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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. SAA is Found on ApoB-Containing Lipoproteins in Obese Diabetic Humans

    OpenAIRE

    Jahangiri, Anisa; Wilson, Patricia G.; Hou, Tianfei; Brown, Aparna; King, Victoria L.; Tannock, Lisa R.

    2013-01-01

    In murine models of obesity/diabetes there is an increase in plasma SAA levels along with redistribution of SAA from high density lipoprotein (HDL) to apo-B containing lipoprotein particles, namely low density lipoprotein (LDL) and very low density lipoprotein (VLDL). The goal of this study was to determine if obesity is associated with similar SAA lipoprotein redistribution in humans. Three groups of obese individuals were recruited from a weight loss clinic: healthy obese (n=14), metabolic ...

  3. Cardiomyocyte Regulation of Systemic Lipid Metabolism by the Apolipoprotein B-Containing Lipoproteins in Drosophila

    Science.gov (United States)

    Ishikawa, Zachary

    2017-01-01

    The heart has emerged as an important organ in the regulation of systemic lipid homeostasis; however, the underlying mechanism remains poorly understood. Here, we show that Drosophila cardiomyocytes regulate systemic lipid metabolism by producing apolipoprotein B-containing lipoproteins (apoB-lipoproteins), essential lipid carriers that are so far known to be generated only in the fat body. In a Drosophila genetic screen, we discovered that when haplo-insufficient, microsomal triglyceride transfer protein (mtp), required for the biosynthesis of apoB-lipoproteins, suppressed the development of diet-induced obesity. Tissue-specific inhibition of Mtp revealed that whereas knockdown of mtp only in the fat body decreases systemic triglyceride (TG) content on normal food diet (NFD) as expected, knockdown of mtp only in the cardiomyocytes also equally decreases systemic TG content on NFD, suggesting that the cardiomyocyte- and fat body-derived apoB-lipoproteins serve similarly important roles in regulating whole-body lipid metabolism. Unexpectedly, on high fat diet (HFD), knockdown of mtp in the cardiomyocytes, but not in fat body, protects against the gain in systemic TG levels. We further showed that inhibition of the Drosophila apoB homologue, apolipophorin or apoLpp, another gene essential for apoB-lipoprotein biosynthesis, affects systemic TG levels similarly to that of Mtp inhibition in the cardiomyocytes on NFD or HFD. Finally, we determined that HFD differentially alters Mtp and apoLpp expression in the cardiomyocytes versus the fat body, culminating in higher Mtp and apoLpp levels in the cardiomyocytes than in fat body and possibly underlying the predominant role of cardiomyocyte-derived apoB-lipoproteins in lipid metabolic regulation. Our findings reveal a novel and significant function of heart-mediated apoB-lipoproteins in controlling lipid homeostasis. PMID:28095410

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

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    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

  5. Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins.

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    Kollerits, Barbara; Coassin, Stefan; Beckmann, Noam D; Teumer, Alexander; Kiechl, Stefan; Döring, Angela; Kavousi, Maryam; Hunt, Steven C; Lamina, Claudia; Paulweber, Bernhard; Kutalik, Zoltán; Nauck, Matthias; van Duijn, Cornelia M; Heid, Iris M; Willeit, Johann; Brandstätter, Anita; Adams, Ted D; Mooser, Vincent; Aulchenko, Yurii S; Völzke, Henry; Kronenberg, Florian

    2009-12-01

    Adiponutrin (PNPLA3) is a predominantly liver-expressed transmembrane protein with phospholipase activity that is regulated by fasting and feeding. Recent genome-wide association studies identified PNPLA3 to be associated with hepatic fat content and liver function, thus pointing to a possible involvement in the hepatic lipoprotein metabolism. The aim of this study was to examine the association between two common variants in the adiponutrin gene and parameters of lipoprotein metabolism in 23,274 participants from eight independent West-Eurasian study populations including six population-based studies [Bruneck (n = 800), KORA S3/F3 (n = 1644), KORA S4/F4 (n = 1814), CoLaus (n = 5435), SHIP (n = 4012), Rotterdam (n = 5967)], the SAPHIR Study as a healthy working population (n = 1738) and the Utah Obesity Case-Control Study including a group of 1037 severely obese individuals (average BMI 46 kg/m2) and 827 controls from the same geographical region of Utah. We observed a strong additive association of a common non-synonymous variant within adiponutrin (rs738409) with age-, gender-, and alanine-aminotransferase-adjusted lipoprotein concentrations: each copy of the minor allele decreased levels of total cholesterol on average by 2.43 mg/dl (P = 8.87 x 10(-7)), non-HDL cholesterol levels by 2.35 mg/dl (P = 2.27 x 10(-6)) and LDL cholesterol levels by 1.48 mg/dl (P = 7.99 x 10(-4)). These associations remained significant after correction for multiple testing. We did not observe clear evidence for associations with HDL cholesterol or triglyceride concentrations. In conclusion, our study suggests that adiponutrin is involved in the metabolism of apoB-containing lipoproteins.

  6. 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...

  7. 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.; 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

  8. Elevated plasma cholesteryl ester transfer in NIDDM : relationships with apolipoprotein B-containing lipoproteins and phospholipid transfer protein

    NARCIS (Netherlands)

    Riemens, S; van Tol, A; Sluiter, W; Dullaart, R

    1998-01-01

    Lecithin:cholesteryl acyl transferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of cholesterol and the subsequent transfer of cholesteryl ester from high density lipoproteins (HDL) towards very low and low density lipoproteins (VLDL + LDL). Phospholip

  9. Green Tea Extract Improves the Post Prandial Overproduction of Intestinal Apolipoprotein B-containing Lipoproteins in Fructose Fed Hamsters

    Science.gov (United States)

    Green tea has putative medicinal properties that may be useful in preventing the metabolic syndrome. However, little is known of the effects of green tea extract (GTE) on postprandial apoB-48 containing lipoproteins and its molecular mechanisms. In a three-hour olive oil loading study, acute GTE ora...

  10. 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.

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

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    Harrison Michael

    2012-07-01

    Full Text Available Abstract Background Many 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. Methods Using 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. Results The 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. Conclusions These findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in

  12. 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

    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...... catabolic rate of LDL (r = -0.38, P = 0.009). These data suggest that the plasma clearance of apoM, despite apoM primarily being associated with HDL, is influenced by LDL receptor-mediated clearance of apoB-containing particles....

  13. 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

  14. 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

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

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    Christoffersen, Christina; Benn, Marianne; Christensen, Pernille M; Gordts, Philip L S M; Roebroek, Anton J M; Frikke-Schmidt, Ruth; Tybjaerg-Hansen, Anne; Dahlbäck, Björn; Nielsen, Lars B

    2012-10-01

    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 LDL receptor-deficient mice, respectively. Finally, we compared the turnover of radio-iodinated LDL and plasma apoM concentrations in 45 normocholesterolemic humans. There was a negative correlation between plasma apoM and the fractional catabolic rate of LDL (r = -0.38, P = 0.009). These data suggest that the plasma clearance of apoM, despite apoM primarily being associated with HDL, is influenced by LDL receptor-mediated clearance of apoB-containing particles.

  16. Modified lipoprotein-derived lipid particles accumulate in human stenotic aortic valves.

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    Lehti, Satu; Käkelä, Reijo; Hörkkö, Sohvi; Kummu, Outi; Helske-Suihko, Satu; Kupari, Markku; Werkkala, Kalervo; Kovanen, Petri T; Oörni, Katariina

    2013-01-01

    In aortic stenosis plasma lipoprotein-derived lipids accumulate in aortic valves. Here, we first compared the lipid compositions of stenotic aortic valves and atherosclerotic plaque cores. Both pathological tissues were found to be enriched in cholesteryl linoleate, a marker of extracellularly accumulated lipoproteins. In addition, a large proportion of the phospholipids were found to contain arachidonic acid, the common precursor of a number of proinflammatory lipid mediators. Next, we isolated and characterized extracellular lipid particles from human stenotic and non-stenotic control valves, and compared them to plasma lipoproteins from the same subjects. The extracellular valvular lipid particles were isolated from 15 stenotic and 14 non-stenotic aortic valves. Significantly more apoB-100-containing lipid particles were found in the stenotic than in the non-stenotic valves. The majority of the lipid particles isolated from the non-stenotic valves had sizes (23±6.2 nm in diameter) similar to those of plasma low density lipoprotein (LDL) (22±1.5 nm), while the lipid particles from stenotic valves were not of uniform size, their sizes ranging from 18 to more than 500 nm. The lipid particles showed signs of oxidative modifications, and when compared to isolated plasma LDL particles, the lipid particles isolated from the stenotic valves had a higher sphingomyelin/phosphatidylcholine -ratio, and also higher contents of lysophosphatidylcholine and unesterified cholesterol. The findings of the present study reveal, for the first time, that in stenotic human aortic valves, infiltrated plasma lipoproteins have undergone oxidative and lipolytic modifications, and become fused and aggregated. The generated large lipid particles may contribute to the pathogenesis of human aortic stenosis.

  17. Green tea catechins prevent low-density lipoprotein oxidation via their accumulation in low-density lipoprotein particles in humans.

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    Suzuki-Sugihara, Norie; Kishimoto, Yoshimi; Saita, Emi; Taguchi, Chie; Kobayashi, Makoto; Ichitani, Masaki; Ukawa, Yuuichi; Sagesaka, Yuko M; Suzuki, Emiko; Kondo, Kazuo

    2016-01-01

    Green tea is rich in polyphenols, including catechins which have antioxidant activities and are considered to have beneficial effects on cardiovascular health. In the present study, we investigated the effects of green tea catechins on low-density lipoprotein (LDL) oxidation in vitro and in human studies to test the hypothesis that catechins are incorporated into LDL particles and exert antioxidant properties. In a randomized, placebo-controlled, double-blind, crossover trial, 19 healthy men ingested green tea extract (GTE) in the form of capsules at a dose of 1 g total catechin, of which most (>99%) was the gallated type. At 1 hour after ingestion, marked increases of the plasma concentrations of (-)-epigallocatechin gallate and (-)-epicatechin gallate were observed. Accordingly, the plasma total antioxidant capacity was increased, and the LDL oxidizability was significantly reduced by the ingestion of GTE. We found that gallated catechins were incorporated into LDL particles in nonconjugated forms after the incubation of GTE with plasma in vitro. Moreover, the catechin-incorporated LDL was highly resistant to radical-induced oxidation in vitro. An additional human study with 5 healthy women confirmed that GTE intake sufficiently increased the concentration of gallated catechins, mainly in nonconjugated forms in LDL particles, and reduced the oxidizability of LDL. In conclusion, green tea catechins are rapidly incorporated into LDL particles and play a role in reducing LDL oxidation in humans, which suggests that taking green tea catechins is effective in reducing atherosclerosis risk associated with oxidative stress.

  18. Crystallization and preliminary X-ray diffraction analysis of apolipoprotein E-containing lipoprotein particles

    Energy Technology Data Exchange (ETDEWEB)

    Newhouse, Yvonne [Gladstone Institutes of Cardiovascular and Neurological Disease, University of California, San Francisco, CA 94158 (United States); Peters-Libeu, Clare [Gladstone Institutes of Cardiovascular and Neurological Disease, University of California, San Francisco, CA 94158 (United States); Cardiovascular Research Institute, University of California, San Francisco, CA 94158 (United States); Weisgraber, Karl H., E-mail: kweisgraber@gladstone.ucsf.edu [Gladstone Institutes of Cardiovascular and Neurological Disease, University of California, San Francisco, CA 94158 (United States); Cardiovascular Research Institute, University of California, San Francisco, CA 94158 (United States); Department of Pathology, University of California, San Francisco, CA 94158 (United States)

    2005-11-01

    Further understanding of the structure and function of plasma apolipoproteins requires the determination of their high-resolution structures when complexed with lipids. In these studies, the production of homogeneous, biologically active lipoprotein particles of apolipoprotein E complexed with dipalmitoylphosphatidylcholine and their crystallization and X-ray diffraction are demonstrated. High-resolution structural information is available for several soluble plasma apolipoproteins (apos) in a lipid-free state. However, this information provides limited insight into structure–function relationships, as this class of proteins primarily performs its functions of lipid transport and modulation of lipid metabolism in a lipid-bound state on lipoprotein particles. Here, the possibility of generating homogeneous lipoprotein particles that could be crystallized was explored, opening the possibility of obtaining high-resolution structural information by X-ray crystallography. To test this possibility, apoE4 complexed with the phospholipid dipalmitoylphosphatidylcholine was chosen. Uniform particles containing 50% lipid and 50% apoE4 were obtained and crystallized using the hanging-drop method. Two crystal forms diffract to beyond 8 Å resolution.

  19. Lipoprotein Particles in Adolescents and Young Women With PCOS Provide Insights Into Their Cardiovascular Risk

    Science.gov (United States)

    Lodish, M.; Shamburek, R.; Keil, M.; Wesley, R.; Walter, M.; Sampson, M.; Bernstein, S.; Khurana, D.; Lyssikatos, C.; Ten, S.; Dobs, A.; Remaley, A. T.; Stratakis, C. A.

    2015-01-01

    Context: Adult women with polycystic ovarian syndrome (PCOS) have an increased risk for cardiovascular disease, but the evidence for this is controversial in adolescents and young women with PCOS. Measurement of low-density lipoprotein (LDL) particle number, measured by nuclear magnetic resonance spectroscopy is a novel technology to assess cardiovascular risk. Objective: The objective of the study was to evaluate lipoprotein particle number and size in young women with PCOS and its relationship with insulin resistance and hyperandrogenism. Design: This was a cross-sectional case control study. Setting: The study was conducted at a clinical research center. Participants: Women with PCOS (n = 35) and normal controls (n = 20) participated in the study. Interventions: Blood samples and anthropometric measures were obtained. Main Outcome Measures: LDL particle size and number were measured using nuclear magnetic resonance spectroscopy. A secondary outcome was to investigate the correlation of LDL particle number with high-sensitivity C-reactive protein, waist to hip ratio, hyperandrogenism, insulin resistance, and adiponectin. Results: Women with PCOS had higher LDL particle number when compared with healthy controls (935 ± 412 vs 735 ± 264, P = .032); LDL particle number correlated strongly with high-sensitivity C-reactive protein (r = 0.37, P = .006) and waist-to-hip (r = 0.57, P = .0003). The higher LDL particle number was driven mainly due to differences in the small LDL particle number (sLDLp), with PCOS patients having more sLDLp (348 ± 305 vs 178 ± 195, P = .015). The sLDLp correlated with the Matsuda index (r = −0.51, P = .0001), homeostasis model assessment index of insulin resistance (r = 0.41, P = .002), and adiponectin (r = −0.46, P = .0004) but not with T. Conclusion: Adolescent and young women with PCOS have an atherogenic lipoprotein profile suggestive of increased cardiovascular risk that appears to be driven by the degree of visceral adiposity

  20. Dysfunctional lipoproteins from young smokers exacerbate cellular senescence and atherogenesis with smaller particle size and severe oxidation and glycation.

    Science.gov (United States)

    Park, Ki-Hoon; Shin, Dong-Gu; Cho, Kyung-Hyun

    2014-07-01

    Until now, there has been limited information on the effects of smoking on atherogenesis and senescence in the context of lipoprotein parameters, particularly in young smokers who have smoked fewer than 10 cigarettes per day for 3 years. In this study, lipoprotein profiles and functions were compared between smoker (n = 21) and control groups (n = 20). In the smoking group, ferric ion reduction abilities of serum and high-density lipoprotein (HDL) fractions were significantly reduced, and low-density lipoprotein (LDL) was severely oxidized. All lipoprotein particles from the smoker group showed higher advanced glycated end products with more triglyceride (TG) content compared with the control group. Lipoproteins from smokers showed faster agarose gel electromobility as well as greater smear band intensity in SDS-PAGE due to oxidation and glycation. LDL from smokers was more sensitive to oxidation and promoted foam cell forma-tion in macrophages. Gel filtration column chromatography revealed that the protein and cholesterol peaks of VLDL and LDL were elevated in the smoker group, whereas those of HDL were reduced. Human dermal fibroblast cells from the smoker group showed severe senescence following treatment with HDL2 and HDL3. Although HDL from young smokers showed impaired antioxidant ability, smaller particle size, and increased TG content, cholesteryl ester transfer protein activities were greatly enhanced in the serum and HDL fractions of the smoker group. In conclusion, smoking can cause production of dysfunctional lipoproteins having a smaller particle size that exacerbate senescence and atherogenic progress due to oxidation and glycation.

  1. 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...

  2. Sexual differences in lipoprotein composition in a family with dyslipidemic hypertension with premature atheroschlerosis: deficiency of high-density lipoprotein-L and high-density lipoprotein-M "apolipoprotein-I alone" particle.

    Science.gov (United States)

    Hughes, T A; Moore, M A; Joyce, M; Go, R C; Segrest, J P; Blackwell, T

    1992-01-01

    This article describes a family with a high incidence of premature atherosclerosis and primary hypertriglyceridemia in the women. The lipoprotein composition of this family was investigated with a new methodology that combines gradient ultracentrifugation to isolate lipoprotein subfractions with high-performance liquid chromatography to quantitate apolipoproteins. The major lipoprotein abnormalities that were identified in the hyperlipidemic women in this family were (1) an increased mass of very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) with triglyceriderich VLDL but normal IDL composition; (2) triglyceride-rich low-density lipoprotein (LDL) with normal cholesterol and apolipoprotein B concentrations; (3) a relatively normal total mass of high-density lipoprotein (HDL)-L and HDL-M but with a reduction in the apolipoprotein A-I/A-II ratio and a decrease in the cholesterol to triglyceride ratio; (4) an elevation of HDL-D apolipoprotein A-I. The reduction in the apolipoprotein A-I/A-II ratio was also seen in the hyperlipidemic men and in most of nonhyperlipidemic family members and was the most common lipoprotein abnormality that was identified in this family (9 of 11 family members who were not on lipid-lowering medications were affected). The hypertriglyceridemic women appeared to have an increase in the "A-I + A-II" HDL particles in all subfractions and an increase in the "A-I alone" particles in HDL-D. These increases provided the apparently normal total mass of HDL that was observed in these women. These increases in HDL were not seen in the hypertriglyceridemic men. We conclude that a deficiency of the "A-I alone" particle in HDL-L and HDL-M may contribute to the premature atherosclerosis that was seen in this family and that it appears to precede the appearance of hypertriglyceridemia. The increase in the "A-I + A-II" HDL particles did not appear to provide the same protection as would be expected from "A-I alone" HDL.

  3. Lipoprotein-like particles in a prokaryote: quinone droplets of Thermoplasma acidophilum.

    Science.gov (United States)

    Nagy, István; Knispel, Roland Wilhelm; Kofler, Christine; Orsini, Massimiliano; Boicu, Marius; Varga, Sándor; Weyher-Stingl, Elisabeth; Sun, Na; Fernandez-Busnadiego, Ruben; Kukolya, József; Nickell, Stephan; Baumeister, Wolfgang

    2016-09-01

    Cytosolic, globular droplets with an average diameter of 50 nm were observed in vitrified Thermoplasma acidophilum cells by means of cryo-electron tomography. These droplets were isolated by column chromatography and immunoprecipitation protein purification methods. Subsequent chemical and biochemical analyses identified lipid and protein components, respectively. Two major lipid components, comigrating menaquinones at the solvent front and the slower migrating Thermoplasma polar lipid U4, were detected by TLC experiments. The major protein component was identified as the 153 amino acid long Ta0547 vitellogenin-N domain protein. This domain has been found so far exclusively in large lipid transport proteins of vertebrates and non-vertebrates. Blast protein database homology searches with Ta0547 did not return any eukaryal hits; homologous sequences were found only in thermo-acidophilic archaeons. However, a profile-sequence domain search performed with the vitellogenin-N domain (PF01347) hmm-profile against the T. acidophilum proteome returned Ta0547 as hit. Electron microscopy appearance of isolated droplets resembled to lipoprotein particles. However, no (tetraether) lipid layer could be detected on the droplets surface, rather hydrophobic compounds of the electron dense lumen were surrounded by a denser discontinuous protein boundary. Based on described features, these particles qualify for a novel lipoprotein particle category, what we nominated Thermoplasma Quinone Droplet.

  4. Association between moderately oxidized low-density lipoprotein and high-density lipoprotein particle subclass distribution in hemodialyzed and post-renal transplant patients

    Institute of Scientific and Technical Information of China (English)

    El(z)bieta KIMAK; Magdalena HA(L)ABI(S); Iwona BARANOWICZ-GA SZCZYK; Janusz SOLSKI; Andrzej KSIA(Z)EK

    2011-01-01

    Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed (HD) and post-renal transplant (Tx) patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein (HDL) reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle,oxidized low-density lipoprotein (ox-LDL) and anti-ox-LDL, and paraoxonase-1 (PON-1) activity in HD (n=33) and Tx (n=71) patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy.HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-Ⅰ (apoA-Ⅰ) and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios (total cholesterol (TC)/HDL-C, LDL-C/HDL-C, triglyceride (TG)/HDL-C, HDL-C/non-HDL-C,apoA-Ⅰ/apoB, HDL-C/apoA-Ⅰ, TG/HDL) were atherogenic. The Spearman's rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level (R=0.363, P=0.004), and negatively with TC (R=-0.306, P=0.012), LDL-C (R=-0.283, P=0.020), and non-HDL-C (R=-0.263, P=0.030) levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and decreased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre

  5. Association between moderately oxidized low-density lipoprotein and high-density lipoprotein particle subclass distribution in hemodialyzed and post-renal transplant patients.

    Science.gov (United States)

    Kimak, Elżbieta; Hałabiś, Magdalena; Baranowicz-Gąszczyk, Iwona; Solski, Janusz; Książek, Andrzej

    2011-05-01

    Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed (HD) and post-renal transplant (Tx) patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein (HDL) reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein (ox-LDL) and anti-ox-LDL, and paraoxonase-1 (PON-1) activity in HD (n=33) and Tx (n=71) patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I (apoA-I) and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios (total cholesterol (TC)/HDL-C, LDL-C/HDL-C, triglyceride (TG)/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL) were atherogenic. The Spearman's rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level (R=0.363, P=0.004), and negatively with TC (R=-0.306, P=0.012), LDL-C (R=-0.283, P=0.020), and non-HDL-C (R=-0.263, P=0.030) levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and decreased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-β-HDL particles

  6. Adsorption of lipoproteins onto mineral dust surfaces: a possible factor in the pathogenesis of particle-induced pulmonary fibrosis?

    Science.gov (United States)

    Bogatu, Bettina; Contag, Bodo

    2005-01-01

    We compare the adsorption behavior of high density lipoproteins (HDL) and low density lipoproteins (LDL) on "fibrogenic" and "nonfibrogenic" mineral dusts. The adsorption tests with bovine lipoprotein concentrate and human serum produced the following results: 1) All seven examined fibrogenic dusts (SiO2 DQ12, SiO2 F600, silica, graphite, TiC, kaolin, talc) adsorbed significantly more high density lipoproteins (HDL), than the five examined nonfibrogenic (inert) dusts (TiO2, SnO2, Al2O3, Fe2O3, Fe3O4). This different behavior was particularly conspicuous in the presence of competing adsorbates (serum proteins). 2) In contrast, the adsorption of LDL did not correlate with the fibrogenicity of the mineral dusts. 3) The known silicosis-protective substance polyvinylpyridine-N-oxide inhibits the HDL adsorption of alpha-quartz. These results indicate that the adsorption of HDL could have a causal relationship with the triggering of a fibrotic reaction. The adsorption on the surface of fibrogenic dust particles provides an exceptional opportunity for the intake of HDL by macrophages. During the phagocytosis of the inhaled dust particles, the HDL adsorbed on the surface of the particles could be taken up by macrophages regardless of the receptor. There the HDL particles and/or compounds associated with them, such as lecithin-cholesterol-acyltransferase, could stimulate the macrophages to release fibrogenic mediators by some yet unknown mechanism.

  7. Dietary Resistant Starch Supplementation Increases High-Density Lipoprotein Particle Number in Pigs Fed a Western Diet.

    Science.gov (United States)

    Rideout, Todd C; Harding, Scott V; Raslawsky, Amy; Rempel, Curtis B

    2017-05-04

    Resistant starch (RS) has been well characterized for its glycemic control properties; however, there is little consensus regarding the influence of RS on blood lipid concentrations and lipoprotein distribution and size. Therefore, this study aimed to characterize the effect of daily RS supplementation in a controlled capsule delivery on biomarkers of cardiovascular (blood lipids, lipoproteins) and diabetes (glucose, insulin) risk in a pig model. Twelve 8-week-old male Yorkshire pigs were placed on a synthetic Western diet and randomly divided into two groups (n = 6/group) for 30 days: (1) a placebo group supplemented with capsules containing unmodified pre-gelatinized potato starch (0 g/RS/day); and (2) an RS group supplemented with capsules containing resistant potato starch (10 g/RS/day). Serum lipids including total-cholesterol (C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides did not differ (p > 0.05) between the RS and placebo groups. Although the total numbers of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles were similar (p > 0.05) between the two groups, total high-density lipoprotein (HDL) particles were higher (+28%, p < 0.05) in the RS group compared with placebo, resulting from an increase (p < 0.05) in the small HDL subclass particles (+32%). Compared with the placebo group, RS supplementation lowered (p < 0.05) fasting serum glucose (-20%) and improved (p < 0.05) insulin resistance as estimated by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) without a change in insulin. Additionally, total serum glucagon-like-peptide 1 (GLP-1) was higher (+141%, p < 0.05) following RS supplementation compared with placebo. This data suggests that in addition to the more well-characterized effect of RS intake in lowering blood glucose and improving insulin sensitivity, the consumption of RS may be beneficial in lipid management strategies by enhancing total

  8. Low normal thyroid function as a determinant of increased large very low density lipoprotein particles

    NARCIS (Netherlands)

    van Tienhoven-Wind, Lynnda; Dullaart, Robin P. F.

    2015-01-01

    Objectives: Low-normal thyroid function may relate to increases in plasma cholesterol and triglycerides, but effects on lipoprotein subfractions are largely unknown. Associations of alterations in lipoprotein metabolism and functionality with low-normal thyroid function could be more pronounced in T

  9. Cholesteryl ester transfer protein, low density lipoprotein particle size and intima media thickness in patients with coronary heart disease.

    Science.gov (United States)

    Tosheska, Katerina; Labudovic, Danica; Jovanova, Silvana; Jaglikovski, Branko; Alabakovska, Sonja

    2011-08-01

    Cholesteryl ester transfer protein (CETP) plays a key role in reverse cholesterol transport and high density lipoprotein (HDL) metabolism. Predominance of small, dense LDL particles is associated with an increased risk of atherosclerosis and coronary heart disease (CHD).The aim of the study was to determine the potential relationship between the CETP concentration and low density lipoprotein (LDL) particle size and their association with intima media thickness (IMT) in patients with CHD. Lipid parameters, CETP concentration and LDL particle size were determined in 100 healthy subjects (control group) and in 100 patients with CHD, aged 43 to 77 years. Plasma CETP concentrations were measured by an enzyme-linked immuno-sorbent assay with two different monoclonal antibodies. LDL subclasses were separated by nondenaturing polyacrilamide 3-31% gradient gel electrophoresis. CETP concentration was higher in patients compared to controls (2.02 ± 0.75 mg/ml vs. 1.74 ± 0.63 mg/ml, p<0.01). Mean LDL particle size (nm) was significantly smaller in patients than in controls (24.5 ± 1.1 vs. 26.1 ± 0.9; p<0.001). There was no relation between LDL particle size and CETP concentration (r=-0.1807, p=0.072). Age, diastolic blood pressure, CETP concentration and LDL particle size were independent factors for determing IMT by multiple linear regression analysis. They accounted for 35.2 % of the observed variability in IMT. CETP is not an independent contributor of LDL particle size. CETP might play a role in determining lipoprotein distributions, but did not seem to be the sole factor in the formation of small LDL particles.

  10. Mechanisms of cinnamon extract-induced suppression of the overproduction of apolipoprotein B48-containing lipoproteins in insulin resistance

    Science.gov (United States)

    Metabolic dyslipidemia is a common feature of insulin resistant states and is associated with aberrant metabolism of apoB-containing lipoprotein particles produced by not only the liver but also the small intestine. We have reported previously that an aqueous extract from cinnamon (CE) improves high...

  11. Plasma clearance of human low-density lipoprotein in human apolipoprotein B transgenic mice is related to particle diameter.

    Science.gov (United States)

    Berneis, Kaspar; Shames, David M; Blanche, Patricia J; La Belle, Michael; Rizzo, Manfredi; Krauss, Ronald M

    2004-04-01

    To test for intrinsic differences in metabolic properties of low-density lipoprotein (LDL) as a function of particle size, we examined the kinetic behavior of 6 human LDL fractions ranging in size from 251 to 265 A injected intravenously into human apolipoprotein (apo) B transgenic mice. A multicompartmental model was formulated and fitted to the data by standard nonlinear regression using the Simulation, Analysis and Modeling (SAAM II) program. Smaller sized LDL particles (251 to 257 A) demonstrated a significantly slower fractional catabolic rate (FCR) (0.050 +/- 0.045 h(-1)) compared with particles of larger size (262 to 265 A) (0.134 +/- -0.015 h(-1), P particles are cleared more slowly from plasma than larger LDL and are exchanged more slowly with the extravascular space. This might be due to compositional or structural features of smaller LDL that lead to retarded clearance.

  12. 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...

  13. 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.

  14. Characterization of in vitro modified human very low-density lipoprotein particles and phospholipids by capillary electrophoresis.

    Science.gov (United States)

    Liu, Yi-Ning; Shu, Ting-Yu; Xie, Huai-Guang; Lai, Wei-Ting; Liao, Yi-Han; Su, Mei-Yu; Lin, You-Sian; Chen, Yen-Yi; Lin, Yi-Jyun; Chong, Chin-Pong; Liu, Mine-Yine

    2012-12-03

    A simple capillary zone electrophoresis (CZE) method was used to characterize human very low-density lipoprotein (VLDL) particles for four healthy donors. One major peak was observed for native, in vitro oxidized and glycated VLDL particles. The effective mobilities and peak areas of the capillary electrophoresis (CE) profiles showed good reproducibility and precision. The mobility of the oxidized VLDL peak was higher than that of the native VLDL. The mobility of the glycated VLDL peak was similar to that of the native VLDL. Phospholipids isolated from VLDL particles were analyzed by our recently developed micellar electrokinetic chromatography (MEKC) with a high-salt stacking method. At absorbance 200 nm, the native VLDL phospholipids showed a major peak and a minor peak for each donor. For oxidized VLDL phospholipids, the area of the major peak reduced for three donors, possibly due to phospholipid decomposition. For glycated VLDL phospholipids, the peak mobilities were more positive than native VLDL phospholipids for two donors, possibly due to phospholipid-linked advanced glycation end products (AGEs). Very interestingly, at absorbance 234 nm, the major peak of oxidized VLDL phospholipids was resolved as two peaks for each donor, possibly due to conjugated dienes formed upon oxidation.

  15. Characterization of in Vitro Modified Human Very Low-Density Lipoprotein Particles and Phospholipids by Capillary Electrophoresis

    Directory of Open Access Journals (Sweden)

    Chin-Pong Chong

    2012-12-01

    Full Text Available A simple capillary zone electrophoresis (CZE method was used to characterize human very low-density lipoprotein (VLDL particles for four healthy donors. One major peak was observed for native, in vitro oxidized and glycated VLDL particles. The effective mobilities and peak areas of the capillary electrophoresis (CE profiles showed good reproducibility and precision. The mobility of the oxidized VLDL peak was higher than that of the native VLDL. The mobility of the glycated VLDL peak was similar to that of the native VLDL. Phospholipids isolated from VLDL particles were analyzed by our recently developed micellar electrokinetic chromatography (MEKC with a high-salt stacking method. At absorbance 200 nm, the native VLDL phospholipids showed a major peak and a minor peak for each donor. For oxidized VLDL phospholipids, the area of the major peak reduced for three donors, possibly due to phospholipid decomposition. For glycated VLDL phospholipids, the peak mobilities were more positive than native VLDL phospholipids for two donors, possibly due to phospholipid-linked advanced glycation end products (AGEs. Very interestingly, at absorbance 234 nm, the major peak of oxidized VLDL phospholipids was resolved as two peaks for each donor, possibly due to conjugated dienes formed upon oxidation.

  16. 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.

  17. Small dense low density lipoprotein particles are associated with poor outcome after angioplasty in peripheral artery disease.

    Directory of Open Access Journals (Sweden)

    Vincenzo Jacomella

    Full Text Available PURPOSE: In patients suffering from symptomatic peripheral artery disease (PAD, percutaneous revascularization is the treatment of choice. However, restenosis may occur in 10 to 60% in the first year depending on a variety of factors. Small dense low density lipoprotein (sdLDL particles are associated with an increased risk for cardiovascular events, but their role in the process of restenosis is not known. We conducted a prospective study to analyze the association of sdLDL particles with the outcome of balloon angioplasty in PAD. The composite primary endpoint was defined as improved walking distance and absence of restenosis. METHODS: Patients with angiographically documented PAD of the lower extremities who were scheduled for lower limb revascularization were consecutively recruited for the study. At baseline and at three month follow-up triglyceride, total cholesterol, LDL size and subclasses and HDL cholesterol and ankle-brachial index (ABI were measured. Three months after the intervention duplex sonography was performed to detect restenosis. RESULTS: Sixty-four patients (53% male with a mean age of 68.6±9.9 years were included. The proportion of small- dense LDL particles (class III and IV was significantly lower (33.1±11.0% vs. 39.4±12.1%, p = 0.038 in patients who reached the primary end-point compared with those who did not. Patients with improved walking distance and without restenosis had a significantly higher LDL size at baseline (26.6±1.1 nm vs. 26.1±1.1 nm, p = 0.046 and at follow-up (26.7±1.1 nm vs. 26.2±0.9 nm, p = 0.044 than patients without improvement. CONCLUSIONS: Small-dense LDL particles are associated with worse early outcome in patients undergoing percutaneous revascularization for symptomatic PAD.

  18. Value of low-density lipoprotein particle number and size as predictors of coronary artery disease in apparently healthy men and women : the EPIC-Norfolk Prospective Population Study

    NARCIS (Netherlands)

    El Harchaoui, Karim; van der Steeg, Wim A; Stroes, Erik S G; Kuivenhoven, Jan Albert; Otvos, James D; Wareham, Nicholas J; Hutten, Barbara A; Kastelein, John J P; Khaw, Kay-Tee; Boekholdt, S Matthijs

    2007-01-01

    OBJECTIVES: We assessed relations of low-density lipoprotein (LDL) particle number (LDL-P) and LDL particle size as measured by nuclear magnetic resonance spectroscopy with LDL cholesterol (LDL-C) and the risk of future coronary artery disease (CAD). BACKGROUND: Whereas LDL-C is an established risk

  19. 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

    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 5 and 1 h (p 5 h LpAII:B:C:D:E reciprocally declined from baseline (p

  20. 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

  1. [Lipoprotein receptors. Old acquaintances and newcomers].

    Science.gov (United States)

    Ducobu, J

    1997-02-01

    Lipoprotein receptors are plasma membrane proteins of high affinity which interact with circulating lipoprotein particles. The well characterized LDL receptor continues to be analysed and some new findings on its intracellular mechanisms of action have emerged. New lipoprotein receptors have recently been described: the chylomicron remnant receptor or LDL-related protein (LRP), the lipolysis stimulated receptor (LSR), the very low density lipoprotein receptor (VLDLR), the HDL receptor (HDLR) and the scavenger receptor (SR). The molecular details of the receptors will facilitate the development of new therapeutic means to improve receptor-mediated clearance of lipoproteins.

  2. 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...

  3. Aerosol preparation of intact lipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Ion mobility analysis of lipoproteins

    Science.gov (United States)

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

    2007-08-21

    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.

  5. High density lipoprotein (HDL) particles from end-stage renal disease patients are defective in promoting reverse cholesterol transport.

    Science.gov (United States)

    Anderson, Josephine L C; Gautier, Thomas; Nijstad, Niels; Tölle, Markus; Schuchardt, Mirjam; van der Giet, Markus; Tietge, Uwe J F

    2017-02-02

    Atherosclerotic cardiovascular disease (CVD) represents the largest cause of mortality in end-stage renal disease (ESRD). CVD in ESRD is not explained by classical CVD risk factors such as HDL cholesterol mass levels making functional alterations of lipoproteins conceivable. HDL functions in atheroprotection by promoting reverse cholesterol transport (RCT), comprising cholesterol efflux from macrophage foam cells, uptake into hepatocytes and final excretion into the feces. ESRD-HDL (n = 15) were compared to healthy control HDL (n = 15) for their capacity to promote in vitro (i) cholesterol efflux from THP-1 macrophage foam cells and (ii) SR-BI-mediated selective uptake into ldla[SR-BI] cells as well as (iii) in vivo RCT. Compared with HDL from controls, ESRD-HDL displayed a significant reduction in mediating cholesterol efflux (p HDL to promote RCT when infused into wild-type mice was significantly impaired (p HDL from healthy controls with hypochloric acid was able to fully mimic the impaired biological activities of ESRD-HDL. In conclusion, we demonstrate that HDL from ESRD patients is dysfunctional in key steps as well as overall RCT, likely due to oxidative modification.

  6. [The impact of a 14- day regular physical exercise regime on the concentration of the classes and subclasses of lipoprotein particles in young subjects with a sedentary lifestyle].

    Science.gov (United States)

    Sabaka, P; Dukát, A; Oravec, S; Mistríková, L; Baláž, D; Bendžala, M; Gašpar, L

    2013-10-01

    Recommendations from the cardiological professional companies working in the area of primary prevention of cardiovascular diseases put an emphasis on regular aerobic physical activity. Its positive effect on both cardiovascular and overall mortality has repea-tedly been proven by the observations of prospective and cross sectional epidemiological studies. One of the possible explanations of this positive effect is a change in the concentration of lipoprotein classes and their subclasses, which is expressed as a change in their average size. In a group of young healthy men and women with a sedentary lifestyle we observed the effect of medium intensive physical exercise in the form of a 30- minute slow run per day lasting for 14 days. The concentration of lipoprotein classes and subclasses were determined through the method of a linear electrophoresis in polyacrylamide gel. In the observed group we found a statistically significant decrease of VLDL, large IDL particles, medium sized LDL, small dense LDL, and medium sized HDL particles. In the light of current knowledge all these lipoprotein particles are deemed as atherogenic. Thus, as little as 14 days of regular exercising has a positive effect on the concentration of plasmatic lipoproteins, and emphasises the role of regular physical activity in the primary prevention of cardiovascular diseases.

  7. 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.

  8. Crystallography and refining mechanism of (Ti, B)-contained salts in pure aluminum

    Institute of Scientific and Technical Information of China (English)

    ZHANG Heng-hua

    2008-01-01

    It is shown from experiment that the pure B contained salt exhibits little refining effect, while the pure Ti contained salt, especially the salt containing 5Ti/1B, shows obvious refining effect on the pure aluminum. Crystallographic study indicates that Al3Ti particle is a more suitable nucleation site for the aluminum matrix than (Ti, Al)B2 type particles (TiB2, AlB2 and (Ti,Al)B2), because there exist more coherent planes with aluminum matrix in the former. Thermodynamics estimation, X-ray diffraction (XRD) and SEM detection show that the refining mechanism of (Ti, B)-contained refiners is mainly contributed to the heterogeneous nuclei of fine Al3Ti particles dispersed in the melting, which comes from the reaction between the Ti and aluminum. (Al, Ti)B2 type particle shows little or no direct refining effect, but it will reduce the size of Al3Ti since the Al3Ti nucleates and grows along the (Al, Ti)B2 type particle interface.

  9. Expression of the human apolipoprotein A-I gene in transgenic mice alters high density lipoprotein (HDL) particle size distribution and diminishes selective uptake of HDL cholesteryl esters

    Energy Technology Data Exchange (ETDEWEB)

    Chajekshaul, T.; Hayek, T.; Walsh, A.; Breslow, J.L. (Rockefeller University, New York, NY (USA))

    1991-08-01

    Transgenic mice carrying the human apolipoprotein (apo) A-I gene (HuAITg mice) were used to examine the effects of overexpression of the human gene on high density lipoprotein (HDL) particle size distribution and metabolism. On a chow diet, control mice had HDL cholesterol and apo A-I levels of 49 {plus minus} 2 and 137 {plus minus} 12 mg/dl of plasma, respectively. HuAITg mice had HDL cholesterol, human apo A-I, and mouse apo A-I levels of 88 {plus minus} 2, 255 {plus minus} 19, and 16 {plus minus} 2 mg/dl, respectively. Nondenaturing gradient gel electrophoresis revealed control mouse plasma HDL to be primarily monodisperse with a particle diameter of 10.2 nm, whereas HuAITg mouse plasma HDL was polydisperse with particles of diameter 11.4, 10.2, and 8.7 nm, which correspond in size to human HDL1, HDL2, and HDL3, respectively. In vivo turnover studies of HDL labeled with (3H)cholesteryl linoleyl ether and 125I-apo A-I were performed. In control animals, the fractional catabolic rate (FCR) for HDL cholesteryl ester was significantly more than the apo A-I FCR. In the HuAITg mice, the HDL cholesteryl ester FCR was the same as the apo A-I FCR. There were no significant differences between control and HuAITg animals in the sites of tissue removal of HDL cholesteryl ester, with the liver extracting most of the injected radioactivity. Control and HuAITg animals had comparable liver and intestinal cholesterol synthesis and LDL FCR. In conclusion, HuAITg mice have principally human and not mouse apo A-I in their plasma. This apparently causes a change in HDL particle size distribution in the transgenic mice to one resembling the human pattern. The replacement of mouse by human apo A-I also apparently causes the loss of the selective uptake pathway of HDL cholesteryl esters present in control mice.

