapy. PMID:25583975

    • Variability of lipid and lipoprotein concentrations during puberty in Brazilian boys.

      Science.gov (United States)

      Mascarenhas, Luis Paulo Gomes; Leite, Neiva; Titski, Ana Cláudia C Kapp; Brito, Lilian Messias Sampaio; Boguszewski, Margaret C S

      2015-01-01

      Evaluation of lipid profile in children and adolescents is important for early diagnosis of dyslipidemias. Physiological changes might be observed in the concentration of the lipid profile components, according to the stage of sexual maturation. To evaluate the variation in lipid and lipoprotein concentrations in boys during puberty. The sample consisted of 570 male adolescents with ages between 10 and 17 years. Weight, height, and body mass index (BMI) were assessed. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) were determined by the enzymatic method, and low-density lipoprotein cholesterol (LDL-C) was calculated. Puberty was classified according to Tanner references. The percentile criterion was adopted for the distribution and identification of lipoprotein levels. The analysis of variance and description tests with ppuberty was observed. LDL-C levels rose during stage 3 of development, decreasing at the end of the pubertal process. TG levels did not change significantly with pubertal status. Lipid and lipoprotein concentrations tend to undergo changes during puberty in boys. The use of percentile values can be very useful to track variations in lipid and lipoprotein levels during the maturation process.

    • The Journey of Lipoproteins Through the Cell: One Birthplace, Multiple Destinations.

      Science.gov (United States)

      Szewczyk, J; Collet, J-F

      2016-01-01

      Bacterial lipoproteins are a very diverse group of proteins characterized by the presence of an N-terminal lipid moiety that serves as a membrane anchor. Lipoproteins have a wide variety of crucial functions, ranging from envelope biogenesis to stress response. In Gram-negative bacteria, lipoproteins can be targeted to various destinations in the cell, including the periplasmic side of the cytoplasmic or outer membrane, the cell surface or the external milieu. The sorting mechanisms have been studied in detail in Escherichia coli, but exceptions to the rules established in this model bacterium exist in other bacteria. In this chapter, we will present the current knowledge on lipoprotein sorting in the cell. Our particular focus will be on the surface-exposed lipoproteins that appear to be much more common than previously assumed. We will discuss the different targeting strategies, provide numerous examples of surface-exposed lipoproteins and discuss the techniques used to assess their surface exposure. © 2016 Elsevier Ltd All rights reserved.

    • Small-molecule inhibitors of gram-negative lipoprotein trafficking discovered by phenotypic screening.

      Science.gov (United States)

      McLeod, Sarah M; Fleming, Paul R; MacCormack, Kathleen; McLaughlin, Robert E; Whiteaker, James D; Narita, Shin-Ichiro; Mori, Makiko; Tokuda, Hajime; Miller, Alita A

      2015-03-01

      In Gram-negative bacteria, lipoproteins are transported to the outer membrane by the Lol system. In this process, lipoproteins are released from the inner membrane by the ABC transporter LolCDE and passed to LolA, a diffusible periplasmic molecular chaperone. Lipoproteins are then transferred to the outer membrane receptor protein, LolB, for insertion in the outer membrane. Here we describe the discovery and characterization of novel pyridineimidazole compounds that inhibit this process. Escherichia coli mutants resistant to the pyridineimidazoles show no cross-resistance to other classes of antibiotics and map to either the LolC or LolE protein of the LolCDE transporter complex. The pyridineimidazoles were shown to inhibit the LolA-dependent release of the lipoprotein Lpp from E. coli spheroplasts. These results combined with bacterial cytological profiling are consistent with LolCDE-mediated disruption of lipoprotein targeting to the outer membrane as the mode of action of these pyridineimidazoles. The pyridineimidazoles are the first reported inhibitors of the LolCDE complex, a target which has never been exploited for therapeutic intervention. These compounds open the door to further interrogation of the outer membrane lipoprotein transport pathway as a target for antimicrobial therapy. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

    • Continuous infusion of adrenocorticotropin elevates circulating lipoprotein cholesterol and corticosterone concentrations in chickens.

      Science.gov (United States)

      Latour, M A; Laiche, S A; Thompson, J R; Pond, A L; Peebles, E D

      1996-11-01

      The purpose of the present study was to investigate the effects of elevated corticosterone (CORT) on circulating lipoprotein cholesterol during a 1-wk period. For this study, 15 commercial broilers were randomly assigned to one of three treatment groups. Group 1 served as the control (CON) and received no treatment, whereas Groups 2 and 3 received subcutaneous mini-osmotic pumps containing either physiological saline (PS) or adrenocorticotropin (ACTH), respectively. The ACTH was delivered at a rate of 8 IU/kg of BW/d. Blood samples were taken at Time 0 (before implants) and on Days 2, 4, and 7 postimplantation. Continuous infusion of ACTH increased plasma glucose, cholesterol, triglycerides, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and CORT during the postimplantation period. The group treated with ACTH also exhibited a decrease in BW during the last 2 sampling d. There were no differences in any of the serum constituents measured between CON and PS birds, which suggest that CON birds can serve as useful controls. These data suggest that birds given a continuous infusion of ACTH at 8 IU/kg of BW/d can experience changes in plasma lipoprotein cholesterol concentrations along with changes in other blood parameters and may serve as a useful model in accelerated lipoprotein production.

    • Dyslipidemia in subclinical hypothyroidism requires assessment of small dense low density lipoprotein cholesterol (sdLDL-C

      Directory of Open Access Journals (Sweden)

      Saric Maida Seferovic

      2017-09-01

      Full Text Available Background. Usually both hypothyroidism and hyperthyroidism are related to the cardiovascular and cerebrovascular disease development. The relationship between subclinical hypothyroidism has been widely investigated but the findings remain controversial. The aim of the present study was to evaluate the lipid profile in patients with subclinical hypothyroidism (SHypo in comparison to controls and to determine the association of SHypo and dyslipidemia in attempt to find importance of small dense low-density lipoprotein cholesterol (sdLDL-C in atherosclerosis. Material and methods. In this study we included 100 women, aged 30 to 70 years that were divided into subgroups according to their age. According to the values of levels of thyroid hormones they were divided into euthyroid (control group (n = 64 and (newly discovered subclinical hypothyroidism (SHypo group (n = 36. A high-sensitivity C-reactive protein (hs-CRP and lipid profile, including small dense low-density lipoprotein cholesterol (sdLDL-C were determined. Body weight and height were measured and BMI calculated. History of the current illness, medication, alcohol consumption and cigarettes smoking were noted. Results. Changed lipid profile as well as elevated triglycerides and sdLDL-C were observed in the group with subclinical hypothyroidism compared to the control group. Conclusions. It is important to determine serum lipid levels, especially serum sdLDL-C levels at an early stage of subclinical hypothyroidism, since they represent atherogenic LDL particles and are better indicators for dyslipidaemia in subclinical hypothyroidism and the development of atherosclerosis with potential complications such as cardiovascular and cerebrovascular diseases.

    • ATP binding cassette A1 (ABCA1) mediates microparticle formation during high-density lipoprotein (HDL) biogenesis.

      Science.gov (United States)

      Hafiane, Anouar; Genest, Jacques

      2017-02-01

      Micro-particles (MP) are secreted by various cells. Their biological roles in health and in disease remain unknown. Here we describe formation of MP in the process of ABCA1-dependent cholesterol efflux in different cell types. The ATP-binding cassette transporter, subfamily A, member 1 (ABCA1) is the rate-limiting step in the biogenesis of high-density lipoproteins (HDL). We have found that ABCA1 and apoA-I contribute to the formation of MP. Using cell-based systems with overexpression and selective inactivation of ABCA1, pharmacological blockade and modulation of membrane cholesterol content, we characterized MP release from various cell lines. We studied MP release in BHK cells stably expressing ABCA1 under mifepristone control, human THP-1 macrophages and HepG2 cells without, or with incubation with human apoA-I. ABCA1 mediates the production of MPs containing cholesterol. This was also confirmed in primary human monocyte-derived macrophages (MDMs). Adding apoA-I markedly increases MP release from cells. Inhibition of ABCA1 with probucol or decreasing plasma membrane cholesterol with methyl-β cyclodextrin (CDX) markedly reduced MP release and nascent HDL formation. MPs do not contain apoA-I, but contain flotilin-2, a marker of plasma membrane, and CD63, an exosome marker. MPs exhibit considerable size heterogeneity (50-250 nm). We show that MPs are lipoprotein-sized structures created by the ABCA1 transporter, and contribute approximately 30% of ABCA1-and apoA-I mediated cholesterol efflux. In addition, we found that MPs release from cells consists, in part, of exosomes and depends on the same pathway used for HDL biogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

    • Lipoprotein profiles and serum peroxide levels of aged women consuming palmolein or oleic acid-rich sunflower oil diets.

      Science.gov (United States)

      Cuesta, C; Ródenas, S; Merinero, M C; Rodríguez-Gil, S; Sánchez-Muniz, F J

      1998-09-01

      To investigate the hypercholesterolemic effects of a dietary exchange between 16:0 and 18:1 while 18:2 was at relatively lower level (approximately 4%) in aged women with initially high total serum cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) values and with high intakes of dietary cholesterol. Subjects were assigned to two consecutive 28 d periods. In the first period all subjects followed an oleic acid-rich diet in the form of oleic acid-rich sunflower oil. This was followed by a second period rich in palmitic acid in the form of palmolein. Nutrient intakes, serum lipids, lipoproteins, antioxidant vitamins, peroxides and LDL-peroxides were measured at two dietary periods. Instituto de Nutrición y Bromatología (CSIC), Departamento de Nutrición y Bromatología I (Nutrición) and Sección Departamental de Quimica Analítica, Universidad Complutense, Madrid, Spain. The palmolein period led to an increase in TC (P or = 6.21 mmol/L or with TC 6.21 mmol/L than in women with TC < 6.21 mmol/L, but palmolein decreased serum and LDL-peroxide in hypercholesterolemics more than in the normocholesterolemics, resulting in serum and LDL-peroxide levels which theoretically are more adequate. Though palmolein increased LDL-C concentrations, it better protected LDL particles, mainly in women with high TC, against peroxidation than did oleic acid-rich sunflower oil.

    • Lipoprotein(a) and coronary atheroma progression rates during long-term high-intensity statin therapy: Insights from SATURN.

      Science.gov (United States)

      Puri, Rishi; Ballantyne, Christie M; Hoogeveen, Ron C; Shao, Mingyuan; Barter, Philip; Libby, Peter; Chapman, M John; Erbel, Raimund; Arsenault, Benoit J; Raichlen, Joel S; Nissen, Steven E; Nicholls, Stephen J

      2017-08-01

      Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL)-like particle that associates with major adverse cardiovascular events (MACE). We examined relationships between Lp(a) measurements and changes in coronary atheroma volume following long-term maximally-intensive statin therapy in coronary artery disease patients. Study of coronary atheroma by intravascular ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) used serial intravascular ultrasound measures of coronary atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. Baseline and follow-up Lp(a) levels were measured in 915 of the 1039 SATURN participants, and were correlated with changes in percent atheroma volume (ΔPAV). Mean age was 57.7 ± 8.6 years, 74% were men, 96% were Caucasian, with statin use prior to study enrolment occurring in 59.3% of participants. Baseline [median (IQR)] LDL-cholesterol (LDL-C) and measured Lp(a) levels (mg/dL) were 114 (99, 137) and 17.4 (7.6, 52.9) respectively; follow-up measures were 60 (47, 77), and 16.5 (6.7, 57.7) (change from baseline: p  50 mg/dL. In coronary artery disease patients prescribed long-term maximally intensive statin therapy with low on-treatment LDL-C levels, measured Lp(a) levels (predominantly below the 50 mg/dL threshold) do not associate with coronary atheroma progression. Alternative biomarkers may thus associate with residual cardiovascular risk in such patients. Copyright © 2017 Elsevier B.V. All rights reserved.

    • Balanced high fat diet reduces cardiovascular risk in obese women although changes in adipose tissue, lipoproteins, and insulin resistance differ by race.

      Science.gov (United States)

      Niswender, Kevin D; Fazio, Sergio; Gower, Barbara A; Silver, Heidi J

      2018-05-01

      We previously reported that consuming a balanced high fat diet (BHFD) wherein total saturated fat was reduced and total unsaturated fat increased by proportionately balancing the type of fat (1/3 saturated, 1/3 monounsaturated, 1/3 polyunsaturated) led to significant improvements in inflammatory burden, blood pressure, and vascular function in obese premenopausal European American (EA) and African American (AA) women. Here we compared changes in adipose tissue, lipoproteins, insulin resistance, and cardiovascular risk between EA and AA women. Dietary intakes, plasma fatty acids, lipids, apolipoproteins, lipoproteins, HOMA-IR and ASCVD risk was measured in 144 women who consumed BHFD for 16 weeks. Generalized linear modeling was performed while controlling for change in body weight. EA women had greater reductions in visceral adipose tissue. Only EA women had significant reductions in fasting insulin levels (↓24.8%) and HOMA-IR (↓29%) scores. In EA women, the most significant improvements occurred in VLDL particle size (↑), apolipoprotein B levels (↑), serum TG (↓), number of plasma LDL particles (↓), and serum LDL-cholesterol (↓). In AA women, significant improvements occurred in HDL particle size (↑), number of large HDL particles (↑), and apolipoprotein AI levels (↑). Consequently, both groups had improved ASCVD risk scores (↓5.5%). Consuming the balanced high fat diet led to significant reduction in cardiovascular risk factors in both groups. However, the pattern of response to BHFD differed with EA women responding more in components of the apolipoprotein B pathway versus AA women responding more in components of the apolipoprotein AI pathway. Published by Elsevier Inc.