  10. An increase in lipoprotein oxidation and endogenous lipid peroxides in serum of obese women.

    Science.gov (United States)

    Mutlu-Türkoğlu, U; Oztezcan, S; Telci, A; Orhan, Y; Aykaç-Toker, G; Sivas, A; Uysal, M

    2003-02-01

    Endogenous malondialdehyde and diene conjugate levels, the susceptibility of apolipoprotein B-containing lipoproteins to copper-induced lipid peroxidation, and antibody titer against oxidized low-density lipoproteins were increased, but serum antioxidant activity was unchanged in obese women. Serum cholesterol, low-density lipoproteincholesterol, and trigliceride levels were also elevated, but high-density lipoprotein-cholesterol levels remained unchanged in obese women. In vitro, oxidation of apolipoprotein B-containing lipoproteins and levels of antibody against oxidized low-density lipoprotein correlated with body mass index, serum total cholesterol, and low-density lipoproteincholesterol levels in obese women. These results indicate that obesity is associated with increases in endogenous lipid peroxides, oxidation of low-density lipoproteins, and lipids in serum.

  11. Lipoprotein apheresis for the treatment of elevated circulating levels of lipoprotein(a): a critical literature review

    Science.gov (United States)

    Franchini, Massimo; Capuzzo, Enrico; Liumbruno, Giancarlo M.

    2016-01-01

    Lipoprotein(a), which consists of a low-density lipoprotein (LDL) particle linked to an apolipoprotein(a) moiety, is currently considered an independent risk factor for cardiovascular disease due to its atherogenic (LDL-like) and prothrombotic (plasminogen-like) properties. The aim of this review is to provide an overview of the current and newer therapies for lowering increased lipoprotein(a) levels, focusing on lipoprotein apheresis. After a systematic literature search, we identified ten studies which, overall, documented that lipoprotein apheresis is effective in reducing increased lipoprotein(a) levels and cardiovascular events. PMID:26710351

  12. Lipoprotein Kinetics in Male Hemodialysis Patients Treated with Atorvastatin

    Science.gov (United States)

    Schwaiger, Johannes P.; Nakada, Yoshinobu; Berberich, Ramona; Ikewaki, Katsunori; Dieplinger, Benjamin; Zitt, Emanuel; Neyer, Ulrich; Salmhofer, Hermann; Kronenberg, Florian; Koenig, Paul

    2013-01-01

    Summary Background and objectives In vivo metabolism of atherogenic apolipoprotein B (apoB)–containing lipoproteins is severely impaired in patients undergoing hemodialysis (HD), resulting in markedly prolonged residence times of these particles. It is unclear whether treatment with statins improves LDL kinetics in HD patients as is known for the general population. Therefore, this kinetic study assessed apoB-containing lipoproteins in these patients. Design, setting, participants, & measurements Kinetic measures were analyzed with stable-isotope technology in six men undergoing HD before and after 3 months of daily administration of 10 mg of atorvastatin. Patients were 18–65 years of age, had LDL cholesterol levels between 90 and 200 mg/dl, and had been treated with HD for >6 months. They consumed a standardized isocaloric diet for 3 days before analysis. Fractional catabolic rates (FCRs) and production rates of very-low-density lipoprotein (VLDL)–apoB, intermediate-density lipoprotein–apoB, and LDL-apoB were determined using multicompartment modeling after plasma lipoprotein separation, precipitation of apoB, and determination of tracer-to-tracee ratios using mass spectrometry. Results Plasma concentrations of VLDL- and LDL-apoB were significantly lower (mean ± SD, 7.77±2.62 versus 11.27±6.15 mg/dl, P<0.05; 56.9±23.9 versus 84.0±21.1 mg/dl, P=0.03) and their FCRs were significantly higher (7.20±3.08 versus 5.20±2.98 days−1, P<0.05; 0.851±0.772 versus 0.446±0.232 days−1, P<0.05) after 3 months of atorvastatin treatment. Accordingly, the residence times in plasma of VLDL- and LDL-apoB were significantly lower after treatment (0.14 versus 0.19 day and 1.2 versus 2.2 days, respectively). Conclusion Lower plasma concentrations and improved kinetics of atherogenic lipoproteins were observed in HD patients after administration of low-dose atorvastatin. PMID:23599405

  13. 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...... of lipid transfer from the mother to the developing fetus....

  14. The pathophysiology of intestinal lipoprotein production

    Directory of Open Access Journals (Sweden)

    Antonina eGiammanco

    2015-03-01

    Full Text Available Intestinal lipoprotein production is a multistep process, essential for the absorption of dietary fats and fat-soluble vitamins. Chylomicron assembly begins in the endoplasmic reticulum with the formation of primordial, phospholipids-rich particles that are then transported to the Golgi for secretion. Several classes of transporters play a role in the selective uptake and/or export of lipids through the villus enterocytes. Once secreted in the lymph stream, triglyceride-rich lipoproteins (TRLs are metabolized by Lipoprotein lipase (LPL, which catalyzes the hydrolysis of triacylglycerols of very low density lipoproteins (VLDLs and chylomicrons, thereby delivering free fatty acids to various tissues. Genetic mutations in the genes codifying for these proteins are responsible of different inherited disorders affecting chylomicron metabolism.This review focuses on the molecular pathways that modulate the uptake and the transport of lipoproteins of intestinal origin and it will highlight recent findings on TRLs assembly.

  15. Green Tea Extract Improves the Postprandial Overproduction of Intestinal Apolipoprotein B-containing Lipoproteins in Fructose-Fed Hamsters

    Science.gov (United States)

    Green tea has putative medicinal properties that may be useful in preventing the metabolic syndrome since increased consumption of green tea extract (GTE) is associated with improved lipid and glucose homeostasis in human and animals. The acute effect of GTE on postprandial intestinal apoB48 product...

  16. Lipoprotein(a)

    DEFF Research Database (Denmark)

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

    2014-01-01

    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......(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

  17. 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...

  18. Glycosaminoglycan-lipoprotein interaction.

    Science.gov (United States)

    Olsson, U; Ostergren-Lundén, G; Moses, J

    2001-10-01

    Glycosaminoglycans (GAGs) bound to various proteoglycans (PGs) present in the cardiovascular system have been proposed to perform a wide range of functions. These include conferring viscoelastic properties; interacting with and modulating growth factors and enzymes; and as receptors and co-receptors in lipoprotein metabolism. Binding of apoB-100 lipoproteins, particularly low density lipoproteins (LDL), to GAGs of extracellular matrix PGs in arteries has been proposed to be an initiating event in development of atherosclerosis. This study was initiated with the aim of getting an overview of the binding patterns of different lipoprotein subclasses with individual GAG categories. We thus evaluated the interaction of lipoproteins with GAGs commonly found in the cardiovascular system using a gel mobility-shift assay developed for this purpose. The same procedure was used to measure lipoproteins binding to metabolically [(35)S]-labeled whole PGs prepared from three cell types, arterial smooth muscle cells, THP-1 macrophages and from HepG2 cells. The effect of GAG composition on PGs on lipoprotein binding was evaluated by enzymatic degradation of the carbohydrate chains. Heparan sulfate was found to bind beta very low density lipoproteins (beta-VLDL) and a chylomicron remnant model (beta-VLDL+apoE), but not LDL. Dermatan sulfate was found to bind LDL, but not beta-VLDL or the chylomicron remnant model. Chondroitin sulfate and heparin were found to bind all lipoproteins tested (LDL, beta-VLDL and beta-VLDL+apoE) although with different affinities. We can conclude that each lipoprotein subclass tested binds a specific assortment of the GAGs tested. The observations made contribute to the understanding of new and complex mechanisms by which carbohydrate and lipid metabolism may be linked.

  19. Pitavastatin versus Pravastatin in Reduction of Remnant Lipoprotein Cholesterol in Patients with Dyslipidemias.

    Science.gov (United States)

    Roever, Leonardo

    2016-05-01

    Remnant lipoproteins cholesterol are products of partially catabolized chylomicrons and very-low-density lipoprotein, from which some triglycerides have been removed. These particles are smaller and are believed to be strongly atherogenic. Elevated Remnant lipoproteins cholesterol levels were reported to be associated with endothelial dysfunction and atherosclerotic disease.

  20. Lipoprotein Receptors Redundantly Participate in Entry of Hepatitis C Virus.

    Directory of Open Access Journals (Sweden)

    Satomi Yamamoto

    2016-05-01

    Full Text Available Scavenger receptor class B type 1 (SR-B1 and low-density lipoprotein receptor (LDLR are known to be involved in entry of hepatitis C virus (HCV, but their precise roles and their interplay are not fully understood. In this study, deficiency of both SR-B1 and LDLR in Huh7 cells was shown to impair the entry of HCV more strongly than deficiency of either SR-B1 or LDLR alone. In addition, exogenous expression of not only SR-B1 and LDLR but also very low-density lipoprotein receptor (VLDLR rescued HCV entry in the SR-B1 and LDLR double-knockout cells, suggesting that VLDLR has similar roles in HCV entry. VLDLR is a lipoprotein receptor, but the level of its hepatic expression was lower than those of SR-B1 and LDLR. Moreover, expression of mutant lipoprotein receptors incapable of binding to or uptake of lipid resulted in no or slight enhancement of HCV entry in the double-knockout cells, suggesting that binding and/or uptake activities of lipid by lipoprotein receptors are essential for HCV entry. In addition, rescue of infectivity in the double-knockout cells by the expression of the lipoprotein receptors was not observed following infection with pseudotype particles bearing HCV envelope proteins produced in non-hepatic cells, suggesting that lipoproteins associated with HCV particles participate in the entry through their interaction with lipoprotein receptors. Buoyant density gradient analysis revealed that HCV utilizes these lipoprotein receptors in a manner dependent on the lipoproteins associated with HCV particles. Collectively, these results suggest that lipoprotein receptors redundantly participate in the entry of HCV.

  1. Lipoprotein Receptors Redundantly Participate in Entry of Hepatitis C Virus.

    Science.gov (United States)

    Yamamoto, Satomi; Fukuhara, Takasuke; Ono, Chikako; Uemura, Kentaro; Kawachi, Yukako; Shiokawa, Mai; Mori, Hiroyuki; Wada, Masami; Shima, Ryoichi; Okamoto, Toru; Hiraga, Nobuhiko; Suzuki, Ryosuke; Chayama, Kazuaki; Wakita, Takaji; Matsuura, Yoshiharu

    2016-05-01

    Scavenger receptor class B type 1 (SR-B1) and low-density lipoprotein receptor (LDLR) are known to be involved in entry of hepatitis C virus (HCV), but their precise roles and their interplay are not fully understood. In this study, deficiency of both SR-B1 and LDLR in Huh7 cells was shown to impair the entry of HCV more strongly than deficiency of either SR-B1 or LDLR alone. In addition, exogenous expression of not only SR-B1 and LDLR but also very low-density lipoprotein receptor (VLDLR) rescued HCV entry in the SR-B1 and LDLR double-knockout cells, suggesting that VLDLR has similar roles in HCV entry. VLDLR is a lipoprotein receptor, but the level of its hepatic expression was lower than those of SR-B1 and LDLR. Moreover, expression of mutant lipoprotein receptors incapable of binding to or uptake of lipid resulted in no or slight enhancement of HCV entry in the double-knockout cells, suggesting that binding and/or uptake activities of lipid by lipoprotein receptors are essential for HCV entry. In addition, rescue of infectivity in the double-knockout cells by the expression of the lipoprotein receptors was not observed following infection with pseudotype particles bearing HCV envelope proteins produced in non-hepatic cells, suggesting that lipoproteins associated with HCV particles participate in the entry through their interaction with lipoprotein receptors. Buoyant density gradient analysis revealed that HCV utilizes these lipoprotein receptors in a manner dependent on the lipoproteins associated with HCV particles. Collectively, these results suggest that lipoprotein receptors redundantly participate in the entry of HCV.

  2. Amphotericin B toxicity as related to the formation of oxidatively modified low-density lipoproteins.

    Science.gov (United States)

    Barwicz, J; Dumont, I; Ouellet, C; Gruda, I

    1998-01-01

    The effect of amphotericin B on the oxidation and degradation of low- and high-density lipoproteins was investigated by UV-vis spectroscopy, electron microscopy, electrophoresis, and size-exclusion chromatography. Two formulations of the drug were used: the commercial Fungizone and a new, less toxic, liposomal formulation, AmBisome. It was shown that Fungizone strongly enhanced the oxidative deformation of low-density lipoprotein structure while AmBisome did not bind to this lipoprotein fraction and did not affect its oxidation. It was shown that amphotericin B contained in Fungizone extracted cholesterol from low-density lipoproteins which sensitized them to oxidation. Both formulations of amphotericin B studied here did not bind to high-density lipoprotein and did not affect the process of its oxidation.

  3. The improvement of large High-Density Lipoprotein (HDL) particle levels, and presumably HDL metabolism, depend on effects of low-carbohydrate diet and weight loss

    Science.gov (United States)

    Finelli, C.; Crispino, P.; Gioia, S.; La Sala, N.; D'amico, L.; La Grotta, M.; Miro, O.; Colarusso, D.

    2016-01-01

    Depressed levels of atheroprotective large HDL particles are common in obesity and cardiovascular disease (CVD). Increases in large HDL particles are favourably associated with reduced CVD event risk and coronary plaque burden. The objective of the study is to compare the effectiveness of low-carbohydrate diets and weight loss for increasing blood levels of large HDL particles at 1 year. This study was performed by screening for body mass index (BMI) and metabolic syndrome in 160 consecutive subjects referred to our out-patient Metabolic Unit in South Italy. We administered dietary advice to four small groups rather than individually. A single team comprised of a dietitian and physician administered diet-specific advice to each group. Large HDL particles at baseline and 1 year were measured using two-dimensional gel electrophoresis. Dietary intake was assessed via 3-day diet records. Although 1-year weight loss did not differ between diet groups (mean 4.4 %), increases in large HDL particles paralleled the degree of carbohydrate restriction across the four diets (p<0.001 for trend). Regression analysis indicated that magnitude of carbohydrate restriction (percentage of calories as carbohydrate at 1 year) and weight loss were each independent predictors of 1-year increases in large HDL concentration. Changes in HDL cholesterol concentration were modestly correlated with changes in large HDL particle concentration (r=0.47, p=.001). In conclusion, reduction of excess dietary carbohydrate and body weight improved large HDL levels. Comparison trials with cardiovascular outcomes are needed to more fully evaluate these findings. PMID:27103896

  4. The improvement of large High-Density Lipoprotein (HDL) particle levels, and presumably HDL metabolism, depend on effects of low-carbohydrate diet and weight loss.

    Science.gov (United States)

    Finelli, C; Crispino, P; Gioia, S; La Sala, N; D'amico, L; La Grotta, M; Miro, O; Colarusso, D

    2016-01-01

    Depressed levels of atheroprotective large HDL particles are common in obesity and cardiovascular disease (CVD). Increases in large HDL particles are favourably associated with reduced CVD event risk and coronary plaque burden. The objective of the study is to compare the effectiveness of low-carbohydrate diets and weight loss for increasing blood levels of large HDL particles at 1 year. This study was performed by screening for body mass index (BMI) and metabolic syndrome in 160 consecutive subjects referred to our out-patient Metabolic Unit in South Italy. We administered dietary advice to four small groups rather than individually. A single team comprised of a dietitian and physician administered diet-specific advice to each group. Large HDL particles at baseline and 1 year were measured using two-dimensional gel electrophoresis. Dietary intake was assessed via 3-day diet records. Although 1-year weight loss did not differ between diet groups (mean 4.4 %), increases in large HDL particles paralleled the degree of carbohydrate restriction across the four diets (p<0.001 for trend). Regression analysis indicated that magnitude of carbohydrate restriction (percentage of calories as carbohydrate at 1 year) and weight loss were each independent predictors of 1-year increases in large HDL concentration. Changes in HDL cholesterol concentration were modestly correlated with changes in large HDL particle concentration (r=0.47, p=.001). In conclusion, reduction of excess dietary carbohydrate and body weight improved large HDL levels. Comparison trials with cardiovascular outcomes are needed to more fully evaluate these findings.

  5. GluN2B-containing NMDA receptors promote glutamate synapse development in hippocampal interneurons.

    Science.gov (United States)

    Kelsch, Wolfgang; Li, Zhijun; Wieland, Sebastian; Senkov, Oleg; Herb, Anne; Göngrich, Christina; Monyer, Hannah

    2014-11-26

    In postnatal development, GluN2B-containing NMDARs are critical for the functional maturation of glutamatergic synapses. GluN2B-containing NMDARs prevail until the second postnatal week when GluN2A subunits are progressively added, conferring mature properties to NMDARs. In cortical principal neurons, deletion of GluN2B results in an increase in functional AMPAR synapses, suggesting that GluN2B-containing NMDARs set a brake on glutamate synapse maturation. The function of GluN2B in the maturation of glutamatergic inputs to cortical interneurons is not known. To examine the function of GluN2B in interneurons, we generated mutant mice with conditional deletion of GluN2B in interneurons (GluN2B(ΔGAD67)). In GluN2B(ΔGAD67) mice interneurons distributed normally in cortical brain regions. After the second postnatal week, GluN2B(ΔGAD67) mice developed hippocampal seizures and died shortly thereafter. Before the onset of seizures, GluN2B-deficient hippocampal interneurons received fewer glutamatergic synaptic inputs than littermate controls, indicating that GluN2B-containing NMDARs positively regulate the maturation of glutamatergic input synapses in interneurons. These findings suggest that GluN2B-containing NMDARs keep the circuit activity under control by promoting the maturation of excitatory synapses in interneurons.

  6. Comparison of apoprotein B of low density lipoproteins of human interstitial fluid and plasma.

    Science.gov (United States)

    Hong, J L; Pflug, J; Reichl, D

    1984-08-15

    Virtually all apoprotein B (apoB)-containing lipoproteins of the peripheral interstitial fluid of subjects with primary lymphoedema float in the ultracentrifugal field in the density interval 1.019-1.063 g/ml; in this respect they are similar to plasma low-density lipoproteins (LDL). 2. Virtually all apo-B-containing lipoproteins of interstitial fluid migrate in the electrophoretic field with pre-beta mobility; in this respect they are similar to plasma very-low-density lipoproteins. 3. The apoB of lipoproteins of interstitial fluid does not differ in terms of Mr from apoB-100 of human plasma [Kane, Hardman & Paulus (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 2465-2469] as determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. 4. Both apoB of interstitial fluid and plasma are heterogenous in terms of their charge as determined by isoelectric focusing of their complexes with the nonionic detergent Nonidet P40. ApoB of plasma LDL focuses between pH5.9 and 6.65, and that of interstitial fluid LDL between pH 5.9 and 6.1. Thus the overall charge of apoB of interstitial fluid is more negative than that of its plasma LDL counterpart.

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

    OpenAIRE

    Manfredi Rizzo; Mikhailidis, Dimitri P.; Isenovic, Esma R.; Dragana Nikolic; Niki Katsiki; Giuseppe Montalto

    2013-01-01

    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) ...

  8. 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 correl...

  9. 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) are essentia...... of interfacial tension becomes significant for particles with a radius of similar to 5 nm, when the area per molecule in the surface region is...

  10. Lipoprotein metabolism indicators improve cardiovascular risk prediction

    NARCIS (Netherlands)

    Schalkwijk, D.B. van; Graaf, A.A. de; Tsivtsivadze, E.; Parnell, L.D.; Werff-van der Vat, B.J.C. van der; Ommen, B. van; Greef, J. van der; Ordovás, J.M.

    2014-01-01

    Background: Cardiovascular disease risk increases when lipoprotein metabolism is dysfunctional. We have developed a computational model able to derive indicators of lipoprotein production, lipolysis, and uptake processes from a single lipoprotein profile measurement. This is the first study to inves

  11. Congenital β-lipoprotein deficiency

    NARCIS (Netherlands)

    Buchem, F.S.P. van; Pol, G.; Gier, J. de; Böttcher, C.J.F.; Pries, C.

    1966-01-01

    There are several degrees of β-lipoprotein deficiency. If there is no β-lipoprotein present, or if there are only traces of it, the Bassen-Kornzweig syndrome develops. A constant feature of this syndrome is disturbed fat absorption with accumulation of fat in the epithelium of intestinal mucosa and

  12. Physiological regulation of lipoprotein lipase

    NARCIS (Netherlands)

    Kersten, A.H.

    2014-01-01

    The enzyme lipoprotein lipase (LPL), originally identified as the clearing factor lipase, hydrolyzes triglycerides present in the triglyceride-rich lipoproteins VLDL and chylomicrons. LPL is primarily expressed in tissues that oxidize or store fatty acids in large quantities such as the heart, skele

  13. 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 ...

  14. Should we change our lipid management strategies to focus on non-high-density lipoprotein cholesterol?

    NARCIS (Netherlands)

    J.S. Rana; S.M. Boekholdt

    2010-01-01

    Purpose of review Despite aggressive low-density lipoprotein cholesterol lowering, patients continue to be at significant risk of cardiovascular events. Assessment of non-high-density lipoprotein cholesterol (non-HDL-C) provides a measure of cholesterol contained in all atherogenic particles. In the

  15. Abnormal high density lipoproteins in cerebrotendinous xanthomatosis

    Energy Technology Data Exchange (ETDEWEB)

    Shore, V. (Lawrence Livermore Lab., CA); Salen, G.; Cheng, F.W.; Forte, T.; Shefer, S.; Tint, G.S.

    1981-11-01

    The plasma lipoprotein profiles and high density lipoproteins (HDL) were characterized in patients with the genetic disease cerebrotendinous xanthomatosis (CTX). The mean HDL-cholesterol concentration in the CTX plasmas was 14.5 +/- 3.2 mg/dl, about one-third the normal value. The low HDL-cholesterol reflects a low concentration and an abnormal lipid composition of the plasma HDL. Relative to normal HDL, the cholesteryl esters are low, free cholesterol and phospholipids essentially normal, and triglycerides increased. The ratio of apoprotein (apo) to total cholesterol in the HDL of CTX was two to three times greater than normal. In the CTX HDL, the ratio of apoAI to apoAII was high, the proportion of apoC low, and a normally minor form of apoAI increased relative to other forms. The HDL in electron micrographs appeared normal morphologically and in particle size. The adnormalities in lipoprotein distribution profiles and composition of the plasma HDL result from metabolic defects that are not understood but may be linked to the genetic defect in bile acid synthesis in CTX. As a consequence, it is probable that the normal functions of the HDL, possibly including modulation of LDL-cholesterol uptake and the removal of excess cholesterol from peripheral tissues, are perturbed significantly in this disease.

  16. Dissecting the proteome of lipoproteins: New biomarkers for cardiovascular diseases?

    Directory of Open Access Journals (Sweden)

    Anne von Zychlinski

    2015-06-01

    Full Text Available Proteomics has proven to be a powerful tool for the characterization of lipoproteins and has provided important insights into the biochemistry and pathophysiology of various lipoprotein classes. It has significantly contributed to the way we now see lipoproteins as complex particles not only involved in lipid transport and exchange, but also in processes such as immune response, inflammation and wound healing. Ongoing proteomics research is focussing on the identification of new candidate markers for cardiovascular disease, the leading cause of death worldwide. The ratio between good cholesterol (high density lipoprotein and bad cholesterol (low density lipoprotein is routinely used to estimate an individual’s risk for developing premature coronary heart disease. While statin therapy has proven effects in reducing cardiovascular events, other therapies such as resins, fibrates and niacin have failed to substantially reduce cardiovascular risk. Thus new targets and candidate biomarkers for risk assessment and for the development of alternative drugs and treatments of disease are needed. Here we review the recent findings in lipoprotein proteomics with the main emphasis on studies that differentially displayed various states of diseases and on new targeted, high throughput strategies with the capability to translate discovery findings into the clinical context of large cohort analyzes.

  17. New and emerging regulators of intestinal lipoprotein secretion.

    Science.gov (United States)

    Xiao, Changting; Dash, Satya; Morgantini, Cecilia; Lewis, Gary F

    2014-04-01

    Overproduction of hepatic apoB100-containing VLDL particles has been well documented in animal models and in humans with insulin resistance such as the metabolic syndrome and type 2 diabetes, and contributes to the typical dyslipidemia of these conditions. In addition, postprandial hyperlipidemia and elevated plasma concentrations of intestinal apoB48-containing chylomicron and chylomicron remnant particles have been demonstrated in insulin resistant states. Intestinal lipoprotein production is primarily determined by the amount of fat ingested and absorbed. Until approximately 10 years ago, however, relatively little attention was paid to the role of the intestine itself in regulating the production of triglyceride-rich lipoproteins (TRL) and its dysregulation in pathological states such as insulin resistance. We and others have shown that insulin resistant animal models and humans are characterized by overproduction of intestinal apoB48-containing lipoproteins. Whereas various factors are known to regulate hepatic lipoprotein particle production, less is known about factors that regulate the production of intestinal lipoprotein particles. Monosacharides, plasma free fatty acids (FFA), resveratrol, intestinal peptides (e.g. GLP-1 and GLP-2), and pancreatic hormones (e.g. insulin) have recently been shown to be important regulators of intestinal lipoprotein secretion. Available evidence in humans and animal models strongly supports the concept that the small intestine is not merely an absorptive organ but rather plays an active role in regulating the rate of production of chylomicrons in fed and fasting states. Metabolic signals in insulin resistance and type 2 diabetes and in some cases an aberrant intestinal response to these factors contribute to the enhanced formation and secretion of TRL. Understanding the regulation of intestinal lipoprotein production is imperative for the development of new therapeutic strategies for the prevention and treatment of

  18. Increased large VLDL particles confer elevated cholesteryl ester transfer in diabetes

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; de Vries, Rindert; Kwakernaak, Arjan J.; Perton, Frank; Dallinga-Thie, Geesje M.

    2015-01-01

    BackgroundPlasma cholesteryl ester transfer (CET), reflecting transfer of cholesteryl esters from high density lipoproteins (HDL) towards apolipoprotein B-containing lipoproteins, may promote atherosclerosis development, and is elevated in Type 2 diabetes mellitus (T2DM). We determined the extent to

  19. Characteristics of Lipoprotein Peak x Eluted from a Column with the Eluent of High-magnesium Ion Concentration in Lipoprotein Analysis Using the Cation-exchange Chromatography

    Directory of Open Access Journals (Sweden)

    Yuji Hirowatari

    2005-01-01

    Full Text Available The new lipoprotein analysis method using a cation-exchange chromatography, which contains a sulfopropyl-ligand column and two magnesium ion-containing eluents was previously reported. This method can separate serum lipoproteins on the column gel with a magnesium ion concentration gradient and high-density lipoprotein (HDL, low-density lipoprotein (LDL, very-low-density lipoprotein (VLDL and an unspecified lipoprotein peak are eluted in order from the column. We have now characterized the unspecified lipoproteins, designated peak x, which is last eluted from the column with the eluent of high-magnesium ion concentration. The peak x was small size chylomicron fraction with a part of VLDL. Furthermore, the cholesterol values in the peak x were significantly correlated with remnant-like particle (RLP-cholesterol values. The peak x separated from a hyperlipidemic patient included apolipoprotein B-100, B-48, E, A-1 and Cs (C-I, C-II, C-III and its composition of free cholesterol, cholesteryl esters, triglyceride (TG and phospholipids in total lipids were 6, 15, 66 and 13%, respectively. These results suggest that a major part of the lipoprotein peak X may be composed of remnants of chylomicron and VLDL, but it remains to be elucidated.

  20. Macrophage uptake of a lipoprotein-sequestered toxicant: a potential route of immunotoxicity.

    Science.gov (United States)

    Kaminski, N E; Wells, D S; Dauterman, W C; Roberts, J F; Guthrie, F E

    1986-03-15

    An experimental system was chosen to investigate the bioactivity of a lipoprotein-sequestered toxicant at the cellular level based on recent studies demonstrating receptor-mediated uptake of lipoproteins by macrophages. Rat peritoneal exudate cell suspensions (PEC) were exposed to DDT and lipoprotein-sequestered DDT, followed by measurement of DDT uptake, metabolism, and cellular toxicity. In vitro uptake assays demonstrated that PEC suspensions treated for 10, 20, and 30 min with 2.5 microM lipoprotein-sequestered DDT had approximately a twofold increase over the amount of DDT associated with PEC treated with 2.5 microM free DDT. PEC were assayed for DDT metabolites to serve as a measure of the cellular internalization of the toxicant after treatment in vitro for 18 hr with either 1.5 microM DDT or lipoprotein-sequestered DDT. Evidence of DDT metabolism was only observed with PEC which had been treated with lipoprotein-sequestered DDT. These cells contained significantly higher amounts of DDT metabolites as compared to cells treated with unsequestered DDT (over an eightfold difference). Assays measuring macrophage phagocytic activity indicated that macrophages treated for 4.5 hr in vitro with 2.5 microM lipoprotein-sequestered DDT showed significant inhibition in their ability to phagocytize yeast particles. These results suggest that serum lipoproteins may facilitate the cellular uptake of lipoprotein-sequestered toxicants leading to altered cellular function (phagocytosis).

  1. Hydrolysis of guinea pig nascent very low density lipoproteins catalyzed by lipoprotein lipase: activation by hjman apolipoprotein C-II.

    Science.gov (United States)

    Fitzharris, T J; Quinn, D M; Goh, E H; Johnson, J D; Kashyap, M L; Srivastava, L S; Jackson, R L; Harmony, J A

    1981-08-01

    Very low density lipoproteins isolated from guinea pig liver perfusate (VLDLp) lack the equivalent of human apolipoprotein C-II (apoC-II), the activator of lipoprotein lipase (LpL). These lipoproteins are therefore ideal substrates with which to investigate the mechanism by which apoC-II activates the enzyme. VLDLp binds apoC-II, and apoC-II associated with VLDLp markedly increases the rate of lipoprotein lipase-catalyzed hydrolysis of VLDLp-triglycerides. The activator potency of apoC-II is independent of the method of enrichment of VLDLp with apoC-II: delipidated human apoC-II and apoC-II transferred from human high density lipoproteins activate lipoprotein lipase to equal extents. ApoC-II causes pH-dependent changes in both apparent Km and VmaX of LpL-catalyzed hydrolysis of VLDLp-triglycerides. At pH l7.4--7.5, the major effects of apoC-II is to decrease the apparent Km by 3.3--4.0 fold. The apparent Vmax is increased 1.3-fold. At pH 6.5 and 8.5, the decrease of apparent Km is less marked, 1.6-fold and 1.4-fold, respectively. At pH 6.5, apoC-II increases the apparent Vmax ty 1.3-fold, while at pH 8.5 the primary effect of apoC-II is a 1.6-fold increase of apparent Vmax. Based on a simple kinetic model, the data suggest that apoC-II favors direct interaction between enzyme and triglyceride within the lipoprotein particle, as well as subsequent catalytic turnover.

  2. Classifying lipoproteins based on their polar profiles.

    Science.gov (United States)

    Polanco, Carlos; Castañón-González, Jorge Alberto; Buhse, Thomas; Uversky, Vladimir N; Amkie, Rafael Zonana

    2016-01-01

    The lipoproteins are an important group of cargo proteins known for their unique capability to transport lipids. By applying the Polarity index algorithm, which has a metric that only considers the polar profile of the linear sequences of the lipoprotein group, we obtained an analytical and structural differentiation of all the lipoproteins found in UniProt Database. Also, the functional groups of lipoproteins, and particularly of the set of lipoproteins relevant to atherosclerosis, were analyzed with the same method to reveal their structural preference, and the results of Polarity index analysis were verified by an alternate test, the Cumulative Distribution Function algorithm, applied to the same groups of lipoproteins.

  3. Tribological Behaviors of S,B-Containing Morpholine Derivatives as Additives in Rapeseed Oil

    Institute of Scientific and Technical Information of China (English)

    Fan Chengkai; Li Fenfang; Sheng Liping

    2008-01-01

    Two novel ashless and non-phosphorus S,B-containing morpholine derivatives,MBOC and MBOD,were prepared and their tribological behaviors in rapeseed oil (RSO) were evaluated using a four-ball tester.Thermal degradation tests were conducted to identify their thermal stabilities using a thermo-gravimetric analyzer.The worn surfaces of the steel balls were investigated by scanning electron microscopy (SEM).The results indicated that the additives possessed high thermal stabilities and good load-carrying capacities.Moreover,they both had good anti-wear and friction reducing property at a relatively high concentration (1.5 m%) and under all test loads.The resuits of XPS analyses illustrated that the prepared compounds as additives in RSO could form a protective film containing inorganic sulfide,sulfate,oxidized compounds and organic nitrogen-containing compounds on the metal surface during the sliding process.

  4. Plasma Lipoprotein-associated Phospholipase A(2) Is Inversely Correlated with Proprotein Convertase Subtilisin-kexin Type 9

    NARCIS (Netherlands)

    Constantinides, Alexander; Kappelle, Paul J.W.H.; Lambert, Gilles; Dullaart, Robin P. F.

    2012-01-01

    Background and Aims. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a proatherogenic phospholipase A(2), which is predominantly complexed to low-density lipoprotein (LDL) particles. Proprotein convertase subtilisin-kexin type 9 (PCSK9) provides a key step in LDL metabolism by stimulating L

  5. 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...... transformed) plasma insulin: beta=0.6 (95% CI: 0.1-1.1); R=0.22; P

  6. 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 iden

  7. 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...

  8. High-density lipoprotein cholesterol on a roller coaster: where will the ride end?

    Science.gov (United States)

    Kronenberg, Florian

    2016-04-01

    Bowe et al. report an association between low high-density lipoprotein cholesterol concentrations and various incident chronic kidney disease end points in a cohort of almost 2 million US veterans followed for 9 years. These impressive data should be a starting point for further investigations including genetic epidemiologic investigations as well as post hoc analyses of interventional trials that target high-density lipoprotein cholesterol and, finally, studies that focus on the functionality of high-density lipoprotein particles.

  9. Regulation of PINK1 by NR2B-containing NMDA receptors in ischemic neuronal injury.

    Science.gov (United States)

    Shan, Yuexin; Liu, Baosong; Li, Lijun; Chang, Ning; Li, Lei; Wang, Hanbin; Wang, Dianshi; Feng, Hua; Cheung, Carol; Liao, Mingxia; Cui, Tianyuan; Sugita, Shuzo; Wan, Qi

    2009-12-01

    Dysfunction of PTEN-induced kinase-1 (PINK1) is implicated in neurodegeneration. We report here that oxygen-glucose deprivation (OGD), an in vitro insult mimicking ischemic neuron injury, resulted in a significant reduction of PINK1 protein expression in cultured cortical neurons. The decrease of PINK1 expression was blocked by the antagonists of NMDA receptors. We revealed that the overactivation of NR2B-containing NMDA receptors (NR2BRs) was responsible for the OGD-induced PINK1 reduction. The overactivated NR2BRs also inhibited the phosphorylation, but not the protein expression, of the cell survival-promoting kinase Akt after OGD insult, indicating that OGD-induced reduction of PINK1 protein is specific in the injury paradigm. We further showed that enhancing the protein expression of PINK1 antagonized OGD-induced reduction of Akt phosphorylation, suggesting that Akt may be a downstream target of PINK1 in ischemic neuron injury. Importantly, we provided evidence that both NR2BR antagonist and PINK1 over-expression protected against OGD-induced neuronal death. These results suggest that the overactivation of NR2BRs may contribute to ischemic neuron death through suppressing PINK1-dependent survival signaling. Thus, selectively antagonizing NR2BR signal pathway-induced neurotoxicity may be a potential neuroprotection strategy.

  10. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. 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.

  13. A Novel Anti-Inflammatory Effect for High Density Lipoprotein.

    Directory of Open Access Journals (Sweden)

    Scott J Cameron

    Full Text Available High density lipoprotein has anti-inflammatory effects in addition to mediating reverse cholesterol transport. While many of the chronic anti-inflammatory effects of high density lipoprotein (HDL are attributed to changes in cell adhesion molecules, little is known about acute signal transduction events elicited by HDL in endothelial cells. We now show that high density lipoprotein decreases endothelial cell exocytosis, the first step in leukocyte trafficking. ApoA-I, a major apolipoprotein of HDL, mediates inhibition of endothelial cell exocytosis by interacting with endothelial scavenger receptor-BI which triggers an intracellular protective signaling cascade involving protein kinase C (PKC. Other apolipoproteins within the HDL particle have only modest effects upon endothelial exocytosis. Using a human primary culture of endothelial cells and murine apo-AI knockout mice, we show that apo-AI prevents endothelial cell exocytosis which limits leukocyte recruitment. These data suggest that high density lipoprotein may inhibit diseases associated with vascular inflammation in part by blocking endothelial exocytosis.

  14. 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.

  15. Nanobiotechnology applications of reconstituted high density lipoprotein.

    Science.gov (United States)

    Ryan, Robert O

    2010-12-01

    High-density lipoprotein (HDL) plays a fundamental role in the Reverse Cholesterol Transport pathway. Prior to maturation, nascent HDL exist as disk-shaped phospholipid bilayers whose perimeter is stabilized by amphipathic apolipoproteins. Methods have been developed to generate reconstituted (rHDL) in vitro and these particles have been used in a variety of novel ways. To differentiate between physiological HDL particles and non-natural rHDL that have been engineered to possess additional components/functions, the term nanodisk (ND) is used. In this review, various applications of ND technology are described, such as their use as miniature membranes for solubilization and characterization of integral membrane proteins in a native like conformation. In other work, ND harboring hydrophobic biomolecules/drugs have been generated and used as transport/delivery vehicles. In vitro and in vivo studies show that drug loaded ND are stable and possess potent biological activity. A third application of ND is their use as a platform for incorporation of amphiphilic chelators of contrast agents, such as gadolinium, used in magnetic resonance imaging. Thus, it is demonstrated that the basic building block of plasma HDL can be repurposed for alternate functions.

  16. 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.

  17. Kinetic studies of atherogenic lipoproteins in hemodialysis patients: do they tell us more about their pathology?

    Science.gov (United States)

    Kronenberg, Florian; Ikewaki, Katsunori; Schaefer, Juergen R; König, Paul; Dieplinger, Hans

    2007-01-01

    Patients with chronic kidney disease have one of the highest risks for atherosclerotic complications. Several large epidemiological studies described an opposite association of total and low density lipoprotein (LDL) cholesterol with cardiovascular complications and total mortality compared to the general population, a circumstance often called "reverse epidemiology." Many factors might contribute to this reversal such as interaction with malnutrition/inflammation, pronounced fluctuations of atherogenic lipoproteins during the course of renal disease, heterogeneity of lipoprotein particles with preponderance of remnant particles, and chemical modification of lipoproteins caused by the uremic environment. A vicious cycle has been suggested in uremia in which the decreased catabolism of atherogenic lipoproteins such as LDL, IDL and Lp(a) leads to their increased plasma residence time and further modification of these lipoproteins by oxidation, carbamylation, and glycation. Using stable isotope techniques, it has been shown recently that the plasma residence time of these particles is more than twice as long in hemodialysis patients as in nonuremic subjects. This reduced catabolism, however, is masked by the decreased production of LDL, resulting in near-normal plasma levels of LDL. The production rate of Lp(a) in hemodialysis patients is similar to that in controls which together with the doubled residence time results in elevated Lp(a) levels. An increased clearance of these altered lipoproteins via the scavenger receptors of macrophages leads to the transformation of macrophages into foam cells in the vascular wall and might contribute to the pronounced risk for cardiovascular complications of these patients. These observations suggest that the real danger of these particles is not reflected by the measured concentrations but by their metabolic qualities.

  18. Characterization of Lipoprotein Lipases interactions with Sortilin and SorLA

    DEFF Research Database (Denmark)

    Klinger, Stine Christensen

    fatty acids, which in turn are used as an energy source in muscle cells or as an energy reserve in adipose tissue. Lack of lipoprotein lipase leads to an elevated level of plasma lipids and results in increased risk of cardiovascular diseases. The regulation of lipoprotein lipase expression takes place...... at both transcriptional and posttranslational levels. While the transcriptional regulation of the lipase is well described, the posttranslational mechanisms affecting lipoprotein lipase expression are far from understood. The functions of the recently discovered apolipoprotein A-V are still a subject...... of discussion. Apolipoprotein A-V is a component of circulating lipoprotein particles. It is only synthesized in the liver, and plasma levels are very low compared to other apolipoproteins. Apolipoprotein A-V expression is inversely correlated to plasma triglyceride level, and a number of models have been...

  19. 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.

  20. 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.

  1. 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

  2. Transport of phytanic acid on lipoproteins in Refsum disease.

    Science.gov (United States)

    Wierzbicki, A S; Sankaralingam, A; Lumb, P J; Hardman, T C; Sidey, M C; Gibberd, F B

    1999-02-01

    Patients with Refsum disease accumulate significant quantities of phytanic acid in adipose and neural tissue. The accumulation can be reversed by following a diet low in phytanic acid, yet the mechanism of transport of this fatty acid is obscure. We investigated the distribution of phytanic acid in different lipoprotein subfractions in 11 patients with Refsum disease and 9 unaffected siblings. Plasma phytanic acid was distributed on VLDL (16.2% +/- 12.2%), IDL (1.77% +/- 1.64%), LDL (34.8% +/- 12.6%) and HDL (14.3% +/- 7.87%). No correlations with any parameter were seen with total phytanic acid content. Weak nonsignificant correlations were found with the fractional distribution of phytanic acid and VLDL triglyceride (r = 0.35; p = 0.12) and plasma HDL-cholesterol (r = 0.32; p = 0.16) and with LDL:HDL cholesterol ratio (r = 0.33; p = 0.14). Significant correlation of the fractional distribution of phytanic acid on lipoprotein particles was noted with the ratio of apolipoprotein B: apolipoprotein A1-containing particles (r = 0.46; p = 0.03) and apolipoprotein B: apolipoprotein A1 in HDL2 (r = 0.53; p = 0.01). This suggests that the import-export balance for phytanic acid in plasma is related to forward and reverse cholesterol transport on lipoprotein particles, and only weakly to plasma cholesterol and triglycerides. These ratios of apolipoprotein particles may play a significant role in determining the rate of phytanic acid elimination in patients with Refsum disease.

  3. Hepatitis C Virus, Cholesterol and Lipoproteins — Impact for the Viral Life Cycle and Pathogenesis of Liver Disease

    Directory of Open Access Journals (Sweden)

    Thomas F. Baumert

    2013-05-01

    Full Text Available Hepatitis C virus (HCV is a leading cause of chronic liver disease, including chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatitis C infection associates with lipid and lipoprotein metabolism disorders such as hepatic steatosis, hypobetalipoproteinemia, and hypocholesterolemia. Furthermore, virus production is dependent on hepatic very-low-density lipoprotein (VLDL assembly, and circulating virions are physically associated with lipoproteins in complexes termed lipoviral particles. Evidence has indicated several functional roles for the formation of these complexes, including co-opting of lipoprotein receptors for attachment and entry, concealing epitopes to facilitate immune escape, and hijacking host factors for HCV maturation and secretion. Here, we review the evidence surrounding pathogenesis of the hepatitis C infection regarding lipoprotein engagement, cholesterol and triglyceride regulation, and the molecular mechanisms underlying these effects.

  4. Systemic Inflammatory Markers Are Closely Associated with Atherogenic Lipoprotein Subfractions in Patients Undergoing Coronary Angiography

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2015-01-01

    Full Text Available Objective. To investigate the relationship between inflammatory markers and atherogenic lipoprotein subfractions. Methods. We studied 520 eligible subjects who were not receiving any lipid-lowering therapy. The inflammatory markers including white blood cell (WBC count, high-sensitivity C-reactive protein (hs-CRP, fibrinogen, erythrocyte sedimentation rate (ESR, and D-dimer were measured. A multimarker inflammatory index was developed. Low-density lipoprotein (LDL and high-density lipoprotein (HDL separation processes were performed using Lipoprint System. Results. In age- and sex-adjusted analysis, several inflammatory markers (WBC count, hs-CRP, fibrinogen, and ESR were positively related to circulating non-HDL cholesterol and remnant cholesterol (p<0.05, all. Among lipoprotein subfractions, we observed a positive association of inflammatory markers with very low-density lipoprotein cholesterol, small LDL cholesterol, and LDL score (p<0.05, all. Meanwhile, a negative association was detected between inflammatory markers and mean LDL particle size (p<0.05 or large HDL cholesterol (p<0.05. Moreover, we found that the relationships between multimarker index quartiles and small LDL cholesterol, LDL score, and mean LDL particle size were slightly stronger in patients with CAD. Conclusions. Systemic inflammatory markers are positively correlated with small LDL cholesterol and LDL score while being negatively linked with mean LDL particle size and large HDL cholesterol, highlighting the potential contribution to increased cardiovascular risk.

  5. Diagnostic markers based on a computational model of lipoprotein metabolism

    NARCIS (Netherlands)

    Schalkwijk, D.B. van; Ommen, B. van; Freidig, A.P.; Greef, J. van der; Graaf, A.A. de

    2011-01-01

    Abstract Background: Dyslipidemia is an important risk factor for cardiovascular disease and type II diabetes. Lipoprotein diagnostics, such as LDL cholesterol and HDL cholesterol, help to diagnose these diseases. Lipoprotein profile measurements could improve lipoprotein diagnostics, but interpreta

  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. Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism

    Directory of Open Access Journals (Sweden)

    Sander Kersten

    2008-01-01

    Full Text Available 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 mediates the effect of dietary fatty acids and certain drugs on plasma lipoproteins are the peroxisome proliferator activated receptors (PPARs. Three PPAR isotypes can be distinguished, all of which have a major role in regulating lipoprotein metabolism. PPARα is the molecular target for the fibrate class of drugs. Activation of PPARα in mice and humans markedly reduces hepatic triglyceride production and promotes plasma triglyceride clearance, leading to a clinically significant reduction in plasma triglyceride levels. In addition, plasma high-density lipoprotein (HDL-cholesterol levels are increased upon PPARα activation in humans. PPARγ is the molecular target for the thiazolidinedione class of drugs. Activation of PPARγ in mice and human is generally associated with a modest increase in plasma HDL-cholesterol and a decrease in plasma triglycerides. The latter effect is caused by an increase in lipoprotein lipase-dependent plasma triglyceride clearance. Analogous to PPARα, activation of PPARβ/δ leads to increased plasma HDL-cholesterol and decreased plasma triglyceride levels. In this paper, a fresh perspective on the relation between PPARs and lipoprotein metabolism is presented. The emphasis is on the physiological role of PPARs and the mechanisms underlying the effect of synthetic PPAR agonists on plasma lipoprotein levels.

  8. Ethanol-withdrawal seizures are controlled by tissue plasminogen activator via modulation of NR2B-containing NMDA receptors.

    Science.gov (United States)

    Pawlak, Robert; Melchor, Jerry P; Matys, Tomasz; Skrzypiec, Anna E; Strickland, Sidney

    2005-01-11

    Chronic ethanol abuse causes up-regulation of NMDA receptors, which underlies seizures and brain damage upon ethanol withdrawal (EW). Here we show that tissue-plasminogen activator (tPA), a protease implicated in neuronal plasticity and seizures, is induced in the limbic system by chronic ethanol consumption, temporally coinciding with up-regulation of NMDA receptors. tPA interacts with NR2B-containing NMDA receptors and is required for up-regulation of the NR2B subunit in response to ethanol. As a consequence, tPA-deficient mice have reduced NR2B, extracellular signal-regulated kinase 1/2 phosphorylation, and seizures after EW. tPA-mediated facilitation of EW seizures is abolished by NR2B-specific NMDA antagonist ifenprodil. These results indicate that tPA mediates the development of physical dependence on ethanol by regulating NR2B-containing NMDA receptors.

  9. Mechanisms responsible for hepatic very low density lipoprotein-apoB100 overproduction in Otsuka Long-Evans Tokushima fatty rats

    Science.gov (United States)

    Overproduction of hepatic very low-density lipoprotein (VLDL)1 particles is a major abnormality of lipoprotein dysregulation in type 2 diabetes (T2D). We sought to examine the mechanisms linking systemic/hepatic inflammation associated with insulin resistance and apolipoprotein (apo) B100-containing...

  10. The iron-regulated staphylococcal lipoproteins

    Directory of Open Access Journals (Sweden)

    Jessica eSheldon

    2012-04-01

    Full Text Available Lipoproteins fulfill diverse roles in antibiotic resistance, adhesion, protein secretion, signaling and sensing, and many also serve as the substrate binding protein (SBP partner to ABC transporters for the acquisition of a diverse array of nutrients including peptides, sugars, and scarcely abundant metals. In the staphylococci, the iron-regulated SBPs are significantly upregulated during iron starvation and function to sequester and deliver iron into the bacterial cell, enabling staphylococci to circumvent iron restriction imposed by the host environment. Accordingly, this subset of lipoproteins has been implicated in staphylococcal pathogenesis and virulence. Lipoproteins also activate the host innate immune response, triggered through Toll-like receptor-2 (TLR2 and, notably, the iron-regulated subset of lipoproteins are particularly immunogenic. In this review, we discuss the iron-regulated staphylococcal lipoproteins with regard to their biogenesis, substrate specificity, and impact on the host innate immune response.

  11. 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.

  12. Chronic consumers of boiled coffee have elevated serum levels of lipoprotein(a).

    NARCIS (Netherlands)

    Urgert, R.; Weusten-van der Wouw, M.P.M.E.; Hovenier, R.; Lund-Larsen, P.G.; Katan, M.B.

    1996-01-01

    OBJECTIVES: Lipoprotein(a) consists of an LDL-particle attached to apolipoprotein(a), which is made by the liver. Diterpenes present in boiled coffee raise serum levels of LDL cholesterol and of the liver enzyme alanine aminotransferase in man. We investigated the association between intake of boile

  13. 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 known to decrease cholester

  14. Understanding Lipoproteins as Transporters of Cholesterol and Other Lipids

    Science.gov (United States)

    Biggerstaff, Kyle D.; Wooten, Joshua S.

    2004-01-01

    A clear picture of lipoprotein metabolism is essential for understanding the pathophysiology of atherosclerosis. Many students are taught that low-density lipoprotein-cholesterol is "bad" and high-density lipoprotein-cholesterol is "good." This misconception leads to students thinking that lipoproteins are types of cholesterol rather than…

  15. Computational models for analyzing lipoprotein profiles

    NARCIS (Netherlands)

    Graaf, A.A. de; Schalkwijk, D.B. van

    2011-01-01

    At present, several measurement technologies are available for generating highly detailed concentration-size profiles of lipoproteins, offering increased diagnostic potential. Computational models are useful in aiding the interpretation of these complex datasets and making the data more accessible f

  16. 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)....

  17. 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...... of such genetic determinants with cardiovascular disease risk will either favor or disfavor that these lipoproteins are causally related to cardiovascular disease....

  18. Low density lipoproteins as circulating fast temperature sensors.

    Directory of Open Access Journals (Sweden)

    Ruth Prassl

    Full Text Available BACKGROUND: The potential physiological significance of the nanophase transition of neutral lipids in the core of low density lipoprotein (LDL particles is dependent on whether the rate is fast enough to integrate small (+/-2 degrees C temperature changes in the blood circulation. METHODOLOGY/PRINCIPAL FINDINGS: Using sub-second, time-resolved small-angle X-ray scattering technology with synchrotron radiation, we have monitored the dynamics of structural changes within LDL, which were triggered by temperature-jumps and -drops, respectively. Our findings reveal that the melting transition is complete within less than 10 milliseconds. The freezing transition proceeds slowly with a half-time of approximately two seconds. Thus, the time period over which LDL particles reside in cooler regions of the body readily facilitates structural reorientation of the apolar core lipids. CONCLUSIONS/SIGNIFICANCE: Low density lipoproteins, the biological nanoparticles responsible for the transport of cholesterol in blood, are shown to act as intrinsic nano-thermometers, which can follow the periodic temperature changes during blood circulation. Our results demonstrate that the lipid core in LDL changes from a liquid crystalline to an oily state within fractions of seconds. This may, through the coupling to the protein structure of LDL, have important repercussions on current theories of the role of LDL in the pathogenesis of atherosclerosis.

  19. Cytisine confers neuronal protection against excitotoxic injury by down-regulating GluN2B-containing NMDA receptors.

    Science.gov (United States)

    Li, Yu-Jiao; Yang, Qi; Zhang, Kun; Guo, Yan-Yan; Li, Xu-Bo; Yang, Le; Zhao, Ming-Gao; Wu, Yu-Mei

    2013-01-01

    Cytisine (CYT), one of the principal bioactive components derived from the seeds of Cytisus laborinum L, has been widely used for central nervous system (CNS) diseases treatment. The present study investigated the protective effect of CYT on cultured cortical neural injury induced by N-methyl-d-aspartate (NMDA). Our data showed that CYT conferred protective effect against loss of cellular viability induced by brief exposure to 200 μM NMDA in a concentration-dependent manner. CYT significantly inhibited the neuronal apoptosis induced by NMDA exposure by reversing intracellular Ca(2+) overload and balancing Bcl-2 and Bax expression levels. Furthermore, CYT significantly reversed the up-regulation of GluN2B-containing NMDA receptors by exposure to NMDA, but it did not affect the level of GluN2A-containing NMDA receptors. These findings suggest that CYT protects cortical neurons, at least partially, by inhibiting the level of GluN2B-containing NMDA receptors and regulating Bcl-2 family.

  20. 新一代脂蛋白(a)颗粒单位检测法的性能评价及临床应用%A new generation of lipoprotein(a)in clinical application and performance evaluation method for the detection of particles per unit

    Institute of Scientific and Technical Information of China (English)

    戴婉如; 周欢; 伍严安

    2015-01-01

    目的:评价利用国际临床化学和试验医学联合会(IFCC)国际参考试剂(SRM2B)标准化的颗粒单位检测法检测脂蛋白(a)[Lp(a)]及临床意义。方法评价以nmol/L表示Lp(a)微粒总数量试剂盒的精密度、线性、临床可报告范围、参考区间等指标,并与以mg/L表示Lp(a)总质量的试剂盒进行比较。同时检测受试者血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、尿素(UREA)、肌酐(CREA)、三酰甘油(TG)、总胆固醇(CHOL)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平,分析LP(a)与上述指标间的相关性。结果该方法批内和批间精密度分别小于1.5%和2.0%;在0.6~236.0 nmol/L范围内线性良好(r2=0.9962),可报告范围为7~720 nmol/L ,健康人群的参考范围小于75 nmol/L ;与以mg/L表示Lp(a)浓度的试剂盒相关性良好。Lp(a)与ALT、AST、TBIL、UREA、CERA、TG、CHOL、HDL-C、LDL-C的相关系数分别为-0.120、-0.091、-0.372、-0.096、-0.087、0.056、0.263、0.226、0.159。结论该检测方法分析性能良好,不受血清ALT、AST、UREA、CERA、TG、HDL-C、LDL-C水平的影响,与血清中TBIL、CHOL水平有关。可溯源至IFCC国际参考方法及参考物质(SRM2B),不受Lp(a)多态性的影响,真实检测Lp(a)颗粒数,以nmol/L准确表示Lp(a)蛋白水平,帮助临床评估心血管疾病风险,增加不同临床研究数据间的可比性。%Objective To evaluate the clinical significance of the International Federation of Clinical Chemistry and Laboratory Medicine international(IFCC) reference reagent(SRM2B) standardized ,particles unit method in detecting the lipoprotein(a)[Lp (a)] .Methods Precision ,linearity ,clinical reportable range ,reference interval index of total number

  1. 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...... 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.......03) versus controls (1.8 +/- 0.05%). In the setting of low density lipoprotein receptor deficiency, apoM-Tg mice with approximately 2-fold increased plasma apoM concentrations developed smaller atherosclerotic lesions than controls. The effect of apoM on atherosclerosis may be facilitated by enzymatic...

  2. Subfractions of high-density lipoprotein (HDL) and dysfunctional HDL in chronic kidney disease patients.

    Science.gov (United States)

    Rysz-Górzyńska, Magdalena; Banach, Maciej

    2016-08-01

    A number of studies have shown that chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease (CVD). Chronic kidney disease is characterized by significant disturbances in lipoprotein metabolism, including differences in quantitative and qualitative content of high-density lipoprotein (HDL) particles. Recent studies have revealed that serum HDL cholesterol levels do not predict CVD in CKD patients; thus CKD-induced modifications in high-density lipoprotein (HDL) may be responsible for the increase in CV risk in CKD patients. Various methods are available to separate several subclasses of HDL and confirm their atheroprotective properties. However, under pathological conditions associated with inflammation and oxidation, HDL can progressively lose normal biological activities and be converted into dysfunctional HDL. In this review, we highlight the current state of knowledge on subfractions of HDL and HDL dysfunction in CKD.

  3. 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.

  4. A case of alcoholic liver injury with an unusual polyacrylamide-gel disc-electrophoretic pattern of serum lipoproteins.

    Directory of Open Access Journals (Sweden)

    Watanabe,Makoto

    1979-06-01

    Full Text Available An unusual lipoprotein pattern on polyacrylamide-gel disc-electrophoresis was observed in 37 year-old male diagnosed as alcoholic liver injury. The electrophoretic lipoprotein pattern consisted of a major band of pre-beta mobility and minor intermediate, fast-beta and slow-alpha bands. The normal beta band was virtually absent and the alpha band was diminished. The abnormal lipoprotein pattern was observed one week after discontinuing alcohol consumption when marked hypertriglyceridemia demonstrated earlier had already normalized leaving a moderate hypercholesterolemia with reduced esterified cholesterol and abnormal liver function tests. The lipoprotein abnormalities were completely normal one month later. The appearance of a major pre-beta band with normal triglyceride and high cholesterol levels is discussed in relation to the formation of larger triglyceride-rich LDL particles in recovery from alcoholic hepatitis.

  5. Effect of Food Status on the Gastrointestinal Transit of Amphotericin B-Containing Solid Lipid Nanoparticles in Rats.

    Science.gov (United States)

    Amekyeh, Hilda; Billa, Nashiru; Yuen, Kah-Hay; Lim, Sheau Chin Sherlyn

    2016-10-01

    Amphotericin B (AmB) is poorly absorbed from the gastrointestinal tract. Recent studies have suggested enhanced drug absorption from solid lipid nanoparticles (SLN). Little is known of the fate of AmB absorption within the gastrointestinal tract, and no gastrointestinal transit study has yet been performed on AmB-containing nano-formulations. We aimed to investigate the effect of food on the gastrointestinal transit properties of an AmB-containing SLN in rats. Three SLNs containing AmB, paracetamol, or sulfasalazine were formulated using cocoa butter and beeswax as lipid matrices and simultaneously administered orally to Sprague-Dawley rats. Paracetamol and sulfapyridine were used as marker drugs for estimating gastric emptying and cecal arrival, respectively. The pharmacokinetic data generated for paracetamol and sulfapyridine were used in estimating the absorption of the AmB SLNs in the small and large intestines, respectively. A delayed rate of AmB absorption was observed in the fed state; however, the extent of absorption was not affected by food. Specifically, the percentages of AmB absorption during the fasted state in the stomach, small intestine, and colon were not significantly different from absorption within the respective regions in the fed state. In both states, however, absorption was highest in the colon and appeared to be a combination of absorption from the small intestine plus absorption proper within the colon. The study suggests that AmB SLN, irrespective of food status, is slowly but predominantly taken up by the lymph, making the small intestine the most favorable site for the delivery of the AmB SLNs.

  6. Quantitative comparison of lipoprotein fractions derived from human plasma and serum by liquid chromatography-tandem mass spectrometry

    Directory of Open Access Journals (Sweden)

    Collins Lisamarie A

    2010-07-01

    Full Text Available Abstract Background Lipoproteins are complex, globular molecules which play essential roles in the transport and metabolism of cholesterol. Their implication in the development of cardiovascular diseases, such as atherosclerosis, has sustained a great deal of interest in these particles. Their various functions, and their contribution to the development of atherosclerosis, are often attributed to their protein constituents, which vary greatly among the different lipoprotein classes. Recent advances in the field of mass spectrometry have provided insight into the array of proteins associated with low-density lipoproteins (LDLs and, even more so, with high-density lipoproteins (HDLs. Plasma and serum are the most commonly used samples for the analysis of lipoproteins. Although these lipoprotein sources are unique, it was our goal to determine whether or not their inherent differences would ultimately affect a quantitative analysis of the LDL and HDL proteomes. To this end, we isolated LDL and HDL fractions with fast protein liquid chromatography-size exclusion chromatography (FPLC-SEC from both human plasma and serum samples from the same individuals. After delipidating these samples, we performed a quantitative proteomic analysis to compare the lipoprotein-associated proteins derived from both plasma and serum. Results Although the primary differences between the samples are found in fibrinogen proteins which are removed from serum, it of interest to note that, with respect to LDL-associated proteins, apolipoproteinB-100 was found at significantly higher levels in serum samples. Complement component 3 was found at significantly higher levels in serum-derived HDL fractions. Both of these proteins are known LDL- and HDL-associated proteins, respectively. Conclusion Overall, the results from our study indicate that both plasma and serum samples are equally suited for proteomic studies, and provide similar results. These findings are particularly

  7. 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.

  8. High-density lipoprotein particles, coronary heart disease, and niacin

    Science.gov (United States)

    In clinical trials, the use of statins in patients with high risk for cardiovascular disease (CVD) has resulted in a 25% to 40% decrease in major clinical events. However, despite a marked reduction (up to 60%) in LDL-C, approximately 50% (or more) of patients continue to have CVD events. This high ...

  9. Hedgehog turns lipoproteins into janus-faced particles

    NARCIS (Netherlands)

    Bijlsma, Maarten F.; Spek, C. Arnold; Peppelenbosch, Maikel P.

    2006-01-01

    Hedgehog is an important morphogenetic signal during embryonic development. The molecule contains several hydrophobic moieties, including cholesterol and palmitoyl groups, apparently incompatible with long-range functioning. Very recent research, however, performed in the fruitfly Drosophila melanog

  10. 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...

  11. Increased transvascular lipoprotein transport in diabetes

    DEFF Research Database (Denmark)

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

    2005-01-01

    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......, possibly explaining increased intimal lipoprotein accumulation and thus atherosclerosis. DESIGN: The study was cross-sectional and was performed in 1999-2002. SETTING: The study took place in the referral center. PATIENTS: The patients included 60 with diabetes mellitus (27 with type 1 diabetes and 33...... 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...

  12. Immune response to lipoproteins in atherosclerosis.

    Science.gov (United States)

    Samson, Sonia; Mundkur, Lakshmi; Kakkar, Vijay V

    2012-01-01

    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.

  13. 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.

  14. Characterization of Lipoprotein Composition and Function in Pediatric Psoriasis Reveals a More Atherogenic Profile.

    Science.gov (United States)

    Tom, Wynnis L; Playford, Martin P; Admani, Shehla; Natarajan, Balaji; Joshi, Aditya A; Eichenfield, Lawrence F; Mehta, Nehal N

    2016-01-01

    Psoriasis is associated with increased cardiovascular disease in adults, but the risk profile of children with psoriasis remains to be fully characterized. We measured lipoprotein composition and function in 44 patients with pediatric psoriasis and 44 age- and sex-matched healthy controls, using nuclear magnetic resonance spectroscopy and a validated ex vivo assay of high-density lipoprotein cholesterol efflux capacity. The mean age of the patients was 13 years and the population was ethnically diverse. Children with psoriasis had higher waist-to-hip ratios (0.85 vs. 0.80; P psoriasis was associated with higher apolipoprotein B concentrations (72.4 vs. 64.6; P = 0.02), decreased large high-density lipoprotein particles (5.3 vs. 6.7; P psoriasis have a more atherogenic cardiometabolic risk profile, with evidence of insulin resistance and lipoprotein dysfunction by particle size, number, and functional assessment. These findings may provide a basis for the observed link later in life between psoriasis and cardiovascular disease, and support the need to screen and educate young patients to minimize later complications.

  15. 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 of such gene......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...

  16. SELDI-TOF mass spectrometry of High-Density Lipoprotein

    Directory of Open Access Journals (Sweden)

    Rezaee Farhad

    2007-09-01

    Full Text Available Abstract Background High-Density Lipoprotein (HDL, one of the main plasma lipoproteins, serves as a docking station for proteins involved in inflammation, coagulation, and lipid metabolism. Methods To elucidate the protein composition of HDL, we employed SELDI-TOF mass spectrometry as a potential high-throughput proteomic candidate for protein profiling of HDL. HDL derived from normolipemic individuals was captured on PS20 protein-chips using covalently bound antibodies against apo A-I or A-II. Results After optimisation, on-chip capture of HDL particles directly from plasma or from pre-purified HDL resulted in comparable fingerprints confirming specific capture of HDL. Depending on the capture antibody some differences in the fingerprint were observed. The most detailed fingerprint was observed up to 50 kDa; approximately 95 peaks were detected in the 3–50 kDa molecular mass range. Between 50 and 160 kDa, 27 more peaks were detected. Conclusion Based on these results, SELDI-TOF MS may be a suitable high-throughput candidate for HDL protein profiling and marker search. This approach may be used to i investigate the underlying mechanisms that lead to increased atherothrombotic risk and ii to investigate the atherothrombotic state of an individual.

  17. 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.

  18. Are post-treatment low-density lipoprotein subclass pattern analyses potentially misleading?

    Directory of Open Access Journals (Sweden)

    Hanson Mary E

    2010-11-01

    Full Text Available Abstract Background Some patients administered cholesterol-lowering therapies may experience an increase in the proportion of small LDL particles, which may be misinterpreted as a worsening of atherosclerotic coronary heart disease risk. This study assessed the lipid effects of adding ezetimibe to atorvastatin or doubling the atorvastatin dose on low-density lipoprotein cholesterol (LDL-C levels (and the cholesterol content of LDL subclasses, LDL particle number (approximated by apolipoprotein B, and LDL particle size. This was a multicenter, double-blind, randomized, parallel-group study of hypercholesterolemic, high atherosclerotic coronary heart disease risk patients. After stabilization of atorvastatin 40 mg, 579 patients with LDL-C >70 mg/dL were randomized to 6 weeks of ezetimibe + atorvastatin 40 mg or atorvastatin 80 mg. Efficacy parameters included changes from baseline in LDL-C, apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C, and lipoprotein subclasses (Vertical Auto Profile II and pattern for the overall population, as well as patient subgroups with baseline triglyceride levels Results Both treatments significantly reduced LDL-C (and the cholesterol content of most LDL subfractions [LDL1-4] apolipoprotein B, non-HDL-C levels, but did not reduce the proportion of smaller, more dense LDL particles; in fact, the proportion of Pattern B was numerically increased. Results were generally similar in patients with triglyceride levels Conclusions When assessing the effects of escalating cholesterol-lowering therapy, effects upon Pattern B alone to assess coronary heart disease risk may be misleading when interpreted without considerations of other lipid effects, such as reductions in LDL-C, atherogenic lipoprotein particle concentration, and non-HDL-C levels. Trial Registration (Registered at clinicaltrials.gov: Clinical trial # NCT00276484

  19. Intestinal SR-BI is upregulated in insulin-resistant states and is associated with overproduction of intestinal apoB48-containing lipoproteins.

    Science.gov (United States)

    Hayashi, Amanda A; Webb, Jennifer; Choi, Joanna; Baker, Chris; Lino, Marsel; Trigatti, Bernardo; Trajcevski, Karin E; Hawke, Thomas J; Adeli, Khosrow

    2011-08-01

    Intestinal lipid dysregulation is a common feature of insulin-resistant states. The present study investigated alterations in gene expression of key proteins involved in the active absorption of dietary fat and cholesterol in response to development of insulin resistance. Studies were conducted in two diet-induced animal models of insulin resistance: fructose-fed hamster and high-fat-fed mouse. Changes in the mRNA abundance of lipid transporters, adenosine triphosphate cassette (ABC) G5, ABCG8, FA-CoA ligase fatty acid translocase P4, Niemann-Pick C1-Like1 (NPC1L1), fatty acid transport protein 4 (FATP4), and Scavenger Receptor Class B Type I (SR-BI), were assessed in intestinal fragments (duodenum, jejunum, and ileum) using quantitative real-time PCR. Of all the transporters evaluated, SR-B1 showed the most significant changes in both animal models examined. A marked stimulation of SR-B1 expression was observed in all intestinal segments examined in both insulin-resistant animal models. The link between SR-BI expression and intestinal lipoprotein production was then examined in the Caco-2 cell model. SR-B1 overexpression in Caco-2 cells increased apolipoprotein B (apoB) 100 and apoB48 secretion, whereas RNAi knock down of SR-B1 decreased secretion of both apoB100 and apoB48. We also observed changes in subcellular distribution of SR-B1 in response to exogenous lipid and insulin. Confocal microscopy revealed marked changes in SR-BI subcellular distribution in response to both exogenous lipids (oleate) and insulin. In summary, marked stimulation of intestinal SR-BI occurs in vivo in animal models of diet-induced insulin resistance, and modulation of SR-BI in vitro regulates production of apoB-containing lipoprotein particles. We postulate that apical and/or basolateral SR-BI may play an important role in intestinal chylomicron production and may contribute to chylomicron overproduction normally observed in insulin-resistant states.

  20. Genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the rat.

    Directory of Open Access Journals (Sweden)

    Miloslava Hodúlová

    Full Text Available The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n = 8-13/strain and two progenitor strains SHR-Lx (n = 13 and BXH2/Cub (n = 18 were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG and cholesterol (C concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl. We have identified 14 loci (encompassing 1 to 65 genes on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b. Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant

  1. Lipoprotein lipase isoelectric point isoforms in humans

    DEFF Research Database (Denmark)

    Badia-Villanueva, M.; Carulla, P.; Carrascal, M.

    2014-01-01

    Lipoprotein lipase (LPL) hydrolyzes circulating triacylglycerols (TAG) into free fatty acids and glycerol. It is present in almost all tissues and its tissue-specific regulation directs the flow of circulating TAG in the body. We demonstrated in a previous study that, in rat heart and post-hepari...

  2. Metabolism of high density lipoproteins in liver cancer

    Institute of Scientific and Technical Information of China (English)

    Jing-Ting Jiang; Ning Xu; Chang-Ping Wu

    2007-01-01

    Liver plays a vital role in the production and catabolism of plasma lipoproteins. It depends on the integrity of cellular function of liver, which ensures homeostasis of lipid and lipoprotein metabolism. When liver cancer occurs these processes are impaired and high-density lipoproteins are changed.

  3. The role of NR2B containing NMDA receptor in place preference conditioned with morphine and natural reinforcers in rats.

    Science.gov (United States)

    Ma, Yao-Ying; Guo, Chang-Yong; Yu, Peng; Lee, David Yue-Wei; Han, Ji-Sheng; Cui, Cai-Lian

    2006-08-01

    It has been reported that N-methyl-D-aspartate (NMDA) receptor is implicated in drug addiction and antagonists of the NMDA receptor complex can inhibit the development and expression of conditioned place preference (CPP) induced by several addictive drugs, implying that this class of compounds might be considered as candidate for the treatment of substance abuse. To explore this possibility, it is important to evaluate whether the inhibitory effect of NMDA receptor antagonists would be confined to behaviors produced by drugs of abuse only, but not by natural reinforcers. According to the quantitative changes of NMDA receptor subunits, including NR1, NR2A, and NR2B, induced by diverse types of reinforcers, we chose NR2B subunit as the target of research. Experimental results showed that (1) an augmented expression of NR2B subunit was revealed by Western blotting in the nucleus accumbens (NAc) and the hippocampus in rats with CPP induced by morphine, but not by natural rewards such as food, novel environment and social interaction. (2) Ifenprodil, an antagonist highly selective for NR2B subunit of the NMDA receptor, produced a dose-dependent reduction in CPP induced by morphine and novel environment, but not that by food consumption and social interaction. Taking together, these findings suggested that NR2B containing NMDA receptor may be more involved with morphine reward rather than natural rewards, and that antagonism of NR2B may have a potential for the treatment of morphine abuse.

  4. Poly-(R)-3-hydroxybutyrates (PHB) are Atherogenic Components of Lipoprotein Lp(a).

    Science.gov (United States)

    Reusch, Rosetta N

    2015-12-01

    The hypothesis is that poly-(R)-3-hydroxybutyrates (PHB), linear polymers of the ketone body, R-3-hydroxybutyrate (R-3HB), are atherogenic components of lipoprotein Lp(a). PHB are universal constituents of biological cells and are thus components of all foods. Medium chain-length PHB (70%) are absorbed by albumin, which transports them to the liver for disposal. When the amount of PHB in the diet exceed the capacity of albumin to safely remove them from the circulation, the excess PHB remain in the lipid core of LDL particles that become constituents of lipoprotein Lp(a), and contribute to the formation of arterial deposits. In summary, the presence of PHB – water-insoluble, dense, viscous, adhesive polymers – in the lipid cores of the LDL moieties of Lp(a) particles supports the hypothesis that PHB are atherogenic components of Lp(a).

  5. Genetic variants associated with VLDL, LDL and HDL particle size differ with race/ethnicity

    Science.gov (United States)

    Specific constellations of lipoprotein particle features, reflected as differences in mean lipoprotein particle diameters, are associated with risk of insulin resistance (IR) and cardiovascular disease (CVD). The associations of lipid profiles with disease risk differ by race/ethnicity, the reason f...

  6. Effect of apolipoprotein E variants on lipolysis of very low density lipoproteins by heparan sulphate proteoglycan-bound lipoprotein lipase

    NARCIS (Netherlands)

    Man, F.H.A.F. de; Beer, F. de; Laarse, A. van der; Smelt, A.H.M.; Leuven, J.A.G.; Havekes, L.M.

    1998-01-01

    Lipoprotein lipase (LPL) is bound to heparan sulphate proteoglycans (HSPG) at the luminal surface of endothelium. It is the key enzyme involved in the hydrolysis of very low density lipoproteins (VLDL). Prior to lipolysis by LPL, the lipoproteins are considered to interact with vessel wall HSPG. Apo

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

    Science.gov (United States)

    1992-08-01

    cardiovascular response to exercise . Since the male pattern of response to exercise has been studied more extensively, it is generally accepted as...may be directly atherogenic and 2) metabolic consequences of hypertriglyceridemia such as elevated postprandial lipoproteins, large VLDL particles...differences in the normal cardiac response to upright exercise . Circulation, 70(3), 357-366. Hjermann, I. (1985). Primary prevention of coronary heart

  8. 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 subjec

  9. Binding of β-VLDL to heparan sulfate proteoglycans requires lipoprotein lipase, whereas apoE only modulates binding affinity

    NARCIS (Netherlands)

    Beer, F. de; Hendriks, W.L.; Vark, L.C. van; Kamerling, S.W.A.; Dijk, K.W. van; Hofker, M.H.; Smelt, A.H.M.; Havekes, L.M.

    1999-01-01

    The binding of β-VLDL to heparan sulfate proteoglycans (HSPG) has been reported to be stimulated by both apoE and lipoprotein lipase (LPL). In the present study we investigated the effect of the isoform and the amount of apoE per particle, as well as the role of LPL on the binding of β-VLDL to HSPG.

  10. High-density lipoprotein endocytosis in endothelial cells

    Institute of Scientific and Technical Information of China (English)

    Stefanie; Fruhwürth; Margit; Pavelka; Robert; Bittman; Werner; J; Kovacs; Katharina; M; Walter; Clemens; Rhrl; Herbert; Stangl

    2013-01-01

    AIM: To describe the way stations of high-density lipoprotein(HDL) uptake and its lipid exchange in endothelial cells in vitro and in vivo. METHODS: A combination of fluorescence microscopy using novel fluorescent cholesterol surrogates and electron microscopy was used to analyze HDL endocytosis in great detail in primary human endothelial cells. Further, HDL uptake was quantified using radio-labeled HDL particles. To validate the in vitro findings mice were injected with fluorescently labeled HDL and particle uptake in the liver was analyzed using fluorescencemicroscopy. RESULTS: HDL uptake occurred via clathrin-coated pits, tubular endosomes and multivesicular bodies in human umbilical vein endothelial cells. During uptake and resecretion, HDL-derived cholesterol was exchanged at a faster rate than cholesteryl oleate, resembling the HDL particle pathway seen in hepatic cells. In addition, lysosomes were not involved in this process and thus HDL degradation was not detectable. In vivo, we found HDL mainly localized in mouse hepatic endothelial cells. HDL was not detected in parenchymal liver cells, indicating that lipid transfer from HDL to hepatocytes occurs primarily via scavenger receptor, class B, type Ⅰ mediated selective uptake without concomitant HDL endocytosis. CONCLUSION: HDL endocytosis occurs via clathrincoated pits, tubular endosomes and multivesicular bodies in human endothelial cells. Mouse endothelial cells showed a similar HDL uptake pattern in vivo indicating that the endothelium is one major site of HDL endocytosis and transcytosis.

  11. Binding of anthracycline derivatives to human serum lipoproteins.

    Science.gov (United States)

    Chassany, O; Urien, S; Claudepierre, P; Bastian, G; Tillement, J P

    1994-01-01

    The binding of eight anthracycline analogues (including mitoxantrone) to isolated serum lipoproteins (high, low and very low density lipoproteins) was studied in order to elucidate some determinants of their interaction with lipidic structures. Serum lipoproteins were isolated by ultracentrifugation. Drug binding experiments were run by ultrafiltration at 37 degrees C and pH 7.4. Anthracycline concentrations (total and free) were determined by HPLC with fluorometric detection. All the ligands were significantly bound to the three lipoprotein classes, and for each ligand the binding increased as the lipidic fraction of lipoprotein increased. From doxorubicin to iododoxorubicin, there was a tenfold increase in lipoprotein binding (doxorubicin < mitoxantrone < epirubicin < daunorubicin < pirarubicin < aclarubicin < zorubicin < iododoxorubicin). For all the ligands studied, the extent of lipoprotein binding appears to be related to chemical determinants of lipophilicity.

  12. 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.

  13. Lipoprotein subfractions in metabolic syndrome and obesity: clinical significance and therapeutic approaches.

    Science.gov (United States)

    Nikolic, Dragana; Katsiki, Niki; Montalto, Giuseppe; Isenovic, Esma R; Mikhailidis, Dimitri P; Rizzo, Manfredi

    2013-03-18

    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.

  14. 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.

  15. Expression of human apolipoprotein B and assembly of lipoprotein(a) in transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Callow, M.J.; Stoltzfus, L.J.; Rubin, E.M. [Lawrence Berkeley Lab., CA (United States); Lawn, R.M. [Stanford Univ., CA (United States)

    1994-03-15

    The atherogenic macromolecule lipoprotein(a) [Lp(a)] has resisted in vivo analyses partly because it is found in a limited number of experimental animals. Although transgenic mice expressing human apolipoprotein (a) [apo(a)] have previously been described, they failed to assemble Lp(a) particles because of the inability of human apo(a) to associate with mouse apolipoprotein B (apoB). The authors isolated a 90-kilobase P1 phagemid containing the human apoB gene and with this DNA generated 13 lines of transgenic mice of which 11 expressed human apoB. The human apoB transcript was expressed and edited in the liver of the transgenic mice. Plasma concentrations of human apoB, as well as low density lipoprotein (LDL), were related to transgene copy number; the transgenic line with the most copies of human apoB had a >4-fold increase in LDL cholesterol compared with nontransgenics and a lipoprotein profile similar to that of humans. When human apoB and apo(a) transgenic mice were bred together, plasma apo(a) in mice expressing both human proteins was tightly associated with lipoproteins in the LDL density region. These studies demonstrate the successful expression of human apoB and the efficient assembly of Lp(a) in mice.

  16. Sortilins: new players in lipoprotein metabolism

    DEFF Research Database (Denmark)

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

    2011-01-01

    PURPOSE OF REVIEW: Sortilins are sorting receptors that direct proteins through secretory and endocytic pathways of the cell. Previously, these receptors have been shown to play important roles in regulating protein transport in neurons and to control neuronal viability and death in many diseases...... 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...... 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....

  17. Mycoplasma lipoproteins and Toll-like receptors

    Institute of Scientific and Technical Information of China (English)

    Ling-ling ZUO; Yi-mou WU; Xiao-xing YOU

    2009-01-01

    Mycoplasmas, the smallest free-living, self-replicating bacteria with diameters of 200 to 800 nm, have been reported to be associated with human diseases. It is well known that the mycoplasma lipoprotein/peptide is able to modulate the host immune system, whose N-terminal structure is an important factor in inducing immunity and distinguishing Toll-like receptors (TLRs). However, there is still no clear elucidation about the pathogenic mechanism of mycoplasma lipoprotein/peptide and the signaling pathway. Some researchers have focused on understanding the structures of these proteins and the relationships between their structure and biological function. This review provides an update on the research in this field.

  18. Lipoprotein secretion: It takes two to TANGO.

    Science.gov (United States)

    Pfeffer, Suzanne R

    2016-05-09

    An unsolved mystery in cell biology is how unusually large secretory cargoes are exported from the endoplasmic reticulum. In this issue, Santos et al. (2016. J. Cell Biol http://dx.doi.org/10.1083/jcb.201603072) report the function of a Mia2/cTAGE5 transcript fusion, named TALI, in the endoplasmic reticulum export of chylomicrons and very low-density lipoproteins, but not collagen XII.

  19. 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.)

  20. Immune Response to Lipoproteins in Atherosclerosis

    OpenAIRE

    Sonia Samson; Lakshmi Mundkur; Kakkar, Vijay V

    2012-01-01

    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 re...

  1. Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis.