    • Ethnicity and lipoprotein(a) polymorphism in Native Mexican populations

      Science.gov (United States)

      Cardoso-Saldaña, Guillermo; De La Peña-Díaz, Aurora; Zamora-González, José; Gomez-Ortega, Rocio; Posadas-Romero, Carlos; Izaguirre-Avila, Raul; Malvido-Miranda, Elsa; Morales-Anduaga, Maria Elena; Angles-Cano, Eduardo

      2006-01-01

      Background Lp(a) is a lipoparticle of unknown function mainly present in primates and humans. It consists of a low-density lipoprotein and apo(a), a polymorphic glycoprotein. Apo(a) shares sequence homology and fibrin-binding with plasminogen inhibiting its fibrinolytic properties. Lp(a) is considered a link between atherosclerosis and thrombosis. Marked inter-ethnic differences in Lp(a) concentration related to the genetic polymorphism of apo(a), have been reported in several populations. Aim To study the structural and functional features of Lp(a) in three Native Mexican populations (Mayos, Mazahuas and Mayas) and in Mestizo subjects. Methods We determined the plasma concentration of Lp(a) by immunonephelometry, apo(a) isoforms by Western blot, Lp(a) fibrin-binding by immuno-enzymatic assay and STR polymorphic markers genetic analysis by capillary electrophoresis. Results Mestizos presented the less skewed distribution and the highest median Lp(a) concentration (13.25 mg/dL) relative to Mazahuas (8.2 mg/dL), Mayas (8.25 mg/dL) and Mayos (6.5 mg/dL). Phenotype distribution was different in Mayas and Mazahuas as compared to the Mestizo group. The higher Lp(a) fibrin-binding capacity was found in the Maya population. There was an inverse relationship between the size of apo(a) polymorphs and both Lp(a) levels and Lp(a) fibrin binding. Conclusion There is evidence of significative differences in Lp(a) plasma concentration and phenotype distribution in Native Mexican and the Mestizo group. PMID:16684693

  1. Lipoprotein (a): a potential biological marker for unruptured intracranial aneurysms.

    Science.gov (United States)

    Phillips, J; Roberts, G; Bolger, C; el Baghdady, A; Bouchier-Hayes, D; Farrell, M; Collins, P

    1997-05-01

    The diagnosis and treatment of intracranial aneurysms (IAs) prior to rupture reduces the high morbidity and mortality associated with their occurrence. Elevated serum lipoprotein (a) [Lp(a)] level, an independent risk factor for atherogenesis, has been demonstrated in sporadic IA disease (1). The purpose of this study was to assess the degree of correlation between elevated Lp(a) levels and the occurrence of IAs in asymptomatic first degree relatives of index cases from three families exhibiting a familial tendency towards IA development. 25 family members and 41 healthy controls were screened by random serum Lp(a) sampling. All family members received 4-vessel cerebral angiography. Eleven family members were found on angiography to harbour asymptomatic aneurysms and all were successfully treated by surgery. Of these 11, ten had significantly raised serum Lp(a) levels (> 30 mg%). Fourteen family members had negative angiograms. Eight of this latter group, mean age 43.6 +/- 3.8 years, had serum Lp(a) levels above the normal range. Mean Lp(a) levels were 53.7 +/- 1.2 mg% in subjects with aneurysms compared with 22.1 +/- 1.45 mg% in subjects without demonstrable aneurysms and 10.5 +/- 0.48 mg% in the control population. The prevalence of elevated Lp(a) levels in these families and the high degree of association of raised Lp(a) levels with the presence of IAs in several family members warrants follow up of angiographically negative young subjects. We require a case-control study to establish whether particular polymorphisms at the apoprotein (a) gene level are associated with the occurrence of IAs in these families.

  2. Oxidative stress and plasma lipoproteins in cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Maia, Fernanda Maria Machado; Santos, Emanuelly Barbosa; Reis, Germana Elias [Universidade Estadual do Ceará, Fortaleza, CE (Brazil)

    2014-07-01

    To evaluate the relation between oxidative stress and lipid profile in patients with different types of cancer. This was an observational cross-sectional. A total of 58 subjects were evaluated, 33 males, divided into two groups of 29 patients each: Group 1, patients with cancer of the digestive tract and accessory organs; Group 2 patients with other types of cancers, all admitted to a public hospital. The plasma levels (lipoproteins and total cholesterol, HDL, and triglycerides, for example) were analyzed by enzymatic kits, and oxidative stress based on thiobarbituric acid-reactive substances, by assessing the formation of malondialdehyde. In general the levels of malondialdehyde of patients were high (5.00μM) as compared to 3.31μM for healthy individuals. The median values of lipids exhibited normal triacylglycerol (138.78±89.88mg/dL), desirable total cholesterol values (163.04±172.38mg/dL), borderline high LDL (151.30±178.25mg/dL) and low HDL (31.70±22.74mg/dL). Median HDL levels in Group 1 were lower (31.32mg/dL) than the cancer patients in Group 2 (43.67mg/dL) (p=0.038). Group 1 also showed higher levels of oxidative stress (p=0.027). The lipid profile of patients with cancer was not favorable, which seems to have contributed to higher lipid peroxidation rate, generating a significant oxidative stress.

  3. Radioiodinated cholesteryl ester analogs as residualizing tracers of lipoproteins disposition

    International Nuclear Information System (INIS)

    DeForge, L.E.

    1989-01-01

    Due to the importance of low density lipoprotein (LDL) in lipid metabolism and atherosclerosis, efforts were made to incorporate 125 I-cholesteryl iopanoate ( 125 I-CI), a residualizing cholesteryl ester (CE) analog, into the lipid core of LDL. This preparation is potentially useful as a scintigraphically detectable tracer of LDL uptake into atheroma and tissues such as the adrenal and liver. Initial studies using a cholesterol-fed rabbit model of atherosclerosis validated the use of 125 I-CI as a tracer of CE deposition. However, scintigraphy revealed considerable nonspecific 125 I-CI uptake due to tissue cholesterol loading. An alternative animal model was the guinea pig, which responds moderately to cholesterol feeding and carries the plasma cholesterol predominantly as LDL. Dietary fat and cholesterol, coupled with chronic aortic injury caused by an indwelling catheter, resulted in lipid containing, smooth muscle cell proliferative lesions in many animals. However, further studies are necessary to fully characterize this model. In additional studies, in vitro methods for incorporating 125 I-CI into LDL were examined. These included a reconstitution procedure described by Krieger et al. and a procedure involving incubation of detergent (Tween 20)-solubilized 125 I-CI with plasma. Although both LDL preparations were taken up normally by cultured fibroblasts, the plasma clearance rate of reconstituted LDL was markedly abnormal in guinea pigs. In contrast, LDL labeled by the detergent method cleared from the plasma identically to a radioiodinated LDL control. Therefore, this latter procedure was also used to incorporate two novel radioiodinated cholesteryl ether analogs 125 I-CI cholesteryl m-iodobenzyl ether [ 125 I-CIDE] and 125 I-cholesteryl 12-(miodophenyl)dodecyl ether [ 125 I-CIDE] into LDL

  4. Effect of soy protein on swine intestinal lipoproteins

    International Nuclear Information System (INIS)

    Ho, H.T.

    1987-01-01

    Hypocholesterolemic effect of soy protein appears to be the result of reduced cholesterol absorption and enhanced cholesterol excretion. The objective of this study is to delineate the underlying mechanism of soy protein effect on cholesterol absorption. At the end of a 5-week soy-protein or casein diet, swine were subjected to cannulation of mesenteric lymph duct under halothane anesthesia. A single dose of 250 μCi [ 14 C]-cholesterol and 10 mCi [ 3 H]-leucine was infused into the upper jejunum two hours after one-fifth of daily food was given. Then lymph was collected hourly for three hours and the lipoprotein fractions were separated by ultracentrifugation. SDS-PAGE (5%) was used to measure the concentrations of individual apoproteins by densitometric scanning. The three-hour lymphatic transport of cholesterol in casein-fed swine was significantly higher than in those fed soy protein. Triglyceride transports were similar in two groups. The [ 3 H]-leucine incorporation study revealed that transport of apo B-48 bore a significant positive relationship to transport of cholesterol in both chylomicron and VLDL fractions of mesenteric lymph. A greater apo B-48 secretion with higher specific activity was probably responsible for the greater transport of cholesterol in chylomicrons in casein-fed swine. On the other hand, the lesser cholesterol transport in chylomicrons in soy protein-fed swine was probably caused by lower apo B-48 secretion. Similarly, the transport of lymph VLDL cholesterol in swine fed casein or soy protein paralleled the amount of accompanying apo B-48. Dietary proteins probably influence the intestinal synthesis of apo B-48 which in turn affects cholesterol transport into the lymphatics

  5. Association of serum lipoprotein (a) with hypertension in diabetic patients

    International Nuclear Information System (INIS)

    Nasri, H.

    2008-01-01

    To evaluate the influence of serum Lp(a) concentration on hypertension in patients with diabetes mellitus (DM) and under treatment with oral hypoglycemic agents or insulin injections, we studied 122 patients, 82 females and 40 males with a mean age of 63+-10 years and duration of DM and HTN of 7.4+-5.8 and 3.2+-4.6 years, respectively. The mean systolic and diastolic blood pressure (BP) was 138+-23 mmHg and 83+-12mmHg, respectively. In this cross-sectional study, we measured serum lipoprotein (a) (Lp(a), glycosilated hemoglobin (HbA1c) and other lipids while the patients were receiving either oral hypoglycemic agents or insulin. In addition, body mass index (BMI) and creatinine clearance (CrCL) were assessed. The mean serum Lp(a) was 22.2+-24.7 mg/dl (median: 18.3 mg/dl), and serum Lp(a) levels >30 mg/dl was found in 29(23.8%) patients. There were significant positive correlations of duration of DM and duration of hypertension, and serum Lp(a) levels with of systoli and diastolic levels of BP. However, a significant inverse correlation of serum Lp(a) with CrCl were observed. This study suggests that kidney function is an independent determination of Lp(a) and HTN in diabetic patients. Furthermore Lp(a) in diabetic patients may have important implications for the increased susceptibility to vascular diseases in these patients. (author)

  6. Use of transgenic mice in lipoprotein metabolism and atherosclerosis research

    NARCIS (Netherlands)

    Havekes, L.M.; Vlijmen, B.J.M. van; Jong, M.C.; Dijk, K.W. van; Hofker, M.H.

    1997-01-01

    In APOE*3-Leiden transgenic mice the atherosclerotic lesion size is correlated with plasma cholesterol. In these mice the plasma lipid levels are positively correlated with the relative amount of APOE 3-Leiden protein on the VLDL particle. The plasma cholesterol levels are influenced by diet, age

  7. Effect of human scavenger receptor class A overexpression in bone marrow-derived cells on lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knockout mice

    NARCIS (Netherlands)

    Herijgers, N.; de Winther, M. P.; van Eck, M.; Havekes, L. M.; Hofker, M. H.; Hoogerbrugge, P. M.; van Berkel, T. J.

    2000-01-01

    Scavenger receptors, which include various classes, play an important role in atherogenesis by mediating the unrestricted uptake of modified lipoproteins, resulting in the massive accumulation of cholesteryl esters. Because macrophage-derived foam cells are considered to be an important feature in

  8. Different effects of diets rich in olive oil, rapeseed oil and sunflower-seed oil on postprandial lipid and lipoprotein concentrations and on lipoprotein oxidation susceptibility

    DEFF Research Database (Denmark)

    Nielsen, Nina Skall; Pedersen, A.; Sandstrøm, B.

    2002-01-01

    oxidation of fasting and postprandial lipoproteins eighteen males consumed diets enriched with rapeseed oil (RO), olive oil (OO), or sunflower-seed oil (SO) in randomised order for periods of 3 weeks followed by a RO test meal. In the postprandial state the concentrations of cholesterol and triacylglycerol...

  9. Post-transcriptional regulation of lipoprotein receptors by the E3-ubiquitin ligase inducible degrader of the low-density lipoprotein receptor.

    Science.gov (United States)

    Sorrentino, Vincenzo; Zelcer, Noam

    2012-06-01

    The hepatic low-density lipoprotein receptor (LDLR) pathway is essential for clearing circulating LDL and is an important therapeutic target for treating cardiovascular disease. Abundance of the LDLR is subject to both transcriptional and nontranscriptional control. Here, we highlight a new post-transcriptional mechanism for controlling LDLR function via ubiquitination of the receptor by the E3-ubiquitin ligase inducible degrader of the LDLR (IDOL). IDOL is a recently identified transcriptional target of the liver X receptors. Acting as an E3-ubiquitin ligase IDOL promotes ubiquitination of the LDLR, thereby marking it for lysosomal degradation. The determinants required for degradation of the LDLR by IDOL have been largely identified. IDOL also targets two related lipoprotein receptors, the very low-density lipoprotein receptor and apolipoprotein E receptor 2. Despite several similarities, the IDOL, and PCSK9 pathways for controlling LDLR abundance seem independent of each other. Genome-wide association studies have recently identified IDOL as a locus influencing variability in circulating levels of LDL, thereby highlighting the possible role of IDOL in human lipoprotein metabolism. Transcriptional induction of IDOL by liver X receptor defines a new post-transcriptional pathway for controlling LDLR abundance and LDL uptake independent of sterol regulatory element binding proteins. Targeting IDOL activity may offer a novel therapeutic approach complementary to statins for treating cardiovascular disease.