    Directory of Open Access Journals (Sweden)

    Daniel I Chasman

    2009-11-01

    Full Text Available While conventional LDL-C, HDL-C, and triglyceride measurements reflect aggregate properties of plasma lipoprotein fractions, NMR-based measurements more accurately reflect lipoprotein particle concentrations according to class (LDL, HDL, and VLDL and particle size (small, medium, and large. The concentrations of these lipoprotein sub-fractions may be related to risk of cardiovascular disease and related metabolic disorders. We performed a genome-wide association study of 17 lipoprotein measures determined by NMR together with LDL-C, HDL-C, triglycerides, ApoA1, and ApoB in 17,296 women from the Women's Genome Health Study (WGHS. Among 36 loci with genome-wide significance (P<5x10(-8 in primary and secondary analysis, ten (PCCB/STAG1 (3q22.3, GMPR/MYLIP (6p22.3, BTNL2 (6p21.32, KLF14 (7q32.2, 8p23.1, JMJD1C (10q21.3, SBF2 (11p15.4, 12q23.2, CCDC92/DNAH10/ZNF664 (12q24.31.B, and WIPI1 (17q24.2 have not been reported in prior genome-wide association studies for plasma lipid concentration. Associations with mean lipoprotein particle size but not cholesterol content were found for LDL at four loci (7q11.23, LPL (8p21.3, 12q24.31.B, and LIPG (18q21.1 and for HDL at one locus (GCKR (2p23.3. In addition, genetic determinants of total IDL and total VLDL concentration were found at many loci, most strongly at LIPC (15q22.1 and APOC-APOE complex (19q13.32, respectively. Associations at seven more loci previously known for effects on conventional plasma lipid measures reveal additional genetic influences on lipoprotein profiles and bring the total number of loci to 43. Thus, genome-wide associations identified novel loci involved with lipoprotein metabolism-including loci that affect the NMR-based measures of concentration or size of LDL, HDL, and VLDL particles-all characteristics of lipoprotein profiles that may impact disease risk but are not available by conventional assay.

  2. 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.

  3. Characteristics of Lipoprotein Peak x Eluted from a Column with the Eluent of High-magnesium Ion Concentration in Lipoprotein Analysis Using the Cation-exchange Chromatography

    OpenAIRE

    Yuji Hirowatari; Hiroshi Yoshida; Yutaka Ogura; Hidekastu Yanai; Hideo Kurosawa; Norio Tada

    2005-01-01

    The new lipoprotein analysis method using a cation-exchange chromatography, which contains a sulfopropyl-ligand column and two magnesium ion-containing eluents was previously reported. This method can separate serum lipoproteins on the column gel with a magnesium ion concentration gradient and high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) and an unspecified lipoprotein peak are eluted in order from the column. We have now characterize...

  4. 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.

  5. Effect of losartan and spironolactone on triglyceride-rich lipoproteins in diabetic nephropathy

    Science.gov (United States)

    Srivastava, Anand; Adams-Huet, Beverley; Vega, Gloria L; Toto, Robert D

    2016-01-01

    Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) can improve dyslipidemia in patients with diabetes and albuminuria. Whether combined ACEi+ARB or ACEi+mineralocorticoid receptor blockade improves dyslipidemia is not known. We hypothesized long-term administration of either losartan 100 mg or spironolactone 25 mg once daily added onto lisinopril 80 mg once daily would improve dyslipidemia in diabetic nephropathy (DN). We measured lipid levels, very-low-density (V), intermediate-density (I), low-density (LDL), high-density (HDL) lipoprotein, LDL particle size with their respective cholesterol (C) and apolipoprotein B levels (ApoB), and urine albumin/creatinine ratio (UACR) at 12-week interval during a 48-week randomized, double-blind placebo-controlled trial in 81 patients with DN. Plasma lipids and lipoprotein C were analyzed enzymatically and Apo B was determined chemically. Data were analyzed by mixed model repeated measures. ΔUACR differed among treatment arms (placebo −24.6%, los −38.2%, spiro −51.6%, p=0.02). No correlation existed between ΔUACR and ΔTG or any of the lipid or lipoprotein measurements. Compared with placebo losartan, but not spironolactone, decreased TG (−20.9% vs +34.3%, p<0.01), V+I C(−18.8% vs +21.3%, p<0.01), and V+I-ApoB (−13.2% vs +21%, p<0.01). There were no significant changes in body weight, HbA1c or other lipoprotein variables. We conclude losartan improves dyslipidemia in patients with DN. We speculate the mechanism improved clearance of VLDL and remnant lipoproteins. Trial registration number NCT00381134; Results. PMID:27388615

  6. Pathophysiological role and clinical significance of lipoprotein-associated phospholipase A₂ (Lp-PLA₂) bound to LDL and HDL.

    Science.gov (United States)

    Tellis, Constantinos C; Tselepis, Alexandros D

    2014-01-01

    Lipoprotein-associated phospholipase A2 (Lp-PLA2), also named as platelet-activating factor (PAF)-acetylhydrolase, exhibits a Ca2+-independent phospholipase A2 activity and catalyzes the hydrolysis of the ester bond at the sn-2 position of PAF and oxidized phospholipids (oxPL). These phospholipids are formed under oxidative and inflammatory conditions, and may play important roles in atherogenesis. The vast majority of plasma Lp-PLA2 mass binds to low-density lipoprotein (LDL) while a smaller amount is associated with high-density lipoprotein (HDL). Lp-PLA2 is also bound to lipoprotein (a) [Lp(a)], very low-density lipoprotein (VLDL) and remnant lipoproteins. Several lines of evidence suggest that the role of plasma Lp-PLA2 in atherosclerosis may depend on the type of lipoprotein particle with which this enzyme is associated. Data from large Caucasian population studies have supported plasma Lp-PLA2 (primarily LDL-associated Lp-PLA2) as a cardiovascular risk marker independent of, and additive to, traditional risk factors. On the contrary, the HDL-associated Lp-PLA2 may express antiatherogenic activities and is also independently associated with lower risk for cardiac death. The present review presents data on the biochemical and enzymatic properties of Lp-PLA2 as well as its structural characteristics that determine the association with LDL and HDL. We also critically discuss the possible pathophysiological and clinical significance of the Lp- PLA2 distribution between LDL and HDL in human plasma, in view of the results of prospective epidemiologic studies on the association of Lp-PLA2 with future cardiovascular events as well the recent studies that evaluate the possible effectiveness of specific Lp-PLA2 inhibitors in reducing residual cardiovascular risk.

  7. 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.

  8. Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection.

    Science.gov (United States)

    Sódar, Barbara W; Kittel, Ágnes; Pálóczi, Krisztina; Vukman, Krisztina V; Osteikoetxea, Xabier; Szabó-Taylor, Katalin; Németh, Andrea; Sperlágh, Beáta; Baranyai, Tamás; Giricz, Zoltán; Wiener, Zoltán; Turiák, Lilla; Drahos, László; Pállinger, Éva; Vékey, Károly; Ferdinandy, Péter; Falus, András; Buzás, Edit Irén

    2016-04-18

    Circulating extracellular vesicles have emerged as potential new biomarkers in a wide variety of diseases. Despite the increasing interest, their isolation and purification from body fluids remains challenging. Here we studied human pre-prandial and 4 hours postprandial platelet-free blood plasma samples as well as human platelet concentrates. Using flow cytometry, we found that the majority of circulating particles within the size range of extracellular vesicles lacked common vesicular markers. We identified most of these particles as lipoproteins (predominantly low-density lipoprotein, LDL) which mimicked the characteristics of extracellular vesicles and also co-purified with them. Based on biophysical properties of LDL this finding was highly unexpected. Current state-of-the-art extracellular vesicle isolation and purification methods did not result in lipoprotein-free vesicle preparations from blood plasma or from platelet concentrates. Furthermore, transmission electron microscopy showed an association of LDL with isolated vesicles upon in vitro mixing. This is the first study to show co-purification and in vitro association of LDL with extracellular vesicles and its interference with vesicle analysis. Our data point to the importance of careful study design and data interpretation in studies using blood-derived extracellular vesicles with special focus on potentially co-purified LDL.

  9. Rosiglitazone improves intestinal lipoprotein overproduction in the fat-fed Syrian Golden hamster, an animal model of nutritionally-induced insulin resistance.

    Science.gov (United States)

    Leung, Nathalie; Naples, Mark; Uffelman, Kristine; Szeto, Linda; Adeli, Khosrow; Lewis, Gary F

    2004-06-01

    We have recently shown that the fructose-fed Syrian Golden hamster, a non-diabetic animal model of nutritionally-induced insulin resistance and hyperlipidemia, is characterized by intestinal lipoprotein overproduction. In order to determine whether intestinal lipoprotein overproduction is specific to fructose feeding or applies generally to other models of insulin resistance, we studied intestinal lipoprotein production and the response to insulin sensitization in the high fat-fed Syrian Golden hamster. Syrian Golden Hamsters were fed either (1). chow (CHOW), (2). 60% fat (FAT) or (3). 60% fat with rosiglitazone, 20 micromol/kg per day (FAT + RSG) for 5 weeks. Euglycemic hyperinsulinemic clamp studies confirmed that FAT is a good model of insulin resistance and rosiglitazone treatment resulted in a significant improvement in insulin sensitivity. In addition, there was a significant approx. two- to four-fold increase in intestinal apoB48 particle production in FAT. Rosiglitazone treatment resulted in partial normalization of apoB48-containing intestinal lipoprotein secretion. In summary: (1). the fat-fed Syrian Golden Hamster is a good model of nutritionally-induced insulin resistance, (2). intestinal overproduction of lipoproteins appear to contribute to the hypertriglyceridemia of insulin resistance in this animal model and (3). insulin sensitization with rosiglitazone ameliorates intestinal apoB48 particle overproduction in the fat-fed Syrian Golden Hamster. These data further support the link between insulin resistance and intestinal lipoprotein overproduction.

  10. Role of sphingosine 1-phosphate in anti-atherogenic actions of high-density lipoprotein

    Institute of Scientific and Technical Information of China (English)

    Koichi; Sato; Fumikazu; Okajima

    2010-01-01

    The reverse cholesterol transport mediated by highdensity lipoprotein(HDL)is an important mechanism for maintaining body cholesterol,and hence,the crucial anti-atherogenic action of the lipoprotein.Recent studies,however,have shown that HDL exerts a variety of anti-inflammatory and anti-atherogenic actions independently of cholesterol metabolism.The present review provides an overview of the roles of sphingosine 1-phosphate(S1P)/S1P receptor and apolipoprotein A-I/ scavenger receptor class B typeⅠsystems in the antiatherogenic HDL actions.In addition,the physiological significance of the existence of S1P in the HDL particles is discussed.

  11. 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

  12. Fish plasma lipoproteins--comparative observations in serranides and sparides.

    Science.gov (United States)

    Santulli, A; Cusenza, L; Modica, A; Curatolo, A; D'Amelio, V

    1991-01-01

    1. Diet, time from last feeding, temperature, season and sexual stage are some of the factors influencing the lipoprotein pattern. 2. Keeping these factors constant species-specific differences observed among lipoprotein patterns of Sparus aurata, Puntazzo puntazzo, Diplodus sargus, Diplodus vulgaris and Dicentrarchus labrax are discussed. 3. Feeding habits and therefore lipid absorption and the rate of lipoprotein maturation process are the factors determining the observed differences.

  13. 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

    BACKGROUND: The increased risk of atherosclerosis associated with diabetes cannot be explained by conventional cardiovascular risk factors alone. We hypothesized that transvascular lipoprotein transport may be increased in patients with diabetes, possibly explaining increased intimal lipoprotein ...... be increased in patients with type 1 diabetes. This suggests that lipoprotein flux into the arterial wall is increased in people with type 1 diabetes, possibly explaining accelerated development of atherosclerosis....

  14. Computational lipidology: predicting lipoprotein density profiles in human blood plasma.

    Directory of Open Access Journals (Sweden)

    Katrin Hübner

    2008-05-01

    Full Text Available Monitoring cholesterol levels is strongly recommended to identify patients at risk for myocardial infarction. However, clinical markers beyond "bad" and "good" cholesterol are needed to precisely predict individual lipid disorders. Our work contributes to this aim by bringing together experiment and theory. We developed a novel computer-based model of the human plasma lipoprotein metabolism in order to simulate the blood lipid levels in high resolution. Instead of focusing on a few conventionally used predefined lipoprotein density classes (LDL, HDL, we consider the entire protein and lipid composition spectrum of individual lipoprotein complexes. Subsequently, their distribution over density (which equals the lipoprotein profile is calculated. As our main results, we (i successfully reproduced clinically measured lipoprotein profiles of healthy subjects; (ii assigned lipoproteins to narrow density classes, named high-resolution density sub-fractions (hrDS, revealing heterogeneous lipoprotein distributions within the major lipoprotein classes; and (iii present model-based predictions of changes in the lipoprotein distribution elicited by disorders in underlying molecular processes. In its present state, the model offers a platform for many future applications aimed at understanding the reasons for inter-individual variability, identifying new sub-fractions of potential clinical relevance and a patient-oriented diagnosis of the potential molecular causes for individual dyslipidemia.

  15. 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.

  16. Lipoprotein glomerulopathy treated with LDL-apheresis (Heparin-induced Extracorporeal Lipoprotein Precipitation system: a case report

    Directory of Open Access Journals (Sweden)

    Rivasi Paolo

    2009-12-01

    Full Text Available Abstract Introduction Lipoprotein glomerulopathy is a glomerulonephritis which was described for the first time by Saito in 1989 and is currently acknowledged as a separate nosological entity. It is histologically characterized by a marked dilatation of the glomerular capillaries and the presence of lipoprotein thrombi in the glomerular lumens. The dyslipidemic profile is similar to that of type III dyslipoproteinemia with Apolipoprotein E values that are often high; proteinuria and renal dysfunction are present. Proteinuria often does not respond to steroid and cytostatic treatments. The phenotypic expression of lipoprotein glomerulopathy is most probably correlated to a genetic alteration of the lipoprotein metabolism (mutation of the Apolipoprotein E coding gene. In literature, lipoprotein glomerulopathies have mainly been reported in Japanese and Chinese subjects, except for three cases in the Caucasian race, reported in France and the USA. Case presentation We describe the case of a 60-year-old female, Caucasian patient suffering from lipoprotein glomerulopathy, carrier of a new mutation on the Apolipoprotein E gene (Apolipoprotein EMODENA, and treated successfully with low density lipoprotein-apheresis with the Heparin induced extracorporeal lipoprotein precipitation system. After a first phase of therapeutic protocol with statins, the patient was admitted for nephrotic syndrome, renal failure and hypertension. Since conventional treatment alone was not able to control dyslipidemia, aphaeretic treatment with heparin-induced Extracorporeal Lipoprotein Precipitation - apheresis (HELP-apheresis was started to maintain angiotensin converting enzyme inhibitor therapy for the treatment of hypertension. Treatment with HELP-apheresis led to a complete remission of the proteinuria in a very short time (four months, as well as control of hypercholesterolemia and renal function recovery. Conclusion According to this case of lipoprotein glomerulopathy

  17. Lipoproteins, cholesterol homeostasis and cardiac health

    Directory of Open Access Journals (Sweden)

    Tyler F. Daniels, Karen M. Killinger, Jennifer J. Michal, Raymond W. Wright Jr., Zhihua Jiang

    2009-01-01

    Full Text Available Cholesterol is an essential substance involved in many functions, such as maintaining cell membranes, manufacturing vitamin D on surface of the skin, producing hormones, and possibly helping cell connections in the brain. When cholesterol levels rise in the blood, they can, however, have dangerous consequences. In particular, cholesterol has generated considerable notoriety for its causative role in atherosclerosis, the leading cause of death in developed countries around the world. Homeostasis of cholesterol is centered on the metabolism of lipoproteins, which mediate transport of the lipid to and from tissues. As a synopsis of the major events and proteins that manage lipoprotein homeostasis, this review contributes to the substantial attention that has recently been directed to this area. Despite intense scrutiny, the majority of phenotypic variation in total cholesterol and related traits eludes explanation by current genetic knowledge. This is somewhat disappointing considering heritability estimates have established these traits as highly genetic. Thus, the continued search for candidate genes, mutations, and mechanisms is vital to our understanding of heart disease at the molecular level. Furthermore, as marker development continues to predict risk of vascular illness, this knowledge has the potential to revolutionize treatment of this leading human disease.

  18. Turkish Heart Study: lipids, lipoproteins, and apolipoproteins.

    Science.gov (United States)

    Mahley, R W; Palaoğlu, K E; Atak, Z; Dawson-Pepin, J; Langlois, A M; Cheung, V; Onat, H; Fulks, P; Mahley, L L; Vakar, F

    1995-04-01

    We examined the plasma lipids, lipoproteins, and selected apolipoproteins in approximately 9,000 men and women from six different regions of Turkey with markedly different diets, ranging from an Aegean coast diet high in olive oil (plasma cholesteryl ester fatty acids enriched in monounsaturated fatty acids) to an inland Anatolian diet high in meat and dairy products (plasma cholesteryl esters enriched in saturated fatty acids). The rural population consuming an olive oil-rich diet had the lowest plasma cholesterol levels (men, 149 mg/dl; women, 150 mg/dl). The urban populations of Istanbul and Adana had higher plasma cholesterol levels (men, 202 and 184 mg/dl, respectively; women, 181 and 190 mg/dl, respectively). Affluent men had the highest cholesterol levels (207 mg/dl). The low density lipoprotein (LDL) cholesterol levels tended to parallel the total cholesterol levels (highest for Istanbul men at 136 mg/dl and lowest for Aegean coast men and women at approximately 100 mg/dl). Strikingly, the Turkish people were found to have very low levels of high density lipoprotein (HDL) cholesterol (HDL-C) (mean values for all six regions: men, 34-38 mg/dl; women, 37-45 mg/dl) and total cholesterol/HDL-C ratios that were high (mean values for all six regions: men, 4.5-5.5; women, 3.9-5.0). The low HDL-C levels appear to be caused, at least in part, by a genetic factor. Triglyceride levels also tended to be high in Turkish men (approximately 120-150 mg/dl) and women (approximately 90-110 mg/dl). Thus, even though the total plasma cholesterol levels are not excessively elevated in comparison to those in other populations, the presence of low HDL-C or low HDL-C coupled with mildly elevated triglyceride levels may represent a significant risk factor for heart disease in the Turkish population. Affluence and higher education were associated with higher cholesterol levels. Lack of physical activity, smoking, and alcohol consumption also tended to be associated with a

  19. 高密度脂蛋白颗粒亚型与心血管病事件关系的荟萃分析%A meta-analysis on the association between high-density lipoprotein particle subfractions and cardiovascular disease events

    Institute of Scientific and Technical Information of China (English)

    范杰; 齐玥; 赵冬

    2014-01-01

    Objective High-density lipoprotein cholesterol (HDL-C) has cardio-protective effects.However,results from clinical trials showed that improving HDL-C levels alone did not reduce the cardiovascular disease (CVD) events and different HDL particles (HDL-P) subfractions may relate to different CVD risk.In this meta-analysis,we reviewed prospective studies reported relationships of HDL-P subfractions with CVD risk.Methods Data sources:MEDLINE,Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched up to July 1st,2013.Study selection:Prospective studies that reported an association of HDL-P subfractions with the incidence of CVD were included and studies did not assess the hazard ratio,relative risk,or odds ratio of HDL-P and studies did not adjust for any other risk factors were excluded.Data extraction and synthesis:All studies were extracted by 1 researcher and verified by another researcher.Full data were extracted from the studies meanwhile the quality was evaluated.Heterogeneity was analyzed.Pooled relative risk (RR) and 95% confidence interval were calculated.Results Six studies were enrolled in this meta-analysis.HDL-P can be grouped into three subfractions:large HDL-P,medium HDL-P and small HDL-P.Only higher large HDL-P concentration was associated with decreased risk for CVD and pooled RR was 0.65 (95% CI:0.55-0.76).Medium HDL-P and small HDL-P were not associated with the incidence of CVD events.Conclusion Higher large HDL-P concentration is associated with lower CVD risk.Assessment of HDL-P subfractions may thus be of great clinical importance for evaluating the CVD risk.%目的 观察性研究显示高密度脂蛋白胆固醇(HDL-C)具有心血管保护功能,但随机对照临床试验发现单纯升高HDL-C并未减少心血管病事件.可能的假设是不同的高密度脂蛋白颗粒(HDL-P)亚型与心血管病发生风险的关联不同.对HDL-P及其亚型与心血管病事件关系的前瞻性

  20. 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 chol

  1. 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...

  2. TRIIODOTHYRONINE RAPIDLY LOWERS PLASMA-LIPOPROTEIN (A) IN HYPOTHYROID SUBJECTS

    NARCIS (Netherlands)

    DULLAART, RPF; VANDOORMAAL, JJ; HOOGENBERG, K; SLUITER, WJ

    1995-01-01

    Background: Increases in plasma low-density-lipoprotein (LDL) cholesterol and apolipoprotein B (apo-B) are well known in primary hypothyroidism, but it is uncertain whether thyroid dysfunction is associated with elevated levels of the atherogenic lipoprotein (a) (Lp(a)). Methods: The effect of short

  3. Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention.

    Science.gov (United States)

    Millán, Jesús; Pintó, Xavier; Muñoz, Anna; Zúñiga, Manuel; Rubiés-Prat, Joan; Pallardo, Luis Felipe; Masana, Luis; Mangas, Alipio; Hernández-Mijares, Antonio; González-Santos, Pedro; Ascaso, Juan F; Pedro-Botet, Juan

    2009-01-01

    Low-density lipoprotein (LDL) cholesterol concentration has been the prime index of cardiovascular disease risk and the main target for therapy. However, several lipoprotein ratios or "atherogenic indices" have been defined in an attempt to optimize the predictive capacity of the lipid profile. In this review, we summarize their pathophysiological aspects, and highlight the rationale for using these lipoprotein ratios as cardiovascular risk factors in clinical practice, specifying their cut-off risk levels and a target for lipid-lowering therapy. Total/high-density lipoprotein (HDL) cholesterol and LDL/HDL cholesterol ratios are risk indicators with greater predictive value than isolated parameters used independently, particularly LDL. Future recommendations regarding the diagnosis and treatment of dyslipidemia, including instruments for calculating cardiovascular risk or action guidelines, should include the lipoprotein ratios with greater predictive power which, in view of the evidence-based results, are none other than those which include HDL cholesterol.

  4. 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.

  5. [Plasma lipoproteins as drug carriers. Effect of phospholipid formulations].

    Science.gov (United States)

    Torkhovskaia, T I; Ipatova, O M; Medvedeva, N V; Ivanov, V S; Ivanova, L I

    2010-01-01

    The extensive development of nanotechnologies in the last two decades has brought about new understanding of plasma lipoproteins (LP) as natural drug nanocarriers that escape interaction with immune and reticuloendothelial systems. Drugs bound to LP (especially LDL) can more actively penetrate into cells of many cancer and inflammation tissues with enhanced expression or/and dysregulation of B,E receptors or possibly scavenger SR-BI receptors. Relevant studies are focused on the development of new dosage forms by conjugating lipophilic drugs either with isolated plasma LP or with their model formulations, such as nanoemulsions, mimetics, lipid nanospheres, etc. Some authors include in these particles serum or recombinant apoproteins, peptides, and modified polymer products. As shown recently, protein-free lipid nanoemulsions in plasma take up free apoA and apoE. Complexes with various LP also form after direct administration of lypophilic drugs into blood especially those enclosed in phospholipid formulations, e.g. liposomes. Results of evaluation of some lipophilic dugs (mainly cytostatics, amphotericin B, cyclosporine A, etc.) are discussed. Original data are presented on the influence of phospholipid formulations on the distribution of doxorubicin and indomethacin between LP classes after in vitro incubation in plasma. On the whole, the review illustrates the importance of research on LP and phospholi pid forms as drug nanocarriers to be used to enhance effect of therapy.

  6. 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.

  7. A novel lipoprotein nanoparticle system for membrane proteins

    Science.gov (United States)

    Frauenfeld, Jens; Löving, Robin; Armache, Jean-Paul; Sonnen, Andreas; Guettou, Fatma; Moberg, Per; Zhu, Lin; Jegerschöld, Caroline; Flayhan, Ali; Briggs, John A.G.; Garoff, Henrik; Löw, Christian; Cheng, Yifan; Nordlund, Pär

    2016-01-01

    Membrane proteins are of outstanding importance in biology, drug discovery and vaccination. A common limiting factor in research and applications involving membrane proteins is the ability to solubilize and stabilize membrane proteins. Although detergents represent the major means for solubilizing membrane proteins, they are often associated with protein instability and poor applicability in structural and biophysical studies. Here, we present a novel lipoprotein nanoparticle system that allows for the reconstitution of membrane proteins into a lipid environment that is stabilized by a scaffold of Saposin proteins. We showcase the applicability of the method on two purified membrane protein complexes as well as the direct solubilization and nanoparticle-incorporation of a viral membrane protein complex from the virus membrane. We also demonstrate that this lipid nanoparticle methodology facilitates high-resolution structural studies of membrane proteins in a lipid environment by single-particle electron cryo-microscopy (cryo-EM) and allows for the stabilization of the HIV-envelope glycoprotein in a functional state. PMID:26950744

  8. 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

    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 a

  9. A disposable electrochemical sensor based on protein G for High-Density Lipoprotein (HDL) detection.

    Science.gov (United States)

    Chammem, H; Hafaid, I; Bohli, N; Garcia, A; Meilhac, O; Abdelghani, A; Mora, L

    2015-11-01

    In this work, two biosensors were developed for the detection of High-Density Lipoproteins (HDL) particles, which are biomarkers inversely correlated with cardiovascular risk and which represent therapeutic targets for atherosclerosis. The electrochemical properties of the grafted antibody on interdigitated gold electrode were achieved by Impedance Spectroscopy (IS). The used deposition method was based on oriented antibody Anti-ApoA1 with an intermediate thin layer of protein G. The developed biosensor was able to detect both native plasma HDL and reconstituted HDL (rHDL) particles respectively with the detection limit of 50n g/mL and 1 ng/mL, respectively. Dynamic contact angle and atomic force microscopy were used. The developed biosensors are able to differentiate the HDL particles according to their differences in size and interactions with the immobilized antibody.

  10. Revealing structural and dynamical properties of high density lipoproteins through molecular simulations

    DEFF Research Database (Denmark)

    Koivuniemi, A.; Vattulainen, I.

    2012-01-01

    The structure and function of high density lipoprotein (HDL) particles have intrigued the scientific community for decades because of their crucial preventive role in coronary heart disease. However, it has been a taunting task to reveal the precise molecular structure and dynamics of HDL. Further......, because of the complex composition of HDL, understanding the impact of its structure and dynamics on the function of HDL in reverse cholesterol transport has also been a major issue. Recent progress in molecular simulation methodology and computing power has made a difference, as it has enabled...... essentially atomistic considerations of HDL particles over microsecond time scales, thereby proving substantial added value to experimental research. In this article, we discuss recent highlights concerning the structure and dynamics of HDL particles as revealed by atomistic and coarse-grained molecular...

  11. 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

  12. Health benefits of high-density lipoproteins in preventing cardiovascular diseases.

    Science.gov (United States)

    Berrougui, Hicham; Momo, Claudia N; Khalil, Abdelouahed

    2012-01-01

    Plasma levels of high-density lipoprotein (HDL) are strongly and inversely correlated with atherosclerotic cardiovascular diseases. However, it is becoming clear that a functional HDL is a more desirable target than simply increasing HDL-cholesterol levels. The best known antiatherogenic function of HDL particles relates to their ability to promote reverse cholesterol transport from peripheral cells. However, HDL also possesses antioxidant, anti-inflammatory, and antithrombotic effects. This review focuses on the state of knowledge regarding assays of HDL heterogeneity and function and their relationship to cardiovascular diseases.

  13. An efficient depyrogenation method for recombinant bacterial outer membrane lipoproteins.

    Science.gov (United States)

    Basto, Afonso P; Morais, Joana; Marcelino, Eduardo; Leitão, Alexandre; Santos, Dulce M

    2014-06-01

    Bacterial outer membrane lipoproteins are anchored in the outer membrane lipid layer in close association with lipopolysaccharides (LPS) and with other hydrophobic membrane proteins, making their purification technically challenging. We have previously shown that a thorough delipidation of outer membrane preparations from the Escherichia coli expression host is an important step to eliminate contaminant proteins when purifying recombinant antigens expressed in fusion with the Pseudomonas aeruginosa OprI lipoprotein. Here we report the cloning and expression of three antigens in fusion with OprI (ovalbumin, eGFP and BbPDI) and our efforts to deal with the variable LPS contamination levels observed in different batches of purified lipoproteins. The use of polymyxin B columns or endotoxin removal polycationic magnetic beads for depyrogenation of purified lipoproteins resulted in high protein losses and the use of Triton X-114 or sodium deoxycholate during the course of affinity chromatography showed to be ineffective to reduce LPS contamination. Instead, performing a hot phenol/water LPS extraction from outer membrane preparations prior to metal affinity chromatography allowed the purification of the recombinant fusion lipoproteins with LPS contents below 0.02EU/μg of protein. The purified recombinant lipoproteins retain their capacity to stimulate bone marrow-derived dendritic cells allowing for the study of their immunomodulatory properties through TLR2/1. This is a simple and easy to scale up method that can also be considered for the purification of other outer membrane lipoproteins.

  14. A systematic approach to obtain validated partial least square models for predicting lipoprotein subclasses from serum NMR spectra.

    Science.gov (United States)

    Mihaleva, Velitchka V; van Schalkwijk, Daniël B; de Graaf, Albert A; van Duynhoven, John; van Dorsten, Ferdinand A; Vervoort, Jacques; Smilde, Age; Westerhuis, Johan A; Jacobs, Doris M

    2014-01-07

    A systematic approach is described for building validated PLS models that predict cholesterol and triglyceride concentrations in lipoprotein subclasses in fasting serum from a normolipidemic, healthy population. The PLS models were built on diffusion-edited (1)H NMR spectra and calibrated on HPLC-derived lipoprotein subclasses. The PLS models were validated using an independent test set. In addition to total VLDL, LDL, and HDL lipoproteins, statistically significant PLS models were obtained for 13 subclasses, including 5 VLDLs (particle size 64-31.3 nm), 4 LDLs (particle size 28.6-20.7 nm) and 4 HDLs (particle size 13.5-9.8 nm). The best models were obtained for triglycerides in VLDL (0.82 < Q(2) <0.92) and HDL (0.69 < Q(2) <0.79) subclasses and for cholesterol in HDL subclasses (0.68 < Q(2) <0.96). Larger variations in the model performance were observed for triglycerides in LDL subclasses and cholesterol in VLDL and LDL subclasses. The potential of the NMR-PLS model was assessed by comparing the LPD of 52 subjects before and after a 4-week treatment with dietary supplements that were hypothesized to change blood lipids. The supplements induced significant (p < 0.001) changes on multiple subclasses, all of which clearly exceeded the prediction errors.

  15. The influence of lipoprotein(a) on fibrinolytic activity

    OpenAIRE

    Rahajuningsih D. Setiabudy; Marzuki Suryaatmadja; Fifi Henrika

    2004-01-01

    Lipoprotein(a) is a plasma lipoprotein whose structure and composition are similar with low density lipoprotein (LDL) with an addition of apo(a) that is bound to apo B100. The structure of apo(a) is similar with plasminogen, a proenzym in fibrinolytic system. Due to this similarity, it is assumed that Lp(a) can inhibit plasminogen activity and decreases fibrinolytic activity. The purpose of this study is to prove that addition of Lp(a) to normal plasma can inhibit fibrinolytic activity. Four ...

  16. Novel double-congenic strain reveals effects of spontaneously hypertensive rat chromosome 2 on specific lipoprotein subfractions and adiposity.

    Science.gov (United States)

    Seda, Ondrej; Sedová, Lucie; Liska, Frantisek; Krenová, Drahomíra; Prejzek, Vratislav; Kazdová, Ludmila; Tremblay, Johanne; Hamet, Pavel; Kren, Vladimír

    2006-10-01

    We have developed a new, double-congenic rat strain BN-Lx.SHR2, which carries two distinct segments of chromosome 2 introgressed from the spontaneously hypertensive rat strain (SHR) into the genetic background of congenic strain BN-Lx, which was previously shown to express variety of metabolic syndrome features. In 16-wk-old male rats of BN-Lx and BN-Lx.SHR2 strains, we compared their glucose tolerance and triacylglycerol and cholesterol concentrations in 20 lipoprotein subfractions and the lipoprotein particle sizes under conditions of feeding standard and high-sucrose diets. Introgression of two distinct SHR-derived chromosome 2 segments resulted in decreased adiposity together with aggravation of glucose intolerance in the double-congenic strain. The BN-Lx.SHR2 rats were more sensitive to sucrose-induced rise in triacylglycerolemia. Although the total cholesterol concentrations of the two strains were comparable after the standard diet and even lower in BN-Lx.SHR2 after sucrose feeding, detailed analysis revealed that under both dietary conditions, the double-congenic strain had significantly higher cholesterol concentrations in low-density lipoprotein fractions and lower high-density lipoprotein fractions. We established a new inbred model showing dyslipidemia and mild glucose intolerance without obesity, attributable to specific genomic regions. For the first time, the chromosome 2 segments of SHR origin are shown to influence other than blood pressure-related features of metabolic syndrome or to be involved in relevant nutrigenomic interactions.

  17. Knockdown of BNST GluN2B-containing NMDA receptors mimics the actions of ketamine on novelty-induced hypophagia.

    Science.gov (United States)

    Louderback, K M; Wills, T A; Muglia, L J; Winder, D G

    2013-12-03

    Administration of a single low dose of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has been demonstrated to elicit long-lasting antidepressant effects in humans with depression, as well as in rodent models of depression. Although pharmacological studies have implicated the GluN2B subunit of the NMDA receptor in these effects, drugs targeting this subunit have off-target actions, and systemic administration of these compounds does not allow for delineation of specific brain regions involved. In this study, we assessed the role of GluN2B in the bed nucleus of the stria terminalis (BNST) in novelty-induced hypophagia (NIH) in mice. First, we verified that ketamine, as well as the GluN2B antagonist Ro25-6981, decreased the latency to consume food in a novel environment in a version of the NIH test. We then hypothesized that GluN2B-containing receptors within the BNST may be a target of systemic ketamine and contribute to behavioral effects. Through the combination of a GluN2B-floxed mouse line and stereotaxic delivery of lentiviral Cre recombinase, we found that targeted knockdown of this subunit within the BNST mimicked the reduction in affective behavior observed with systemic ketamine or Ro25-6981 in the NIH test. These data suggest a role for GluN2B-containing NMDARs within the BNST in the affective effects of systemic ketamine.

  18. Lipoprotein X Causes Renal Disease in LCAT Deficiency.

    Science.gov (United States)

    Ossoli, Alice; Neufeld, Edward B; Thacker, Seth G; Vaisman, Boris; Pryor, Milton; Freeman, Lita A; Brantner, Christine A; Baranova, Irina; Francone, Nicolás O; Demosky, Stephen J; Vitali, Cecilia; Locatelli, Monica; Abbate, Mauro; Zoja, Carlamaria; Franceschini, Guido; Calabresi, Laura; Remaley, Alan T

    2016-01-01

    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.

  19. Effects of feeding fish oil on the properties of lipoproteins isolated from rhesus monkeys consuming an atherogenic diet.

    Science.gov (United States)

    Soltys, P A; Mazzone, T; Wissler, R W; Vahed, S; Rangnekar, V; Lukens, J; Vesselinovitch, D; Getz, G S

    1989-04-01

    This study examined plasma lipids and lipoproteins of rhesus monkeys fed fish oil incorporated into a highly atherogenic diet containing saturated fat and cholesterol. The animals were fed diets containing 2% cholesterol and either 25% coconut oil (group I), 25% fish oil/coconut oil (1:1; group II), or 25% fish oil/coconut oil (3:1; group III) for 12 months (n = 8/group). Adding menhaden fish oil to the diet increased plasma eicosapentaenoic acid and docosahexaenoic acid and decreased plasma linoleic acid in animals fed the fish oil containing diets. Plasma concentrations of all lipoprotein fractions were decreased in the fish oil groups. VLDL isolated from group I animals exhibited beta-mobility on agarose gels but the VLDL from groups II and III animals did not. The group I VLDL was more highly enriched in cholesteryl ester than was VLDL from groups II and III. Group I LDL had a small but significant increase in cholesteryl ester content compared to group III LDL. No differences in HDL composition were observed in the 3 groups. At least 6 times less apo E was recovered in VLDL, IDL, and LDL from group III animals than from group I animals. Assuming 1 molecule of apo B per lipoprotein particle, there were 50% fewer VLDL, IDL, and LDL particles in group III than in group I animals. Group III also had significantly lower molar ratios of apo E/apo B in VLDL, IDL, and LDL than did group I animals. When VLDL from all 3 groups were incubated with J774 macrophages at equal protein concentrations, only the VLDL from the group I animals stimulated cholesterol esterification. Thus, introducing fish oil into an atherogenic diet reduced the number of VLDL, IDL and LDL particles in plasma by as much as 50%, reduced the cholesteryl ester content of the circulating lipoprotein, and reduced the ability of the VLDL to stimulate cholesterol esterification in macrophages.

  20. 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.

  1. Drosophila Lipophorin Receptors Recruit the Lipoprotein LTP to the Plasma Membrane to Mediate Lipid Uptake.

    Directory of Open Access Journals (Sweden)

    Míriam Rodríguez-Vázquez

    2015-06-01

    Full Text Available Lipophorin, the main Drosophila lipoprotein, circulates in the hemolymph transporting lipids between organs following routes that must adapt to changing physiological requirements. Lipophorin receptors expressed in developmentally dynamic patterns in tissues such as imaginal discs, oenocytes and ovaries control the timing and tissular distribution of lipid uptake. Using an affinity purification strategy, we identified a novel ligand for the lipophorin receptors, the circulating lipoprotein Lipid Transfer Particle (LTP. We show that specific isoforms of the lipophorin receptors mediate the extracellular accumulation of LTP in imaginal discs and ovaries. The interaction requires the LA-1 module in the lipophorin receptors and is strengthened by a contiguous region of 16 conserved amino acids. Lipophorin receptor variants that do not interact with LTP cannot mediate lipid uptake, revealing an essential role of LTP in the process. In addition, we show that lipophorin associates with the lipophorin receptors and with the extracellular matrix through weak interactions. However, during lipophorin receptor-mediated lipid uptake, LTP is required for a transient stabilization of lipophorin in the basolateral plasma membrane of imaginal disc cells. Together, our data suggests a molecular mechanism by which the lipophorin receptors tether LTP to the plasma membrane in lipid acceptor tissues. LTP would interact with lipophorin particles adsorbed to the extracellular matrix and with the plasma membrane, catalyzing the exchange of lipids between them.

  2. The Role of Dietary Cholesterol in Lipoprotein Metabolism and Related Metabolic Abnormalities: A Mini-review.

    Science.gov (United States)

    Kapourchali, Fatemeh Ramezani; Surendiran, Gangadaran; Goulet, Amy; Moghadasian, Mohammed H

    2016-10-25

    Cholesterol plays a vital role in cell biology. Dietary cholesterol or "exogenous" cholesterol accounts for approximately one-third of the pooled body cholesterol, and the remaining 70% is synthesized in the body (endogenous cholesterol). Increased dietary cholesterol intake may result in increased serum cholesterol in some individuals, while other subjects may not respond to dietary cholesterol. However, diet-increased serum cholesterol levels do not increase the low-density lipoprotein/high-density lipoprotein (LDL/HDL) cholesterol ratio, nor do they decrease the size of LDL particles or HDL cholesterol levels. Elevated levels of LDL cholesterol, reduced HDL cholesterol levels, and small, dense LDL particles are independent risk factors for coronary artery disease. Dietary cholesterol is the primary approach for treatment of conditions such as the Smith-Lemli-Opitz syndrome. Recent studies have highlighted mechanisms for absorption of dietary cholesterol. These studies have help understand how dietary and/or pharmaceutical agents inhibit cholesterol absorption and thereby reduce LDL cholesterol concentrations. In this article, various aspects of cholesterol metabolism, including dietary sources, absorption, and abnormalities in cholesterol metabolism, have been summarized and discussed.

  3. Modulation of lipoprotein receptor functions by intracellular adaptor proteins.

    Science.gov (United States)

    Stolt, Peggy C; Bock, Hans H

    2006-10-01

    Members of the low density lipoprotein (LDL) receptor gene family are critically involved in a wide range of physiological processes including lipid and vitamin homeostasis, cellular migration, neurodevelopment, and synaptic plasticity, to name a few. Lipoprotein receptors exert these diverse biological functions by acting as cellular uptake receptors or by inducing intracellular signaling cascades. It was discovered that a short sequence in the intracellular region of all lipoprotein receptors, Asn-Pro-X-Tyr (NPXY) is important for mediating either endocytosis or signal transduction events, and that this motif serves as a binding site for phosphotyrosine-binding (PTB) domain containing scaffold proteins. These molecular adaptors connect the transmembrane receptors with the endocytosis machinery and regulate cellular trafficking, or function as assembly sites for dynamic multi-protein signaling complexes. Whereas the LDL receptor represents the archetype of an endocytic lipoprotein receptor, the structurally closely related apolipoprotein E receptor 2 (apoER2) and very low density lipoprotein (VLDL) receptor activate a kinase-dependent intracellular signaling cascade after binding to the neuronal signaling molecule Reelin. This review focuses on two related PTB domain containing adaptor proteins that mediate these divergent lipoprotein receptor responses, ARH (autosomal recessive hypercholesterolemia protein) and Dab1 (disabled-1), and discusses the structural and molecular basis of this different behaviour.

  4. 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.

  5. Mechanisms and signiifcance of lipoprotein(a) in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jing-Ting Jiang; Chang-Ping Wu; Ning Xu; Xue-Guang Zhang

    2009-01-01

    BACKGROUND: The liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. It has been demonstrated that plasma lipid proifles are changed in liver cancer. DATA SOURCES: A MEDLINE database search was performed to identify relevant articles using the keywords "hepatocellular carcinoma" and "lipoprotein(a)". The search was conducted and research articles were reviewed from 1960 to 2008. RESULTS: Production and homeostasis of lipids, apo-lipoproteins and lipoproteins depend on the integrity of hepatocellular functions, which ensures normal lipid and lipoprotein metabolismin vivo. When hepatocellular injury or liver cancer occurs these processes can be impaired. It has been suggested that plasma levels of apolipoprotein(a) (apo(a)) and/or lipoprotein(a) (Lp(a)) may be considered as sensitive markers of hepatic impairment. CONCLUSIONS: Plasma levels of apo(a) and Lp(a) display signiifcant correlations with hepatic status. Most studies demonstrated that the plasma levels of apo(a) and Lp(a) can be considered as an additional clinical index of liver function.

  6. Mycobacterium tuberculosis 19-kDa lipoprotein promotes neutrophil activation.

    Science.gov (United States)

    Neufert, C; Pai, R K; Noss, E H; Berger, M; Boom, W H; Harding, C V

    2001-08-01

    Certain microbial substances, e.g., LPS, can activate neutrophils or prime them to enhance their response to other activating agents, e.g., fMLP. We investigated the role of the Mycobacterium tuberculosis (MTB) 19-kDa lipoprotein in activation of human neutrophils. MTB 19-kDa lipoprotein initiated phenotypic changes characteristic of neutrophil activation, including down-regulation of CD62 ligand (L-selectin) and up-regulation of CD35 (CR1) and CD11b/CD18 (CR3, Mac-1). In addition, exposure of neutrophils to MTB 19-kDa lipoprotein enhanced the subsequent oxidative burst in response to fMLP as assessed by oxidation of dihydrorhodamine 123 (determined by flow cytometry). LPS also produced these effects with similar kinetics, but an oligodeoxynucleotide containing a CpG motif failed to induce any priming or activation response. Although the effects of LPS required the presence of serum, neutrophil activation by MTB 19-kDa lipoprotein occurred independently of serum factors, suggesting the involvement of different receptors and signaling mechanisms for LPS and MTB 19-kDa lipoprotein. Thus, MTB 19-kDa lipoprotein serves as a pathogen-associated molecular pattern that promotes neutrophil priming and activation.

  7. High-density lipoprotein and atherosclerosis: Roles of lipid transporters

    Institute of Scientific and Technical Information of China (English)

    Yoshinari; Uehara; Keijiro; Saku

    2014-01-01

    Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-terol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette trans-porters(ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mi-metic peptide, Fukuoka University ApoA-I Mimetic Pep-tide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an an-tiatherosclerotic effect by enhancing the biological func-tions of HDL without changing circulating HDL choles-terol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases.

  8. 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.

  9. Pistachio intake increases high density lipoprotein levels and inhibits low-density lipoprotein oxidation in rats.

    Science.gov (United States)

    Aksoy, Nur; Aksoy, Mehmet; Bagci, Cahit; Gergerlioglu, H Serdar; Celik, Hakim; Herken, Emine; Yaman, Abdullah; Tarakcioglu, Mehmet; Soydinc, Serdar; Sari, Ibrahim; Davutoglu, Vedat

    2007-05-01

    There is increasing evidence that nuts have protective effects against coronary artery disease by improving lipid profile and inhibiting lipid oxidation. However, data about pistachio nuts are limited, and to our knowledge, there is no study investigating the effects of pistachio intake on lipid oxidation and serum antioxidant levels. This study, therefore, sought to determine the effects of pistachio intake on serum lipids and determine whether consumption of pistachio would alter serum antioxidant levels. Rats were randomly divided into three groups (n=12 for each): control group fed basic diet for 10 weeks and treated groups fed basic diet plus pistachio which constituted 20% and 40% of daily caloric intake, respectively. Consumption of pistachio as 20% of daily caloric intake increased high-density lipoprotein (HDL) levels and decreased total cholesterol (TC)/HDL ratio, compared with those not taking pistachio. However, TC, low-density lipoprotein (LDL) cholesterol and triglyceride levels were unaffected by pistachio consumption. Consumption of pistachio as 20% of daily caloric intake increased serum paraoxonase activity by 35% and arylesterase activity by 60%, which are known to inhibit LDL cholesterol oxidation, compared with the control group. However, increased antioxidant activity was blunted when pistachio intake was increased to 40% of daily caloric intake. In conclusion, the present results show that consumption of pistachio as 20% of daily caloric intake leads to significant improvement in HDL and TC/HDL ratio and inhibits LDL cholesterol oxidation. These results suggest that pistachio may be beneficial for both prevention and treatment of coronary artery disease.

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

    Science.gov (United States)

    Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M; Brown, Robert J

    2014-09-05

    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.

  11. Lipoprotein abnormalities in South Asians and its association with cardiovascular disease:Current state and future directions

    Institute of Scientific and Technical Information of China (English)

    Ozlem Bilen; Ayeesha Kamal; Salim S Virani

    2016-01-01

    South Asians have a high prevalence of coronary heart disease(CHD) and suffer from early-onset CHD compared to other ethnic groups. Conventional risk factors may not fully explain this increased CHD risk in this population. Indeed, South Asians have a unique lipid profile which may predispose them to premature CHD. Dyslipidemia in this patient population seems to be an important contributor to the high incidence of coronary atherosclerosis. The dyslipidemia in South Asians is characterized by elevated levels of triglycerides, low levels of high-density lipoprotein(HDL) cholesterol, elevated lipoprotein(a) levels, and a higher atherogenic particle burden despite comparable low-density lipoprotein cholesterol levels compared with other ethnic subgroups. HDL particles also appear to be smaller, dysfunctional, and proatherogenic in South Asians. Despite the rapid expansion of the current literature with better understanding of the specific lipid abnormalities in this patient population, studies with adequate sample sizes are needed to assess the significance and contribution of a given lipid parameter on overall cardiovascular risk in this population. Specific management goals and treatment thresholds do not exist for South Asians because of paucity of data. Current treatment recommendations are mostly extrapolated from Western guidelines. Lastly, large, prospective studies with outcomes data are needed to assess cardiovascular benefit associated with various lipid-lowering therapies(including combination therapy) in this patient population.

  12. 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

    2014-01-01

    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 fr

  13. 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.

  14. Experimental Animal Models Evaluating the Causal Role of Lipoprotein(a) in Atherosclerosis and Aortic Stenosis.

    Science.gov (United States)

    Yeang, Calvin; Cotter, Bruno; Tsimikas, Sotirios

    2016-02-01

    Lipoprotein(a) [Lp(a)], comprised of apolipoprotein(a) [apo(a)] and a low-density lipoprotein-like particle, is a genetically determined, causal risk factor for cardiovascular disease and calcific aortic valve stenosis. Lp(a) is the major plasma lipoprotein carrier of oxidized phospholipids, is pro-inflammatory, inhibits plasminogen activation, and promotes smooth muscle cell proliferation, as defined mostly through in vitro studies. Although Lp(a) is not expressed in commonly studied laboratory animals, mouse and rabbit models transgenic for Lp(a) and apo(a) have been developed to address their pathogenicity in vivo. These models have provided significant insights into the pathophysiology of Lp(a), particularly in understanding the mechanisms of Lp(a) in mediating atherosclerosis. Studies in Lp(a)-transgenic mouse models have demonstrated that apo(a) is retained in atheromas and suggest that it promotes fatty streak formation. Furthermore, rabbit models have shown that Lp(a) promotes atherosclerosis and vascular calcification. However, many of these models have limitations. Mouse models need to be transgenic for both apo(a) and human apolipoprotein B-100 since apo(a) does not covalently associated with mouse apoB to form Lp(a). In established mouse and rabbit models of atherosclerosis, Lp(a) levels are low, generally model whereas over 40 isoforms exist in humans. Mouse models should also ideally be studied in an LDL receptor negative background for atherosclerosis studies, as mice don't develop sufficiently elevated plasma cholesterol to study atherosclerosis in detail. With recent data that cardiovascular disease and calcific aortic valve stenosis is causally mediated by the LPA gene, development of optimized Lp(a)-transgenic animal models will provide an opportunity to further understand the mechanistic role of Lp(a) in atherosclerosis and aortic stenosis and provide a platform to test novel therapies for cardiovascular disease.

  15. Low density lipoproteins mediated nanoplatforms for cancer targeting

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Anupriya; Jain, Keerti; Kesharwani, Prashant, E-mail: prashant_pharmacy04@rediffmail.com; Jain, Narendra K., E-mail: jnarendr@yahoo.co.in [Dr. H. S. Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India)

    2013-09-15

    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.

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

    Science.gov (United States)

    Jain, Anupriya; Jain, Keerti; Mehra, Neelesh Kumar; Jain, N. K.

    2013-10-01

    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.

  17. 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.

  18. Changes in lipoprotein(a), oxidized phospholipids, and LDL subclasses with a low-fat high-carbohydrate diet.

    Science.gov (United States)

    Faghihnia, Nastaran; Tsimikas, Sotirios; Miller, Elizabeth R; Witztum, Joseph L; Krauss, Ronald M

    2010-11-01

    Low-fat diets have been shown to increase plasma concentrations of lipoprotein(a) [Lp(a)], a preferential lipoprotein carrier of oxidized phospholipids (OxPLs) in plasma, as well as small dense LDL particles. We sought to determine whether increases in plasma Lp(a) induced by a low-fat high-carbohydrate (LFHC) diet are related to changes in OxPL and LDL subclasses. We studied 63 healthy subjects after 4 weeks of consuming, in random order, a high-fat low-carbohydrate (HFLC) diet and a LFHC diet. Plasma concentrations of Lp(a) (P diet compared with the HFLC diet whereas LDL peak particle size was significantly smaller (P Diet-induced changes in Lp(a) were strongly correlated with changes in OxPL/apoB (P diet were also correlated with decreases in medium LDL particles (P diet is associated with increases in OxPLs and with changes in LDL subclass distribution that may reflect altered metabolism of Lp(a) particles.

  19. 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.

  20. Influence of liver cancer on lipid and lipoprotein metabolism

    Directory of Open Access Journals (Sweden)

    Nilsson-Ehle Peter

    2006-03-01

    Full Text Available Abstract Liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma (HCC is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. This has been attributed to the high incidence of hepatitis B infection. Hepatitis B proteins, such as the hepatitis B X protein (HBx that is large hepatitis B surface protein could regulate transcription of many candidate genes for liver carcinogenesis. It has known that patients who suffered from acute hepatitis B could have lipid disorders such as decreased plasma level of high-density lipoproteins (HDL. Furthermore, aberrations of lipid metabolism are often seen in the chronic hepatitis B infection. Plasma lipid profiles could be changed under HCC. In majority of the reports in HCC, plasma levels of triglycerides (TG, cholesterol, free fatty acids (FFA, HDL, low-density lipoproteins (LDL, lipoprotein (a (Lp(a, apolipoprotein AI (apoAI and apoB were slight to significantly decreased, however, in some cases plasma levels of TG and Lp(a might be increased. It has been suggested that analysis of plasma levels of lipids, lipoproteins and apolipoproteins in the patients suffered from HCC reflects on the hepatic cellular impairment status. Studies revealed that alterations seen in the plasma levels of lipids, lipoproteins and apolipoproteins reflecting patients' pathologic conditions. Decreased serum levels of cholesterol and apoAI may indicate a poor prognosis. Human leukaemic cells and certain tumor tissues have a higher receptor-mediated uptake of HDL and LDL than the corresponding normal cells or tissues. LDL and HDL have therefore been proposed as a carrier for the water-insoluble anti-cancer agents.

  1. Inhibition of cholesterol ester transfer protein CGS 25159 and changes in lipoproteins in hamsters.

    Science.gov (United States)

    Kothari, H V; Poirier, K J; Lee, W H; Satoh, Y

    1997-01-03

    As a result of screening, several isoflavans were identified to be antagonists of cholesterol ester transfer protein (CETP) activity. The present study evaluates CGS 25159, a synthetic isoflavan, as a putative inhibitor of CETP activity of human and hamster plasma. Determined by [3]CE transfer from HDL to VLDL + LDL fraction or by fluorescent-CE transfer assay, CGS 25159 inhibited CETP in both human plasma bottom fraction (d = 1.21 g/ml) and in plasma from Golden Syrian Hamsters with an IC50 time dependent changes in CETP activity. After two weeks of treatment at 10 mg/kg, the changes in VLDL + LDL cholesterol, total triglycerides and HDL cholesterol were -22 +/- 4.6*, -23 +/- 7.5 and +10 +/- 2.8%, respectively. The corresponding changes at 30 mg/kg were -28 +/- 5.5*, -38 +/- 6.8* and +29 +/-4.4.*%, (*, P, 0.05; mean +/- S.E.M., n = 6). A single spin gradient density ultracentrifugation of plasma lipoproteins and treated animals showed an increase in HDL cholesterol and a redistribution to larger HDL particles. These data support the contention that pharmacological down regulation of CETP activity could result in favorable changes in lipoprotein profile.

  2. 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 ...

  3. Diet × genotype interactions in hepatic cholesterol and lipoprotein metabolism in Atlantic salmon (Salmo salar) in response to replacement of dietary fish oil with vegetable oil.

    Science.gov (United States)

    Morais, Sofia; Pratoomyot, Jarunan; Torstensen, Bente E; Taggart, John B; Guy, Derrick R; Bell, J Gordon; Tocher, Douglas R

    2011-11-01

    The present study investigates the effects of genotype on responses to alternative feeds in Atlantic salmon. Microarray analysis of the liver transcriptome of two family groups, lean or fat, fed a diet containing either a fish oil (FO) or a vegetable oil (VO) blend indicated that pathways of cholesterol and lipoprotein metabolism might be differentially affected by the diet depending on the genetic background of the fish, and this was further investigated by real-time quantitative PCR, plasma and lipoprotein biochemical analysis. Results indicate a reduction in VLDL and LDL levels, with no changes in HDL, when FO is replaced by VO in the lean family group, whereas in fat fish fed FO, levels of apoB-containing lipoproteins were low and comparable with those fed VO in both family groups. Significantly lower levels of plasma TAG and LDL-TAG were measured in the fat group that was independent of diet, whereas plasma cholesterol was significantly higher in fish fed the FO diet in both groups. Hepatic expression of genes involved in cholesterol homeostasis, β-oxidation and lipoprotein metabolism showed relatively subtle changes. A significantly lower expression of genes considered anti-atherogenic in mammals (ATP-binding cassette transporter A1, apoAI, scavenger receptor class B type 1, lipoprotein lipase (LPL)b (TC67836) and LPLc (TC84899)) was found in lean fish, compared with fat fish, when fed VO. Furthermore, the lean family group appeared to show a greater response to diet composition in the cholesterol biosynthesis pathway, mediated by sterol-responsive element-binding protein 2. Finally, the presence of three different transcripts for LPL, with differential patterns of nutritional regulation, was demonstrated.

  4. 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...

  5. Improving lipoprotein profiles by liver-directed gene transfer of low density lipoprotein receptor gene in hypercholesterolaemia mice

    Indian Academy of Sciences (India)

    HAILONG OU; QINGHAI ZHANG; JIA ZENG

    2016-06-01

    The defect of low density lipoprotein receptor disturbs cholesterol metabolism and causes familial hypercholesterolaemia(FH). In this study, we directly delivered exogenousLdlrgene into the liver of FH model mice (Ldlr − / −) by lentiviral genetransfer system. The results showed that theLdlrgene controlled by hepatocyte-specific human thyroxine-binding globulin(TBG) promoter successfully and exclusively expressed in livers. We found that, although, the content of high density lipopro-tein in serum was not significantly affected by theLdlrgene expression, the serum low density lipoprotein level was reducedby 46%, associated with a 30% and 28% decrease in triglyceride and total cholesterol, respectively, compared to uninjectedLdlr − / −mice. Moreover, the TBG directed expression ofLdlrsignificantly decreased the lipid accumulation in liver andreduced plaque burden in aorta (32%). Our results indicated that the hepatocyte-specific expression ofLdlrgene strikinglylowered serum lipid levels and resulted in amelioration of hypercholesterolaemia.

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

    Science.gov (United States)

    Srisen, Kaemisa; Röhrl, Clemens; Meisslitzer-Ruppitsch, Claudia; Ranftler, Carmen; Ellinger, Adolf; Pavelka, Margit; Neumüller, Josef

    2013-01-01

    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 intraellular

  7. 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

  8. Circulating lipoproteins are a crucial component of host defense against invasive Salmonella typhimurium infection.

    NARCIS (Netherlands)

    Netea, M.G.; Joosten, L.A.B.; Keuter, M.; Wagener, F.A.D.T.G.; Stalenhoef, A.F.H.; Meer, J.W.M. van der; Kullberg, B.J.

    2009-01-01

    BACKGROUND: Circulating lipoproteins improve the outcome of severe Gram-negative infections through neutralizing lipopolysaccharides (LPS), thus inhibiting the release of proinflammatory cytokines. METHODS/PRINCIPAL FINDINGS: Low density lipoprotein receptor deficient (LDLR-/-) mice, with a 7-fold i

  9. Gene silencing of NR2B-containing NMDA receptor by intrathecal injection of short hairpin RNA reduces formalin-induced nociception in C57BL/6 mouse.

    Science.gov (United States)

    Zhang, Rao-Xiang; Yan, Xue-Bin; Gu, Yong-Hong; Huang, Dong; Gan, Li; Han, Rui; Huang, Li-Hua

    2013-09-01

    Spinal NR2B-containing N-methyl-D-aspartate receptors (NR2B) play a critical role in the formation of central sensitization and persistent pain. Previous studies show that gene silencing of the spinal NR2B subunit by small interfering RNA (siRNA) could alleviate nociception in animals. The siRNA is a 19- to 23-nt RNA duplex, which can be synthesized in vitro or derived from short hairpin RNAs (shRNAs). In the present study, we investigated whether intrathecal injection of shRNAs targeting NR2B (GRIN2B shRNA) could affect nociception on formalin-induced pain in mice. Our results showed that intrathecal injection of GRIN2B shRNA could decrease NR2B mRNA and protein expression levels and hence effectively relieve formalin-induced nociception in mice, suggesting that intrathecal delivery of GRIN2B shRNA can be an efficient way to silence the target gene and provide new insights into the treatment of chronic pain.

  10. 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.

  11. Circulating Oxidized Low-Density Lipoproteins and Antibodies against Oxidized Low-Density Lipoproteins as Potential Biomarkers of Colorectal Cancer

    OpenAIRE

    2015-01-01

    Introduction. The aim of the study was evaluation of the diagnostic utility of serum oxidized low-density lipoproteins (oxLDL), antibodies against oxLDLs (o-LAB), and CEA as risk markers of colorectal cancer (CRC). Material and Methods. The serum levels of study factors were measured in 73 patients with CRC and in 35 healthy controls who were gender- and BMI-matched to the study group. Concentrations of oxLDL, o-LAB, and CEA were detected in ELISA tests. Serum lipids, lipoproteins, and gl...

  12. Lipoprotein lipase release from BFC-1 beta adipocytes. Effects of triglyceride-rich lipoproteins and lipolysis products.

    Science.gov (United States)

    Sasaki, A; Goldberg, I J

    1992-07-25

    Lipoprotein lipase (LPL), synthesized by adipocytes and myocytes, must be transported to the luminal endothelial cell surface where it then interacts with circulating lipoproteins. The first step in this extracellular LPL transport pathway is LPL release from the surface of LPL-synthesizing cells. Because hydrolysis of triglyceride (TG)-rich lipoproteins releases LPL from the apical surface of endothelial cells, we hypothesized that the same substances dissociate LPL from adipocytes. 125I-LPL was bound to the surface of brown adipocytes (BFC-1 beta). LPL binding to the adipocyte surface was greater than to endothelial cell surfaces. Using low concentrations of heparin, more LPL was released from endothelial cells than BFC-1 beta, suggesting that the affinity of LPL binding to the adipocytes was greater than LPL affinity for endothelial cells. Greater than 3-fold more LPL was released from the cell surface when very low density lipoproteins (VLDL) were added to culture medium containing 3% bovine serum albumin. LPL remaining on the cell surface decreased with VLDL addition. Endogenously produced LPL activity was also released from the cells by VLDL. Low and high density lipoproteins did not release 125I-LPL or LPL activity from the adipocytes. To assess whether lipolysis was necessary for LPL release, BFC-1 beta were incubated with TG-rich lipoproteins from a patient with apoCII deficiency. The apoCII-deficient lipoproteins did not release LPL unless an exogenous source of apoCII was added. Apolipoproteins E and Cs and high molar ratios of oleic acid:bovine serum albumin did not release surface-associated LPL. Lysolecithin (25 and 100 microM), but not lecithin, monoglycerides, or diglycerides, released adipocyte surface LPL. Because lysolecithin also released LPL during a 4 degrees C incubation, cellular metabolic functions are not required for LPL dissociation from the cells. Lysolecithin also inhibited LPL binding to endothelial cells; however, this effect was

  13. Low-density lipoprotein apheresis by membrane differential filtration (cascade filtration) via arteriovenous fistula performed in children with familial hypercholesterolemia.

    Science.gov (United States)

    Gülle, Saniye; Bak, Mustafa; Serdaroglu, Erkin; Can, Demet; Karabay, Ozalp

    2010-02-01

    Membrane differential filtration (cascade filtration) is an apheresis technique by which atherogenic lipoproteins can be eliminated from plasma on the basis of particle size. In this study, we aim to discuss the efficacy of low-density lipoprotein (LDL) apheresis performed by providing alternative vascular routes in two siblings with familial hypercholesterolemia who did not respond to medical treatment and diet. Of the two siblings, one was nine years old and the other one was three-and-a-half years old. Of the total of 78 apheresis processes performed, 24 were done via a permanent subclavian catheter, 36 were done via a subsequently provided arteriovenous fistula, and 18 were done via an arteriovenous graft. We observed a mean reduction in the plasma levels of total cholesterol (61.6%), LDL cholesterol (65.5%), and high-density lipoprotein cholesterol (38.6%). We noted that cascade filtration apheresis was effective in decreasing the LDL cholesterol in plasma, and no serious complications were noted. The success of the apheresis program depends on well-functioning blood access. An arteriovenous fistula may be the best route for the long-term treatment of familial hypercholesterolemia, which requires complication-free apheresis treatments.

  14. Associations between airway hyperresponsiveness, obesity, and lipoproteins in a longitudinal cohort

    DEFF Research Database (Denmark)

    Rasmussen, Finn; Hancox, Robert; Nair, Parameswaran;

    2013-01-01

    . The present study investigated the association between airway hyperresponsiveness (AHR) to methacholine and body mass index (BMI) and plasma lipoproteins [low-density lipoprotein (LDL), high-density lipoprotein (HDL) and total cholesterol]. Methods Associations between AHR, BMI and plasma lipoproteins were...... assessed in a population-based cohort at ages 14 and 20 years. Results In unadjusted analyses, higher LDL cholesterol levels at age 14 were associated with AHR at age 20 in both sexes (P...

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

    NARCIS (Netherlands)

    Nordestgaard, Børge G; Chapman, M John; Ray, Kausik; Borén, Jan; Andreotti, Felicita; Watts, Gerald F; Ginsberg, Henry; Amarenco, Pierre; Catapano, Alberico; Descamps, Olivier S; Fisher, Edward; Kovanen, Petri T; Kuivenhoven, Jan Albert; Lesnik, Philippe; Masana, Luis; Reiner, Zeljko; Taskinen, Marja-Riitta; Tokgözoglu, Lale; Tybjærg-Hansen, Anne

    2010-01-01

    AIMS: 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. METHODS AND RESULTS: The robust and specific association between e

  16. 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...

  17. [Residual risk: The roles of triglycerides and high density lipoproteins].

    Science.gov (United States)

    Grammer, Tanja; Kleber, Marcus; Silbernagel, Günther; Scharnagl, Hubert; März, Winfried

    2016-06-01

    In clinical trials, the reduction of LDL-cholesterol (LDL-C) with statins reduces the incidence rate of cardiovascular events by approximately one third. This means, that a sizeable "residual risk" remains. Besides high lipoprotein (a), disorders in the metabolism of triglyceride-rich lipoproteins and high density liproteins have been implicated as effectors of the residual risk. Both lipoprotein parameters correlate inversely with each other. Therefore, the etiological contributions of triglycerides and / or of HDL for developing cardiovascular disease can hardly be estimated from either observational studies or from intervention studies. The largely disappointing results of intervention studies with inhibitors of the cholesteryl ester transfer protein and in particular the available set of genetically-epidemiological studies suggest that in the last decade, the importance of HDL cholesterol has been overvalued, while the importance of triglycerides has been underestimated. High triglycerides not always atherogenic, but only if they are associated with the accumulation relatively cholesterol-enriched, incompletely catabolized remnants of chylomicrons and very low density lipoproteins (familial type III hyperlipidemia, metabolic syndrome, diabetes mellitus). The normalization of the concentration of triglycerides and remnants by inhibiting the expression of apolipoprotein C3 is hence a new, promising therapeutic target.

  18. Effects of progestational agents on serum lipids and lipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, R.M.

    1982-08-01

    Though progestins with relatively strong androgenic or antiestrogenic effects (e.g., levonorgestrel and norethindrone acetate) tend to have the greatest capacity to offset the major estrogen effects (e.g., on serum triglyceride and, to a greater extent, HDL-cholesterol), this association is not sufficiently strong to allow prediction of the effects of other progestins on lipid and lipoprotein metabolism.

  19. 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 LDL tur

  20. 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.

  1. 21 CFR 862.1475 - Lipoprotein test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lipoprotein test system. 862.1475 Section 862.1475 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  2. 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...9287290 Title Lipoprotein trafficking in vascular cells. Molecular Trojan horses ...ularsaboteurs. Hajjar DP, Haberland ME. J Biol Chem. 1997 Sep 12;272(37):22975-8. (.png) (.svg) (.html) (.csml) Show Lipoprotein traf...ficking in vascular cells. Molecular Trojan horses and cellularsaboteurs. PubmedID

  3. Low density lipoprotein: structure, dynamics, and interactions of apoB-100 with lipids

    DEFF Research Database (Denmark)

    Murtola, T.; Vuorela, T. A.; Hyvonen, M. T.;

    2011-01-01

    Low-density lipoprotein (LDL) transports cholesterol in the bloodstream and plays an important role in the development of cardiovascular diseases, in particular atherosclerosis. Despite its importance to health, the structure of LDL is not known in detail. This is worrying since the lack of LDL......'s structural information makes it more difficult to understand its function. In this work, we have combined experimental and theoretical data to construct LDL models comprised of the apoB-100 protein wrapped around a lipid droplet of about 20 nm in size. The models are considered by near-atomistic multi......-microsecond simulations to unravel structural as well as dynamical properties of LDL, with particular attention paid to lipids and their interactions with the protein. We find that the distribution and the ordering of the lipids in the LDL particle are rather complex. The previously proposed 2- and 3- layer models turn...

  4. Giardia lamblia low-density lipoprotein receptor-related protein is involved in selective lipoprotein endocytosis and parasite replication.

    Science.gov (United States)

    Rivero, Maria R; Miras, Silvana L; Quiroga, Rodrigo; Rópolo, Andrea S; Touz, Maria C

    2011-03-01

    As Giardia lamblia is unable to synthesize cholesterol de novo, this steroid might be obtained from the host's intestinal milieu by endocytosis of lipoproteins. In this work, we identified a putative Giardia lamblia low-density lipoprotein receptor-related proteins (GlLRP), a type I membrane protein, which shares the substrate N-terminal binding domain and a FXNPXY-type endocytic motif with human LRPs. Expression of tagged GlLRP showed that it was localized predominantly in the endoplasmic reticulum, lysosomal-like peripheral vacuoles and plasma membrane. However, the FXNPXY-deleted GlLRP was retained at the plasma membrane suggesting that it is abnormally transported and processed. The low-density lipoprotein and chylomicrons interacted with GlLRP, with this interaction being necessary for lipoprotein internalization and cell proliferation. Finally, we show that GlLRP binds directly to the medium subunit of Giardia adaptor protein 2, indicating that receptor-mediated internalization occurs through an adaptin mechanism.

  5. Segments in the C-terminal folding domain of lipoprotein lipase important for binding to the low density lipoprotein receptor-related protein and to heparan sulfate proteoglycans

    DEFF Research Database (Denmark)

    Nielsen, Morten Schallburg; Brejning, Jeanette; García, R.;

    1997-01-01

    Lipoprotein lipase (LpL) can mediate cellular uptake of chylomicron and VLDL remnants via binding to heparan sulfate proteoglycans (HSPG) and the endocytic alpha2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha2MR/LRP). Whereas it is established that the C-terminal ......Lipoprotein lipase (LpL) can mediate cellular uptake of chylomicron and VLDL remnants via binding to heparan sulfate proteoglycans (HSPG) and the endocytic alpha2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha2MR/LRP). Whereas it is established that the C...

  6. Lipoprotein(a) and risk of myocardial infarction--genetic epidemiologic evidence of causality

    DEFF Research Database (Denmark)

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

    2011-01-01

    Elevated levels of lipoprotein(a) are associated with an increased risk of myocardial infarction. Our study aimed to test whether genetic data are consistent with this association being causal. Accordingly, we developed a high-throughput realtime PCR assay to genotype for the lipoprotein(a) kringle...... effect on plasma levels of lipoprotein(a). The association of LPA KIV-2 genotypes raising plasma levels of lipoprotein(a) with increased risk of myocardial infarction strongly supports a causal association of lipoprotein(a) with risk of myocardial infarction....

  7. 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.

  8. Distinct Hepatic Receptors for Low Density Lipoprotein and Apolipoprotein E in Humans

    Science.gov (United States)

    Hoeg, Jeffrey M.; Demosky, Stephen J.; Gregg, Richard E.; Schaefer, Ernst J.; Brewer, H. Bryan

    1985-02-01

    Since the liver is a central organ for lipid and lipoprotein synthesis and catabolism, hepatic receptors for specific apolipoproteins on plasma lipoproteins would be expected to modulate lipid and lipoprotein metabolism. The role of hepatic receptors for low density lipoproteins and apolipoprotein E-containing lipoproteins was evaluated in patients with complementary disorders in lipoprotein metabolism: abetalipoproteinemia and homozygous familial hypercholesterolemia. In addition, hepatic membranes from a patient with familial hypercholesterolemia were studied and compared before and after portacaval shunt surgery. The results establish that the human liver has receptors for apolipoproteins B and E. Furthermore, in the human, hepatic receptors for low density lipoproteins and apolipoprotein E are genetically distinct and can undergo independent control.

  9. Association of small low density lipoprotein particles with the incidence of the patients of the atherosclerosic cerebral infarction%动脉粥样硬化性脑梗死与低密度脂蛋白亚组分颗粒大小关系的研究

    Institute of Scientific and Technical Information of China (English)

    谷月宇; 郭阳; 李强; 韩顺昌

    2003-01-01

    AIM: To study the correlation of the diameter of small LDL particles with the incidence of atherosclerosic cerebral infarction( ACI) . METHODS: The LDL plasmas were obtained by using density ladder supercentryfugation method in 32 ACI patients and another 32 healthy persons in the control group.The diameter, distribution and electrophoresis areas graphs of the LDL particles were analyzed by using 2.5%- 16.0% non denaturing polyacylamide gradient gels electrophresised method. RESULTS: ① The levels of TG,TC,LDL C, and Apo B in ACI group were significantly high (t=4.03- 8.37,P< 0.01).② The mean diameter of LDL particles in ACI group[(24.8± 0.7)nm] were more smaller than the mean diameter in the control group [(26.0± 0.6)nm,t=4.78,P< 0.01];the distribution of A and B pattern subfraction between the two groups was different, the distribution of B pattern LDL subfraction in ACI group was more significantly high than that in the control group.(t=6.80,P< 0.05).③ The relative percentage of small and density LDL particles in the ACI group(50± 10)% increased more significantly than that in the control group (t=7.76,P< 0.001). ④ There were negatively correlations between the diameter of LDL subfraction in ACI group with TG(r=- 0.47,P< 0.01),TC(r=- 0.51,P< 0.01),LDL C(r=- 0.36, P< 0.05)and Apo B (r=- 0.46, P< 0.05). CONCLUSION: The dominant LDL subfractions in ACI group were the small and density B pattern LDL that had a closely correlation with the incidence of ACI.It might be one of the dangerous factors of ACI.There was negative correlation between B pattern LDL with the levels of TG that adjusted the diameter and formulation of LDL subfractions.%目的 研究动脉粥样硬化性脑梗死 (ACI)发病与低密度脂蛋白 (LDL)亚组分颗粒直径大小之间的关系. 方法梯度密度超速离心 32例 ACI患者及 32例对照者的血浆 LDL,采用 2.5%~ 16.0%聚丙烯酰胺凝胶梯度电泳分析 LDL颗粒

  10. 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

  11. [Lipoprotein metabolism in menopause. Effect of hormonal substitution therapy].

    Science.gov (United States)

    Heckers, H; Platt, D

    1991-06-20

    Oral administration of conjugated estrogens, estradiol valerate and micronized estradiol--but not the percutaneous application--in the postmenopause modifies the plasmic lipoprotein profile by lowering, dose-dependently, LDL and elevating HDL (HDL2). In parallel, the cardiovascular mortality is decreased by 50-66%, with smokers also benefiting to the same extent. On account of the increased risk for endometrial carcinoma associated with postmenopausal estrogen monotherapy, combination with a lowest-dose gestagen is imperative. However, the very numerous synthetic gestagens can antagonize the favorable effects of the estrogen on lipoprotein metabolism. This applies in particular to the gestagens of the 19-nortestosterone type, such as norethisterone acetate and, in particular, levonorgestrel, but less so the 17-hydroxyprogesterone derivatives medroxyprogesterone acetate and medrogestone with their very low androgenic effect.

  12. [Various lipoprotein fractions and their relation to ischemic heart disease].

    Science.gov (United States)

    Palazzuoli, V; Mondillo, S; Kristodhullu, A; De Stefano, R; Amatucci, G

    1983-01-01

    In a study carried out on over 700 patients with three different manifestations of aterosclerosis (cerebrovascular, coronary and peripheral), we could not find any statistically significant difference between the total cholesterol and triglyceride concentration in these three groups. Also, there was o difference in cholesterol and triglyceride levels between these three groups and 200 normal subjects. The same held true when we compared a selected group of 76 patients with ischaemic heart disease who had no other risk factor, with a group of 80 control subjects. On the contrary, when we compared several fractions of serum lipoproteins and the ratios of apolipoprotein A to Apolipoprotein B, LDL Cholesterol to HDL Cholesterol, and total Cholesterol to HDL Cholesterol of the two groups, the differences were statistically significant. We conclude that when other risk factors are excluded, the protein component, rather than the lipid component of the plasma lipoproteins correlates the presence of coronary artery disease.

  13. Oxidized low-density lipoprotein in postmenopausal women

    DEFF Research Database (Denmark)

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

    2014-01-01

    of this study was to determine the prevalence of serum oxLDL in postmenopausal women and to identify possible associations of clinical and laboratory features with oxLDL in these patients. METHOD: After clinical examination and completing a clinical questionnaire, an ultrasound examination of both carotid.......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 high-density lipoprotein, impaired glucose intolerance, and DBP were independently associated...... with the occurrence of oxLDL. If oxLDL was present, higher high-density lipoprotein and glucose intolerance were associated with higher concentrations of oxLDL. In contrast, higher blood urea concentrations were associated with lower concentrations of oxLDL. CONCLUSION: This study presents the prevalence...

  14. 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.

  15. Transgenic rabbit that expresses a functional human lipoprotein (a)

    Science.gov (United States)

    Rouy, Didier; Duverger, Nicolas; Emmanuel, Florence; Denefle, Patrice; Houdebine, Louis-Marie; Viglietta, Celine; Rubin, Edward M.; Hughes, Steven D.

    2003-01-01

    A transgenic rabbit which has in its genomic DNA sequences that encode apolipoprotein (a) and apolipoprotein B polypeptides which are capable of combining to produce lipoprotein (a), a process for creating such a rabbit, and the use of the rabbit to identify compounds which are effective in the treatment of human diseases which are associated with, induced and/or exacerbated by Lp(a) expression.

  16. Methods for studying rodent intestinal lipoprotein production and metabolism

    OpenAIRE

    Kohan, Alison B.; Howles, Philip N.; Tso, Patrick

    2012-01-01

    Lipid absorption begins with the digestion of dietary triacylglycerol and ultimately results in the secretion of triacylglycerol in chylomicrons into the lymphatics. Additionally, the intestine also secretes numerous proteins and peptides involved in lipid and lipoprotein metabolism in response to food. Ultimately, chylomicrons and these proteins, peptides, and hormones are found in lymph. The lymph fistula rat model has traditionally been used to study this intestinal absorption of nutrients...

  17. Lipoprotein Modification by Advanced Glycosylation Endproducts (AGEs): Role in Atherosclerosis.

    Science.gov (United States)

    Bucala, R

    1997-02-01

    Recent progress in our understanding of advanced glycosylation reactions in vivo has affirmed the hypothesis that these products play an important role in the evolution of both diabetic and nondiabetic vascular disease. Utilizing newly developed advanced glycosylation end-products (AGE)-specific enzyme-linked immunosorbent assay (ELISA) techniques, AGEs have been identified to be present on a variety of vascular wall, lipoprotein, and lipid constituents. Vascular wall AGEs contribute to vascular pathology by increasing vascular permeability, enhancing subintimal protein and lipoprotein deposition, and inactivating nitric oxide. Lipid-linked AGEs present in low-density lipoprotein (LDL) also have been shown to initiate oxidative modification, promoting oxidation reactions that may proceed without the involvement of free metals or other radical generating systems. AGE-specific ELISA analysis has demonstrated a significantly increased level of AGE-modified LDL in the plasma of diabetic patients when compared to normal controls. AGE-modification impairs LDL-receptor-mediated clearance mechanisms in vivo and may contribute to elevated LDL levels in patients with diabetes. This concept has been substantiated further by the recent clinical observations that administration of the advanced glycosylation inhibitor aminoguanidine to diabetic patients significantly decreases circulating LDL levels. (Trends Cardiovasc Med 1997;7:39-47). © 1997, Elsevier Science Inc.

  18. Functional Roles of the Interaction of APP and Lipoprotein Receptors

    Science.gov (United States)

    Pohlkamp, Theresa; Wasser, Catherine R.; Herz, Joachim

    2017-01-01

    The biological fates of the key initiator of Alzheimer’s disease (AD), the amyloid precursor protein (APP), and a family of lipoprotein receptors, the low-density lipoprotein (LDL) receptor-related proteins (LRPs) and their molecular roles in the neurodegenerative disease process are inseparably interwoven. Not only does APP bind tightly to the extracellular domains (ECDs) of several members of the LRP group, their intracellular portions are also connected through scaffolds like the one established by FE65 proteins and through interactions with adaptor proteins such as X11/Mint and Dab1. Moreover, the ECDs of APP and LRPs share common ligands, most notably Reelin, a regulator of neuronal migration during embryonic development and modulator of synaptic transmission in the adult brain, and Agrin, another signaling protein which is essential for the formation and maintenance of the neuromuscular junction (NMJ) and which likely also has critical, though at this time less well defined, roles for the regulation of central synapses. Furthermore, the major independent risk factors for AD, Apolipoprotein (Apo) E and ApoJ/Clusterin, are lipoprotein ligands for LRPs. Receptors and ligands mutually influence their intracellular trafficking and thereby the functions and abilities of neurons and the blood-brain-barrier to turn over and remove the pathological product of APP, the amyloid-β peptide. This article will review and summarize the molecular mechanisms that are shared by APP and LRPs and discuss their relative contributions to AD.

  19. Inherited susceptibility determines the distribution of dense low-density lipoprotein subfraction profiles in familial combined hyperlipidemia

    Energy Technology Data Exchange (ETDEWEB)

    Bredie, S.J.H.; Demacker, P.N.M.; Stalenhoef, A.F.H. [Univ. of Nijmegen (Netherlands)

    1996-04-01

    Familial combined hyperlipidemia (FCH) is a heritable lipid disorder, in which dense low-density lipoprotein (LDL) subfraction profiles due to a predominance of small dense LDL particles are frequently observed. These small dense LDL particles are associated with cardiovascular disease. Using segregation analysis, we investigated to what extent these LDL subfraction profiles are genetically determined; also, the mode of inheritance was studied. Individual LDL subfraction profiles were determined by density gradient ultracentrifugation in 623 individuals of 40 well-defined Dutch FCH families. The individual LDL subfraction profile was defined as a quantitative trait by the continuous variable K, a reliable estimate of the relative contribution of each LDL subfraction to the overall profile. Variation in parameter K due to age, sex, and hormonal status was taken into account by introducing liability classes. Segregation analysis was performed by fitting a series of class D regressive models were compared using log-likelihoot ratio tests. Our data show that 60% of the variability of parameter K could be explained by lipid and lipoprotein levels and that a major autosomal locus, recessively inherited, with a population frequency of .42 {+-} .07, and an additional polygenic component of .25 best explained the clustering of atherogenic dense LDL subfraction profiles in these FCH families. Therefore, dense LDL subfraction profiles, associated with elevated lipid levels, appear to have a genetic basis in FCH.