  10. Identification of a loss-of-function inducible degrader of the low-density lipoprotein receptor variant in individuals with low circulating low-density lipoprotein

    NARCIS (Netherlands)

    Sorrentino, Vincenzo; Fouchier, Sigrid W.; Motazacker, Mohammad M.; Nelson, Jessica K.; Defesche, Joep C.; Dallinga-Thie, Geesje M.; Kastelein, John J. P.; Kees Hovingh, G.; Zelcer, Noam

    2013-01-01

    Recent genome-wide association studies suggest that IDOL (also known as MYLIP) contributes to variation in circulating levels of low-density lipoprotein cholesterol (LDL-C). IDOL, an E3-ubiquitin ligase, is a recently identified post-transcriptional regulator of LDLR abundance. Briefly, IDOL

  11. Post-transcriptional regulation of lipoprotein receptors by the E3-ubiquitin ligase inducible degrader of the low-density lipoprotein receptor

    NARCIS (Netherlands)

    Sorrentino, Vincenzo; Zelcer, Noam

    2012-01-01

    Purpose of review The hepatic low-density lipoprotein receptor (LDLR) pathway is essential for clearing circulating LDL and is an important therapeutic target for treating cardiovascular disease. Abundance of the LDLR is subject to both transcriptional and nontranscriptional control. Here, we

  12. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

    DEFF Research Database (Denmark)

    Chapman, M John; Ginsberg, Henry N; Amarenco, Pierre

    2011-01-01

    Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipop...... cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥ 1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (......Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high...... studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated...

  13. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

    DEFF Research Database (Denmark)

    Chapman, M John; Ginsberg, Henry N; Amarenco, Pierre

    2011-01-01

    Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipop...... cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (= 1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (......Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high...... studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated...

  14. Particle Mechanics

    CERN Document Server

    Collinson, Chris

    1995-01-01

    * Assumes no prior knowledge* Adopts a modelling approach* Numerous tutorial problems, worked examples and exercises included* Elementary topics augmented by planetary motion and rotating framesThis text provides an invaluable introduction to mechanicsm confining attention to the motion of a particle. It begins with a full discussion of the foundations of the subject within the context of mathematical modelling before covering more advanced topics including the theory of planetary orbits and the use of rotating frames of reference. Truly introductory , the style adoped is perfect for those u

  15. The Association Between Small Dense Low Density Lipoprotein,Apolipoprotein B, Apolipoprotein B/apolipoprotein A1 Ratio and coronary Artery Stenosis

    Directory of Open Access Journals (Sweden)

    Abbas Zavarehee

    2009-05-01

    Full Text Available Background:Recently,small dense low density lipoprotein (sdLDL has been highlighted as a new risk factor for the coronary artery disease(CAD.Small dense LDLs are believed to be atherogenic since these particles are taken up more easily by arterial wall.They are readily oxidized and have reduced affinity for low density lipoprotein (LDL receptor and increased affinity for arterial proteoglicans.LDL cholesterol is only a measure of the cholesterol level in the LDL whereas apolipoprotein B(apo B is a measure of the cholesterol levels of all the atherogenic particles,including very low density lipoprotein, intermediate density, and low density lipoproteins. Therefore,it might be a better marker than other traditional lipids. The aim of the present study was to evaluate the association between serum small dense LDL, apolipoprotein B, apolipoprotein A1 (apo A1 and apoB/apoA1 ratio and the coronary stenosis.Methods: 86 patients with coronary stenosis, 35 patients without coronary stenosis   identified by angiography who were referred to Rajaii Heart Center , and 30 healthy individuals were studied.SdLDL was measured by a direct homogenous LDL-C assay in the supernatant of serum which remained after heparin-magnesium precipitation.Serum apolipoprotein A1 and apolipoprotein B were measured by using immunoturbidimetric method.Results: The results showed that the sdLDL levels were higher in patients with coronary stenosis than patients without coronary stenosis and healthy individuals   (21.54±7.1, 16.88±4.4 and 15.45±5mg/dl, p=0.001, respectively. In addition the level   of apoB (with stenosis: 113.71±21.8, without stenosis:100.88±18.7 and healthy:102.30±9.6, p=0.003 and apoB/apoA1 ratio (with stenosis:1.100±0.24, without stenosis :0.589±0.26 and healthy:0.751±0.16, p=0.001 were significantly higher in patients with coronary stenosis. SdLDL levels were positively correlated with the level of apoB(r=0.589, apoB/apoA1 ratio(r=0.416, triglyceride

  16. Effect of functional sympathetic nervous system impairment of the liver and abdominal visceral adipose tissue on circulating triglyceride-rich lipoproteins.

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    Michael F La Fountaine

    Full Text Available Interruption of sympathetic innervation to the liver and visceral adipose tissue (VAT in animal models has been reported to reduce VAT lipolysis and hepatic secretion of very low density lipoprotein (VLDL and concentrations of triglyceride-rich lipoprotein particles. Whether functional impairment of sympathetic nervous system (SNS innervation to tissues of the abdominal cavity reduce circulating concentrations of triglyceride (TG and VLDL particles (VLDL-P was tested in men with spinal cord injury (SCI.One hundred-three non-ambulatory men with SCI [55 subjects with neurologic injury at or proximal to the 4th thoracic vertebrae (↑T4; 48 subjects with SCI at or distal to the 5th thoracic vertebrae (↓T5] and 53 able-bodied (AB subjects were studied. Fasting blood samples were obtained for determination of TG, VLDL-P concentration by NMR spectroscopy, serum glucose by autoanalyzer, and plasma insulin by radioimmunoassay. VAT volume was determined by dual energy x-ray absorptiometry imaging with calculation by a validated proprietary software package.Significant group main effects for TG and VLDL-P were present; post-hoc tests revealed that serum TG concentrations were significantly higher in ↓T5 group compared to AB and ↑T4 groups [150±9 vs. 101±8 (p<0.01 and 112±8 mg/dl (p<0.05, respectively]. VLDL-P concentration was significantly elevated in ↓T5 group compared to AB and ↑T4 groups [74±4 vs. 58±4 (p<0.05 and 55±4 μmol/l (p<0.05]. VAT volume was significantly higher in both SCI groups than in the AB group, and HOMA-IR was higher and approached significance in the SCI groups compared to the AB group. A linear relationship between triglyceride rich lipoproteins (i.e., TG or Large VLDL-P and VAT volume or HOMA-IR was significant only in the ↓T5 group.Despite a similar VAT volume and insulin resistance in both SCI groups, the ↓T5 group had significantly higher serum TG and VLDL-P values than that observed in the ↑T4 and the AB

  17. The relationship between oxidized lipoprotein(a and carotid atherosclerosis in asymptomatic subjects: A comparison with native lipoprotein(a

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    Taniguchi Nobuyuki

    2011-10-01

    Full Text Available Abstract Background Oxidized lipoprotein(a (oxLp(a can be a more potent marker of atherogenesis than native Lp(a, although Lp(a is considered to be a risk factor for atherosclerotic diseases. Limited clinical data are available regarding the significance of oxLp(a in atherosclerotic manifestations. This study aimed to investigate the association between the serum oxLp(a and carotid artery intima-media thickness (CIMT, in comparison to the serum Lp(a levels, among asymptomatic subjects. Methods The atheroscrerosis-related variables including Lp(a and oxLp(a were measured in 136 cardiovascular disease-free subjects (61 males and 75 females, mean age of 64 years. The serum oxLp(a level was quantified using a sandwich ELISA system. The CIMT level was ultrasonographically measured on bilateral carotid arteries. Results The median level of Lp(a was 120 μmol/L, oxLp(a was 0.06 nmol/L, and CIMT was 0.7 mm, respectively. A simple correlation test showed that the CIMT was significantly and positively correlated with age, systolic blood pressure and oxLp(a (r = 0.208, P Conclusions These results suggest that oxLp(a may be more closely associated with accelerated carotid atherosclerosis, in comparison to Lp(a, in this population. This finding can be important for obtaining a better understanding of the different atherogenic roles played by oxLp(a in comparison to Lp(a.

  18. Mutation of the maturase lipoprotein attenuates the virulence of Streptococcus equi to a greater extent than does loss of general lipoprotein lipidation.

    Science.gov (United States)

    Hamilton, Andrea; Robinson, Carl; Sutcliffe, Iain C; Slater, Josh; Maskell, Duncan J; Davis-Poynter, Nick; Smith, Ken; Waller, Andrew; Harrington, Dean J

    2006-12-01

    Streptococcus equi is the causative agent of strangles, a prevalent and highly contagious disease of horses. Despite the animal suffering and economic burden associated with strangles, little is known about the molecular basis of S. equi virulence. Here we have investigated the contributions of a specific lipoprotein and the general lipoprotein processing pathway to the abilities of S. equi to colonize equine epithelial tissues in vitro and to cause disease in both a mouse model and the natural host in vivo. Colonization of air interface organ cultures after they were inoculated with a mutant strain deficient in the maturase lipoprotein (DeltaprtM(138-213), with a deletion of nucleotides 138 to 213) was significantly less than that for cultures infected with wild-type S. equi strain 4047 or a mutant strain that was unable to lipidate preprolipoproteins (Deltalgt(190-685)). Moreover, mucus production was significantly greater in both wild-type-infected and Deltalgt(190-685)-infected organ cultures. Both mutants were significantly attenuated compared with the wild-type strain in a mouse model of strangles, although 2 of 30 mice infected with the Deltalgt(190-685) mutant did still exhibit signs of disease. In contrast, only the DeltaprtM(138-213) mutant was significantly attenuated in a pony infection study, with 0 of 5 infected ponies exhibiting pathological signs of strangles compared with 4 of 4 infected with the wild-type and 3 of 5 infected with the Deltalgt(190-685) mutant. We believe that this is the first study to evaluate the contribution of lipoproteins to the virulence of a gram-positive pathogen in its natural host. These data suggest that the PrtM lipoprotein is a potential vaccine candidate, and further investigation of its activity and its substrate(s) are warranted.

  19. Mutation of the Maturase Lipoprotein Attenuates the Virulence of Streptococcus equi to a Greater Extent than Does Loss of General Lipoprotein Lipidation▿

    Science.gov (United States)

    Hamilton, Andrea; Robinson, Carl; Sutcliffe, Iain C.; Slater, Josh; Maskell, Duncan J.; Davis-Poynter, Nick; Smith, Ken; Waller, Andrew; Harrington, Dean J.

    2006-01-01

    Streptococcus equi is the causative agent of strangles, a prevalent and highly contagious disease of horses. Despite the animal suffering and economic burden associated with strangles, little is known about the molecular basis of S. equi virulence. Here we have investigated the contributions of a specific lipoprotein and the general lipoprotein processing pathway to the abilities of S. equi to colonize equine epithelial tissues in vitro and to cause disease in both a mouse model and the natural host in vivo. Colonization of air interface organ cultures after they were inoculated with a mutant strain deficient in the maturase lipoprotein (ΔprtM138-213, with a deletion of nucleotides 138 to 213) was significantly less than that for cultures infected with wild-type S. equi strain 4047 or a mutant strain that was unable to lipidate preprolipoproteins (Δlgt190-685). Moreover, mucus production was significantly greater in both wild-type-infected and Δlgt190-685-infected organ cultures. Both mutants were significantly attenuated compared with the wild-type strain in a mouse model of strangles, although 2 of 30 mice infected with the Δlgt190-685 mutant did still exhibit signs of disease. In contrast, only the ΔprtM138-213 mutant was significantly attenuated in a pony infection study, with 0 of 5 infected ponies exhibiting pathological signs of strangles compared with 4 of 4 infected with the wild-type and 3 of 5 infected with the Δlgt190-685 mutant. We believe that this is the first study to evaluate the contribution of lipoproteins to the virulence of a gram-positive pathogen in its natural host. These data suggest that the PrtM lipoprotein is a potential vaccine candidate, and further investigation of its activity and its substrate(s) are warranted. PMID:17015455

  20. Characterization of Two Metal Binding Lipoproteins as Vaccine Candidates for Enterococcal Infections.

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    Felipe Romero-Saavedra

    Full Text Available Enterococcus faecium and faecalis are Gram-positive opportunistic pathogens that have become leading causes of nosocomial infections over the last decades. Especially multidrug resistant enterococci have become a challenging clinical problem worldwide. Therefore, new treatment options are needed and the identification of alternative targets for vaccine development has emerged as a feasible alternative to fight the infections caused by these pathogens.We extrapolate the transcriptomic data from a mice peritonitis infection model in E. faecalis to identify putative up-regulated surface proteins under infection conditions in E. faecium. After the bionformatic analyses two metal binding lipoproteins were identified to have a high homology (>72% between the two species, the manganese ABC transporter substrate-binding lipoprotein (PsaAfm, and the zinc ABC transporter substrate-binding lipoprotein (AdcAfm. These candidate lipoproteins were overexpressed in Escherichia coli and purified. The recombinant proteins were used to produce rabbit polyclonal antibodies that were able to induce specific opsonic antibodies that mediated killing of the homologous strain E. faecium E155 as well as clinical strains E. faecium E1162, Enterococcus faecalis 12030, type 2 and type 5. Mice were passively immunized with the antibodies raised against recombinant lipoproteins, showing significant reduction of colony counts in mice livers after the bacterial challenge and demonstrating the efficacy of these metal binding lipoproteins as promising vaccine candidates to treat infections caused by these enterococcal pathogens.Overall, our results demonstrate that these two metal binding lipoproteins elicited specific, opsonic and protective antibodies, with an extensive cross-reactivity and serotype-independent coverage among these two important nocosomial pathogens. Pointing these two protein antigens as promising immunogens, that can be used as single components or as carrier

  1. Relationship of exercise, oral contraceptive use, and body fat to concentrations of plasma lipids and lipoprotein cholesterol in young women.

    Science.gov (United States)

    Merians, D R; Haskell, W L; Vranizan, K M; Phelps, J; Woods, P D; Superko, R

    1985-06-01

    To investigate the relationship of exercise and oral contraceptive use to plasma lipids and lipoproteins, a cross-sectional study was designed to compare lipid levels in 96 exercising and non-exercising women who used or did not use oral contraceptives. Exercisers had significantly lower plasma triglyceride concentrations and low-density/high-density lipoprotein ratios than non-exercisers after adjustment for differences in pill type distribution between groups. Women using progestin-dominant pills had significantly lower plasma triglyceride and high-density lipoprotein concentrations and significantly higher low-density/high-density lipoprotein ratios compared with women using estrogen/progestin-balanced pills. As body fat was significantly associated with both pill type and physical activity, it is unclear how much of these lipoprotein differences were due to body fat, exercise, or pill use. Regular physical activity together with reduced body fat partially compensated for plasma lipoprotein differences associated with oral contraceptive use.

  2. Synthetic high-density lipoprotein nanodisks for targeted withalongolide delivery to adrenocortical carcinoma

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    Kuai R

    2017-09-01

    Full Text Available Rui Kuai,1,2,* Chitra Subramanian,3,* Peter T White,3,* Barbara N Timmermann,4 James J Moon,1,2,5 Mark S Cohen,3,6 Anna Schwendeman1,2 1Department of Pharmaceutical Sciences, College of Pharmacy, 2Biointerfaces Institute, University of Michigan, 3Department of Surgery, University of Michigan, Ann Arbor, MI, 4Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, 5Department of Biomedical Engineering, 6Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA *These authors contributed equally to this work Abstract: Adrenocortical carcinoma (ACC is a rare endocrine malignancy and has a 5-year survival rate of <35%. ACC cells require cholesterol for steroid hormone production, and this requirement is met via expression on the cell surface of a high level of SRB1, responsible for the uptake of high-density lipoproteins (HDLs, which carry and transport cholesterol in vivo. Here, we describe how this natural lipid carrier function of SRB1 can be utilized to improve the tumor-targeted delivery of a novel natural product derivative – withalongolide A 4,19,27-triacetate (WGA-TA – which has shown potent antitumor efficacy, but poor aqueous solubility. Our strategy was to use synthetic HDL (sHDL nanodisks, which are effective in tumor-targeted delivery due to their smallness, long circulation half-life, documented safety, and ability to bind to SRB1. In this study, we prepared sHDL nanodisks using an optimized phospholipid composition combined with ApoA1 mimetic peptide (22A, which has previously been tested in clinical trials, to load WGA-TA. Following optimization, WGA-TA nanodisks showed drug encapsulation efficiency of 78%, a narrow particle size distribution (9.81±0.41 nm, discoid shape, and sustained drug release in phosphate buffered saline. WGA-TA-sHDL nanodisks exhibited higher cytotoxicity in the ACC cell line H295R half maximal inhibitory concentration ([IC50] 0.26±0.045 µM than free WGA-TA (IC50 0.492±0

  3. Large-scale preparation of the homogeneous LolA–lipoprotein complex and efficient in vitro transfer of lipoproteins to the outer membrane in a LolB-dependent manner

    OpenAIRE

    Watanabe, Shoji; Oguchi, Yuki; Yokota, Naoko; Tokuda, Hajime

    2007-01-01

    An ATP-binding cassette transporter LolCDE complex of Escherichia coli releases lipoproteins destined to the outer membrane from the inner membrane as a complex with a periplasmic chaperone, LolA. Interaction of the LolA–lipoprotein complex with an outer membrane receptor, LolB, then causes localization of lipoproteins to the outer membrane. As far as examined, formation of the LolA–lipoprotein complex strictly depends on ATP hydrolysis by the LolCDE complex in the presence of LolA. It has be...

  4. Functional outcome in young adult ischemic stroke: impact of lipoproteins.

    Science.gov (United States)

    Putaala, J; Strbian, D; Mustanoja, S; Haapaniemi, E; Kaste, M; Tatlisumak, T

    2013-01-01

    To determine the functional outcome in a cohort of young adults with ischemic stroke patients, focusing on components of lipid profile. In our registry including consecutive patients with first-ever ischemic stroke aged 15-49 from 1994 to 2007, we analyzed predictors of 3-month functional outcome (modified Rankin Scale, mRS). Infarct size fell into small, medium, large posterior, or large anterior. Stroke severity was assessed with NIH Stroke Scale (NIHSS). Serum lipids were measured within 72 h after admission. Binary, multinomial ordinal, and Poisson regressions allowed revealing factors associated with size of infarct, stroke severity, and unfavorable outcome or death (mRS, 2-6) or mRS as an ordinal measure. In the 968 patients included (mean age, 41.3 ± 7.6; 62.6% men; 49.5% with mRS 0-1), factors associated with unfavorable outcome after multivariable analysis were increasing age (odds ratio, 1.03 per year; 95% confidence interval, 1.01-1.05), higher NIHSS score (1.23 per point, 1.17-1.29), large anterior (4.37, 2.26-8.42) or posterior (1.73, 1.05-2.85) infarcts, bilateral lesions (2.28, 1.30-3.98), internal carotid artery dissection (ICAD) (3.65, 1.41-9.47), and inversely high-density lipoprotein (HDL) levels (0.58 per unit increase, 0.38-0.86). Increasing HDL associated with smaller infarct size (0.71, 0.51-0.98). Both higher total and HDL cholesterol associated with lower NIHSS score (0.96, 0.93-0.98 for total cholesterol and 0.82, 0.75-0.88 for HDL) and lower 3-month mRS (0.87, 0.78-0.97 for total cholesterol and 0.65, 0.47-0.90 for HDL). In addition to known prognosticators, ICAD and lower HDL levels were independently associated with adverse clinical outcomes in our young adult stroke cohort. © 2012 John Wiley & Sons A/S.

  5. Genetic analysis of intracapillary glomerular lipoprotein deposits in aging mice.

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    Gerda A Noordmans

    Full Text Available Renal aging is characterized by functional and structural changes like decreased glomerular filtration rate, and glomerular, tubular and interstitial damage. To gain insight in pathways involved in renal aging, we studied aged mouse strains and used genetic analysis to identify genes associated with aging phenotypes.Upon morphological screening in kidneys from 20-month-old mice from 26 inbred strains we noted intracapillary PAS-positive deposits. The severity of these deposits was quantified by scoring of a total of 50 glomeruli per section (grade 0-4. Electron microscopy and immunohistochemical staining for apoE, apoB, apoA-IV and perilipin-2 was performed to further characterize the lesions. To identify loci associated with these PAS-positive intracapillary glomerular deposits, we performed haplotype association mapping.Six out of 26 mouse strains showed glomerular PAS-positive deposits. The severity of these deposits varied: NOD(0.97, NZW(0.41, NON(0.30, B10(0.21, C3 H(0.9 and C57BR(0.7. The intracapillary deposits were strongly positive for apoE and weakly positive for apoB and apoA-IV. Haplotype association mapping showed a strong association with a 30-Kb haplotype block on Chr 1 within the Esrrg gene. We investigated 1 Mb on each site of this region, which includes the genes Spata17, Gpatch2, Esrrg, Ush2a and Kctd3.By analyzing 26 aged mouse strains we found that some strains developed an intracapillary PAS and apoE-positive lesion and identified a small haplotype block on Chr 1 within the Esrrg gene to be associated with these lipoprotein deposits. The region spanning this haplotype block contains the genes Spata17, Gpatch2, Esrrg, Ush2a and Kctd3, which are all highly expressed in the kidney. Esrrg might be involved in the evolvement of these glomerular deposits by influencing lipid metabolism and possibly immune reponses.

  6. Identification, Characterization, and Expression of Three New Members of the Borrelia burgdorferi Mlp (2.9) Lipoprotein Gene Family

    OpenAIRE

    Yang, Xiaofeng; Popova, Taissia G.; Hagman, Kayla E.; Wikel, Stephen K.; Schoeler, George B.; Caimano, Melissa J.; Radolf, Justin D.; Norgard, Michael V.

    1999-01-01

    We previously reported on the existence of a family of lipoprotein genes, designated 2.9 lipoprotein genes, encoded in at least seven versions on the circular (supercoiled) cp32 and cp18 plasmids of Borrelia burgdorferi 297. A distinguishing feature of the 2.9 lipoproteins were highly similar signal sequences but variable mature polypeptides that segregated into two antigenic classes. Further screenings of B. burgdorferi 297 genomic libraries led to the identification of three additional 2.9 ...

  7. Association between concentration of melatonin, and lipoproteins, LPO, hsCRP, NTproBNP in chronic heart failure patients

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    Kimak Elzbieta

    2014-09-01

    Full Text Available The aim of the study was to examine concentrations and relationships between melatonin levels assessed at 0:200 hrs and 0:700 hrs, lipid hydroperoxide (LPO assessed at 0:200 hrs and 0:700 hrs, and apolipoprotein (apoAI, apoAII, apoB, high sensitivity C-reactive protein (hsCRP and NT-proBNP, in 27 patients with chronic heart failure (CHF (17 patients - with NYHA class II and 10 - with NYHA class III. In the study, Lipoproteins apoAI, apoAII, apoB, high sensitivity C-reactive protein (hsCRP levels were determined by way of immunonephelometric methods, serum melatonin concentration was measured by using a competitive enzyme immunoassay technique, while serum LPO concentration was measured by using Cayman’s Lipid Hydroperoxide Assay Kit. In the study, CHF patients without acute inflammatory response demonstrated a decreased concentration of high density lipoprotein cholesterol (HDL-C, apoAI, apoAII levels, but an increased concentration of NT-proBNP, hsCRP and LPO at night, and LPO at daytime; however, the concentration of LPO at 0:700 was lower than at 0:200. Pearson’s correlation test and multiple ridge stepwise regression showed that melatonin administered at night exerts an effect on the composition of apoAI and apoAII of HDL particles, and induces decreased LPO at 0:700, but has no effect upon NT-proBNP levels in patients with NYHA class II. However, in patients with NYHA class III, melatonin administered at night induces an increase in the content of apoAII and apoAI, which further decreases hsCRP, and this, together with the administered melatonin, brings about daytime decreases in NT-proBNP and hsCRP levels. The results indicated that the content of apoAII and apoAI in HDL particles and melatonin demonstrate an anti-oxidative and anti-inflammatory effect, and together, have a cardio-protective effect on patients with advanced CHF. Hence, the results support melatonin being a cardio-protective agent. These relationships, however, need to

  8. [Abnormal Serum Total Protein Measurement by Lipoprotein-X in an Infant with Biliary Atresia].

    Science.gov (United States)

    Futatsugi, Akiko; Hidaka, Eiko; Kubota, Noriko; Nishijima, Fumie; Yoshizawa, Katsumi; Ishimine, Nau; Sugano, Mitsutoshi; Hori, Atsushi; Hidaka, Hiroya

    2015-11-01

    Lipoprotein-X (LP-X) in cholestatic jaundice causes abnormal reaction in assays for low-density lipoprotein-cholesterol, but the effects on other test items are unknown. Here, we report an infant with biliary atresia showing abnormal reaction in total serum protein assay using the biuret method, and lipoprotein-X (LP-X) was then detected. In this 11-month-old female infant, jaundice was observed at 2 months old, and a diagnosis of biliary atresia was made. On biochemical tests at 12 months old, the total serum protein concentrations detected by the biuret method were very high, and the response curve and linearity of dilution were abnormal. LP-X was detected by agar electrophoresis. In addition and recovery experiments with normal serum fractionation of the patient's LP-X-rich lipoprotein fraction prepared by ultracentrifugation, normal γ-globulin fractionation showed an abnormal reaction by the biuret method. In infants with biliary atresia, we showed that the total serum protein assay by the biuret method was influenced by LP-X-rich lipoprotein, which may be caused by abnormal reaction of LP-X and γ-globulin. [Case Report].

  9. Relationship between Serum Lipoprotein Ratios and Insulin Resistance in Polycystic Ovary Syndrome

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    Shou-Kui Xiang

    2012-01-01

    Full Text Available Objective. To investigate the association between serum lipoprotein ratios and insulin resistance in women with polycystic ovarian syndrome (PCOS. Methods. 105 PCOS patients and 109 controls were randomly enrolled in the study. Serum levels of luteinizing hormone (LH, follicle-stimulating hormone (FSH, estradiol (E2, total testosterone (T, fasting glucose (FBG, fasting insulin (FINS, serum triglycerides (TG, total cholesterol (TC, high-density lipoprotein (HDL-C, and low-density lipoprotein (LDL-C levels were checked, and then TG/HDL-C ratio, TC/HDL-C, ratio and LDL-C/HDL-C ratio were calculated. The homeostasis model assessment of insulin resistance (HOMA-IR was used to calculate the insulin resistance. Results. All lipoprotein ratios were significantly higher in PCOS patients as compared to healthy controls (<0.05. TG/HDL-C ratio, TC/HDL-C ratio, and LDL-C/HDL-C ratio were significantly correlated with HOMA-IR (<0.05. The ROC curve demonstrated that TC/HDL-C ratio had higher sensitivity and specificity in diagnosing PCOS with insulin resistance. Conclusion. This study demonstrates that serum lipoprotein ratio significantly correlates with insulin resistance and can be used as the marker of insulin resistance in PCOS patients.

  10. Investigations on the transport and metabolism of high density lipoprotein cholesteryl esters in African green monkeys

    International Nuclear Information System (INIS)

    Sorci-Thomas, M.G.

    1984-01-01

    The metabolic fate of circulating high density lipoprotein cholesteryl esters was studied in African green monkeys to determine the significance of the lipid transfer reaction on the catabolism of lipoprotein cholesteryl esters. A method of doubly labeling both moieties of lipoprotein cholesteryl esters with [ 3 He]cholesteryl oleate and cholesteryl [ 14 C]oleate was developed for the purpose of studying plasma cholesteryl ester metabolism in vivo. In these studies the total plasma [ 3 He]cholesterol turnover resulted in production rates, which ranged from 10-17 mg/kg day, similar to previously reported values in African green monkeys and in normal lipoproteinemic humans. In contrast to the production rates calculated from the decay of plasma 3 He-radioactivity, the production rates calculated from lipoproteins labeled with cholesteryl [ 14 C]oleate were approximately 2-3 times greater. In addition to these studies, a plasma cholesteryl ester transacylation activity was demonstrated in vitro when HDL containing doubly labeled cholesteryl esters were incubated with fresh plasma. These results demonstrated that high density lipoprotein cholesteryl esters undergo transacylation in vitro, resulting in release and reesterification of free [ 3 H]cholesterol

  11. Changes in chemical composition and physico-chemical properties of chick low- and high-density lipoproteins induced by supplementation of coconut oil to the diet.