  20. In situ delipidation of low-density lipoproteins in capillary electrochromatography yields apolipoprotein B-100-coated surfaces for interaction studies.

    Science.gov (United States)

    D'Ulivo, Lucia; Chen, Jie; Meinander, Kristoffer; Oörni, Katariina; Kovanen, Petri T; Riekkola, Marja-Liisa

    2008-12-01

    An electrochromatographic method was developed for the in situ delipidation of intact low-density lipoprotein (LDL) particles immobilized on the inner wall of a 50-microm inner diameter silica capillary. In this method, the immobilized LDL particles were delipidated with nonionic surfactant Nonidet P-40 at pH 7.4 and 25 degrees C, resulting in an apolipoprotein B-100 (apoB-100)-coated capillary surface. The mobility of the electroosmotic flow marker dimethyl sulfoxide gave information about the surface charge, and the retention factors of beta-estradiol, testosterone, and progesterone were informative of the surface hydrophobicity. The calculated distribution coefficients of the steroids produced specific information about the affinity interactions of the steroids, with capillary surfaces coated either with intact LDL particles or with apoB-100. Delipidation with Nonidet P-40 resulted in a strong decrease in the hydrophobicity of the LDL coating. Atomic force microscopy images confirmed the loss of lipids from the LDL particles and the presence of apoB-100 protein coating. The in situ delipidation of LDL particles in capillaries represents a novel approach for the isolation of immobilized apoB-100 and for the determination of its pI value. The technique requires extremely low quantities of LDL particles, and it is simple and fast.

  1. 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...

  2. Intracellular maturation of apolipoprotein[a] and assembly of lipoprotein[a] in primary baboon hepatocytes.

    Science.gov (United States)

    White, A L; Rainwater, D L; Lanford, R E

    1993-03-01

    The glycoprotein apolipoprotein[a] (apo[a]) is present in plasma at highly variable concentrations and appears as a number of genetically determined size isoforms (400-800 kDa), disulfide linked to apoB-100 in low density lipoprotein to produce lipoprotein [a](Lp[a]). Apo[a] is synthesized by the liver, but the site of association of apo[a] and apoB and factors that regulate its production are unknown. To examine the morphogenesis of the Lp[a] particle, baboon hepatocytes expressing a single, low molecular weight isoform of apo[a] were labeled with [35S]cysteine and methionine, and apo[a] was analyzed by immunoprecipitation and SDS-PAGE. Steady-state labeling revealed two molecular weight forms of apo[a] inside the cell. Only the large form was recovered from the culture medium. Pulse-chase studies and endoglycosidase treatment revealed that the lower molecular weight form of apo[a] represented a precursor with a prolonged residence time in the endoplasmic reticulum or an early Golgi compartment, after which it was processed to the mature form. A proportion of the mature form of apo[a] was rapidly secreted after synthesis, whereas the remainder had a prolonged residence time in a late Golgi compartment. In all experiments, apoB co-precipitated with apo[a] from the culture medium, but not from cell lysates. Density gradient ultracentrifugation and immunoblot analysis revealed that the majority of apo[a] was secreted into the medium in a free form, suggesting that the association between apo[a] and apoB occurred after secretion. Regulation of the movement of apo[a] between intracellular compartments may be one mechanism by which the plasma levels of Lp[a] are influenced.

  3. Residual Cardiovascular Risk in Chronic Kidney Disease: Role of High-density Lipoprotein

    Science.gov (United States)

    Kon, Valentina; Yang, Haichun; Fazio, Sergio

    2016-01-01

    Although reducing low-density lipoprotein-cholesterol (LDL-C) levels with lipid-lowering agents (statins) decreases cardiovascular disease (CVD) risk, a substantial residual risk (up to 70% of baseline) remains after treatment in most patient populations. High-density lipoprotein (HDL) is a potential contributor to residual risk, and low HDL-cholesterol (HDL-C) is an established risk factor for CVD. However, in contrast to conventional lipid-lowering therapies, recent studies show that pharmacologic increases in HDL-C levels do not bring about clinical benefits. These observations have given rise to the concept of dysfunctional HDL where increases in serum HDL-C may not be beneficial because HDL loss of function is not corrected by or even intensified by the therapy. Chronic kidney disease (CKD) increases CVD risk, and patients whose CKD progresses to end-stage renal disease (ESRD) requiring dialysis are at the highest CVD risk of any patient type studied. The ESRD population is also unique in its lack of significant benefit from standard lipid-lowering interventions. Recent studies indicate that HDL-C levels do not predict CVD in the CKD population. Moreover, CKD profoundly alters metabolism and composition of HDL particles and impairs their protective effects on functions such as cellular cholesterol efflux, endothelial protection, and control of inflammation and oxidation. Thus, CKD-induced perturbations in HDL may contribute to the excess CVD in CKD patients. Understanding the mechanisms of vascular protection in renal disease can present new therapeutic targets for intervention in this population. PMID:26009251

  4. Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention

    Directory of Open Access Journals (Sweden)

    Jesús Millán

    2009-09-01

    Full Text Available Jesús Millán1, Xavier Pintó2, Anna Muñoz3, Manuel Zúñiga4, Joan Rubiés-Prat5, Luis Felipe Pallardo6, Luis Masana7, Alipio Mangas8, Antonio Hernández-Mijares9, Pedro González-Santos10, Juan F Ascaso11, Juan Pedro-Botet121Hospital Universitario Gregorio Marañón, Madrid, Spain; 2Hospital Universitario Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain; 3Solvay Pharma, Barcelona, Spain; 4Hospital Marqués de Valdecilla, Santander, Spain; 5Hospital Vall d’Hebrón, Barcelona, Spain; 6Hospital Universitario La Paz, Madrid, Spain; 7Hospital Sant Joan, Reus, Tarragona, Spain; 8Hospital Universitario Puerta del Mar, Cádiz, Spain; 9Hospital Universitario Dr Peset, Valencia, Spain; 10Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain; 11Hospital Clínico Universitario, Valencia, Spain; 12Hospital del Mar, Barcelona, SpainAbstract: Low-density lipoprotein (LDL cholesterol concentration has been the prime index of cardiovascular disease risk and the main target for therapy. However, several lipoprotein ratios or “atherogenic indices” have been defined in an attempt to optimize the predictive capacity of the lipid profile. In this review, we summarize their pathophysiological aspects, and highlight the rationale for using these lipoprotein ratios as cardiovascular risk factors in clinical practice, specifying their cut-off risk levels and a target for lipid-lowering therapy. Total/high-density lipoprotein (HDL cholesterol and LDL/HDL cholesterol ratios are risk indicators with greater predictive value than isolated parameters used independently, particularly LDL. Future recommendations regarding the diagnosis and treatment of dyslipidemia, including instruments for calculating cardiovascular risk or action guidelines, should include the lipoprotein ratios with greater predictive power which, in view of the evidence-based results, are none other than those which include HDL cholesterol.Keywords: apolipoproteins

  5. 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.

  6. Influence of Abdominal Obesity on the Lipid-Lipoprotein Profile in Apoprotein E2/4 Carriers: The Effect of an Apparent Duality

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    Sylvia Villeneuve

    2015-01-01

    Full Text Available Background. Apolipoprotein (Apo E plays a key role in the handling of lipoprotein particles with ApoE2 and ApoE4 frequently having opposite effects compared to ApoE3. Some individuals simultaneously carry both E2 and E4 alleles. The impact of the ApoE2/4 genotype on lipid concentrations and its consequences on health remain poorly documented. Objective. This study compared the lipid profile between ApoE2/4 carriers and other ApoE genotypes in relation to the waist circumference. Methods. Cholesterol, triglyceride (TG, and ApoB concentrations were measured among 2,680 Caucasians. Multivariate logistic regression models were used to estimate the contribution of ApoE2/4 to various dyslipidemic profiles associated with abdominal obesity. Results. In presence of abdominal obesity, the lipid profile was as deteriorated in ApoE2/4 carriers as in carriers of other ApoE genotypes. There was a more pronounced effect on TG-rich lipoproteins, particularly in ApoE2/2 (a feature of type III dysbetalipoproteinemia, and non-high-density lipoprotein (HDL cholesterol in ApoE4/4. Compared to ApoE2/2, ApoE2/4 carriers presented lower very-low-density lipoprotein (VLDL cholesterol concentrations and VLDL-cholesterol/TG ratios, with or without obesity, and higher low-density lipoprotein (LDL cholesterol concentrations. Conclusion. In presence of abdominal obesity, the influence of the ApoE2 allele could be less pronounced than that of ApoE4 among ApoE2/4 individuals.

  7. Influence of Abdominal Obesity on the Lipid-Lipoprotein Profile in Apoprotein E2/4 Carriers: The Effect of an Apparent Duality

    Science.gov (United States)

    Villeneuve, Sylvia; Brisson, Diane; Gaudet, Daniel

    2015-01-01

    Background. Apolipoprotein (Apo) E plays a key role in the handling of lipoprotein particles with ApoE2 and ApoE4 frequently having opposite effects compared to ApoE3. Some individuals simultaneously carry both E2 and E4 alleles. The impact of the ApoE2/4 genotype on lipid concentrations and its consequences on health remain poorly documented. Objective. This study compared the lipid profile between ApoE2/4 carriers and other ApoE genotypes in relation to the waist circumference. Methods. Cholesterol, triglyceride (TG), and ApoB concentrations were measured among 2,680 Caucasians. Multivariate logistic regression models were used to estimate the contribution of ApoE2/4 to various dyslipidemic profiles associated with abdominal obesity. Results. In presence of abdominal obesity, the lipid profile was as deteriorated in ApoE2/4 carriers as in carriers of other ApoE genotypes. There was a more pronounced effect on TG-rich lipoproteins, particularly in ApoE2/2 (a feature of type III dysbetalipoproteinemia), and non-high-density lipoprotein (HDL) cholesterol in ApoE4/4. Compared to ApoE2/2, ApoE2/4 carriers presented lower very-low-density lipoprotein (VLDL) cholesterol concentrations and VLDL-cholesterol/TG ratios, with or without obesity, and higher low-density lipoprotein (LDL) cholesterol concentrations. Conclusion. In presence of abdominal obesity, the influence of the ApoE2 allele could be less pronounced than that of ApoE4 among ApoE2/4 individuals. PMID:26605088

  8. Beneficial effects of omega-3 fatty acids in the proteome of high-density lipoprotein proteome

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    Burillo Elena

    2012-09-01

    Full Text Available Abstract Background Omega-3 poly-unsaturated fatty acids (ω-3 PUFAs have demonstrated to be beneficial in the prevention of cardiovascular disease, however, the mechanisms by which they perform their cardiovascular protection have not been clarified. Intriguingly, some of these protective effects have also been linked to HDL. The hypothesis of this study was that ω-3 PUFAs could modify the protein cargo of HDL particle in a triglyceride non-dependent mode. The objective of the study was to compare the proteome of HDL before and after ω-3 PUFAs supplemented diet. Methods A comparative proteomic analysis in 6 smoker subjects HDL before and after a 5 weeks ω-3 PUFAs enriched diet has been performed. Results Among the altered proteins, clusterin, paraoxonase, and apoAI were found to increase, while fibronectin, α-1-antitrypsin, complement C1r subcomponent and complement factor H decreased after diet supplementation with ω-3 PUFAs. Immunodetection assays confirmed these results. The up-regulated proteins are related to anti-oxidant, anti-inflammatory and anti-atherosclerotic properties of HDL, while the down-regulated proteins are related to regulation of complement activation and acute phase response. Conclusions Despite the low number of subjects included in the study, our findings demonstrate that ω-3 PUFAs supplementation modifies lipoprotein containing apoAI (LpAI proteome and suggest that these protein changes improve the functionality of the particle.

  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. Pharmacogenetic interaction between dexamethasone and Cd36-deficient segment of spontaneously hypertensive rat chromosome 4 affects triacylglycerol and cholesterol distribution into lipoprotein fractions.

    Science.gov (United States)

    Krupková, Michaela; Sedová, Lucie; Liska, Frantisek; Krenová, Drahomíra; Kren, Vladimír; Seda, Ondrej

    2010-04-16

    Dexamethasone (DEX) is known to induce diabetes and dyslipidemia. We have compared fasting triacylglycerol and cholesterol concentrations across 20 lipoprotein fractions and glucose tolerance in control (standard diet) and DEX-treated 7-month-old males of two rat strains, Brown Norway (BN) and congenic BN.SHR-(Il6-Cd36)/Cub (BN.SHR4). These two inbred strains differ in a defined segment of chromosome 4, originally transferred from the spontaneously hypertensive rat (SHR) including the mutant Cd36 gene, a known target of DEX. Compared to BN, the standard-diet-fed BN.SHR4 showed higher cholesterol and triacylglycerol concentrations across many lipoprotein fractions, particularly in small VLDL and LDL particles. Total cholesterol was decreased by DEX by more than 21% in BN.SHR4 contrasting with the tendency to increase in BN (strain*DEX interaction p = 0.0017). Similar pattern was observed for triacylglycerol concentrations in LDL. The LDL particle size was significantly reduced by DEX in both strains. Also, while control BN and BN.SHR4 displayed comparable glycaemic profiles during oral glucose tolerance test, we observed a markedly blunted DEX induction of glucose intolerance in BN.SHR4 compared to BN. In summary, we report a pharmacogenetic interaction between limited genomic segment with mutated Cd36 gene and dexamethasone-induced glucose intolerance and triacylglycerol and cholesterol redistribution into lipoprotein fractions.

  11. Studies on the Formation of Murein-Bound Lipoprotein in Escherichia coli

    Science.gov (United States)

    1992-05-15

    Proteus mirabilis, Morqanella morqanii, Erwinia amylovora and serratia marcescens, and in Pseudomonas aeruqinosa lipoprotein I (Fig. 5., YU, 1987... Erwinia amylovora lipoprotein gene. J. Biol. Chern. 256:2194-2198. Yamaguchi, K., and Inouye, M. (1988). Lipoprotein 28, an inner membrane protein of...et AI., 1983), ~. amylovora (Yamagata et li., 1981) and ~. marcescens (Braun et al., 1970), and in .E. aeruginosa (Mizuno and Kageyama, 1979). Like

  12. Recurrent Embolic Strokes of Undetermined Source in a Patient with Extreme Lipoprotein(a) Levels.

    Science.gov (United States)

    Bulwa, Zachary; Kim, Audrey; Singh, Karandeep; Kantorovich, Alexander; Suhail, Faten

    2016-01-01

    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.

  13. 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.

  14. 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.

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

    Science.gov (United States)

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

    1984-09-01

    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. [14C]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 [14C]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.

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

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    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. Acidity and lipolysis by group V secreted phospholipase A(2) strongly increase the binding of apoB-100-containing lipoproteins to human aortic proteoglycans.

    Science.gov (United States)

    Lähdesmäki, Katariina; Öörni, Katariina; Alanne-Kinnunen, Mervi; Jauhiainen, Matti; Hurt-Camejo, Eva; Kovanen, Petri T

    2012-02-01

    Local acidic areas characterize diffuse intimal thickening (DIT) and advanced atherosclerotic lesions. The role of acidity in the modification and extra- and intracellular accumulation of triglyceride-rich VLDL and IDL particles has not been studied before. Here, we examined the effects of acidic pH on the activity of recombinant human group V secreted phospholipase A(2) (sPLA(2)-V) toward small VLDL (sVLDL), IDL, and LDL, on the binding of these apoB-100-containing lipoproteins to human aortic proteoglycans, and on their uptake by human monocyte-derived macrophages. At acidic pH, the ability of sPLA(2)-V to lipolyze the apoB-100-containing lipoproteins was moderately, but significantly, increased while binding of the lipoproteins to proteoglycans increased >60-fold and sPLA(2)-V-modification further doubled the binding. Moreover, acidic pH more than doubled macrophage uptake of soluble complexes of sPLA(2)-V-LDL with aortic proteoglycans. Proteoglycan-affinity chromatography at pH 7.5 and 5.5 revealed that sVLDL, IDL, and LDL consisted of populations with different proteoglycan-binding affinities, and, surprisingly, the sVLDL fractions with the highest proteoglycan-affinity contained only low amounts of apolipoproteins E and C-III. Our results suggest that in atherosclerotic lesions with acidic extracellular pH, sPLA(2)-V is able to lipolyze sVLDL, IDL, and LDL, and increase their binding to proteoglycans. This is likely to provoke extracellular accumulation of lipids derived from these atherogenic lipoprotein particles and to increase the progression of the atherosclerotic lesions.

  18. Lipoprotein(a: Metabolismus und Beeinflussung des Plasmaspiegels

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    Kostner GM

    2002-01-01

    Full Text Available Lipoprotein(a [Lp(a] ist eines der atherogensten Lipoproteine. Es besteht aus einem Core Low Density Lipoprotein (LDL und dem spezifischen Antigen, Apo(a. Letzteres ist ein extrem polymorphes Glykoprotein, welches aus zwischen 11 und mehr als 40 Kringel-IV-Einheiten besteht, die homolog zum Kringel-IV des Plasminogens sind. Die Atherogenität von Lp(a, die einerseits auf seine Strukturähnlichkeit mit Plas-minogen, andererseits auf seine extrem hohe Affinität zu Proteoglykanen der Blutgefäße zurückzuführen ist, wurde in zahlreichen prospektiven Studien dokumentiert. Die Mittel- bzw. Medianwerte für Lp(a in der weißen Bevölkerung betragen 17 bzw. 9 mg/dl. Als Grenzwert, ab welchem ein erhöhtes Atheroskleroserisiko auftritt, gilt allgemein 25?30 mg/dl. Die Plasmakonzentration von Lp(a ist streng genetisch determiniert und korreliert negativ mit der Kringelzahl. Andererseits wird die Plasmakonzentration von der Syntheserate und nicht vom Katabolismus bestimmt. Hormone wie T3/T4, Steroid- und im besonderen Wachstumshormone und ILG-1 zeigen sehr deutliche Einflüsse auf den Lp(a-Metabolismus. Leberpatienten haben im Verhältnis zu ihrer Kringelzahl stark erniedrigte und Nierenpatienten stark erhöhte Plasma-Lp(a-Spiegel. Die stärkste pharmakologische Wirkung auf Lp(a haben anabole Steroide. Aber auch Alkohol, Acetylsalicylsäure, Ascorbinsäure und vor allem Nikotinsäure wirken Lp(a-senkend. Die herkömmlichen Lipidsenker zeigen - wenn überhaupt - nur eine geringe Wirkung. Bisher ist kein nennenswert Lp(a-senkendes Statin gefunden worden. Eine futuristische Möglichkeit, therapeutisch einzugreifen, wurde von uns mittels "anti-sense Oligonucleotide"-Therapie an Versuchstieren getestet. Es gelang damit, die Apo(a-Synthese praktisch auf Null zu senken.

  19. 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)

  20. The influence of lipoprotein(a on fibrinolytic activity

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    Rahajuningsih D. Setiabudy

    2004-09-01

    Full Text Available Lipoprotein(a is a plasma lipoprotein whose structure and composition are similar with low density lipoprotein (LDL with an addition of apo(a that is bound to apo B100. The structure of apo(a is similar with plasminogen, a proenzym in fibrinolytic system. Due to this similarity, it is assumed that Lp(a can inhibit plasminogen activity and decreases fibrinolytic activity. The purpose of this study is to prove that addition of Lp(a to normal plasma can inhibit fibrinolytic activity. Four healthy people whose fibrinogen levels, plasminogen activities and euglobulin clot lysis time were within normal range were enrolled in this study. Fibrinolytic activity were assessed by euglobulin clot lysis time (ECLT. In the first experiment, the addition of Lp(a was done before centrifugation to obtain euglobulin precipitates, while in the second experiment, Lp(a was added to the euglobulin precipitates. As a control, ECLT was performed in the plasma with the addition of NaCl 0.9% in the same volume with Lp(a. The results of the study showed that in the first experiment, there was no clot formation. It is assumed that Lp(a can bind fibrinogen and both of them floated in the supernatant, so there was no fibrinogen in the euglobulin precipitate that can be clotted by thrombin. In the second experiment, the clot did not dissolve until the fourth day. In conclusion, the addition of Lp(a to normal plasma can inhibit the activity of fibrinolytic system. (Med J Indones 2004; 13: 135-9 Keywords: plasminogen, fibrinogen, apo(a, euglobulin clot lysis time (ECLT

  1. Development of a New High-throughput Screening Model for Human High Density Lipoprotein Receptor (CLA-1) Agonists

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To develop a new high-throughput screening model for human high-density lipoprotein (HDL) receptor (CD36 and LIMPII analogous-1, CLA-1) agonists using CLA-1-expressing insect cells. Methods With the total RNA of human hepatoma cells BEL-7402 as template, the complementary DNA (cDNA) of CLA-1 was amplified by reverse transcription-polymerase chain reaction (RT-PCR). Bac-to-Bac baculovirus expression system was used to express CLA-1 in insect cells. CLA-1 cDNA was cloned downstream of polyhedrin promoter of Autographa californica nuclear polyhedrosis virus (AcNPV) into donor vector pFastBac1 and recombinant pFastBac1-CLA-1 was transformed into E. coli DH10Bac to transpose CLA-1 cDNA to bacmid DNA. Recombinant bacmid-CLA-1 was transfected into Spodoptera frugiperda Sf9 insect cells to produce recombinant baculovirus particles. Recombinant CLA-1 was expressed on the membrane of Sf9 cells infected with the recombinant baculoviruses. A series of parameters of DiI-lipoprotein binding assays of CLA-1-expressing Sf9 cells in 96-well plates were optimized. Results Western blot analysis and DiI-lipoprotein binding assays confirmed that CLA-1 expressed in insect cells had similar immunoreactivity and ligand binding activity as its native counterpart. A reliable and sensitive in vitro cell-based assay was established to assess the activity of CLA-1 and used to screen agonists from different sample libraries. Conclusion Human HDL receptor CLA-1 was successfully expressed in Sf9 insect cells and a novel high-throughput screening model for CLA-1 agonists was developed. Utilization of this model allows us to identify potent and selective CLA-1 agonists which might possibly be used as therapeutics for atherosclerosis.

  2. Carbohydrate composition of circulating multiple-modified low-density lipoprotein

    Science.gov (United States)

    Zakiev, Emile R; Sobenin, Igor A; Sukhorukov, Vasily N; Myasoedova, Veronika A; Ivanova, Ekaterina A; Orekhov, Alexander N

    2016-01-01

    Atherogenic modification of low-density lipoprotein (LDL) plays a crucial role in the pathogenesis of atherosclerosis, as modified LDL, but not native LDL, induces pronounced accumulation of cholesterol and lipids in the arterial wall. It is likely that LDL particles undergo multiple modifications in human plasma: desialylation, changes in size and density, acquisition of negative electric charge, oxidation, and complex formation. In a total LDL preparation isolated from pooled plasma of patients with coronary atherosclerosis and from healthy subjects, two subfractions of LDL could be identified: desialylated LDL bound by a lectin affinity column and normally sialylated (native) LDL that passed through the column. The desialylated LDL subfraction therefore represents circulating modified LDL. In this work, we performed a careful analysis of LDL particles to reveal changes in the composition of glycoconjugates associated with proteins and lipids. Protein fraction of LDL from atherosclerotic patients contained similar amounts of glucosamine, galactose, and mannose, but a 1.6-fold lower level of sialic acid as compared to healthy donors. Lipid-bound glycoconjugates of total LDL from patients with coronary atherosclerosis contained 1.5–2-fold less neutral monosaccharides than total LDL from healthy donors. Patient-derived LDL also contained significantly less sialic acid. Our results demonstrate that carbohydrate composition of LDL from atherosclerotic patients was altered in comparison to healthy controls. In particular, prominent decrease in the sialic acid content was observed. This strengthens the hypothesis of multiple modification of LDL particles in the bloodstream and underscores the clinical importance of desialylated LDL as a possible marker of atherosclerosis progression.

  3. Lipoprotein apheresis in the management of severe hypercholesterolemia and of elevation of lipoprotein(a): current perspectives and patient selection

    Science.gov (United States)

    Julius, Ulrich

    2016-01-01

    This review reports the current situation with respect to therapeutic options (lifestyle and drugs) reducing the concentrations of atherogenic low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]). Three lipoprotein apheresis (LA) principles have been realized: precipitation, filtration, and adsorption. Available LA methods are herein described in detail – major components, pumps, extracorporeal volume, treated volume, and anticoagulation. General features of all LA methods as well as pleotropic effects are elaborated. Indications for LA therapy are quoted: homozygous familial hypercholesterolemia (HCH), severe HCH, and isolated elevation of Lp(a) and progress of atherosclerotic disease. A major focus is on the evidence of the effect of LA on cardiovascular outcome data, and the most important publications are cited in this context. The best studies have been performed in patients with elevated Lp(a) in whom cardiovascular events were reduced by more than 80%. Major adverse effects and contraindications are listed. The impact of an LA therapy on patient quality of life and the requirements they have to fulfill are also highlighted. Finally, the future role of LA in treating high-risk patients with high LDL-C and/or high Lp(a) is discussed. It is probable that the significance of LA for treating patients with elevated LDL-C will decrease (with the exception of homozygous familial HCH) due to the application of PCSK9 inhibitors. The antisense oligonucleotide against apolipoprotein(a) could replace LA in patients with high Lp(a), provided positive outcome data are generated. PMID:27785114

  4. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans

    OpenAIRE

    Kathiresan, Sekar; Melander, Olle; Guiducci, Candace; Surti, Aarti; Burtt, Noël P.; Rieder, Mark J; Cooper, Gregory M.; Roos, Charlotta; Benjamin F Voight; Havulinna, Aki S.; Wahlstrand, Björn; Hedner, Thomas; Corella, Dolores; Tai, E Shyong; Ordovas, Jose M.

    2008-01-01

    Blood concentrations of lipoproteins and lipids are heritable1 risk factors for cardiovascular disease2,3. Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue4) and targeted replication associat...

  5. 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.

  6. Lipid profiling of lipoprotein X: Implications for dyslipidemia in cholestasis.

    Science.gov (United States)

    Heimerl, Susanne; Boettcher, Alfred; Kaul, Harald; Liebisch, Gerhard

    2016-08-01

    Lipoprotein X (Lp-X) is an abnormal lipoprotein that may typically be formed in intra- and extrahepatic cholestasis and potentially interfere with lipid analysis in the routine lab. To gain insight into lipid class and species composition, Lp-X, LDL and HDL from cholestatic and control serum samples were subjected to mass spectrometric analysis including phospholipids (PL), sphingolipids, free cholesterol (FC), cholesteryl esters (CE) and bile acids. Our analysis of Lp-X revealed a content of 46% FC, 49% PL with 34% phosphatidylcholine (PC) as main PL component. The lipid species pattern of Lp-X showed remarkable high fractions of mono-unsaturated species including PC 32:1 and PC 34:1 and phosphatidylethanolamine (PE) 32:1 and 34:1. LDL and HDL lipid composition in the same specimens strongly reflected the lipid composition of Lp-X with increased PC 32:1, PC 34:1, PE 32:1, PE 34:1 and FC accompanied by decreased CE compared to controls. Comparison of Lp-X and biliary lipid composition clearly indicates that Lp-X does not originate from a sole release of bile lipids. Moreover, these data present evidence for increased hepatic fatty acid and PL synthesis which may represent a reaction to high hepatic FC level observed during cholestasis.

  7. Lipoprotein (a) and cardiovascular risk factors in children and adolescents

    Science.gov (United States)

    Palmeira, Ástrid Camêlo; Leal, Adriana Amorim de F.; Ramos, Nathaly de Medeiros N.; de Alencar F., José; Simões, Mônica Oliveira da S.; Medeiros, Carla Campos M.

    2013-01-01

    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. PMID:24473960

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

    NARCIS (Netherlands)

    DULLAART, RPF

    1995-01-01

    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 pla

  9. Genetic evidence that lipoprotein(a) associates with atherosclerotic stenosis rather than venous thrombosis

    DEFF Research Database (Denmark)

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

    2012-01-01

    The aim of the present study was to determine whether lipoprotein(a) [Lp(a)], considered a causal risk factor for cardiovascular disease, primarily promotes thrombosis or atherosclerosis.......The aim of the present study was to determine whether lipoprotein(a) [Lp(a)], considered a causal risk factor for cardiovascular disease, primarily promotes thrombosis or atherosclerosis....

  10. Screening for apolipoprotein E gene mutations in 4 patients with lipoprotein glomerulopathy

    Institute of Scientific and Technical Information of China (English)

    潘永利

    2006-01-01

    Objective To study the mutations of apolipoprotein E (apoE) gene in 4 Chinese lipoprotein glomerulopathy (LPG) patients and their family members, and to investigate the pathogenesis of LPG. Methods Urinalysis was performed on the family members of two patients, and they were screened for the level of serum creatinine, serum lipid and serum lipoprotein. The mutation of apoE

  11. Gene therapy for genetic lipoprotein lipase deficiency : from promise to practice

    NARCIS (Netherlands)

    Nierman, M C; Rip, J; Twisk, J; Meulenberg, J J M; Kastelein, J J P; Stroes, E S G; Kuivenhoven, J A

    2005-01-01

    Lipoprotein lipase (LPL) deficiency is a rare, hereditary disorder of lipoprotein metabolism characterised by severely increased triglyceride levels, and associated with an increased risk for pancreatitis. Since no adequate treatment modality is available for this disorder, we set out to develop an

  12. 21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-lipoprotein immuno-logical test system. 866.5580 Section 866.5580 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...-lipoprotein may aid in the diagnosis of Tangier disease (a hereditary disorder of fat metabolism)....

  13. 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...

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

    NARCIS (Netherlands)

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

    1999-01-01

    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

  15. Adaptive immune response to lipoproteins of Staphylococcus aureus in healthy subjects

    NARCIS (Netherlands)

    Vu, Chi Hai; Kolata, Julia; Stentzel, Sebastian; Beyer, Anica; Salazar, Manuela Gesell; Steil, Leif; Pané-Farré, Jan; Rühmling, Vanessa; Engelmann, Susanne; Götz, Friedrich; van Dijl, Jan Maarten; Hecker, Michael; Mäder, Ulrike; Schmidt, Frank; Völker, Uwe; Bröker, Barbara M

    2016-01-01

    Staphylococcus aureus is a frequent commensal but also a dangerous pathogen, causing many forms of infection ranging from mild to life-threatening conditions. Among its virulence factors are lipoproteins, which are anchored in the bacterial cell membrane. Lipoproteins perform various functions in co

  16. Nanoporous carbon sorbent for molecular-sieve chromatography of lipoprotein complex

    Science.gov (United States)

    Kerimkulova, A. R.; Mansurova, B. B.; Gil'manov, M. K.; Mansurov, Z. A.

    2012-06-01

    The physicochemical characteristics of carbon sorbents are investigated. Electron microscopy data for the sorbent and separated lipoprotein complex are presented. It is found that the obtained carbon sorbent possess high porosity. Nanoporous carbon sorbents for the chromatography of molecular-sieve markers are obtained and tested. The applicability of nanoporous carbon sorbents for separation of lipoprotein complexes (LPC) is investigated.

  17. 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 chromatographi...

  18. Outer membrane protein A, peptidoglycan-associated lipoprotein, and murein lipoprotein are released by Escherichia coli bacteria into serum.

    Science.gov (United States)

    Hellman, J; Loiselle, P M; Tehan, M M; Allaire, J E; Boyle, L A; Kurnick, J T; Andrews, D M; Sik Kim, K; Warren, H S

    2000-05-01

    Complexes containing lipopolysaccharide (LPS) and three outer membrane proteins (OMPs) are released by gram-negative bacteria incubated in human serum and into the circulation in an experimental model of sepsis. The same OMPs are bound by immunoglobulin G (IgG) in the cross-protective antiserum raised to Escherichia coli J5 (anti-J5 IgG). This study was performed to identify the three OMPs. The 35-kDa OMP was identified as outer membrane protein A (OmpA) by immunoblotting studies using OmpA-deficient bacteria and recombinant OmpA protein. The 18-kDa OMP was identified as peptidoglycan-associated lipoprotein (PAL) based on peptide sequences from the purified protein and immunoblotting studies using PAL-deficient bacteria. The 5- to 9-kDa OMP was identified as murein lipoprotein (MLP) based on immunoblotting studies using MLP-deficient bacteria. The studies identify the OMPs released into human serum and into the circulation in an experimental model of sepsis as OmpA, PAL, and MLP.

  19. Identification and quantification of regioisomeric cholesteryl linoleate hydroperoxides in oxidized human low density lipoprotein and high density lipoprotein.

    Science.gov (United States)

    Kenar, J A; Havrilla, C M; Porter, N A; Guyton, J R; Brown, S A; Klemp, K F; Selinger, E

    1996-06-01

    Oxidation of human LDL is implicated as an initiator of atherosclerosis. Isolated low density lipoprotein (LDL) and high density lipoprotein (HDL2) were exposed to aqueous radicals generated from the thermolabile azo compound 2,2'-azobis(2-amidinopropane) dihydrochloride. The primary nonpolar lipid products formed from the autoxidation of LDL and HDL were the regioisomeric cholesteryl linoleate hydroperoxides. In LDL oxidations, 9- and 13-hydroperoxides with trans,cis conjugated diene were formed as the major oxidation products if endogenous alpha-tocopheral was present in the LDL. After extended oxidation of LDL, at the time when endogenous alpha-tocopherol was consumed, the two trans,cis conjugated diene hydroperoxides began to disappear and the 9- and 13-hydroperoxides with trans,trans conjugated diene appeared. At very long oxidation times, none of the primary products, the conjugated diene hydroperoxides, were present. In HDL2, which has only very low levels of antioxidants, both the 9- and 13-hydroperoxides with trans,cis conjugated diene and the 9- and 13-hydroperoxides with trans,trans conjugated diene were formed at early stages of oxidation. The corresponding alcohols were also formed in the HDL2 oxidations. A mechanistic hypothesis consistent with these observations is presented.

  20. 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...

  1. A comparison of the kinetics of low-density lipoprotein oxidation initiated by copper or by azobis (2-amidinopropane).

    Science.gov (United States)

    Thomas, M J; Chen, Q; Franklin, C; Rudel, L L

    1997-01-01

    This article describes the kinetics of low density lipoprotein (LDL) oxidation catalyzed by azobis (2-amidinopropane) dihydrochloride, ABAP, or by copper. The LDLs were isolated from nonhuman primates fed diets enriched in one of three types of fatty acids: saturated fatty acids, monounsaturated fatty acids, predominantly, oleic acid, or polyunsaturated fatty acids, predominantly linoleic acid. Oxidation was followed by monitoring the formation of conjugated diene hydroperoxides from polyunsaturated fatty acids (PUFA). For both copper and ABAP-initiated oxidation, the rate of LDL oxidation depended on the concentrations of initiator, PUFA, and LDL. Except for the dependence on PUFA concentration the rate of LDL oxidation was not directly influenced by the fatty acid composition of the LDL particle. The two initiators had very different dependence on initiator concentration. Because LDL particles are essentially small, lipid-rich droplets, the kinetic descriptions of LDL oxidation assumed: (1), that there was only one chain per particle, and (2) that the radical chain was terminated when a second radical either entered or was formed in the particle. When two LDL samples having very different lag times were mixed, the oxidation profile was bimodal. This finding demonstrated that the oxidation of native LDL particles was independent of the oxidation state of the other native LDL particles in solution, i.e., LDL particles do not rapidly exchange radicals, for example, hydroperoxyl radicals. Oxidation initiated by ABAP was proportional to [ABAP]0.5, suggesting that hydroperoxyl radical recombination between the lipid hydroperoxyl radical and the ABAP-hydroperoxyl radical was the chain-terminating step. The reciprocal of the rate of copper oxidation was linearly related to the reciprocal copper concentration, demonstrating that the binding of copper to LDL was necessary to initiate oxidation. This binding constant showed considerable variability among LDL samples. The

  2. Roles of lipoprotein receptors in the entry of hepatitis C virus

    Institute of Scientific and Technical Information of China (English)

    Jingya; Lyu; Hitomi; Imachi; Kensaku; Fukunaga; Takuo; Yoshimoto; Huanxiang; Zhang; Koji; Murao

    2015-01-01

    Infection by hepatitis C virus(HCV), a plus-stranded RNA virus that can cause cirrhosis and hepatocellular carcinoma, is one of the major health problems in the world. HCV infection is considered as a multistep complex process and correlated with abnormal metabolism of lipoprotein. In addition, virus attacks hepatocytes by the initial attaching viral envelop glycoprotein E1/E2 to receptors of lipoproteins on host cells. With the development of HCV model system, mechanisms of HCV cell entry through lipoprotein uptake and its receptor have been extensively studied in detail. Here we summarize recent knowledge about the role of lipoprotein receptors, scavenger receptor class B type Ⅰ and low-density lipoprotein receptor in the entry of HCV, providing a foundation of novel targeting therapeutic tools against HCV infection.

  3. 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...... 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.......84. The models were tested with an independent test set giving prediction errors between 19 and 46% and r between 0.96 and 0.76. Prediction of High, Low and Very Low Density Lipoprotein (HDL, LDL and VLDL) and total cholesterol was conducted in a study where rats had been supplemented with two doses of air...

  4. Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy.

    Science.gov (United States)

    Annema, Wijtske; von Eckardstein, Arnold

    2016-07-01

    Low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risks of coronary heart disease. HDL mediates cholesterol efflux from macrophages for reverse transport to the liver and elicits many anti-inflammatory and anti-oxidative activities which are potentially anti-atherogenic. Nevertheless, HDL has not been successfully targeted by drugs for prevention or treatment of cardiovascular diseases. One potential reason is the targeting of HDL cholesterol which does not capture the structural and functional complexity of HDL particles. Hundreds of lipid species and dozens of proteins as well as several microRNAs have been identified in HDL. This physiological heterogeneity is further increased in pathologic conditions due to additional quantitative and qualitative molecular changes of HDL components which have been associated with both loss of physiological function and gain of pathologic dysfunction. This structural and functional complexity of HDL has prevented clear assignments of molecules to the functions of normal HDL and dysfunctions of pathologic HDL. Systematic analyses of structure-function relationships of HDL-associated molecules and their modifications are needed to test the different components and functions of HDL for their relative contribution in the pathogenesis of atherosclerosis. The derived biomarkers and targets may eventually help to exploit HDL for treatment and diagnostics of cardiovascular diseases.

  5. Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein Nanoparticles

    Directory of Open Access Journals (Sweden)

    Mian M.K. Shahzad

    2011-04-01

    Full Text Available RNA interference holds tremendous potential as a therapeutic approach, especially in the treatment of malignant tumors. However, efficient and biocompatible delivery methods are needed for systemic delivery of small interfering RNA (siRNA. To maintain a high level of growth, tumor cells scavenge high-density lipoprotein (HDL particles by overexpressing its receptor: scavenger receptor type B1 (SR-B1. In this study, we exploited this cellular characteristic to achieve efficient siRNA delivery and established a novel formulation of siRNA by incorporating it into reconstituted HDL (rHDL nanoparticles. Here, we demonstrate that rHDL nanoparticles facilitate highly efficient systemic delivery of siRNA in vivo, mediated by the SR-B1. Moreover, in therapeutic proof-of-concept studies, these nanoparticles were effective in silencing the expression of two proteins that are key to cancer growth and metastasis (signal transducer and activator of transcription 3 and focal adhesion kinase in orthotopic mouse models of ovarian and colorectal cancer. These data indicate that an rHDL nanoparticle is a novel and highly efficient siRNA carrier, and therefore, this novel technology could serve as the foundation for new cancer therapeutic approaches.

  6. 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.

  7. [The receptor-mediated endocytosis of influenza viruses and low-density lipoproteins by tissue cells].

    Science.gov (United States)

    Pleskov, V M; Bannikov, A I; Zaĭtsev, Iu V

    1994-01-01

    The experimental data obtained by immunological, immunomorphological, biochemical, and virological methods are presented which substantiate a concept that various strains of influenza virus under study may penetrate tissue cells at sites of high affinity usually meant for low-density lipoproteins (LDLP) providing the cells with cholesterol for construction of outer and inner membranes. A computer analysis of a bank of data on the primary structure of proteins (the package of GENBER programme) revealed significant similarity of amino acid sequences between the area of viral hemagglutinin site attachment to cells and corresponding amino acids comprising apoB LDLP. The presented proofs are a convincing example of virus particles mimicry realized at the molecular level and give new concepts concerning the mechanisms of virus penetration into body cells which are important for the development of a principally new approach to creation of highly effective antiviral compounds. Moreover, the observed phenomenon may serve for explanation of the nature and mechanism of action of the so-called thermostable virus-neutralizing blood serum inhibitor.

  8. 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.

  9. 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.