    Science.gov (United States)

    Talavera, E M; Zafra, M F; Gil-Villarino, A; Pérez, M I; Alvarez-Pez, J M; García-Peregrín, E

    1997-06-01

    Supplementation of coconut oil to the diet for 1-2 weeks produced a significant hypercholesterolemia in 14-day-old chicks. Changes in plasma fatty acid composition correlated positively with those of diets. In this study, we have shown a different response of low- and high-density lipoprotein (LDL and HDL) fractions to dietary saturated fat (coconut oil) rich in lauric and myristic acids. Although all the components of these particles seemed to increase, the percentages of increases found in total (TC), free (FC) and esterified cholesterol (EC) were higher in LDL than in HDL. TC/phospholipid (PL) ratio, considered as an inverse index of membrane fluidity, also increased with the dietary regimen in LDL, while no significant differences were found in HDL. These results suggest that supplementation of coconut oil to the diet decreased the fluidity of LDL. The EC/triglycerides (TG) ratio was also significantly increased in LDL, corroborating the main atherogenic function of this lipoprotein fraction in response to lauric and myristic acids. We have also estimated the lipidic order parameter, S, from the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH)-labelled low- and high-density lipoproteins. In LDL, temperature dependence of S shows two different behaviour zones at about 20 degrees C. In HDL, the plot of S values versus T is linear. DPH anisotropy and S increased in both LDL and HDL from treated chicks. This increase becomes more evident as temperature rises and also with dietary treatment.

  12. Circulating Oxidized Low-Density Lipoprotein Levels Independently Predict 10-Year Progression of Subclinical Carotid Atherosclerosis: A Community-Based Cohort Study.

    Science.gov (United States)

    Gao, Shen; Zhao, Dong; Qi, Yue; Wang, Wei; Wang, Miao; Sun, Jiayi; Liu, Jun; Li, Yan; Liu, Jing

    2018-03-07

    To investigate the association between circulating oxidized low-density lipoprotein (ox-LDL) levels and progression of subclinical atherosclerosis and to examine whether this link is independent of other low-density lipoprotein (LDL)-related parameters. Totally, 804 subjects who were free of cardiovascular disease at baseline completed risk factor surveys and carotid ultrasound measurements in 2002 and 2012. Modified Poisson regression was performed to examine the association between baseline serum ox-LDL levels and the 10-year risk of progression of carotid atherosclerosis which was defined as the development of at least one new plaque in a previously plaque-free carotid segment at re-examination. The mean age of the subjects was 58.6±7.7 years at baseline and 43.3% were men. A total of 504 (62.7%) subjects had carotid plaque progression at re-examination. Subjects in the intermediate and highest tertiles of ox-LDL had a significantly higher adjusted risk of atherosclerosis progression than those in the lowest tertile [relative risk (95% confidence interval) 1.17 (1.01-1.34) for the intermediate tertile and 1.23 (1.07-1.42) for the highest tertile]. This association was independent of baseline levels of LDL-C, total LDL particle number, and small LDL particle number. This study demonstrates that serum ox-LDL levels predict 10-year progression of subclinical atherosclerosis. Moreover, this effect is independent of the cholesterol content, the number, and the size of LDL particles.

  13. Thermodynamics of the interaction between bovine binder of sperm BSP1 and low-density lipoprotein from hen's egg yolk

    Energy Technology Data Exchange (ETDEWEB)

    Lusignan, Marie-France; Manjunath, Puttaswamy [Maisonneuve-Rosemont Hospital Research Center and Department of Medicine, Universite de Montreal, C.P. 6128, Succ. Centre Ville, Montreal, Quebec, Canada H3C 3J7 (Canada); Lafleur, Michel, E-mail: michel.lafleur@umontreal.ca [Department of Chemistry, Centre for Self-Assembled Chemical Structures (CSACS), Universite de Montreal, C.P. 6128, Succ. Centre Ville, Montreal, Quebec, Canada H3C 3J7 (Canada)

    2011-03-20

    Research highlights: {yields} Isothermal titration calorimetry revealed Binder-of-SPerm BSP1 protein has high affinity for egg yolk low density lipoproteins. {yields} It is estimated that 104 BSP1 molecules could bind one LDL particle. {yields} BSP1 has 2 phosphocholine binding sites and the BSP1/LDL ratio corresponds to 1.6 phosphatidylcholine per bound BSP1. {yields} The strong interaction between LDL particles and BSP1 is proposed to be important for sperm protection by egg yolk extender. - Abstract: Egg yolk is used in extender to protect sperm from cold shock and freezing during preservation. It is the low-density lipoprotein (LDL) fraction of egg yolk that protects sperm. Even though essential for sperm capacitation, the major proteins from bull seminal plasma, the Binder of SPerm (BSP) proteins, are detrimental for sperm preservation because they induce a continual phospholipids and cholesterol efflux from sperm membranes. The BSP proteins were proposed to bind to egg yolk LDL, preventing the sperm membrane damage. We characterized the binding between the BSP proteins and the LDL by isothermal titration calorimetry, providing the thermodynamics and quantitative description of this putative association. The association between BSP1 (major BSP proteins) and LDL is characterized by an affinity constant (K{sub a}) of 3.4 {+-} 0.4 {mu}M{sup -1}. A protein/LDL ratio of 104 {+-} 5 was determined indicating that 104 molecules of BSP1 would bind to one LDL particle. This stoichiometry leads to proposing that the association involves 1.6 {+-} 0.1 phosphatidylcholines (PC) per BSP protein. This finding is satisfactorily consistent with the fact that each BSP1 protein has 2 binding sites for choline group. In conclusion, the formation of a high affinity complex between BSP1 and LDL is proposed to be important for the protection of sperm by egg yolk extender.

  14. GluN2B-containing NMDA receptors contribute to the beneficial effects of hydrogen sulfide on cognitive and synaptic plasticity deficits in APP/PS1 transgenic mice.

    Science.gov (United States)

    Yang, Yuan-Jian; Zhao, Ying; Yu, Bin; Xu, Guo-Gang; Wang, Wei; Zhan, Jin-Qiong; Tang, Zhen-Yu; Wang, Ting; Wei, Bo

    2016-10-29

    Alzheimer's disease (AD) is the most common type of clinical dementia. Previous studies have demonstrated that hydrogen sulfide (H2S) is implicated with the pathology of AD, and exogenous H2S attenuates spatial memory impairments in AD animal models. However, the molecular mechanism by which H2S improves cognition in AD has not been fully explored. Here, we report that chronic administration of sodium hydrosulfide (NaHS, a H2S donor) elevated hippocampal H2S levels and enhanced hippocampus-dependent contextual fear memory and novel object recognition in amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice. In parallel with these behavioral results, treating transgenic mice with NaHS reversed impaired hippocampal long-term potentiation (LTP), which is deemed as the neurobiological basis of learning and memory. At the molecular level, we found that treatment with NaHS did not affect the expression of the GluN1 and GluN2A subunits of NMDA receptor (NMDAR), but did prevent the downregulation of GluN2B subunit and restored its synaptic abundance, response and downstream signaling in the hippocampus in transgenic mice. Moreover, applying Ro 25-6981, a specific GluN2B antagonist, abolished the beneficial effects of NaHS on cognitive performance and hippocampal LTP in transgenic mice. Collectively, our results indicate that H2S can reverse cognitive and synaptic plasticity deficits in AD model mice by restoring surface GluN2B expression and the function of GluN2B-containing NMDARs. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. High density lipoprotein cholesterol in relation to food consumption and running distance.

    Science.gov (United States)

    Hagan, R D; Smith, M G; Gettman, L R

    1983-03-01

    The effects of diet and exercise on serum triglycerides (Trig), total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and the HDL to TC ratio (HDL/TC) were evaluated in 45 men training continuously for a duration of 6 months. Body mass index (BMI), percentage body fat, and serum values for Trig, TC, HDL, and HDL/TC were constant throughout the observation period. Bivariate correlations indicated that Trig, TC, and LDL were linearly related and HDL and HDL/TC were related to HDL and HDL/TC. Multiple regression analysis suggested that BMI was the best predictor of Trig, TC, and LDL, while distance run per month was the best predictor of HDL and HDL/TC and second best predictor of Trig. The weekly intakes of fish, bread, cooked cereal, wine, beer, soft drinks, and vegetables were less significant predictors of lipoprotein levels.

  16. Lipophilic antioxidants and polyunsaturated fatty acids in lipoprotein classes: distribution and interaction

    DEFF Research Database (Denmark)

    Sunesen, V.H.; Weber, Christine; Hølmer, Gunhild Kofoed

    2001-01-01

    Objective: To study the lipoprotein distribution of supplemented coenzyme Q(10) (CoQ(10)), vitamin E, and polyunsaturated fatty acids (PUFA). Design: Balanced three- period crossover study. Setting: University research unit. Subjects: Eighteen apparently healthy free-living non-smoking volunteers...... (nine women, nine men), mean age 26 +/- 3 y, recruited among the university students; no dropouts. Interventions: Three supplementation periods of 10 days: 100 m/day CoQ(10), 350 mg/day D-alpha -tocopherol, and 2g/day concentrated fish oil. Fasting venous blood samples were collected twice before...... the first period and then after each period. Plasma and isolated lipoproteins were analysed for cholesterol, triacylglycerol, alpha- and gamma -tocopherol, CoQ(10), and fatty acid composition. Results: Significant (P CoQ(10) and -tocopherol occurred in all lipoprotein classes after...

  17. Direct effects of fatty meals and adiposity on oxidised low-density lipoprotein.

    Science.gov (United States)

    Laguna-Camacho, Antonio; Alonso-Barreto, Arely S; Mendieta-Zerón, Hugo

    2015-01-01

    High-fat intake and high adiposity contribute to hyperlipaemia. In a hyperlipaemic state, lipoproteins infiltrate arterial wall where they are modified and cause an immune response characteristic of atherosclerosis. A small fraction of modified lipoproteins including oxidised low-density lipoprotein (ox-LDL) returns to circulation. The present study tracked high-fat meals during four weeks as to find effects of sustained frequency change on adiposity and ox-LDL. The findings indicated that changes in frequency of consumption of high-fat eating episodes correlated directly with changes in adiposity and ox-LDL. Hence the number of fatty meals consumed by people with overweight or obesity in few weeks could affect the atherogenic process. Copyright © 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  18. Lipoprotein predictors of cardiovascular events in statin-treated patients with coronary heart disease

    DEFF Research Database (Denmark)

    Holme, Ingar; Cater, Nilo B; Faergeman, Ole

    2008-01-01

    the relationships between on-treatment levels of lipoprotein components to subsequent major coronary events (MCE). FINDINGS: Variables related to low-density lipoprotein cholesterol (LDL-C) carried more predictive information than those related to high-density lipoprotein cholesterol (HDL-C), but LDL-C was less...... predictive than both non-HDL-C and apoB. The ratio of apoB to apoA-1 was most strongly related to MCE. However, for estimating differences in relative risk reduction between the treatment groups, apoB and non-HDL-C were the strongest predictors. INTERPRETATION: The on-treatment level of apoB/apoA-1...

  19. Cardiac metabolism and mechanics are altered by genetic loss of lipoprotein triglyceride lipolysis.

    Science.gov (United States)

    Noh, Hye-Lim; Yamashita, Haruyo; Goldberg, Ira J

    2006-12-01

    Most circulating fatty acids are contained in lipoprotein triglycerides. For the heart to acquire these lipids, they must be broken down into free fatty acids via the enzyme lipoprotein lipase (LpL). Although it has long been known that hearts primarily use esterified fatty acids as fuel, different sources of fatty acids were thought to be interchangeable. By creating mice with neonatal and acute LpL deletion we showed that lipoprotein-derived fatty acids could not be replaced by albumin-associated free fatty acids. Loss of cardiac LpL forces the heart to increase its uptake of glucose, reduce fatty acid oxidation, and eventually leads to cardiac dysfunction. In contrast, cardiomyocyte specific overexpression of an anchored form of LpL leads to excess lipid uptake, induction of fatty acid oxidation genes, and dilated cardiomyopathy. Increasing lipid secretion from the heart or redirecting lipids to adipose tissue can alleviate this lipotoxic situation.

  20. Lipoprotein subclasses in genetic studies: The Berkeley Data Set

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, R.M.; Williams, P.T.; Blanche, P.J.; Cavanaugh, A.; Holl, L.G. [Lawrence Berkeley Lab., CA (United States); Austin, M.A. [Washington Univ., Seattle, WA (United States). Dept. of Epidemiology

    1992-10-01

    Data from the Berkeley Data Set was used to investigate familial correlations of HDL-subclasses. Analysis of the sibling intraclass correlation coefficient by HDL particle diameter showed that sibling HDL levels were significantly correlated for HDL{sub 2b}, HDL{sub 3a} and HDL{sub 3b} subclasses. The percentage of the offsprings` variance explained by their two parents. Our finding that parents and offspring-have the highest correlation for HDL{sub 2b} is consistent with published reports that show higher heritability estimates for HDL{sub 2} compared with HDL{sub 3}{minus} cholesterol.

  1. Particle kickers

    CERN Multimedia

    Antonella Del Rosso

    2014-01-01

    These devices are designed to provide a current pulse of 5000 Amps which will in turn generate a fast magnetic pulse that steers the incoming beam into the LHC. Today, the comprehensive upgrade of the LHC injection kicker system is entering its final stages. The upgraded system will ensure the LHC can be refilled without needing to wait for the kicker magnets to cool, thus enhancing the performance of the whole accelerator.   An upgraded kicker magnet in its vacuum tank, with an upgraded beam screen. The LHC is equipped with two kicker systems installed at the injection points (near points 2 and 8, see schematic diagram) where the particle beams coming from the SPS are injected into the accelerator’s orbit. Each system comprises four magnets and four pulse generators in which the field rises to 0.12 Tesla in less than 900 nanoseconds and for a duration of approximately 8 microseconds. Although the injection kickers only pulse 12 times to fill the LHC up with beam, the LHC beam circ...

  2. Disruption of human plasma high-density lipoproteins by streptococcal serum opacity factor requires labile apolipoprotein A-I.

    Science.gov (United States)

    Han, Mikyung; Gillard, Baiba K; Courtney, Harry S; Ward, Kathryn; Rosales, Corina; Khant, Htet; Ludtke, Steven J; Pownall, Henry J

    2009-02-24

    Human plasma high-density lipoproteins (HDL), the primary vehicle for reverse cholesterol transport, are the target of serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes that turns serum opaque. HDL comprise a core of neutral lipidscholesteryl esters and some triglyceridesurrounded by a surface monolayer of cholesterol, phospholipids, and specialized proteins [apolipoproteins (apos) A-I and A-II]. A HDL is an unstable particle residing in a kinetic trap from which it can escape via chaotropic, detergent, or thermal perturbation. Recombinant (r) SOF catalyzes the transfer of nearly all neutral lipids of approximately 100,000 HDL particles (D approximately 8.5 nm) into a single, large cholesteryl ester-rich microemulsion (CERM; D > 100 nm), leaving a new HDL-like particle [neo HDL (D approximately 5.8 nm)] while releasing lipid-free (LF) apo A-I. CERM formation and apo A-I release have similar kinetics, suggesting parallel or rapid consecutive steps. By using complementary physicochemical methods, we have refined the mechanistic model for HDL opacification. According to size exclusion chromatography, a HDL containing nonlabile apo A-I resists rSOF-mediated opacification. On the basis of kinetic cryo-electron microscopy, rSOF (10 nM) catalyzes the conversion of HDL (4 microM) to neo HDL via a stepwise mechanism in which intermediate-sized particles are seen. Kinetic turbidimetry revealed opacification as a rising exponential reaction with a rate constant k of (4.400 +/- 0.004) x 10(-2) min(-1). Analysis of the kinetic data using transition state theory gave an enthalpy (DeltaH()), entropy (DeltaS(++)), and free energy (DeltaG()) of activation of 73.9 kJ/mol, -66.87 J/K, and 94.6 kJ/mol, respectively. The free energy of activation for opacification is nearly identical to that for the displacement of apo A-I from HDL by guanidine hydrochloride. We conclude that apo A-I lability is required for HDL opacification, LF apo A-I desorption is the

  3. Blood lipid concentrations and lipoprotein patterns in captive and wild American black bears (Ursus americanus).

    Science.gov (United States)

    Frank, Nicholas; Elliott, Sarah B; Allin, Shawn B; Ramsay, Edward C

    2006-02-01

    To compare blood lipid concentrations and lipoprotein patterns for captive and wild American black bears (Ursus americanus). 7 captive and 9 wild adult (> or = 4 years old) black bears. Blood was collected from 2 groups of captive black bears (groups A and B) and 1 group of wild black bears (group C). Blood triglyceride (TG) and cholesterol concentrations were compared among groups. Plasma lipoproteins were isolated by use of a self-generating gradient of iodixanol, and lipoprotein patterns were compared between groups A and B. Captive bears (mean +/- SD, 187.8 +/- 44.4 kg) weighed significantly more than wild bears (mean, 104.8 +/- 41.4 kg), but mean body weight did not differ between groups A and B. Mean blood TG concentrations for groups B (216.8 +/- 16.0 mg/dL) and C (190.7 +/- 34.0 mg/dL) were significantly higher than that of group A (103.9 +/- 25.3 mg/dL). Mean blood cholesterol concentration was also significantly higher for group B (227.8 +/- 8.2 mg/dL) than for groups A (171.7 +/- 35.5 mg/dL) or C (190.8 +/- 26.8 mg/dL). Mean very-low-density lipoprotein TG and low-density lipoprotein cholesterol concentrations were 2- and 3-fold higher, respectively, for group B, compared with concentrations for group A. Blood lipid concentrations vary significantly among populations of black bears. Plasma lipoprotein patterns of captive bears differed significantly between colonies and may have reflected differences in diet or management practices.

  4. A receptor-based biosensor for lipoprotein docking at the endothelial surface and vascular matrix.

    Science.gov (United States)

    Siegel, G; Malmsten, M; Klüssendorf, D; Michel, F

    2001-12-01

    Proteoheparan sulfate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution, representing a receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques showing that HDL has a high binding affinity to the receptor and a protective effect on interfacial heparan sulfate proteoglycan layers, with respect to LDL and Ca(2+) complexation. LDL was found to deposit strongly at the proteoheparan sulfate, particularly in the presence of Ca(2+), thus creating the complex formation "proteoglycan-low density lipoprotein-calcium". This ternary complex build-up may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. On the other hand, HDL bound to heparan sulfate proteoglycan protected against LDL docking and completely suppressed calcification of the proteoglycan-lipoprotein complex. In addition, HDL and aqueous garlic extract were able to reduce the ternary complex deposition and to disintegrate HS-PG/LDL/Ca(2+) aggregates. Although much remains unclear regarding the mechanism of lipoprotein depositions at proteoglycan-coated surfaces, it seems clear that the use of such systems offers possibilities for investigating lipoprotein deposition at a "nanoscopic" level under close to physiological conditions. In particular, Ca(2+)-promoted LDL deposition and the protective effect of HDL, even at high Ca(2+) and LDL concentrations, agree well with previous clinical observations regarding risk and beneficial factors for early stages of atherosclerosis. Therefore, we believe that the system can be of some use in investigations, e.g. of the interplay between different lipoproteins in arteriosclerotic

  5. Functional characterization of a lipoprotein-encoding operon in Campylobacter jejuni.

    Directory of Open Access Journals (Sweden)

    Mayumi Oakland

    Full Text Available BACKGROUND: Bacterial lipoproteins have important functions in bacterial pathogenesis and physiology. In Campylobacter jejuni, a major foodborne pathogen causing gastroenteritis in humans, the majority of lipoproteins have not been functionally characterized. Previously, we showed by DNA microarray that CmeR, a transcriptional regulator repressing the expression of the multidrug efflux pump CmeABC, modulates the expression of a three-gene operon (cj0089, cj0090, and cj0091 encoding a cluster of lipoproteins in C. jejuni. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we characterized the function and regulation of the cj0089-cj0090-cj0091 operon. In contrast to the repression of cmeABC, CmeR activates the expression of the lipoprotein genes and the regulation is confirmed by immunoblotting using anti-Cj0089 and anti-Cj0091 antibodies. Gel mobility shift assay showed that CmeR directly binds to the promoter of the lipoprotein operon, but the binding is much weaker compared with the promoter of cmeABC. Analysis of different cellular fractions indicated that Cj0089 was associated with the inner membrane, while Cj0091 was located on the outer membrane. Inactivation of cj0091, but not cj0089, significantly reduced the adherence of C. jejuni to INT 407 cells in vitro, indicating that Cj0091 has a function in adherence. When inoculated into chickens, the Cj0091 mutant also showed a defect in early colonization of the intestinal tract, suggesting that Cj0091 contributes to Campylobacter colonization in vivo. It was also shown that Cj0091 was produced and immunogenic in chickens that were naturally infected by C. jejuni. CONCLUSION/SIGNIFICANCE: These results indicate that the lipoprotein operon is subject to direct regulation by CmeR and that Cj0091 functions as an adhesion mechanism in C. jejuni and contributes to Campylobacter colonization of the intestinal tract in animal hosts.

  6. Mice with chimeric livers are an improved model for human lipoprotein metabolism.

    Directory of Open Access Journals (Sweden)

    Ewa C S Ellis

    Full Text Available Rodents are poor model for human hyperlipidemias because total cholesterol and low density lipoprotein levels are very low on a normal diet. Lipoprotein metabolism is primarily regulated by hepatocytes and we therefore assessed whether chimeric mice extensively repopulated with human cells can model human lipid and bile acid metabolism.FRG [ F ah(-/- R ag2(-/-Il2r g (-/-] mice were repopulated with primary human hepatocytes. Serum lipoprotein lipid composition and distribution (VLDL, LDL, and HDL was analyzed by size exclusion chromatography. Bile was analyzed by LC-MS or by GC-MS. RNA expression levels were measured by quantitative RT-PCR.Chimeric mice displayed increased LDL and VLDL fractions and a lower HDL fraction compared to wild type, thus significantly shifting the ratio of LDL/HDL towards a human profile. Bile acid analysis revealed a human-like pattern with high amounts of cholic acid and deoxycholic acid (DCA. Control mice had only taurine-conjugated bile acids as expcted, but highly repopulated mice had glycine-conjugated cholic acid as found in human bile. RNA levels of human genes involved in bile acid synthesis including CYP7A1, and CYP27A1 were significantly upregulated as compared to human control liver. However, administration of recombinant hFGF19 restored human CYP7A1 levels to normal.Humanized-liver mice showed a typical human lipoprotein profile with LDL as the predominant lipoprotein fraction even on a normal diet. The bile acid profile confirmed presence of an intact enterohepatic circulation. Although bile acid synthesis was deregulated in this model, this could be fully normalized by FGF19 administration. Taken together these data indicate that chimeric FRG-mice are a useful new model for human lipoprotein and bile-acid metabolism.

  7. Echium oil reduces plasma triglycerides by increasing intravascular lipolysis in apoB100-only low density lipoprotein (LDL) receptor knockout mice.

    Science.gov (United States)

    Forrest, Lolita M; Lough, Christopher M; Chung, Soonkyu; Boudyguina, Elena Y; Gebre, Abraham K; Smith, Thomas L; Colvin, Perry L; Parks, John S

    2013-07-12

    Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.

  8. Echium Oil Reduces Plasma Triglycerides by Increasing Intravascular Lipolysis in apoB100-Only Low Density Lipoprotein (LDL Receptor Knockout Mice

    Directory of Open Access Journals (Sweden)

    John S. Parks

    2013-07-01

    Full Text Available Echium oil (EO, which is enriched in SDA (18:4 n-3, reduces plasma triglyceride (TG concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%, EO (10% EO + 10% PO, or FO (10% FO + 10% PO. Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL particle size was ordered: PO (63 ± 4 nm > EO (55 ± 3 nm > FO (40 ± 2 nm. Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.

  9. Novel lipoprotein density profiling in healthy dogs of various breeds, healthy miniature schnauzers, and miniature schnauzers with hyperlipidemia

    Science.gov (United States)

    2013-01-01

    Background Despite the importance of abnormalities in lipoprotein metabolism in clinical canine medicine, the fact that most previously used methods for lipoprotein profiling are rather laborious and time-consuming has been a major obstacle to the wide clinical application and use of lipoprotein profiling in this species. The aim of the present study was to assess the feasibility of a continuous lipoprotein density profile (CLPDP) generated within a bismuth sodium ethylenediaminetetraacetic acid (NaBiEDTA) density gradient to characterize and compare the lipoprotein profiles of healthy dogs of various breeds, healthy Miniature Schnauzers, and Miniature Schnauzers with primary hypertriacylglycerolemia. A total of 35 healthy dogs of various breeds with serum triacylglycerol (TAG) and cholesterol concentrations within their respective reference intervals were selected for use as a reference population. Thirty-one Miniature Schnauzers with serum TAG and cholesterol concentrations within their respective reference intervals and 31 Miniature Schnauzers with hypertriacylglyceridemia were also included in the study. Results The results suggest that CLPDP using NaBiEDTA provides unique diagnostic information in addition to measurements of serum TAG and cholesterol concentrations and that it is a useful screening method for dogs with suspected lipoprotein metabolism disorders. Using the detailed and continuous density distribution information provided by the CLPDP, important differences in lipoprotein profiles can be detected even among dogs that have serum TAG and cholesterol concentrations within the reference interval. Miniature Schnauzers with serum TAG and cholesterol concentrations within the reference interval had significantly different lipoprotein profiles than dogs of various other breeds. In addition, it was further established that specific lipoprotein fractions are associated with hypertriacylglyceridemia in Miniature Schnauzers. Conclusions The results of the

  10. Enzymatic Modification of Plasma Low Density Lipoproteins in Rabbits: A Potential Treatment for Hypercholesterolemia

    Science.gov (United States)

    Labeque, Regine; Mullon, Claudy J. P.; Ferreira, Joao Paulo M.; Lees, Robert S.; Langer, Robert

    1993-04-01

    Phospholipase A_2 (EC 3.1.1.4) hydrolyzes certain phospholipids of low density lipoprotein (LDL). Plasma clearance of phospholipase A_2-modified human LDL is up to 17 times faster than that of native human LDL in hypercholesterolemic rabbits. Modification of blood lipoproteins of hypercholesterolemic rabbits was performed by using an extracorporeal circuit containing immobilized phospholipase A_2. After 90-min treatments, nearly 30% decreases in plasma cholesterol concentrations were observed. Erythrocyte, leukocyte, and platelet counts showed no net change after treatment. This technique does not require any fluid replacement or sorbent regeneration and offers a potential approach for lowering serum cholesterol and LDL levels.

  11. Elevated plasma YKL-40, lipids and lipoproteins, and ischemic vascular disease in the general population

    DEFF Research Database (Denmark)

    Kjaergaard, Alisa D; Johansen, Julia S; Bojesen, Stig E

    2015-01-01

    BACKGROUND AND PURPOSE: We tested the hypothesis that observationally and genetically elevated YKL-40 is associated with elevated lipids and lipoproteins and with increased risk of ischemic vascular disease. METHODS: We conducted cohort and Mendelian randomization studies in 96 110 individuals from...... the Danish general population, with measured plasma levels of YKL-40 (n=21 647), plasma lipids and lipoproteins (n=94 461), and CHI3L1 rs4950928 genotype (n=94 579). RESULTS: From 1977 to 2013, 3256 individuals developed ischemic stroke, 5629 ischemic cerebrovascular disease, 4183 myocardial infarction...