  10. Stability of serum high-density lipoprotein-microRNAs for preanalytical conditions.

    Science.gov (United States)

    Ishikawa, Hiroaki; Yamada, Hiroya; Taromaru, Nao; Kondo, Kanako; Nagura, Ayuri; Yamazaki, Mirai; Ando, Yoshitaka; Munetsuna, Eiji; Suzuki, Koji; Ohashi, Koji; Teradaira, Ryoji

    2017-01-01

    Background Recently, several studies have shown that microRNAs are present in high-density lipoprotein, and high-density lipoprotein-microRNA may be a promising disease biomarker. We investigated the stability of high-density lipoprotein-microRNAs in different storage conditions as this is an important issue for its application to the field of clinical research. Methods microRNAs were extracted from the high-density lipoprotein fraction that was purified from the serum. miR-135 a and miR-223, which are known to be present in high-density lipoprotein, were quantified by quantitative real-time PCR. The influence of preanalytical parameters on the analysis of high-density lipoprotein-miRNAs was examined by the effect of RNase, storage conditions, and freezing and thawing. Results The concentrations of microRNA in high-density lipoprotein were not altered by RNase A treatment (0-100 U/mL). No significant change in these microRNAs was observed after storing serum at room temperature or 4℃ for 0-24 h, and there was a similar result in the cryopreservation for up to two weeks. Also, high-density lipoprotein-microRNAs were stable for, at least, up to five freeze-thaw cycles. Conclusions These results demonstrated that high-density lipoprotein-microRNAs are relatively resistant to various storage conditions. This study provides new and important information on the stability of high-density lipoprotein-microRNAs.

  11. Skin autofluorescence is inversely related to HDL anti-oxidative capacity in type 2 diabetes mellitus

    NARCIS (Netherlands)

    Mulder, Douwe J.; de Boer, Jan Freark; Graaff, Reindert; de Vries, Rindert; Annema, Wijtske; Lefrandt, Joop D.; Smit, Andries J.; Tietge, Uwe J. F.; Dullaart, Robin P. F.

    2011-01-01

    Objective: High density lipoprotein (HDL) particles protect apolipoprotein B-containing lipoproteins from oxidative modification. An impaired anti-oxidative functionality of HDL in type 2 diabetes mellitus (T2DM) may contribute to enhanced formation of oxidative stress products, such as Advanced Gly

  12. Low density lipoprotein receptor-related protein-2/megalin is expressed in oligodendrocytes in the mouse spinal cord white matter

    DEFF Research Database (Denmark)

    Wicher, Grzegorz; Larsson, Mårten; Svenningsen, Åsa Fex;

    2006-01-01

    Lipoprotein receptor-related protein-2 (LRP2)/megalin is a member of the low density lipoprotein receptor (LDLR) family, and is essential in absorptive epithelia for endocytosis of lipoproteins, low molecular weight proteins, cholesterol and vitamins, as well as in cellular signaling. Previous...

  13. Effect of improving glycemic control in patients with type 2 diabetes mellitus on low-density lipoprotein size, electronegative low-density lipoprotein and lipoprotein-associated phospholipase A2 distribution.

    Science.gov (United States)

    Sánchez-Quesada, José L; Vinagre, Irene; de Juan-Franco, Elena; Sánchez-Hernández, Juan; Blanco-Vaca, Francisco; Ordóñez-Llanos, Jordi; Pérez, Antonio

    2012-07-01

    The aim of this study was to determine the effect of intensified hypoglycemic therapy in patients with type 2 diabetes mellitus on the distribution of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity between high-density lipoprotein and low-density lipoprotein (LDL) and its relation with the lipid profile and other qualitative properties of LDL. Forty-two patients with type 2 diabetes on the basis of poor glycemic control and normal or near normal LDL cholesterol were recruited. Lifestyle counseling and pharmacologic hypoglycemic therapy were intensified to improve glycemic control, but lipid-lowering therapy was unchanged. At 4 ± 2 months, glycosylated hemoglobin had decreased by a mean of 2.1%, but the only effect on the lipid profile were statistically significant decreases in nonesterified fatty acids and apolipoprotein B concentration. LDL size increased and the proportion of electronegative LDL decreased significantly. In parallel, total Lp-PLA2 activity decreased significantly, promoting a redistribution of Lp-PLA2 activity toward a higher proportion in high-density lipoprotein. Improvements in glycemic control led to more marked changes in Lp-PLA2 activity and distribution in patients with diabetes who had not received previous lipid-lowering therapy. In conclusion, optimizing glycemic control in patients with type 2 diabetes promotes atheroprotective changes, including larger LDL size, decreased electronegative LDL, and a higher proportion of Lp-PLA2 activity in high-density lipoprotein.

  14. [Comparison of remnant lipoprotein-cholesterol measurements: the immune adsorption method (RLP-C) and the direct assay with detergent (RemL-C)].

    Science.gov (United States)

    Hihara, Mari; Sato, Itsuko; Hayashi, Fujio; Sugiyama, Daisuke; Kawano, Seiji; Fujioka, Yoshio; Ishikawa, Yuichi; Kumagai, Shunichi

    2009-01-01

    Elevation of serum remnant lipoprotein concentration is an emerging risk factor for coronary artery disease. An immunoseparation procedure for remnant-like particle cholesterol(RLP-C) has been evaluated extensively in recent years. In addition, a new detergent-based method has been developed and applied to automated analyzer as "MetaboLead RemL-C" (RemL-C, KYOWA MEDEX CO., LTD.). Then, we compared the concentrations of remnant lipoproteins as RemL-C with those as RLP-C in various conditions. RemL-C assay was intra-assay-reproducible (n=20, CVs: 0.6-2.2%), and reproducible for 2 days in the refrigeration and for 8 hours in room temperature. This assay was also inter-assay-reproducible (during 5 days in the deep freezing, CVs: 1.6-3.0%). The available range for RemL-C assay was between 0.09 and 121.1 mg/dl. There were no detectable interferences from hemoglobin, free/conjugated bilirubin, chyle, and Intrafat. However, heparin influenced the titer of RemL-C concentrations. Correlation of values between RLP-C and RemL-C in 123 samples was excellent (r=0.924, p<0.001). However, different responses to intermediate lipoprotein fraction derived from a patients with type III hyperlipidemia were observed. In conclusion, RemL-C and RLP-C measurements may have a similar clinical significance. Differences in sensitivity for intermediate lipoprotein fraction between both methods may exist.

  15. Interaction of variable bacterial outer membrane lipoproteins with brain endothelium.

    Directory of Open Access Journals (Sweden)

    Gaurav Gandhi

    Full Text Available BACKGROUND: Previously we reported that the variable outer membrane lipoprotein Vsp1 from the relapsing fever spirochete Borrelia turicatae disseminates from blood to brain better than the closely related Vsp2 [1]. Here we studied the interaction between Vsp1 and Vsp2 with brain endothelium in more detail. METHODOLOGY/PRINCIPAL FINDINGS: We compared Vsp1 to Vsp2 using human brain microvascular endothelial cell (HBMEC association assays with aminoacid radiolabeled Vsp-expressing clones of recombinant Borrelia burgdorferi and lanthanide-labeled purified lipidated Vsp1 (LVsp1 and Vsp2 (LVsp2 and inoculations of the lanthanide-labeled proteins into mice. The results showed that heterologous expression of LVsp1 or LVsp2 in B. burgdorferi increased its association with HBMEC to a similar degree. Purified lanthanide-labeled lipidated Vsp1 (LVsp1 and LVsp2 by themselves were capable of associating with HBMEC. The association of LVsp1 with brain endothelium was time-dependent, saturable, and required the lipidation. The association of Vsp1 with HBMEC was inhibited by incubation at lower temperature or with excess unlabeled LVsp1 or LVsp2 but not with excess rVsp1 or mouse albumin or an anti Vsp1 monoclonal antibody. The association of LVsp2 with HBMEC and its movement from blood to brain parenchyma significantly increased in the presence of LVsp1. CONCLUSIONS/SIGNIFICANCE: Variable bacterial outer membrane lipoproteins interact with brain endothelium differently; the lipidation and variable features at the protein dome region are key modulators of this interaction.

  16. 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

  17. Association of small dense lowdensity lipoprotein cholesterol in type 2 diabetics with coronary artery disease

    Directory of Open Access Journals (Sweden)

    Ya-Ching Huang

    2014-12-01

    Full Text Available Background: The risk of coronary artery disease (CAD increases two- to fourfold in diabetes. Small dense low-density lipoprotein (sdLDL particles have been linked to an increased risk for CAD. In this study, we sought to compare the sdLDL cholesterol (sdLDL-C level between the healthy control group and diabetics with CAD in the Taiwanese population. Methods: Serum specimens were collected from healthy females and males of various age groups (n = 294, type 2 diabetics (DM without complications (n = 113, and patients having DM with CAD (DM-CAD (n = 46. The commercial kit was used for the measurement of sdLDL-C level, which employs a simpler method. After heparin-magnesium precipitation of lipoproteins with density <1.044 g/ml, sdLDL (density = 1.044-1.063 g/ml remained in the supernatant and this sdLDL-C was measured using an automated chemistry analyzer. Results: The sdLDL-C level was significantly higher in males than in females (p < 0.001 and there was an age effect on sdLDL-C (p < 0.001. The DM-CAD group had significantly higher sdLDL-C levels than the healthy control group (p < 0.001, but there was no statistical difference in the LDL-C level between DM-CAD group and the healthy control group. In addition, only individuals having both high LDL-C and sdLDL-C levels had a higher risk for DM-CAD, compared to those with low LDL-C levels and low sdLDL-C levels [Odds Ratio (OR 4.97; 95% Confidence Interval (CI 1.96-12.57; p = 0.001]. Conclusions: Our data suggest that the sdLDL-C level together with the LDL-C level are better risk assessment markers for type 2 diabetics with CAD than the LDL-C level alone.

  18. Thermal transitions in the low-density lipoprotein and lipids of the egg yolk of hens.

    Science.gov (United States)

    Smith, M B; Back, J F

    1975-05-22

    1. Differential sanning calorimetry and light-scattering have been used to investigate temperature-dependent transitions in low-density lipoprotein and in lipids from hens' egg yolk. Yolks of different fatty acid composition were obtained by varying the dietary lipid and by adding methyl sterculate to the hen's diet. 2. Lipoprotein solutions in 50 percent glycerol/water gave characteristic melting curves between -25 degrees C and 50 degrees C, and on cooling showed increases in light-scattering between 10 degrees C and -20 degrees C. The temperatures at which major changes occurred depended on the proportions of saturated and unsaturated fatty acids. 3. The thermal transitions in the intact lipoprotein in glycerol solution were reversible, but with marked hysteresis. Lipid extracted from the lipoprotein did not show temperature hystersis but the transition heats and melting curves similar to those of the intact lipoprotein. The results support the hypothesis of a "lipid-core" structure for low-density lipoproteins. 4. Scanning calorimetry of egg-yolk lecithins indicated a strong dependence of transition temperature on water content in the rane 3 percent-20 percent water. A rise in the mid-temperature of the liquid-crystalline to gel transition as the water content is lowered on freezing may be the primary event in the irreversible gelation of egg yolk and aggregation of lipoprotein.

  19. Effect of Antiepileptic drugs on plasma lipoprotein (a) and other lipid levels in childhood.

    Science.gov (United States)

    Aynaci, F M; Orhan, F; Orem, A; Yildirmis, S; Gedik, Y

    2001-05-01

    Antiepileptic drugs may alter plasma lipid status in epileptic patients. We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on plasma levels of lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A, and apolipoprotein B in 22 epileptic children. The children were separated as group 1, seven children, mean age 1.6+/-0.2 years, treated with phenobarbital, 5 mg/kg/day, twice daily; group 2, seven children, mean age 9.8+/-1.2 years, treated with carbamazepine, 20 mg/kg/day, twice daily; and group 3, eight children, mean age 6.8+/-0.6 years, treated with valproate, 20 mg/kg/day, twice daily. Plasma lipoprotein (a) and other lipid levels were studied before (pretreatment) and at 3 and 6 months of treatment. Friedman two-way analysis of variance and Wilcoxon's signed-rank test were used for statistical analysis, and the results were expressed as the mean and standard error of the mean. The mean age of children in group 1 was significantly low, compared with groups 2 and, 3 (P < .001). The mean pretreatment lipid levels between the groups were not significant. The increase in lipoprotein (a) at 3 and 6 months and high-density lipoprotein cholesterol at 6 months was statistically significant in group 1 (P < .025). We suggest a careful monitoring of plasma levels of lipoprotein (a) and other lipids in epileptic children treated with antiepileptic drugs.

  20. Effect of antiepileptic drugs on plasma lipids, lipoprotein (a), and liver enzymes.

    Science.gov (United States)

    Sonmez, Fatma Mujgan; Demir, Ercan; Orem, Asim; Yildirmis, Sermet; Orhan, Fazil; Aslan, Adnan; Topbas, Murat

    2006-01-01

    We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on serum lipid profiles and lipoprotein (a) in 64 children with epilepsy (aged between 1 and 15 years) admitted to the child neurology outpatient clinic between July 2000 and July 2002. The children were separated as group 1 (18 children), treated with phenobarbital, 5 mg/kg/day; group 2 (22 children), treated with carbamazepine, 10 to 15 mg/kg/day; and group 3 (24 children), treated with sodium valproate, 20 mg/kg/day. Plasma lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A and apolipoprotein B levels, and liver enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase were determined before the initiation of the treatment and at 3, 6, and 12 months of the treatment period. The mean age of children in group 1 was significantly low compared with those in groups 2 and 3 (P 30 mg/dL) were observed only in carbamazepine-treated patients at 6 and 12 months. The percentage of children with lipoprotein (a) levels over 30 mg/dL was 44%, 63%, and 33% in the phenobarbital-, carbamazepine-, and valproate-treated children, respectively. Antiepileptic drugs significantly increase the level of lipoprotein (a), which is a major risk factor for atherosclerosis, and also have variable effects on other lipid parameters. Lipoprotein (a) levels should be closely followed in patients receiving antiepileptic drugs. (J Child Neurol 2006;21:70-74).

  1. High density lipoprotein level is negatively associated with the increase of oxidized low density lipoprotein lipids after a fatty meal.

    Science.gov (United States)

    Tiainen, Sanna; Ahotupa, Markku; Ylinen, Petteri; Vasankari, Tommi

    2014-12-01

    Recent reports show that a fatty meal can substantially increase the concentration of oxidized lipids in low density lipoprotein (LDL). Knowing the LDL-specific antioxidant effects of high density lipoprotein (HDL), we aimed to investigate whether HDL can modify the postprandial oxidative stress after a fatty meal. Subjects of the study (n = 71) consumed a test meal (a standard hamburger meal) rich in lipid peroxides, and blood samples were taken before, 120, 240, and 360 min after the meal. The study subjects were divided into four subgroups according to the pre-meal HDL cholesterol value (HDL subgroup 1, 0.66-0.91; subgroup 2, 0.93-1.13; subgroup 3, 1.16-1.35; subgroup 4, 1.40-2.65 mmol/L). The test meal induced a marked postprandial increase in the concentration of oxidized LDL lipids in all four subgroups. The pre-meal HDL level was associated with the extent of the postprandial rise in oxidized LDL lipids. From baseline to 6 h after the meal, the concentration of ox-LDL increased by 48, 31, 24, and 16% in the HDL subgroup 1, 2, 3, and 4, respectively, and the increase was higher in subgroup 1 compared to subgroup 3 (p = 0.028) and subgroup 4 (p = 0.0081), respectively. The pre-meal HDL correlated with both the amount and the rate of increase of oxidized LDL lipids. Results of the present study show that HDL is associated with the postprandial appearance of lipid peroxides in LDL. It is therefore likely that the sequestration and transport of atherogenic lipid peroxides is another significant mechanism contributing to cardioprotection by HDL.

  2. Apolipoprotein AV Accelerates Plasma Hydrolysis OfTriglyceride-Rich Lipoproteins By Interaction With Proteoglycan BoundLipoprotein Lipase

    Energy Technology Data Exchange (ETDEWEB)

    Merkel, Martin; Loeffler, Britta; Kluger, Malte; Fabig, Nathalie; Geppert, Gesa; Pennacchio, Len A.; Laatsch, Alexander; Heeren, Joerg

    2005-02-22

    Apolipoprotein A5 (APOA5) is associated with differences intriglyceride levels and familial combined hyperlipidemia. In genetically engineered mice, apoAV plasma levels are inversely correlated with plasmatriglycerides. To elucidate the mechanism by which apoAV influences plasma triglycerides, metabolic studies and in vitro assays resembling physiological conditions were performed. In hAPOA5 transgenic mice(hAPOA5tr), catabolism of chylomicrons and VLDL was accelerated due to a faster plasma hydrolysis of triglycerides by lipoprotein lipase (LPL).Hepatic VLDL and intestinal chylomicron production were not affected. The functional interplay between apoAV and LPL was further investigated by crossbreeding a human LPL transgene with the apoa5 knockout, and the hAPOA5tr to an LPL deficient background. Increased LPL activity completely normalized hypertriglyceridemia of apoa5 deficient mice,however, over expression of human apoAV modulated triglyceride levels only slightly when LPL was reduced. To reflect the physiological situation in which LPL is bound to cell surface proteoglycans, we examined hydrolysis in the presence or absence of proteoglycans. Without proteoglycans, apoAV derived either from triglyceride-rich lipoproteins, hAPOA5tr HDL, or a recombinant source did not alter the LPL hydrolysis rate. In the presence of proteoglycans, however, apoAV led to a significant and dose-dependent increase in LPL mediated hydrolysis of VLDL triglycerides. These results were confirmed in cell culture using a proteoglycan-deficient cell line.A direct interaction between LPL and apoAV was found by ligand blotting.It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycans bound LPL for lipolysis.

  3. Measurement of cholesterol and other lipoprotein constituents in the clinical laboratory.

    Science.gov (United States)

    Warnick, G R

    2000-04-01

    Measurements of lipids and lipoproteins in the clinical laboratory have become increasingly important because of their predictive association with cardiovascular diseases, especially coronary artery disease. The US National Institutes of Health-sponsored National Cholesterol Education Program and counterparts in other countries have developed national consensus guidelines for diagnosis and treatment of coronary artery disease which provide risk cut-points and define use of the lipid/lipoprotein analytes in case finding and therapy. Total and low density lipoprotein cholesterol and triglycerides are measured as positive risk factors and high density lipoprotein cholesterol as an inverse risk factor for coronary artery disease. A National Cholesterol Education Program-sponsored expert laboratory panel has developed guidelines for measurements with requisite analytical performance targets for total error and corresponding precision and bias. The US Centers for Disease Control and Prevention have established reference methods for total and high density lipoprotein cholesterol and for triglycerides, with a method for low density lipoprotein cholesterol in development. Standardization programs for research laboratories and a Cholesterol Reference Method Laboratory Network for diagnostic manufacturers and clinical laboratories provide reliable access and documentation of traceability to accepted reference methods. Methods for the lipid/lipoprotein analytes have improved dramatically in recent years and, coupled with improved chemistry analyzer systems and more attention to standardization by manufacturers, offer considerable improvement in analytical performance. Fully automated homogeneous assays for high density lipoprotein cholesterol and newer similar assays for low-density lipoprotein cholesterol have potential for better precision as well as more convenient and cost-effective measurements. Attention to pre-analytical sources of variation is also important in making

  4. Particle therapy

    Energy Technology Data Exchange (ETDEWEB)

    Raju, M.R.

    1993-09-01

    Particle therapy has a long history. The experimentation with particles for their therapeutic application got started soon after they were produced in the laboratory. Physicists played a major role in proposing the potential applications in radiotherapy as well as in the development of particle therapy. A brief review of the current status of particle radiotherapy with some historical perspective is presented and specific contributions made by physicists will be pointed out wherever appropriate. The rationale of using particles in cancer treatment is to reduce the treatment volume to the target volume by using precise dose distributions in three dimensions by using particles such as protons and to improve the differential effects on tumors compared to normal tissues by using high-LET radiations such as neutrons. Pions and heavy ions combine the above two characteristics.

  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. [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.

  7. 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.

  8. 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

    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.......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...

  9. Obstructive jaundice leads to accumulation of oxidized low density lipoprotein in human liver tissue

    Institute of Scientific and Technical Information of China (English)

    Mustafa Comert; Yucel Ustundag; Ishak Ozel Tekin; Banu Dogan Gun; Figen Barut

    2006-01-01

    Oxidized low density lipoprotein (ox-LDL) molecule is one of the most important modified lipoproteins produced during the oxidative stress. Modified lipoproteins have been defined as being part of the immune inflammatory mechanisms in association with oxidant stress. We have reported the accumulation of ox-LDL in Balb/c mice liver after bile duct ligation previously. Here, we investigated this finding in human beings with obstructive jaundice.Our study demonstrates that obstructive jaundice results in tremendous accumulation of ox-LDL in the liver tissue of patients.

  10. Crystal structures of bacterial lipoprotein localization factors, LolA and LolB

    OpenAIRE

    Takeda, Kazuki; Miyatake, Hideyuki; Yokota, Naoko; Matsuyama, Shin-ichi; Tokuda, Hajime; Miki, Kunio

    2003-01-01

    Lipoproteins having a lipid-modified cysteine at the N-terminus are localized on either the inner or the outer membrane of Escherichia coli depending on the residue at position 2. Five Lol proteins involved in the sorting and membrane localization of lipoprotein are highly conserved in Gram-negative bacteria. We determined the crystal structures of a periplasmic chaperone, LolA, and an outer membrane lipoprotein receptor, LolB. Despite their dissimilar amino acid sequences, the structures of ...

  11. 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

  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......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...

  13. [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

  14. 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

    including the pesticide DDT (p,p'-dichlorodiphenyltrichloroethane), and especially its metabolite DDE (p,p'-dichlorodiphenyldichloroethene), interacts with nuclear hormone receptors causing these to malfunction, which in turn results in a range of deleterious health effects in humans. The aim of the present...... 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...... receptor-related protein) and LDLR (low density lipoprotein receptor) present and MEF4 cells with no LRP and LDLR expression. Cells were incubated together with the complex of LDL and [14C]DDT. The receptor function was further evaluated by adding the 40 kDa receptor-associated protein (RAP) which blocks...

  15. Quantitative Lipoproteomics in Clostridium difficile Reveals a Role for Lipoproteins in Sporulation.

    Science.gov (United States)

    Charlton, Thomas M; Kovacs-Simon, Andrea; Michell, Stephen L; Fairweather, Neil F; Tate, Edward W

    2015-11-19

    Bacterial lipoproteins are surface exposed, anchored to the membrane by S-diacylglyceryl modification of the N-terminal cysteine thiol. They play important roles in many essential cellular processes and in bacterial pathogenesis. For example, Clostridium difficile is a Gram-positive anaerobe that causes severe gastrointestinal disease; however, its lipoproteome remains poorly characterized. Here we describe the application of metabolic tagging with alkyne-tagged lipid analogs, in combination with quantitative proteomics, to profile protein lipidation across diverse C. difficile strains and on inactivation of specific components of the lipoprotein biogenesis pathway. These studies provide the first comprehensive map of the C. difficile lipoproteome, demonstrate the existence of two active lipoprotein signal peptidases, and provide insights into lipoprotein function, implicating the lipoproteome in transmission of this pathogen.

  16. 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.

  17. 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.

  18. 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.

    2013-01-01

    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 cholest

  19. Polyacrylate adsorbents for the selective adsorption of cholesterol-rich lipoproteins from plasma or blood

    Directory of Open Access Journals (Sweden)

    Heuck, Claus-Chr.

    2011-01-01

    Full Text Available Polyacrylate (PAA adsorbents selectively bind low density lipoproteins (LDL from human plasma and blood, whereas very low density lipoproteins (VLDL are only minimally adsorbed. The adsorption of cholesterol-rich lipoproteins to PAA adsorbents is related to the molecular weight (mw of the polyanion ligand. Ca++ and Mg++ inhibit the binding of LDL to PAA adsorbents. The chemical composition of the organic hardgels of the adsorbents does not have an influence on adsorption. The selective adsorption of LDL to PAA adsorbents can be explained to result from their low negative surface charge density and the specific colloid-chemical properties of the surface-bound PAA, which do not prevent LDL from binding to charge-like domains of the ligand. By contrast, VLDL and high density lipoproteins (HDL are repelled from the adsorbents due to their higher negative surface charge density.

  20. Polyacrylate adsorbents for the selective adsorption of cholesterol-rich lipoproteins from plasma or blood.

    Science.gov (United States)

    Heuck, Claus-Chr

    2011-01-24

    Polyacrylate (PAA) adsorbents selectively bind low density lipoproteins (LDL) from human plasma and blood, whereas very low density lipoproteins (VLDL) are only minimally adsorbed. The adsorption of cholesterol-rich lipoproteins to PAA adsorbents is related to the molecular weight (mw) of the polyanion ligand. Ca(++) and Mg(++) inhibit the binding of LDL to PAA adsorbents. The chemical composition of the organic hardgels of the adsorbents does not have an influence on adsorption. The selective adsorption of LDL to PAA adsorbents can be explained to result from their low negative surface charge density and the specific colloid-chemical properties of the surface-bound PAA, which do not prevent LDL from binding to charge-like domains of the ligand. By contrast, VLDL and high density lipoproteins (HDL) are repelled from the adsorbents due to their higher negative surface charge density.

  1. Lipoprotein(a) and ischemic heart disease-A causal association? A review

    DEFF Research Database (Denmark)

    Kamstrup, P.R.

    2010-01-01

    The aim of this review is to summarize present evidence of a causal association of lipoprotein(a) with risk of ischemic heart disease (IHD). Evidence for causality includes reproducible associations of a proposed risk factor with risk of disease in epidemiological studies, evidence from in vitro...... 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...... 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...

  2. Exercise attenuates the increase in plasma monounsaturated fatty acids and high-density lipoprotein cholesterol but not high-density lipoprotein 2b cholesterol caused by high-oleic ground beef in women.

    Science.gov (United States)

    Gilmore, L Anne; Crouse, Stephen F; Carbuhn, Aaron; Klooster, Jennifer; Calles, José Antonio Elias; Meade, Thomas; Smith, Stephen B

    2013-12-01

    We hypothesized that dietary monounsaturated fatty acids (MUFA) and exercise increase high-density lipoprotein cholesterol (HDL-C) by independent mechanisms, so there would be additive effects between a single, intensive session of exercise and high-MUFA ground beef on HDL-C and blood risk factors for cardiovascular disease. Seventeen postmenopausal women completed a 2-way crossover design in which they consumed five 114-g ground beef patties per week for two 6-week periods separated by a 4-week washout (habitual diet) period. The ground beef patties contained 21% total fat with either 9.97 (low-MUFA) or 12.72 (high-MUFA) g total MUFA. Blood was taken at entry, at the end of each 6-week diet period, after the 4-week washout period, and 24 hours after aerobic exercise sessions (75% VO₂peak, 2.07 MJ). After the ground beef intervention, the high-MUFA ground beef increased plasma palmitoleic acid and oleic acid, low-density lipoprotein (LDL) particle density, HDL-C, and HDL2b-C (all P density. After the washout (habitual diet) period, the single exercise session increased serum LDL cholesterol, HDL-C, and HDL2a and decreased TAG and oleic acid. After the low-MUFA ground beef diet, exercise increased LDL size and HDL density and decreased LDL density and very low-density lipoprotein cholesterol, but had no effect on HDL-C fractions. After the high-MUFA ground beef intervention, exercise decreased palmitioleic acid, oleic acid, HDL-C, and HDL2a-C, but not HDL2b-C. Contrary to our hypothesis, the effects of exercise and a high-MUFA diet were not additive; instead, exercise attenuated the effects of the high-MUFA ground beef on HDL-C and plasma MUFAs. The differential effects of high-MUFA ground beef and exercise on HDL2a-C and HDL2b-C indicate that diet and exercise affect HDL-C by different mechanisms.

  3. Simvastatin but not bezafibrate decreases plasma lipoprotein-associated phospholipase A(2) mass in type 2 diabetes mellitus : Relevance of high sensitive C-reactive protein, lipoprotein profile and low-density lipoprotein (LDL) electronegativity

    NARCIS (Netherlands)

    Constantinides, Alexander; de Vries, Rindert; van Leeuwen, Jeroen J. J.; Gautier, Thomas; van Pelt, L. Joost; Tselepis, Alexandros D.; Lagrost, Laurent; Dullaart, Robin P. F.

    2012-01-01

    Objective: Plasma lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels predict incident cardiovascular disease, impacting Lp-PLA(2) as an emerging therapeutic target. We determined Lp-PLA(2) responses to statin and fibrate administration in type 2 diabetes mellitus, and assessed relationship

  4. 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

  5. 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.

  6. Relationship between Serum Lipoprotein Ratios and Insulin Resistance in Polycystic Ovary Syndrome

    OpenAIRE

    Shou-Kui Xiang; Fei Hua; Ying Tang; Xiao-Hong Jiang; Qi Zhuang; Feng-Juan Qian

    2012-01-01

    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 lip...

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

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Eckoldt, J.; Winkler, K.;

    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...... with physical activity, moderate alcohol consumption, and dietary intake of MUFA, which might be exploited in future interventions for prevention of age- and BMI-associated atherogenic shifts of lipoprotein subfractions....

  8. Preparation and Adsorption Properties of PAM Based Adsorbents for Plasma Lipoproteins

    Institute of Scientific and Technical Information of China (English)

    Hai Tao LI; Zhi YUAN; Xin Fu CHEN; Bin LIU; Bin SHEN; Bing Lin HE

    2004-01-01

    Crosslinked macroporous polyacrylamide(PAM)was prepared with inverse phase suspension polymerization technique.After treatment with hydrazine,the polymer was functionalized with chloroacetic acid,trifluoroacetic acid diethylenetriaminepentaacetic acid (DEPAA), and maleic acid, respectively,and PAM based adsorbents bearing carboxyl functional groups for low density lipoprotein(LDL)apheresis use were obtained.The blood compatibility and the adsorption properties for plasma lipoproteins of PAM based adsorbents were investigated.

  9. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance

    OpenAIRE

    Kim, Jason K.; Fillmore, Jonathan J.; Chen, Yan; Yu, Chunli; Moore, Irene K.; Pypaert, Marc; Lutz, E. Peer; Kako, Yuko; Velez-Carrasco, Wanda; Goldberg, Ira J.; Breslow, Jan L.; Shulman, Gerald I.

    2001-01-01

    Insulin resistance in skeletal muscle and liver may play a primary role in the development of type 2 diabetes mellitus, and the mechanism by which insulin resistance occurs may be related to alterations in fat metabolism. Transgenic mice with muscle- and liver-specific overexpression of lipoprotein lipase were studied during a 2-h hyperinsulinemic–euglycemic clamp to determine the effect of tissue-specific increase in fat on insulin action and signaling. Muscle–lipoprotein lipase mice had a 3...

  10. Simulated lipoprotein transport in the wall of branched arteries.

    Science.gov (United States)

    Darbeau, M Z; Lutz, R J; Collins, W E

    2000-01-01

    Study of arterial blood flow dynamics improves our understanding of the development of cardiovascular diseases such as atherosclerosis. The transport and accumulation of macromolecules in the arterial wall can be influenced by local fluid mechanics. We used numeric simulations to investigate such transport in a T-junction model. Presumably an in vitro experiment would consist of gel segments inserted in the walls of a mechanical flow T-junction model near branch points where separation and recirculation zones are expected. The transport of low density lipoprotein (LDL) was investigated theoretically at these sites in a two dimensional numeric T-branch model. In the numeric model, the hydraulic conductivity of the porous gel wall segments was varied for a fixed species diffusivity to provide simulations with wall transmural Peclet numbers ranging from 0.3 to 30. Steady state flow patterns in the lumen of the two dimensional T-branch were simulated at Reynolds numbers of 250 and 500, using the software package FIDAP 7.61 to implement the finite element method. The simulations demonstrated that wall Peclet numbers greater than 1.0 were needed to achieve species concentration gradients within the wall that varied in the axial direction, thereby reflecting the influence of disturbed flow and pressure patterns in the lumen. As expected, the transmural concentration gradients were steeper when convection predominated. Blood flow in the lumen can influence the distribution of macromolecules in the arterial wall and needs to be investigated for the relevance to atherosclerosis.

  11. Serum lipoproteins of patients with glycogen storage disease.

    Science.gov (United States)

    Rosenfeld, E L; Chibisov, I V; Karmansky, I M; Tabolin, V A; Chistova, L V; Leontiev, A F

    1980-03-14

    Seventeen patients with different types of glycogen storage disease (GSD) were under observation. The type of the disease was defined from glucaemic and lactotaemic curves obtained in glucose, galactose and adrenaline tolerance tests and by biochemical analysis of liver biopsy specimens. Seven patients were found to have Type I; five patients, Type III; one patient, Type VI; and four patients, the Type IX (or X) of GSD. The serum lipoprotein (LP) content was determined in all patients using analytical ultracentrifugation. Hyperlipoproteinaemia (HLP) was found in virtually all patients. Patients with Type I of GSD were found to have Types 2b and 4 of HLP; and patients with Type III of GSD, 2b Type of HLP. 2a Type of HLP was diagnosed in patients with GSD of VI and IX (X) Types. Patients with Type III GSD, in contrast to those with GSD of other types, had enhanced levels of Sf 12-20 LP. The levels of Sf 100-400 and Sf 20-100 LP were greatly increased only in patients with Type I GSD.

  12. Low fasting low high-density lipoprotein and postprandial lipemia

    Directory of Open Access Journals (Sweden)

    Sorodila Konstandina

    2004-07-01

    Full Text Available Abstract Background Low levels of high density lipoprotein (HDL cholesterol and disturbed postprandial lipemia are associated with coronary heart disease. In the present study, we evaluated the variation of triglyceride (TG postprandially in respect to serum HDL cholesterol levels. Results Fifty two Greek men were divided into 2 main groups: a the low HDL group (HDL p = 0.002. The low HDL group had significantly higher TG at 4, 6 and 8 h postprandially compared to the controls (p = 0.006, p = 0.002, and p p = 0.017 compared to the matched-control group. ROC analysis showed that fasting TG ≥ 121 mg/dl have 100% sensitivity and 81% specificity for an abnormal TG response (auc = 0.962, p Conclusions The delayed TG clearance postprandially seems to result in low HDL cholesterol even in subjects with low fasting TG. The fasting TG > 121 mg/dl are predictable for abnormal response to fatty meal.

  13. Lipoprotein(a) and risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Mora, Samia; Kamstrup, Pia R; Rifai, Nader;

    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...

  14. Lipoprotein(a) and risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Mora, S.; Kamstrup, Pia R; Rifai, N.;

    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...

  15. [Effects of antihypertensive agents on lipoproteins and thrombocyte function].

    Science.gov (United States)

    Birkebaek, N H

    1990-09-24

    This article is a review of the literature concerning the effects of antihypertensive agents on the lipid status and thrombocyte function. Many investigations have revealed that thiazide diuretics, non-selective beta-blockers and beta-1 selective beta-blockers have resulted in alteration of lipids in a potentially atherogenic direction. Only thiazide diruetics have caused increase in low density lipoprotein, which is causally connected with increased tendency to atheroschlerosis. In some investigations, alpha-1 blockers have had a favourable effect on lipids in an atherogenic direction. Other antihypertensive agents appear, by and large, to be lipid neutral even although isolated investigations have demonstrated displacement of lipids both in positive and negative directions. Non-selective beta-blockers appear to alter thrombocyte function towards a greater tendency to aggregation while beta-1 selective beta-blockers are neutral. Ca-antagonists, angiotensin converting enzyme inhibitors and ketanserin have, theoretically, anti-aggregatory effects on the thrombocytes but only few ex vivo and in vivo experiments have confirmed this effect. Monitoring of lipids is recommended before and after antihypertensive treatment. Finally, the effect on thrombocyte function should be considered in the choice of hypertensive agent.

  16. Probucol alleviates atherosclerosis and improves high density lipoprotein function

    Directory of Open Access Journals (Sweden)

    Zhong Jian-Kai

    2011-11-01

    Full Text Available Abstract Background Probucol is a unique hypolipidemic agent that decreases high density lipoprotein cholesterol (HDL-C. However, it is not definite that whether probucol hinders the progression of atherosclerosis by improving HDL function. Methods Eighteen New Zealand White rabbits were randomly divided into the control, atherosclerosis and probucol groups. Control group were fed a regular diet; the atherosclerosis group received a high fat diet, and the probucol group received the high fat diet plus probucol. Hepatocytes and peritoneal macrophages were isolated for [3H] labeled cholesterol efflux rates and expression of ABCA1 and SR-B1 at gene and protein levels; venous blood was collected for serum paraoxonase 1, myeloperoxidase activity and lipid analysis. Aorta were prepared for morphologic and immunohistochemical analysis after 12 weeks. Results Compared to the atherosclerosis group, the paraoxonase 1 activity, cholesterol efflux rates, expression of ABCA1 and SR-BI in hepatocytes and peritoneal macrophages, and the level of ABCA1 and SR-BI in aortic lesions were remarkably improved in the probucol group, But the serum HDL cholesterol concentration, myeloperoxidase activity, the IMT and the percentage plaque area of aorta were significantly decreased. Conclusion Probucol alleviated atherosclerosis by improving HDL function. The mechanisms include accelerating the process of reverse cholesterol transport, improving the anti-inflammatory and anti-oxidant functions.

  17. Tiliroside and gnaphaliin inhibit human low density lipoprotein oxidation.

    Science.gov (United States)

    Schinella, Guillermo R; Tournier, Horacio A; Máñez, Salvador; de Buschiazzo, Perla M; Del Carmen Recio, María; Ríos, José Luis

    2007-01-01

    Two flavonoids, gnaphaliin and tiliroside, isolated from Helichrysum italicum, were studied in vitro for their capacity to inhibit Cu(2+)-induced human low density lipoprotein (LDL) and diluted plasma oxidation. LDL oxidation was monitored by conjugated diene, thiobarbituric acid-reactive substances (TBARS) formation and electrophoretic mobility on agarose gel. Gnaphaliin and tiliroside increased the lag-phase for diene conjugate production in a dose-dependent manner. The reduction of TBARS production confirmed the antioxidant activity of gnaphaliin and tiliroside with 50% inhibitory concentration (IC(50)) values of 8.0+/-3.9 microM and 7.0+/-2.6 microM respectively. Furthermore, the flavonoids negated the Cu(2+)-induced increase in electrophoretic mobility of LDL. Antioxidant activity of gnaphaliin and tiliroside was significantly different when diluted plasma was oxidised by adding 1 mM CuSO(4). Although both flavonoids again reduced the TBARS production, tiliroside showed higher activity than gnaphaliin (IC(50)=10.6+/-2.5 microM vs. IC(50)>50 microM). In conclusion, tiliroside and gnaphaliin are antioxidants against in vitro Cu(2+)-induced LDL oxidation in the same order of magnitude compared to that of the reference drug, probucol.

  18. Iatrogenic severe depression of high-density lipoprotein cholesterol.

    Science.gov (United States)

    Mymin, D; Dembinski, T; Friesen, M H

    2009-07-01

    The authors present 5 cases of paradoxical depression of high-density lipoprotein (HDL) cholesterol induced by fibrate drugs. In a 24-month review of all cases seen in one physician's practice at the Winnipeg Health Sciences Centre Lipid Clinic, 492 patients made a total of 1187 visits. Sixty-eight of them were given a fibrate drug (14%). Ten patients had HDL cholesterol levels that were less than 0.5 mmol/L (2%), and of these, 5 cases were due to exposure to fenofibrate (1%). These 5 cases comprised 7.4% of the 68 patients who were given any fibrate drug during that period. Mean levels were as follows: HDL cholesterol on fenofibrate 0.27, off fenofibrate 1.0 mmol/L and apo A1 on fenofibrate 0.41, off fenofibrate 1.17 g/L. A literature review revealed documented cases in 37 patients involving fibrates alone or in combination with other drugs known to cause decreased HDL cholesterol levels. In 13 patients, exposure was to fibrate therapy alone; in those exposed to combinations, the effect was clearly attributable to fibrates in 9; in 14, the nonfibrates (mostly rosiglitazone) were the attributable drugs; and in 1, it was impossible to tell. Thus, fibrate therapy should always be suspected as a cause of profoundly depressed HDL cholesterol.

  19. 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.

  20. Parathyroid hormone is not an inhibitor of lipoprotein lipase activity.

    Science.gov (United States)

    Arnadottir, M; Nilsson-Ehle, P

    1994-01-01

    The reduced lipoprotein lipase (LPL) activities in uraemia are reflected by increased serum triglyceride concentrations and reduced HDL cholesterol concentrations. Both hyperparathyroidism and circulating inhibitor(s) of LPL have been associated with the disturbances of lipid metabolism in uraemia. The aim of the present study was to investigate if parathyroid hormone (PTH) had an inhibitory effect on LPL activity. Plasma post-heparin LPL activities, plasma LPL inhibitory activities, serum PTHintact and serum PTHC-terminal concentrations were analysed in 20 patients on haemodialysis and 20 healthy controls. The effects of purified, human PTHintact and a carboxyterminal fragment of PTH (PTH39-84) on LPL activities in post-heparin plasma from healthy individuals and on the enzyme activity of purified, bovine milk LPL, activated with apolipoprotein CII, were studied. Patients had significantly higher plasma LPL inhibitory activities than controls, but there was no correlation between plasma LPL inhibitory activities and serum PTH concentrations. Neither PTHintact nor PTH39-84 had a significant effect on LPL activities in vitro. Thus there was no evidence of a direct inhibition of LPL activity by PTH under the present in-vivo or in-vitro conditions.