  12. Transvascular low-density lipoprotein transport in patients with diabetes mellitus (type 2)

    DEFF Research Database (Denmark)

    Kornerup, Karen; Nordestgaard, Børge Grønne; Feldt-Rasmussen, Bo

    2002-01-01

    accumulation and, thus, atherosclerosis. METHODS AND RESULTS: We developed an in vivo method for measurement of transvascular transport of low density lipoprotein (LDL) and applied it in 16 patients with maturity-onset diabetes (type 2) and 29 healthy control subjects. Autologous 131I-labeled LDL...... plasma insulin levels in diabetic patients. CONCLUSIONS: Transvascular LDL transport may be increased in patients with type 2 diabetes. This suggests that lipoprotein flux into the arterial wall is increased in people with diabetes, possibly explaining the accelerated development of atherosclerosis....... in patients with diabetes and control subjects, respectively (P2.5%/h and 5.3+/-1.6%/h (P

  13. Social Inclusion Predicts Lower Blood Glucose and Low-Density Lipoproteins in Healthy Adults.

    Science.gov (United States)

    Floyd, Kory; Veksler, Alice E; McEwan, Bree; Hesse, Colin; Boren, Justin P; Dinsmore, Dana R; Pavlich, Corey A

    2017-08-01

    Loneliness has been shown to have direct effects on one's personal well-being. Specifically, a greater feeling of loneliness is associated with negative mental health outcomes, negative health behaviors, and an increased likelihood of premature mortality. Using the neuroendocrine hypothesis, we expected social inclusion to predict decreases in both blood glucose levels and low-density lipoproteins (LDLs) and increases in high-density lipoproteins (HDLs). Fifty-two healthy adults provided self-report data for social inclusion and blood samples for hematological tests. Results indicated that higher social inclusion predicted lower levels of blood glucose and LDL, but had no effect on HDL. Implications for theory and practice are discussed.

  14. Lipoprotein metabolism in familial hypercholesterolemia: Serial assessment using a one-step ultracentrifugation method

    Directory of Open Access Journals (Sweden)

    Hayato Tada

    2015-04-01

    Full Text Available Objectives: It is well known that familial hypercholesterolemia (FH is a common inherited disorder that can markedly elevate the level of plasma LDL cholesterol. However, little data exists regarding the clinical impact of the plasma triglyceride (TG-rich lipoprotein fraction, including VLDL and IDL, in FH. Thus, we assessed the hypothesis that the mutations in the LDL receptor modulate lipoprotein metabolism other than the LDL fraction. Design and methods: We investigated plasma lipoprotein with a one-step ultracentrifugation method for 146 controls (mean age=61.4±17.1 yr, mean LDL cholesterol=92.7±61.2 mg/dl, 213 heterozygous mutation-determined FH subjects (mean age=46.0±18.0 yr, mean LDL cholesterol=225.1±61.2 mg/dl, and 16 homozygous/compound heterozygous mutation-determined FH subjects (mean age=26.9±17.1 yr, mean LDL cholesterol=428.6±86.1 mg/dl. In addition, we evaluated cholesterol/TG ratio in each lipoprotein fraction separated by ultracentrifugation. Results: In addition to total cholesterol and LDL cholesterol levels, VLDL cholesterol (19.5±10.4, 25.2±19.3, 29.5±21.4 mg/dl, respectively and IDL cholesterol (8.3±3.7, 16.8±11.5, 40.0±37.3 mg/dl, respectively exhibited a tri-model distribution according to their status in LDL receptor mutation(s. Moreover, the ratios of cholesterol/TG of each lipoprotein fraction increased significantly in heterozygous FH and homozygous/compound heterozygous FH groups, compared with that of controls, suggesting that the abnormality in LDL receptor modulates the quality as well as the quantity of each lipoprotein fraction. Conclusions: Our results indicate that cholesterol in TG-rich lipoproteins, including VLDL and IDL, are significantly higher in FH subjects, revealing a tri-modal distribution according to the number of LDL receptor mutations. Keywords: LDL cholesterol, Familial hypercholesterolemia, Ultracentrifugation, Lipoprotein

  15. Lipoprotein lipase gene polymorphisms: associations with myocardial infarction and lipoprotein levels, the ECTIM study. Etude Cas Témoin sur l'Infarctus du Myocarde.

    Science.gov (United States)

    Jemaa, R; Fumeron, F; Poirier, O; Lecerf, L; Evans, A; Arveiler, D; Luc, G; Cambou, J P; Bard, J M; Fruchart, J C

    1995-10-01

    Several lipoprotein lipase (LPL) gene polymorphisms have been found associated with fasting lipid levels, but their impact on coronary heart disease (CHD) is less clearly established. We investigated associations of LPL polymorphisms (HindIII, PvuII, Ser447-->Ter) and the newly described mutation Asn291-->Ser with the risk of myocardial infarction (MI), severity of atherosclerosis, and fasting plasma lipoprotein concentrations in the ECTIM study (614 patients and 733 controls). The Ter447 allele had a lowering effect on triglycerides (P Ser polymorphisms did not exhibit any significant association with the biochemical traits examined. The HindIII genotype distributions differed between cases and controls, the odds ratios for MI associated with H+H+ and H+H- genotypes being 2.05 (P Ter and MI suggested that this mutation was unlikely to be the cause of the association found with HindIII. In some cases, the severity of atherosclerosis assessed by coronarography increased with the presence of P+ allele (coronary scores: 1.41, 1.57, and 1.64 in P-P-, P-P+, and P+P+ individuals respectively, P Ser mutation (1.58 vs. 1.90, P = 0.06). Our results suggest that the LPL gene is involved in the determination of lipoprotein profiles, the predisposition to CHD, and the severity of atherosclerosis.

  16. Caenorhabditis elegans reveals a FxNPxY-independent low-density lipoprotein receptor internalization mechanism mediated by epsin1

    Science.gov (United States)

    Kang, Yuan-Lin; Yochem, John; Bell, Leslie; Sorensen, Erika B.; Chen, Lihsia; Conner, Sean D.

    2013-01-01

    Low-density lipoprotein receptor (LDLR) internalization clears cholesterol-laden LDL particles from circulation in humans. Defects in clathrin-dependent LDLR endocytosis promote elevated serum cholesterol levels and can lead to atherosclerosis. However, our understanding of the mechanisms that control LDLR uptake remains incomplete. To identify factors critical to LDLR uptake, we pursued a genome-wide RNA interference screen using Caenorhabditis elegans LRP-1/megalin as a model for LDLR transport. In doing so, we discovered an unanticipated requirement for the clathrin-binding endocytic adaptor epsin1 in LDLR endocytosis. Epsin1 depletion reduced LDLR internalization rates in mammalian cells, similar to the reduction observed following clathrin depletion. Genetic and biochemical analyses of epsin in C. elegans and mammalian cells uncovered a requirement for the ubiquitin-interaction motif (UIM) as critical for receptor transport. As the epsin UIM promotes the internalization of some ubiquitinated receptors, we predicted LDLR ubiquitination as necessary for endocytosis. However, engineered ubiquitination-impaired LDLR mutants showed modest internalization defects that were further enhanced with epsin1 depletion, demonstrating epsin1-mediated LDLR endocytosis is independent of receptor ubiquitination. Finally, we provide evidence that epsin1-mediated LDLR uptake occurs independently of either of the two documented internalization motifs (FxNPxY or HIC) encoded within the LDLR cytoplasmic tail, indicating an additional internalization mechanism for LDLR. PMID:23242996

  17. Paraoxonase-3 is depleted from the high-density lipoproteins of autoimmune disease patients with subclinical atherosclerosis.

    Science.gov (United States)

    Marsillach, Judit; Becker, Jessica O; Vaisar, Tomas; Hahn, Bevra H; Brunzell, John D; Furlong, Clement E; de Boer, Ian H; McMahon, Maureen A; Hoofnagle, Andrew N

    2015-05-01

    Patients with autoimmune diseases have a significantly increased risk of developing cardiovascular disease. In disease, high-density lipoprotein (HDL) particles lose their anti-inflammatory and antioxidant properties and become dysfunctional. The purpose of this study was to test the hypothesis that alterations in the HDL proteomic profile are associated with subclinical atherosclerosis and HDL dysfunction in patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and type 1 diabetes. Targeted proteomics was used to quantify the relative abundance of 18 proteins in HDL from SLE patients with and without atherosclerotic plaque detectable by carotid ultrasound. Changes in the proteomic profile were compared against the in vitro ability of HDL to protect against lipid oxidation. The same proteins were quantified in HDL from patients with type 1 diabetes with or without coronary artery calcification as determined by computed tomography. In each population, paraoxonase-3 (PON3), a potent antioxidant protein, was depleted from the HDL of patients with subclinical atherosclerosis. PON3 expression in HDL was positively correlated with HDL antioxidant function. These results suggest that PON3 may be an important protein in preventing atherosclerosis and highlight the importance of antioxidant proteins in the prevention of atherosclerosis in vivo.

  18. Selective uptake of a toxic lipophilic anthracycline derivative by the low-density lipoprotein receptor pathway in cultured fibroblasts

    International Nuclear Information System (INIS)

    Vitols, S.G.; Masquelier, M.; Peterson, C.O.

    1985-01-01

    N-(N-Retinoyl)-L-leucyldoxorubicin 14-linoleate (r11-DOX), a new lipophilic derivative of doxorubicin, was synthesized and incorporated into low-density lipoprotein (LDL). The drug-LDL complex contained 100- 200 drug molecules/LDL particle. When cultured normal human fibroblasts were incubated with 125 I-LDL-incorporated drug, there was a perfect correlation between the cellular uptake plus degradation of 125 I-LDL and the cellular drug accumulation. The presence of excess native LDL inhibited the cellular uptake and degradation of 125 I-LDL and the drug accumulation to the same extent. In contrast, methylated LDL, which does not bind to the LDL receptor, did not alter the cellular uptake and degradation of 125 I-LDL nor did it alter the drug accumulation. When LDL receptor negative fibroblasts from a patient with the homozygous form of familial hypercholesterolemia were incubated with the drug- 125 I-LDL complex, cellular drug accumulation was very low. The drug-LDL complex inhibited the growth of cultured normal human fibroblasts. The drug incorporated into methylated LDL was much less toxic. These findings suggest that r11-DOX incorporated into LDL is delivered to cells selectively by the LDL receptor pathway. This might be of value in the treatment of leukemia, since it has been previously found that leukemic cells exhibit higher LDL receptor activity than white blood cells and bone marrow cells from healthy subjects

  19. Lipoprotein-Associated Phospholipase A2 Mass Level Is Increased in Elderly Subjects with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    J. Fortunato

    2014-01-01

    Full Text Available Objective. Lipoprotein-associated phospholipase A2 (Lp-PLA2 is extensively expressed by advanced atherosclerotic lesions and may play a role in plaque instability. We selected a group of elderly subjects that underwent transcatheter aortic valve implantation (TAVI or balloon angioplasty (BA and separated them into two groups, diabetic and nondiabetic, to compare the level of Lp-PLA2 mass between them. Methods. 44 patients aged 79.6±5.6 years with symptomatic severe aortic valve stenosis underwent TAVI (n=35 or BA (n=9. 21 subjects had confirmed type 2 diabetes mellitus. Lp-PLA2 mass was measured using an enzyme-linked immunosorbent assay kit (USCN Life Science, China before and 3 days after the procedure. Results. Lp-PLA2 mass was significantly elevated in this population (1296±358 ng/mL before TAVI; 1413±268 ng/mL before BA and further increased after TAVI (1604±437 ng/mL, P<0.01 or BA (1808±303 ng/mL, P<0.01. Lp-PLA2 mass was significantly increased on the diabetic group before these interventions. Conclusion. Lp-PLA2 may be a novel biomarker for the presence of rupture-prone atherosclerotic lesions in elderly patients. Levels of Lp-PLA2 in diabetic patients may accompany the higher amount of small dense LDL particles seen in these subjects.

  20. Ten years of lipoprotein apheresis for familial hypercholesterolemia in Malaysia: A creative approach by a cardiologist in a developing country

    NARCIS (Netherlands)

    Khoo, Kah Lin; Page, Michael M.; Liew, Yin Mei; Defesche, Joep C.; Watts, Gerald F.

    2016-01-01

    Familial hypercholesterolemia (FH) leads to premature coronary artery disease and aortic stenosis, with undertreated severe forms causing death at a young age. Lipoprotein apheresis (LA) is often required for lowering low-density lipoprotein cholesterol levels in severe FH. The objective of this

  1. Effect of theobromine consumption on serum lipoprotein profiles in apparently healthy humans with low HDL-cholesterol concentrations

    NARCIS (Netherlands)

    Jacobs, Doris M.; Smolders, Lotte; Lin, Yuguang; Roo, de Niels; Trautwein, Elke A.; Duynhoven, van John; Mensink, Ronald P.; Plat, Jogchum; Mihaleva, Velitchka V.

    2017-01-01

    Scope: Theobromine is a major active compound in cocoa with allegedly beneficial effect on high-density-lipoprotein-cholesterol (HDL-CH). We have investigated the effect of theobromine (TB) consumption on the concentrations of triglyceride (TG) and cholesterol (CH) in various lipoprotein (LP)

  2. Effects of aerobic exercise, diet, or both on lipids and lipoproteins in adults: a meta-analysis

    Science.gov (United States)

    BACKGROUND: Studies addressing the effects of aerobic exercise (E), diet (D), or both (ED) on lipids and lipoproteins have led to conflicting results. OBJECTIVE: Determine the effects of E, D, and ED on lipids and lipoproteins. METHODS: Using the aggregate data meta-analytic approach, studies were ...

  3. Increased lipogenesis and resistance of lipoproteins to oxidative modification in two patients with glycogen storage disease type 1a

    NARCIS (Netherlands)

    Bandsma, RHJ; Rake, JP; Visser, G; Neese, RA; Hellerstein, MK; van Duyvenvoorde, W; Princen, HMG; Stellaard, F; Smit, GPA; Kuipers, F

    We describe 2 patients with glycogen storage disease type la and severe hyperlipidemia without premature atherosclerosis. Susceptibility of low-density lipoproteins to oxidation was decreased, possibly related to the similar to40-fold increase in palmitate synthesis altering lipoprotein saturated

  4. Lipoprotein lipase-catalyzed hydrolysis of tri[14C]oleoylglycerol in a phospholipid interface : A monolayer study

    NARCIS (Netherlands)

    Demel, R.A.; Shirai, K.; Jackson, R.L.

    1982-01-01

    The lipoprotein lipase-catalyzed hydrolysis of triacylglycerol was determined in a lipid monolayer containing egg phosphatidylcholine and tri[14C]oleoylglycerol. In the presence of purified bovine milk lipoprotein lipase and fatty acid-free albumin, the rate of hydrolysis of tri[14C]oleoylglycerol,

  5. Moderate alcohol consumption and changes in postprandial lipoproteins of premenopausal and postmenopausal women : a diet-controlled, randomized intervention study

    NARCIS (Netherlands)

    Gaag, van der M.S.; Sierksma, A.; Schaafsma, G.; Bakker, M.; Hendriks, J.F.J.

    2000-01-01

    Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Earlier studies in men have shown that moderate alcohol consumption affects lipoprotein metabolism and hemostasis. In this diet-controlled, randomized, crossover trial, we investigated the effect on lipoprotein

  6. A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis

    NARCIS (Netherlands)

    Reymer, P.W.A.; Gagné, S E; Groenemeyer, B E; Zhang, H; Forsyth, I; Jansen, H; Seidell, J C; Kromhout, D.; Lie, K E; Kastelein, J.J.

    1995-01-01

    A reduction of high density lipoprotein cholesterol (HDC) is recognized as an important risk factor for coronary artery disease (CAD). We now show in approximately 1 in 20 males with proven atherosclerosis that an Asn291Ser mutation in the human lipoprotein lipase (LPL) gene is associated with

  7. ROLE OF ELEVATED LECITHIN - CHOLESTEROL ACYLTRANSFERASE AND CHOLESTERYL ESTER TRANSFER PROTEIN ACTIVITIES IN ABNORMAL LIPOPROTEINS FROM PROTEINURIC PATIENTS

    NARCIS (Netherlands)

    DULLAART, RPF; GANSEVOORT, RT; DIKKESCHEI, BD; DEZEEUW, D; DEJONG, PE; VANTOL, A

    Lecithin-cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of free cholesterol, and the distribution of cholesteryl ester among lipoproteins in plasma. Alterations in these processes may play a role in the lipoprotein abnormalities

  8. An extrahepatic receptor-associated protein-sensitive mechanism is involved in the metabolism of triglyceride-rich lipoproteins

    NARCIS (Netherlands)

    Vlijmen, B.J.M. van; Rohlmann, A.; Page, S.T.; Bensadoun, A.; Bos, I.S.T.; Berkel, T.J.C. van; Havekes, L.M.; Herz, J.

    1999-01-01

    We have used adenovirus-mediated gene transfer in mice to investigate low density lipoprotein receptor (LDLR) and LDLR-related protein (LRP)- independent mechanisms that control the metabolism of chylomicron and very low density lipoprotein (VLDL) remnants in vivo. Overexpression of receptor-

  9. Study of particle swarm optimization particle trajectories

    CSIR Research Space (South Africa)

    Van den Bergh, F

    2006-01-01

    Full Text Available Particle swarm optimization (PSO) has shown to be an efficient, robust and simple optimization algorithm. Most of the PSO studies are empirical, with only a few theoretical analyses that concentrate on understanding particle trajectories...

  10. Characterization of blood lipoproteins and validation of cholesterol and triacylglycerol assays for free-ranging polar bears (Ursus maritimus).

    Science.gov (United States)

    Whiteman, John P; Frank, Nicholas; Greller, Katie A; Harlow, Henry J; Ben-David, Merav

    2013-05-01

    Blood triacylglycerol (TG) and lipoproteins are important variables for evaluating nutritional status of wildlife, but measurements are often expensive and difficult. Performance of a small, portable blood analyzer intended for human medical diagnostics was evaluated in measuring these variables in plasma and serum from free-ranging polar bears (Ursus maritimus), which are experiencing nutritional stress related to sea ice loss. The analyzer accurately tracked changes in concentration of total cholesterol (Ctotal), cholesterol associated with high-density lipoprotein (CHDL), and TG during a validation protocol of diluting samples and spiking them with exogenous cholesterol and glycerol. Values of Ctotal and TG agreed well with values obtained by other methods (ultracentrifugation followed by colorimetric assays); agreement was variable for values of cholesterol associated with specific lipoproteins. Similar to a study of captive polar bears, ultracentrifugation methods revealed greater TG in very low-density lipoproteins than in low-density lipoprotein, which is unusual and merits additional study.

  11. Lipoprotein Lipase and PPAR Alpha Gene Polymorphisms, Increased Very-Low-Density Lipoprotein Levels, and Decreased High-Density Lipoprotein Levels as Risk Markers for the Development of Visceral Leishmaniasis by Leishmania infantum

    Directory of Open Access Journals (Sweden)

    Márcia Dias Teixeira Carvalho

    2014-01-01

    Full Text Available In visceral leishmaniasis (VL endemic areas, a minority of infected individuals progress to disease since most of them develop protective immunity. Therefore, we investigated the risk markers of VL within nonimmune sector. Analyzing infected symptomatic and, asymptomatic, and noninfected individuals, VL patients presented with reduced high-density lipoprotein cholesterol (HDL-C, elevated triacylglycerol (TAG, and elevated very-low-density lipoprotein cholesterol (VLDL-C levels. A polymorphism analysis of the lipoprotein lipase (LPL gene using HindIII restriction digestion (N = 156 samples (H+ = the presence and H− = the absence of mutation revealed an increased adjusted odds ratio (OR of VL versus noninfected individuals when the H+/H+ was compared with the H−/H− genotype (OR = 21.3; 95% CI = 2.32–3335.3; P = 0.003. The H+/H+ genotype and the H+ allele were associated with elevated VLDL-C and TAG levels (P < 0.05 and reduced HDL-C levels (P < 0.05. An analysis of the L162V polymorphism in the peroxisome proliferator-activated receptor alpha (PPARα gene (n = 248 revealed an increased adjusted OR when the Leu/Val was compared with the Leu/Leu genotype (OR = 8.77; 95% CI = 1.41–78.70; P = 0.014. High TAG (P = 0.021 and VLDL-C (P = 0.023 levels were associated with susceptibility to VL, whereas low HDL (P = 0.006 levels with resistance to infection. The mutated LPL and the PPARα Leu/Val genotypes may be considered risk markers for the development of VL.

  12. Reference values assessment in a Mediterranean population for small dense low-density lipoprotein concentration isolated by an optimized precipitation method

    Directory of Open Access Journals (Sweden)

    Fernández-Cidón B

    2017-06-01

    Full Text Available Bárbara Fernández-Cidón,1–3 Ariadna Padró-Miquel,1 Pedro Alía-Ramos,1 María José Castro-Castro,1 Marta Fanlo-Maresma,4 Dolors Dot-Bach,1 José Valero-Politi,1 Xavier Pintó-Sala,4 Beatriz Candás-Estébanez1 1Clinical Laboratory, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Spain; 2Department of Biochemistry, Molecular Biology and Biomedicine, Autonomous University of Barcelona (UAB, Barcelona, Spain; 3Department of Pharmacotherapy, Pharmacogenetics and Pharmaceutical Technology, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL, L’Hospitalet de Llobregat, Spain; 4Cardiovascular Risk Unit, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Spain Background: High serum concentrations of small dense low-density lipoprotein cholesterol (sd-LDL-c particles are associated with risk of cardiovascular disease (CVD. Their clinical application has been hindered as a consequence of the laborious current method used for their quantification. Objective: Optimize a simple and fast precipitation method to isolate sd-LDL particles and establish a reference interval in a Mediterranean population. Materials and methods: Forty-five serum samples were collected, and sd-LDL particles were isolated using a modified heparin-Mg2+ precipitation method. sd-LDL-c concentration was calculated by subtracting high-density lipoprotein cholesterol (HDL-c from the total cholesterol measured in the supernatant. This method was compared with the reference method (ultracentrifugation. Reference values were estimated according to the Clinical and Laboratory Standards Institute and The International Federation of Clinical Chemistry and Laboratory Medicine recommendations. sd-LDL-c concentration was measured in serums from 79 subjects with no lipid metabolism abnormalities. Results: The Passing–Bablok regression equation is y = 1.52 (0.72 to 1.73 + 0.07x (−0.1 to 0.13, demonstrating no significant statistical differences

  13. Lipid composition and lipopolysaccharide binding capacity of lipoproteins in plasma and lymph of patients with systemic inflammatory response syndrome and multiple organ failure

    NARCIS (Netherlands)

    Levels, Johannes H. M.; Lemaire, Luciënne C. J. M.; van den Ende, Abraham E.; van Deventer, Sander J. H.; van Lanschot, J. Jan B.

    2003-01-01

    Background. Lipopolysaccharide (LPS), the major glycolipid component of Gram-negative bacterial outer membranes, is a potent endotoxin responsible for many of the directly or indirectly induced symptoms of infection. Lipoproteins (in particular, high-density lipoproteins) sequester LPS, thereby

  14. Lipid, lipoprotein and apolipoprotein profiles in active and sedentary men with tetraplegia

    NARCIS (Netherlands)

    Dallmeijer, A.J.; van der Woude, L.H.V.; Hopman, M.T.E.

    1997-01-01

    Objective: To investigate whether the risk profile of coronary heart disease (CHD) is more favorable in physically active men with tetraplegia compared with sedentary men with tetraplegia. Design: Using a cross-sectional design, the lipid and (apo)lipoprotein concentrations of 11 active and 13

  15. High-density lipoproteins: a novel therapeutic target for cardiovascular disease

    Directory of Open Access Journals (Sweden)

    TS Mohamed Saleem

    2011-01-01

    Full Text Available TS Mohamed Saleem1, PV Sandhya Rani1, K Gauthaman21Department of Pharmacology, Annamacharya College of Pharmacy, New Boyanapalli, Andhrapradesh, India; 2Department of Drug Technology, Faculty of Medical Technology, Derna, LibyaAbstract: Cardiovascular disease has a high rate of mortality in both Western and developing countries. Atherosclerosis and generation of reactive oxygen species through oxidative stress is the major risk factor for cardiovascular disease. Atherothrombosis with low levels of high-density lipoprotein (HDL and high levels of low-density lipoprotein is a major risk factor for atherosclerosis-induced cardiovascular disease. Lipid-lowering drugs like statins, niacin, fibrates, and some newer agents, ie, the apolipoprotein A-I mimetics and the cholesteryl ester transfer protein inhibitors, not only increase HDL levels but are also effective in reducing key atherogenic lipid components, including triglyceride-rich lipoproteins. The aim of this review is to discuss the accumulating evidence suggesting that HDL possesses a diverse range of biological actions, and that increasing HDL levels by drug treatment may be beneficial in the prevention of cardiovascular disease.Keywords: cardiovascular disease, lipoproteins, statins, apolipoprotein, atherosclerosis

  16. Lipid, lipoprotein, and apolipoprotein profiles in active and sedentary men with tetraplegia

    NARCIS (Netherlands)

    Dallmeijer, A J; Hopman, M T; van der Woude, L H

    1997-01-01

    OBJECTIVE: To investigate whether the risk profile of coronary heart disease (CHD) is more favorable in physically active men with tetraplegia compared with sedentary men with tetraplegia. DESIGN: Using a cross-sectional design, the lipid and (apo)lipoprotein concentrations of 11 active and 13

  17. The influence of ApoE genotype on the lipid profile and lipoproteins ...

    African Journals Online (AJOL)

    plasma triglyceride concentration (in mmol/L) was significantly higher in pregnancy (median = 1.5, IQR 1.0-2.0 vs median = 0.6,. IQR 0.5-0.8 respectively, ... remnants of the triglycerides (TG)-rich lipoproteins or of lipolysis by genetic defects in ... anti-aggregatory effects on platelets.20 However, preg- nancy may precipitate ...

  18. Mutation of tryptophan residues in lipoprotein lipase. Effects on stability, immunoreactivity, and catalytic properties

    NARCIS (Netherlands)

    Lookene, A.; Groot, N. B.; Kastelein, J. J.; Olivecrona, G.; Bruin, T.

    1997-01-01

    Previous studies had pointed to an important function of a putative exposed loop in the C-terminal domain of lipoprotein lipase for activity against emulsified lipid substrates. This loop contains 3 tryptophan residues (Trp390, Trp393, and Trp394). We have expressed and characterized lipase mutants

  19. Kinetics of incorporation/redistribution of photosensitizer hypericin to/from high-density lipoproteins

    Czech Academy of Sciences Publication Activity Database

    Joniova, J.; Buriánková, L.; Búzová, Diana; Miškovský, P.; Jančura, D.

    2014-01-01

    Roč. 475, 1-2 (2014), s. 578-584 ISSN 0378-5173 Institutional support: RVO:67179843 Keywords : aggregation * drug delivery * fluorescence * high- and low- density lipoproteins * Hypericin Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 3.650, year: 2014

  20. Induction of oxygen free radical generation in human monocytes by lipoprotein(a)

    DEFF Research Database (Denmark)

    Riis Hansen, P; Kharazmi, A; Jauhiainen, M

    1994-01-01

    The mechanism behind the association of elevated plasma lipoprotein(a) [Lp(a)] levels with atherosclerotic disease is unknown. In the present study, Lp(a) induced generation of oxygen free radicals by monocytes from selected healthy individuals in vitro. This observation may provide a link between...