  1. Native low density lipoprotein promotes lipid raft formation in macrophages.

    Science.gov (United States)

    Song, Jian; Ping, Ling-Yan; Duong, Duc M; Gao, Xiao-Yan; He, Chun-Yan; Wei, Lei; Wu, Jun-Zhu

    2016-03-01

    Oxidized low‑density lipoprotein (LDL) has an important role in atherogenesis; however, the mechanisms underlying cell‑mediated LDL oxidation remain to be elucidated. The present study investigated whether native‑LDL induced lipid raft formation, in order to gain further insight into LDL oxidation. Confocal microscopic analysis revealed that lipid rafts were aggregated or clustered in the membrane, which were colocalized with myeloperoxidase (MPO) upon native LDL stimulation; however, in the presence of methyl‑β‑cyclodextrin (MβCD), LDL‑stimulated aggregation, translocation, and colocalization of lipid rafts components was abolished.. In addition, lipid raft disruptors MβCD and filipin decreased malondialdehyde expression levels. Density gradient centrifugation coupled to label‑free quantitative proteomic analysis identified 1,449 individual proteins, of which 203 were significantly upregulated following native‑LDL stimulation. Functional classification of the proteins identified in the lipid rafts revealed that the expression levels of translocation proteins were upregulated. In conclusion, the results of the present study indicated that native‑LDL induced lipid raft clustering in macrophages, and the expression levels of several proteins were altered in the stimulated macrophages, which provided novel insights into the mechanism underlying LDL oxidation.

  2. Fully mechanized latex immunoassay for serum lipoprotein(a).

    Science.gov (United States)

    Abe, A; Yoshimura, Y; Sekine, T; Maeda, S; Yamashita, S; Noma, A

    1994-03-01

    We have developed a fully automated system to quantify lipoprotein(a) (Lp(a)) in human serum, based on the latex-enhanced turbidimetric immunoassay by application of the Immuno Chemistry Analyzer 501X. This assay was carried out with undiluted serum and was able to detect at Lp(a) levels higher than 4.0 mg/l. When judged to be out of range of the calibration (> 600 mg/l), the sample was automatically re-tested after automatic 10-fold dilution. Within-run C.V.s ranged from 1.9 to 2.1% and between-run C.V.s from 2.7 to 3.9%. Results by the present method were in good agreement with those by the in-house ELISA (r = 0.978) and the commercial ELISA (r = 0.990). The distribution of Lp(a) levels in sera from 508 healthy donors was highly skewed; the mean and median were 158 mg/l and 105 mg/l, respectively.

  3. 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.

  4. 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.

  5. Lipoprotein(a) accelerates atherosclerosis in uremic mice

    DEFF Research Database (Denmark)

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

    2010-01-01

    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...... = 19), human apoB-100 (n = 20), or human apo(a) + human apoB [Lp(a)] (n = 15), and in wild-type (WT) controls (n = 21). The uremic mice received a high-fat diet, and aortic atherosclerosis was examined 35 weeks later. LDL-cholesterol was increased in apoB-Tg and Lp(a)-Tg mice, but it was normal in apo...... with both apo(a) and Lp(a). In conclusion, expression of apo(a) or Lp(a) increased uremia-induced atherosclerosis. Binding of OxPL on apo(a) and Lp(a) may contribute to the atherogenicity of Lp(a) in uremia....

  6. Inhibitory effect of morinda citrifolia L. On lipoprotein lipase activity.

    Science.gov (United States)

    Pak-Dek, M S; Abdul-Hamid, A; Osman, A; Soh, C S

    2008-10-01

    Efficacy of Morinda citrifolia L. leaf (MLE) and fruit extracts (MFE) in inhibiting lipoprotein lipase (LPL) was determined in vitro. The result of the study showed that the highest inhibition on the LPL activity was exhibited by MLE (66%+/- 2.1%), which is significantly higher than that demonstrated by MFE (54.5%+/- 2.5%), green tea extract (GTE) (54.5%+/- 2.6%), and catechin (43.6%+/- 6.1%). Percent of LPL inhibition increase with concentration of the extracts. Quantitative analysis of the extracts revealed the presence of high levels of (+)-catechin at 63.5 +/- 17 and 53.7 +/- 5.7 mg/g in MLE and MFE, respectively, although not as high as that found in GTE (530.6 +/- 42 mg/g). Appreciable amount of epicatechin was found in all extracts tested, while rutin was only found in MLE and MFE. The study suggested that both leaf and fruit of M. citrifolia may be used as antiobesity agents in body weight management.

  7. 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.

  8. Lipoprotein Abnormalities in Cholestasis I. Electro-phoretic and Ultracentrifugal Analyses

    Directory of Open Access Journals (Sweden)

    Watanabe,Makoto

    1979-08-01

    Full Text Available The alterations of lipid composition in sera of patients with liver diseases, particularly intrahepatic cholestasis and biliary obstruction, were studied by ultracentrifugation and polyacrylamide-gel disc-electrophoresis of lipoproteins and apoproteins. The elevation of serum cholesterol in intrahepatic cholestasis was greater than in biliary obstruction. The appearance of lipoprotein X in obstructive disease accounted for most of the increased cholesterol. The level of non-lipoprotein X cholesterol in intrahepatic cholestasis was significantly elevated, this being in part ascribed to the appearance of a new class of cholestatic lipoprotein, Slow-migrating HDL. The electrophoretic pattern of lipoprotein in cholestasis was generally characterized by a decrease in alpha band intensity and, in some types of cholestasis, by the appearance of Slow-migrating HDL. In addition, other abnormal lipoproteins exhibiting the characteristics of triglyceride-rich LDL (LP-Y, LP-X-like HDL and LDL-like HDL were found in some cases of intrahepatic cholestasis and biliary obstruction.

  9. Relapsing-remitting multiple sclerosis patients display an altered lipoprotein profile with dysfunctional HDL

    Science.gov (United States)

    Jorissen, Winde; Wouters, Elien; Bogie, Jeroen F.; Vanmierlo, Tim; Noben, Jean-Paul; Sviridov, Denis; Hellings, Niels; Somers, Veerle; Valcke, Roland; Vanwijmeersch, Bart; Stinissen, Piet; Mulder, Monique T.; Remaley, Alan T.; Hendriks, Jerome J. A.

    2017-01-01

    Lipoproteins modulate innate and adaptive immune responses. In the chronic inflammatory disease multiple sclerosis (MS), reports on lipoprotein level alterations are inconsistent and it is unclear whether lipoprotein function is affected. Using nuclear magnetic resonance (NMR) spectroscopy, we analysed the lipoprotein profile of relapsing-remitting (RR) MS patients, progressive MS patients and healthy controls (HC). We observed smaller LDL in RRMS patients compared to healthy controls and to progressive MS patients. Furthermore, low-BMI (BMI ≤ 23 kg/m2) RRMS patients show increased levels of small HDL (sHDL), accompanied by larger, triglyceride (TG)-rich VLDL, and a higher lipoprotein insulin resistance (LP-IR) index. These alterations coincide with a reduced serum capacity to accept cholesterol via ATP-binding cassette (ABC) transporter G1, an impaired ability of HDL3 to suppress inflammatory activity of human monocytes, and modifications of HDL3’s main protein component ApoA-I. In summary, lipoprotein levels and function are altered in RRMS patients, especially in low-BMI patients, which may contribute to disease progression in these patients. PMID:28230201

  10. [Serum lipid and lipoprotein fractions in 2 age groups of male rabbits].

    Science.gov (United States)

    Kiriakov, A; Tinterova, Z; Stoianova, S; Kavrŭkova, Iu; Rashev, M

    1980-01-01

    The authors examined in 125 young sexually mature and in 50 young sexually immature male rabbits of a New Zealand improved Bulgarian breed the following serum lipid indices: total lipids, total and free cholesterol triglycerides, phospholipids, cholesterol and triglyceride content of VLDL (very low density lipoproteins), LDL (high density lipoproteins), HDL (high density lipoproteins) and the percentage concentration of serum lipopropteins, examined electrophoretically. The concentrations of the examined lipid and lipoprotein fractions in the sera of both age groups of rabbits showed asymetrical distribution. The hystograms of the total lipids and total cholesterol in younger animals was excluded. The logarithnictrandsformation of asymetricaly distributed concentrations of the examined fractions normalized their distribution in a part of them. The authors determined the ranges of the norm with the help of the percentile analysis in the remaining indices with asymetric distribution. Serum lipid and lipoprotein profile revealed substantial differnces in both age groups of animals. Serum lipids and lipoproteins in young sexually mature male rabbits differed from those of a man not only by their absolute concentrations, but also by their structural characteristics.

  11. Serum prolactin, leptin, lipids and lipoproteins levels during antipsychotics treatment in Parkinson's disease and related psychosis.

    Science.gov (United States)

    Rustembegovic, Avdo; Sofic, Emin; Wichart, Ildiko

    2006-01-01

    Weight gain is a common adverse effect associated with the use of most typical and atypical antipsychotic. Aim of this study was to investigate serum prolactin, leptin, cholesterol, triglyceride, lipoproteins, such high density lipoprotein (HDL), and low density lipoprotein (LDL) levels in patients with Parkinson's disease (PD)-related psychosis during long-term medication with atypical antipsychotic. The study population comprised 40 patients, who were divided into 4 groups: olanzapine (n=10), risperidone (n=10), seroquel (n=10) monotherapy, a group of 10 patients receiving only antiparkinson drugs and a control group of 8 healthy persons. The patients were evaluated at baseline and at the sixth and twelfth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), and fasting serum prolactin, leptin, lipids and lipoproteins levels. Treatment of patients with olanzapine caused marked increase of serum LDL, cholesterol, triglyceride, and leptin levels (p<0,02). No changes in HDL concentrations. There was positive relationship between serum leptin, lipid levels and BMI. However, treatment of patients with seroquel did not cause changes in serum prolactin, leptin, lipids, and lipoproteins levels. Our results suggest that treatment of patients with PD-related psychosis with seroquel appears to have minimal influence on serum leptin, prolactin, lipids, lipoproteins and BMI compared with olanzapine and risperidone.

  12. Lycopene stabilizes lipoprotein levels during D-galactosamine/lipopolysaccharide induced hepatitis in experimental rats

    Institute of Scientific and Technical Information of China (English)

    Sheik Abdulazeez Sheriff; Thiruvengadam Devaki

    2012-01-01

    Objective: To investigate the effect of lycopene on lipoprotein metabolism during D-galactosamine/lipopolysaccharide (D-Gal/LPS) induced hepatitis in experimental rats. Methods: The efficacy of lycopene was validated during D-Gal/LPS induced hepatitis by analyzing the activity of lipid metabolizing enzymes such as lipoprotein lipase (LPL), lecithin-cholesterol acyl transferase (LCAT) and hepatic triglyceride lipase (HTGL). Lipo protein analyses were done by the estimation of very low density lipoprotein cholesterol (VLDL), low density lipoprotein cholesterol (LDL) and high density lipoprotein cholesterol (HDL). Results: The toxic insult of D-galactosamine/lipopolysaccharide (D-Gal/LPS) in experimental group of animals reduces the normal values of lipid metabolizing enzymes due to liver injury. The significant drop in the levels of HDL and concomitant increase in the values of VLDL and LDL were observed. The pretreatment of lycopene restore these altered values to near normal level in experimental group of animals. Conclusions: In the light of results, it can be concluded that administration lycopene stabilizes the lipoprotein levels by regulating the lipid metabolizing enzymes through its antioxidant defense and helps to maintain the normal lipid metabolism during toxic injury in liver.

  13. The effects of low density lipoproteins modified by incubation with chondroitin 6-sulfate on human aortic smooth muscle cells.

    Science.gov (United States)

    Tîrziu, D; Jinga, V V; Serban, G; Simionescu, M

    1999-11-01

    One of the first changes that take place within the artery intima at the inception of atherosclerosis is the accumulation of LDL-derived modified lipoproteins which appear as subendothelial lipid droplets and vesicles. With time, the LDL retention and interaction with intimal chondroitin sulfate-proteoglycans may induce further structural and functional modification of the lipoproteins. The aim of this study was to produce 'in vitro' modified lipoproteins by LDL incubation with chondroitin 6-sulfate (CS, at 37 degrees C, for 48 h, in the absence of antioxidants) and to test their effects on cultured human aortic smooth muscle cells (SMCs). CS induced LDL modification (CS-mLDL) consisted in formation of a mixture of fused particles (up to 150 nm diameter) and monomers with a small content of lipid peroxides and a partially degraded apo B-100, corresponding to a mild oxidation. Upon incubation with SMCs, CS-mLDL produced a concentration-dependent stimulation of 3H-thymidine incorporation, that, at low concentration (25 microg/ml), was 2-3-fold higher than that obtained when native LDL was used; this increase correlates well with the level of CS-mLDL uptake at the same concentration. Besides the mitogenic effect, CS-mLDL induced a significant stimulation of SMCs migration, comparable with that reported for oxidized LDL. Upon incubation with CS-mLDL, SMCs accumulated lipid droplets of various number and dimension, as revealed by Nile red staining and electron microscopy. Competition studies performed in the presence of 20-fold excess of native LDL and acetyl LDL showed that 125I-CS-mLDL were taken up both by LDL receptor and scavenger receptor. At high concentration (200 microg/ml), CS-mLDL had a cytotoxic effect that was not significantly different from that of native LDL. Together these results provide evidence of (i) the direct alteration produced by CS on LDL and (ii) the effect of CS-mLDL on SMCs migration, proliferation and transformation in lipid-laden cells

  14. Retroendocytosis of high density lipoproteins by the human hepatoma cell line, HepG2

    Energy Technology Data Exchange (ETDEWEB)

    Kambouris, A.M.; Roach, P.D.; Calvert, G.D.; Nestel, P.J. (CSIRO, Division of Human Nutrition, Adelaide (Australia))

    1990-07-01

    When human HepG2 hepatoma cells were pulsed with 125I-labeled high density lipoproteins (HDL) and chased in fresh medium, up to 65% of the radioactivity released was precipitable with trichloroacetic acid. Cell-internalized 125I-HDL contributed to the release of acid-precipitable material; when cells were treated with trypsin before the chase to remove 125I-HDL bound to the outer cell membrane, 50% of the released material was still acid-precipitable. Characterization of the radioactive material resecreted by trypsinized cells revealed the presence of particles that were similar in size and density to mature HDL and contained intact apolipoproteins (apo) A-I and A-II. The release of internalized label occurred at 37 degrees C but not at 4 degrees C. Monensin, which inhibits endosomal recycling of receptors, decreased the binding of 125I-HDL to cells by 75%, inhibited the release of internalized radioactivity as acid-precipitable material by 80%, and increased the release of acid-soluble material by 90%. In contrast, the lysosomal inhibitor chloroquine increased the association of 125I-HDL to cells by 25%, inhibited the release of precipitable material by 10%, and inhibited the release of acid-soluble radioactivity by 80%. Pre-incubation with cholesterol caused a 50% increase in the specific binding, internalization, and resecretion of HDL label. Cholesterol affected the release of acid-precipitable label much more (+90%) than that of acid-soluble material (+20%). Taken together, these findings suggest that HepG2 cells can bind, internalize, and resecrete HDL by a retroendocytotic process. Furthermore, the results with cholesterol and monensin indicate that a regulated, recycling, receptor-like molecule is involved in the binding and intracellular routing of HDL.

  15. Interplay between basic residues of hepatitis C virus glycoprotein E2 with viral receptors, neutralizing antibodies and lipoproteins.

    Science.gov (United States)

    Koutsoudakis, George; Dragun, Jakub; Pérez-Del-Pulgar, Sofia; Coto-Llerena, Mairene; Mensa, Laura; Crespo, Gonzalo; González, Patricia; Navasa, Miquel; Forns, Xavier

    2012-01-01

    Positively-charged amino acids are located at specific positions in the envelope glycoprotein E2 of the hepatitis C virus (HCV): two histidines (H) and four arginines (R) in two conserved WHY and one RGERCDLEDRDR motifs, respectively. Additionally, the E2 hypervariable region 1 (HVR1) is rich in basic amino acids. To investigate the role(s) of these residues in HCV entry, we subjected to comparative infection and sedimentation analysis cell culture-produced (HCVcc, genotype 2a) wild type virus, a panel of alanine single-site mutants and a HVR1-deletion variant. Initially, we analyzed the effects of these mutations on E2-heparan sulfate (HS) interactions. The positive milieu of the HVR1, formulated by its basic amino acids (key residues the conserved H³⁸⁶ and R⁴⁰⁸), and the two highly conserved basic residues H⁴⁸⁸ and R⁶⁴⁸ contributed to E2-HS interactions. Mutations in these residues did not alter the HCVcc-CD81 entry, but they modified the HCVcc-scavenger receptor class B type I (SR-BI) dependent entry and the neutralization by anti-E2 or patients IgG. Finally, separation by density gradients revealed that mutant viruses abolished partially or completely the infectivity of low density particles, which are believed to be associated with lipoproteins. This study shows that there exists a complex interplay between the basic amino acids located in HVR1 and other conserved E2 motifs with the HS, the SR-BI, and neutralizing antibodies and suggests that HCV-associated lipoproteins are implicated in these interactions.

  16. Measurement of the nonlinear optical response of low-density lipoprotein solutions from patients with periodontitis before and after periodontal treatment: evaluation of cardiovascular risk markers

    Science.gov (United States)

    Monteiro, Andréa M.; Jardini, Maria A. N.; Giampaoli, Viviana; Alves, Sarah; Figueiredo Neto, Antônio M.; Gidlund, Magnus

    2012-11-01

    The Z-Scan (ZS) technique in the thermal regime has been used to measure the nonlinear optical response of low-density lipoprotein (LDL). The ZS technique is carried out in LDL from 40 patients with chronic periodontitis before and after three, six, and 12 months of periodontal treatment. Clinical parameters such as probing depths, bleeding on probing, total and differential white blood cells counts, lipid profiles, cytokine levels, and antibodies against oxidized LDL are also determined and compared over time. Before the treatment, the ZS experimental results reveal that the LDL particles of these patients are heavily modified. Only after 12 months of the periodontal treatment, the ZS results obtained reveal behavioral characteristics of healthy particles. This conclusion is also supported by complementary laboratorial analysis showing that the periodontal treatment induces systemic changes in several inflammatory markers.

  17. High-density lipoprotein as a potential carrier for delivery of a lipophilic antitumoral drug into hepatoma cells

    Institute of Scientific and Technical Information of China (English)

    Bin Lou; Xue-Ling Liao; Man-Ping Wu; Pei-Fang Cheng; Chun-Yan Yin; Zheng Fei

    2005-01-01

    AIM: To investigate the possibility of recombinant highdensity lipoprotein (rHDL) being a carrier for delivering antitumoral drug to hepatoma cells.METHODS: Recombinant complex of HDL and aclacinomycin(rHDL-ACM) was prepared by cosonication of apoproteins from HDL (Apo HDL) and ACM as well as phosphatidylcholine.Characteristics of the rHDL-ACM were elucidated by electrophoretic mobility, including the size of particles,morphology and entrapment efficiency. Binding activity of rHDL-ACM to human hepatoma cells was determined by competition assay in the presence of excess native HDL. The cytotoxicity of rHDL-ACM was assessed by MTT method.RESULTS: The density range of rHDL-ACM was 1.063-1.210g/mL, and the same as that of native HDL. The purity of all rHDL-ACM preparations was more than 92%.Encapsulated efficiencies of rHDL-ACM were more than90%. rHDL-ACM particles were typical sphere model of lipoproteins and heterogeneous in particle size. The average diameter was 31.26±5.62 nm by measure of 110rHDL-ACM particles in the range of diameter of lipoproteins.rHDL-ACM could bind on SMMC-7721 cells, and such binding could be competed against in the presence of excess native HDL. rHDL-ACM had same binding capacity as native HDL. The cellular uptake of rHDL-ACM by SMMC-7721 hepatoma cells was significantly higher than that of free ACM at the concentration range of 0.5-10 μg/mL(P<0.01). Cytotoxicity of rHDL-ACM to SMMC-7721 cells was significantly higher than that of free ACM at concentration range of less than 5 μg/mL (P<0.01) and IC50 of rHDL-ACM was lower than IC50 of free ACM(1.68 nmol/L vs3 nmol/L). Compared to L02 hepatocytes,a normal liver cell line, the cellular uptake of rHDL-ACM by SMMC-7721 cells was significantly higher (P<0.01) and in a dose-dependent manner at the concentration range of 0.5-10 μg/mL. Cytotoxicity of the rHDL-ACM to SMMC-7721 cells was significantly higher than that to L02 cells at concentration range of 1-7.5 μg/mL (P<0.01). IC50 for

  18. Is the oxidation of high-density lipoprotein lipids different than the oxidation of low-density lipoprotein lipids?

    Science.gov (United States)

    Thomas, M J; Chen, Q; Zabalawi, M; Anderson, R; Wilson, M; Weinberg, R; Sorci-Thomas, M G; Rudel, L L

    2001-02-13

    This article gives detailed insight into the kinetics of high-density lipoprotein (HDL) oxidation catalyzed by azobis(2-amidinopropane).dihydrochloride (ABAP) or by copper. ABAP initialized oxidation of human HDL 3-4 times faster than non-human primate HDL with a similar composition. The oxidizability of non-human primate HDL was 1000 times lower than the oxidizability calculated from rate constants derived from liposome oxidation, suggesting that there is a slow step in HDL oxidation not present in liposomes. Saturable binding of copper to HDL was a significant feature of copper-catalyzed oxidation. Binding constants (K(m)) for non-human primate HDL were 2-3-fold lower than those for human HDL. Copper-catalyzed oxidation of non-human primate HDL was slower than that of human HDL, but human HDL(2) and HDL(3) oxidized at about the same rate. Overall, the kinetics describing the oxidation of HDL were mechanistically similar to those reported for LDL, suggesting that HDL lipids were as easily oxidized as LDL lipids and that HDL will be easily oxidized in vivo when exposed to agents that oxidize LDL.

  19. 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

    • Mutilocus genetic determinants of LDL particle size in coronary artery disease families

      Energy Technology Data Exchange (ETDEWEB)

      Rotter, J.I.; Bu, X.; Cantor, R.M. [and others

      1996-03-01

      Recent interest in atherosclerosis has focused on the genetic determinants of low-density lipoprotein (LDL) particle size, because of (1) the association of small dense LDL particles with a three-fold increased risk for coronary artery disease (CAD) and (2) the recent report of linkage of the trait to the LDL receptor (chromosome 19). By utilizing nonparametric quantitative sib-pair and relative-pair-analysis methods in CAD families, we tested for linkage of a gene or genes controlling LDL particle sizes with the genetic loci for the major apolipoproteins and enzymes participating in lipoprotein metabolism. We confirmed evidence for linkage to the LDL receptor locus (P = .008). For six candidate gene loci, including apolipoprotein(apo)B, apoAII, apo(a), apoE-CI-CII, lipoprotein lipase, and high-density lipoprotein-binding protein, no evidence for linkage was observed by sib-pair linkage analyses (P values ranged from .24 to .81). However, in addition, we did find tentative evidence for linkage with the apoAI-CIII-AIV locus (chromosome 11) (P = .06) and significant evidence for linkage of the cholesteryl ester transfer protein locus (chromosome 16) (P = .01) and the manganese superoxide dismutase locus (chromosome 6) (P = .001), thus indicating multilocus determination of this atherogenic trait. 73 refs., 3 figs., 4 tabs.

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

    Science.gov (United States)

    Dashty, M; Motazacker, M M; Levels, J; de Vries, M; Mahmoudi, M; Peppelenbosch, M P; Rezaee, F

    2014-03-03

    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 from the site of synthesis to effector locations. To better understand the role of VLDL and LDL in the transport of proteins, we applied a combination of LTQ ORBITRAP-XL (nLC-MS/MS) with both in-SDS-PAGE gel and in-solution tryptic digestion of pure and defined VLDL and LDL fractions. We identified the presence of 95 VLDL- and 51 LDL-associated proteins including all known apolipoproteins and lipid transport proteins, and intriguingly a set of coagulation proteins, complement system and anti- microbial proteins. Prothrombin, protein S, fibrinogen γ, PLTP, CETP, CD14 and LBP were present on VLDL but not on LDL. Prenylcysteine oxidase 1, dermcidin, cathelicidin antimicrobial peptide, TFPI-1 and fibrinogen α chain were associated with both VLDL and LDL. Apo A-V is only present on VLDL and not on LDL. Collectively, this study provides a wealth of knowledge on the protein constituents of the human plasma lipoprotein system and strongly supports the notion that protein shuttling through this system is involved in the regulation of biological processes. Human diseases related to proteins carried by VLDL and LDL can be divided in three major categories: 1 - dyslipidaemia, 2 - atherosclerosis and vascular disease, and 3 - coagulation disorders.

  2. Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women

    Science.gov (United States)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) has been associated with a decreased risk of these complications. We evaluated the ut...

  3. 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...

  4. Effect of functional sympathetic nervous system impairment of the liver and abdominal visceral adipose tissue on circulating triglyceride-rich lipoproteins

    Science.gov (United States)

    Cirnigliaro, Christopher M.; Kirshblum, Steven C.; McKenna, Cristin

    2017-01-01

    Background 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). Methods 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. Results 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. Conclusions 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

  5. 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.

  6. High-density lipoprotein proteome dynamics in human endotoxemia

    Directory of Open Access Journals (Sweden)

    Stroes Erik SG

    2011-06-01

    Full Text Available Abstract Background A large variety of proteins involved in inflammation, coagulation, lipid-oxidation and lipid metabolism have been associated with high-density lipoprotein (HDL and it is anticipated that changes in the HDL proteome have implications for the multiple functions of HDL. Here, SELDI-TOF mass spectrometry (MS was used to study the dynamic changes of HDL protein composition in a human experimental low-dose endotoxemia model. Ten healthy men with low HDL cholesterol (0.7+/-0.1 mmol/L and 10 men with high HDL cholesterol levels (1.9+/-0.4 mmol/L were challenged with endotoxin (LPS intravenously (1 ng/kg bodyweight. We previously showed that subjects with low HDL cholesterol are more susceptible to an inflammatory challenge. The current study tested the hypothesis that this discrepancy may be related to differences in the HDL proteome. Results Plasma drawn at 7 time-points over a 24 hour time period after LPS challenge was used for direct capture of HDL using antibodies against apolipoprotein A-I followed by subsequent SELDI-TOF MS profiling. Upon LPS administration, profound changes in 21 markers (adjusted p-value Conclusions This study shows that the semi-quantitative differences in the HDL proteome as assessed by SELDI-TOF MS cannot explain why subjects with low HDL cholesterol are more susceptible to a challenge with LPS than those with high HDL cholesterol. Instead the results indicate that hierarchical clustering could be useful to predict HDL functionality in acute phase responses towards LPS.

  7. 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

  8. Impact of lipoprotein lipase gene polymorphisms on ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Toshihito Kosaka; Taizou Shiraishi; Masatoshi Watanabe; Takayuki Yamamoto; Ai Nakahara; Takahiko Katoh; Junji Yoshino; Kazuo Inui; Takao Wakabayashi; Kazumu Okushima; Takashi Kobayashi; Hironao Miyoshi; Yuta Nakamura; Shigekazu Hayashi

    2006-01-01

    AIM: To examine the influence of lipoprotein lipase (LPL)gene polymorphism in ulcerative colitis (UC) patients.METHODS: Peripheral blood was obtained from 131 patients with UC and 106 healthy controls for DNA extraction. We determined LPL gene polymorphisms affecting the enzyme at Ser447stop, as well as Hind Ⅲ and Pvu Ⅱ polymorphisms using PCR techniques. PCR products were characterized by PCR-RFLP and direct sequencing.Polymorphisms were examined for association with clinical features in UC patients. Genotype frequencies for LPL polymorphisms were also compared between UC patients and controls.RESULTS: In patients with onset at age 20 years or younger, C/G and G/G genotypes for Ser447stop polymorphism were more prevalent than C/C genotype (OR= 3.13, 95% CI = 0.95-10.33). Patients with H+/- or H-/-genotype for HindⅢ polymorphism also were more numerous than those with H+/+ genotype (OR = 2.51, 95%CI = 0.85-7.45). In the group with H+/+ genotype for HindⅢ polymorphism, more patients had serum triglyceride concentrations over 150 mg/dL than patients with H+/- or H-/- genotype (P < 0.01, OR = 6.46, 95% CI =1.39-30.12). Hypertriglycemia was also more prevalent in patients with P+/+ genotypes for Pvu Ⅱ polymorphism (P< 0.05, OR = 3.0, 95% CI = 1.06-8.50). Genotype frequency for LPL polymorphism did not differ significantly between UC patients and controls.CONCLUSION: Ser447stop and HindⅢ LPL polymorphisms may influence age of onset of UC, while HindⅢand PvuⅡ polymorphisms influence serum triglyceride in UC patients.

  9. 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...

  10. Characterization of Two Metal Binding Lipoproteins as Vaccine Candidates for Enterococcal Infections.

    Directory of Open Access Journals (Sweden)

    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

  11. EFFECTS OF EXERCISE TRAINING ON BLOOD LIPIDS AND LIPOPROTEINS IN CHILDREN AND ADOLESCENTS

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    Kerstin Stoedefalke

    2007-09-01

    Full Text Available The following review aims to describe what is known about the effects of exercise training in children and adolescents on the following blood lipids and lipoproteins: total cholesterol (TC, high density lipoprotein cholesterol (HDL-C, low density lipoprotein cholesterol (LDL-C, and triglycerides (TG. Only studies that described mode, frequency, duration and intensity of the exercise were included in the review. The results of the studies reviewed were equivocal. Clearly the effects of exercise training on the blood lipid and lipoprotein levels of normolipidemic children and adolescents are equivocal. Of the 14 studies reviewed, six observed a positive alteration in the blood lipid and lipoprotein profile, four of the studies observed no alteration in the blood lipid and lipoprotein profile and one study observed a negative effect on HDL-C but an overall improvement in the lipid and lipoprotein profile due to the decrease in the TC/HDL ratio. It appears that methodological problems present in the majority of the exercise training studies limits the ability to make a conclusive, evidence based statement regarding the effect exercise training has on blood lipid levels in normolipidemic children. Most of the research design flaws can be linked to one or more of the following: small numbers of subjects in each study, low or no representation of girls, inclusion of both boys and girls in the subject pool, inclusion of boys and girls at different maturational stages in the subject pool, exercise training regimes that do not adequately control for exercise intensity, exercise training regimes that do not last longer than 8 weeks and exercise training studies that do not have an adequate exercise volume to elicit a change. Ideally, future research should focus on longitudinal studies which examine the effects of exercise training from the primary school years through adulthood

  12. Metabolism of a Lipid Nanoemulsion Resembling Low-Density Lipoprotein in Patients with Grade III Obesity

    Science.gov (United States)

    Dantas, Simone Alves; Ficker, Elisabeth Salvatori; Vinagre, Carmen G. C.; Ianni, Barbara Maria; Maranhão, Raul Cavalcante; Mady, Charles

    2010-01-01

    INTRODUCTION: Obesity increases triglyceride levels and decreases high-density lipoprotein concentrations in plasma. Artificial emulsions resembling lipidic plasma lipoprotein structures have been used to evaluate low-density lipoprotein metabolism. In grade III obesity, low density lipoprotein metabolism is poorly understood. OBJECTIVE: To evaluate the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion) binds to low-density lipoprotein receptors in a group of patients with grade III obesity by the fractional clearance rate. METHODS: A low-density emulsion was labeled with [14C]-cholesterol ester and [3H]-triglycerides and injected intravenously into ten normolipidemic non-diabetic patients with grade III obesity [body mass index higher than 40 kg/m2] and into ten non-obese healthy controls. Blood samples were collected over 24 hours to determine the plasma decay curve and to calculate the fractional clearance rate. RESULTS: There was no difference regarding plasma levels of total cholesterol or low-density lipoprotein cholesterol between the two groups. The fractional clearance rate of triglycerides was 0.086 ± 0.044 in the obese group and 0.122 ± 0.026 in the controls (p = 0.040), and the fractional clearance rate of cholesterol ester (h−1) was 0.052 ± 0.021 in the obese subjects and 0.058 ± 0.015 (p = 0.971) in the controls. CONCLUSION: Grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower. PMID:20126342

  13. The impact of lipoprotein apheresis in patients with refractory angina and raised lipoprotein(a): Objectives and methods of a randomised controlled trial.

    Science.gov (United States)

    Khan, Tina Z; Pottle, Alison; Pennell, Dudley J; Barbir, Mahmoud S

    2015-05-01

    It is well established that Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor and predictor of major adverse cardiovascular events. Lipoprotein apheresis is currently the most effective approved treatment available, with minimal effect conferred by conventional lipid lowering agents. A growing body of evidence suggests that aggressively lowering raised Lp(a) may improve cardiovascular and clinical outcomes, although more prospective research is required in this field. Angina which is refractory to conventional medical therapy and revascularisation is extremely challenging to manage. There is a significant unmet need to establish therapeutic options. Our goal is to determine the impact of lipoprotein apheresis on clinical parameters and symptoms of patients with refractory angina secondary to advanced coronary disease and raised Lp(a). Determining whether we should aggressively lower Lp(a) in such patients remains a very important question, which could potentially impact on the management of a large population. We will also gain insight into how this treatment works and the mechanisms via which Lp(a) increases cardiovascular risk. We are currently conducting a prospective, randomised controlled crossover study of patients with refractory angina and raised Lp(a), randomised to undergoing three months of weekly lipoprotein apheresis or sham apheresis. Patients will then crossover to the opposite study arm after a 1 month wash-out phase. We will assess myocardial perfusion, carotid atherosclerosis, endothelial vascular function, thrombogenesis, oxidised LDL and their antibodies, exercise capacity, angina and quality of life at the beginning and end of treatment, to determine the net true treatment effect on the above parameters. This is a novel area of research, as previous studies have not assessed the role of lipoprotein apheresis in patients with refractory angina and raised Lp(a) in a prospective randomised controlled manner.

  14. Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to Fenofibrate

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    Alexis C. Frazier-Wood

    2014-08-01

    Full Text Available Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewide association study (GWAS associated several single nucleotide polymorphisms (SNPs with lipoprotein measures, and validated these associations in two independent populations. We used this information to construct genetic risk scores (GRSs for fasting lipoprotein measures at baseline (pre-fenofibrate, and aimed to examine whether these GRSs also associated with the responses of lipoproteins to fenofibrate. Fourteen lipoprotein subclass measures were assayed in 817 men and women before and after a three week fenofibrate trial. We set significance at a Bonferroni corrected alpha <0.05 (p < 0.004. Twelve subclass measures changed with fenofibrate administration (each p = 0.003 to <0.0001. Mixed linear models which controlled for age, sex, body mass index (BMI, smoking status, pedigree and study-center, revealed that GRSs were associated with eight baseline lipoprotein measures (p < 0.004, however no GRS was associated with fenofibrate response. These results suggest that the mechanisms for changes in lipoprotein subclass concentrations with fenofibrate treatment are not mediated by the genetic risk for fasting levels.

  15. Genes encoding two lipoproteins in the leuS-dacA region of the Escherichia coli chromosome

    Energy Technology Data Exchange (ETDEWEB)

    Takase, I.; Ishino, F.; Wachi, M.; Kamata, H.; Doi, M.; Asoh, S.; Matsuzawa, H.; Ohta, T.; Matsuhashi, M.

    1987-12-01

    The coding of two rare lipoproteins by two genes, rlpA and rlpB, located in the leuS-dacA region (15 min) on the Escherichia coli chromosome was demonstrated by expression of subcloned genes in a maxicell system. The formation of these two proteins was inhibited by globomycin, which is an inhibitor of the signal peptidase for the known lipoproteins of E. coli. In each case, this inhibition was accompanied by formation of a new protein, which showed a slightly lower mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and which we suppose to be a prolipoprotein with an N-terminal signal peptide sequence similar to those of the bacterial major lipoproteins and lysis proteins of some bacteriocins. The incorporation of /sup 3/H-labeled palmitate and glycerol into the two lipoproteins was also observed. Sequencing of DNA showed that the two lipoprotein genes contained sequences that could code for signal peptide sequences of 17 amino acids (rlpA lipoprotein) and 18 amino acids (rlpB lipoprotein). The deduced sequences of the mature peptides consisted of 345 amino acids (M/sub r/ 35,615, rlpA lipoprotein) and 175 amino acids (M/sub r/ 19,445, rlpB lipoprotein), with an N-terminal cysteine to which thioglyceride and N-fatty acyl residues may be attached. These two lioproteins may be important in duplication of the cells.

  16. The relationship between oxidized lipoprotein(a and carotid atherosclerosis in asymptomatic subjects: A comparison with native lipoprotein(a

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. 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.

  19. Expression of the very low-density lipoprotein receptor (VLDL-r), an apolipoprotein-E receptor, in the central nervous system and in Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Christie, R.H.; Chung, Haeyong; Rebeck, G.W.; Hyman, B.T. [Massachusetts General Hospital, Boston, MA (United States)] [and others

    1996-04-01

    The very low density lipoprotein receptor (VLDL-r) is a cell-surface molecule specialized for the internalization of multiple diverse ligands, including apolipoprotein E (apoE)-containing lipoprotein particles, via clathrin-coated pits. Its structure is similar to the low-density lipoprotein receptor (LDL-r), although the two have substantially different systemic distributions and regulatory pathways. The present work examines the distribution of VLDL-r in the central nervous system (CNS) and in relation to senile plaques in Alzheimer disease (AD). VLDL-r is present on resting and activated microglia, particularly those associated with senile plaques (SPs). VLDL-r immunoreactivity is also found in cortical neurons. Two exons of VLDL-r mRNA are differentially spliced in the mature receptor mRNA. One set of splice forms gives rise to receptors containing (or lacking) an extracellular O-linked glycosylation domain near the transmembrane portion of the molecule. The other set of splice forms appears to be brain-specific, and is responsible for the presence or absence of one of the cysteine-rich repeat regions in the binding region of the molecule. Ratios of the receptor variants generated from these splice forms do not differ substantially across different cortical areas or in AD. We hypothesize that VLDL-r might contribute to metabolism of apoE and apoE/A{beta} complexes in the brain. Further characterization of apoE receptors in Alzheimer brain may help lay the groundwork for understanding the role of apoE in the CNS and in the pathophysiology of AD. 43 refs., 5 figs.

  20. Vegetable oils affect the composition of lipoproteins in sea bream (Sparus aurata).

    Science.gov (United States)

    Caballero, Maria José; Torstensen, Bente E; Robaina, Lidia; Montero, Daniel; Izquierdo, Marisol

    2006-11-01

    The aim of the present study was to determine the influence of the dietary fatty acid profile on the lipoprotein composition in sea bream fed different vegetable oils. Six experimental diets were formulated combining fish oil with three vegetable oils (soybean, rapeseed, linseed) in order to obtain 60-80 % (w/w) fish-oil replacement. VLDL, LDL and HDL in plasma samples were obtained by sequential centrifugal flotation. The lipid class, protein content and fatty acid composition of each lipoprotein fraction were analysed. HDL was the predominant lipoprotein in sea bream plasma containing the highest proportion of protein (34 %) and phosphatidylcholine. LDL presented a high content of cholesterol, whereas triacylglycerol comprised a larger proportion of VLDL. The lipid class of the lipoprotein fractions was affected by the dietary vegetable oils. Thus, a high dietary inclusion of soyabean and linseed oil (80 %) increased the cholesterol in HDL and LDL in comparison to fish oil. Similarly, the triacylglycerol concentration of VLDL was increased in fish fed 80 % soyabean and linseed oils owing to the low n-3 highly unsaturated fatty acid content of these diets. Lipoprotein fatty acid composition easily responded to dietary fatty acid composition. VLDL was the fraction more affected by dietary fatty acid, followed by LDL and HDL. The n-3 highly unsaturated fatty acid content increased in the order VLDL less than LDL and less than HDL, regardless of dietary vegetable oils.

  1. Relationship between Serum Lipoprotein Ratios and Insulin Resistance in Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    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.

  2. Circulating lipoproteins are a crucial component of host defense against invasive Salmonella typhimurium infection.

    Directory of Open Access Journals (Sweden)

    Mihai G Netea

    Full Text Available BACKGROUND: Circulating lipoproteins improve the outcome of severe Gram-negative infections through neutralizing lipopolysaccharides (LPS, thus inhibiting the release of proinflammatory cytokines. METHODS/PRINCIPAL FINDINGS: Low density lipoprotein receptor deficient (LDLR-/- mice, with a 7-fold increase in LDL, are resistant against infection with Salmonella typhimurium (survival 100% vs 5%, p<0.001, and 100 to 1000-fold lower bacterial burden in the organs, compared with LDLR+/+ mice. Protection was not due to differences in cytokine production, phagocytosis, and killing of Salmonella organisms. The differences were caused by the excess of lipoproteins, as hyperlipoproteinemic ApoE-/- mice were also highly resistant to Salmonella infection. Lipoproteins protect against infection by interfering with the binding of Salmonella to host cells, and preventing organ invasion. This leads to an altered biodistribution of the microorganisms during the first hours of infection: after intravenous injection of Salmonella into LDLR+/+ mice, the bacteria invaded the liver and spleen within 30 minutes of infection. In contrast, in LDLR-/- mice, Salmonella remained constrained to the circulation from where they were efficiently cleared, with decreased organ invasion. CONCLUSIONS: plasma lipoproteins are a potent host defense mechanism against invasive Salmonella infection, by blocking adhesion of Salmonella to the host cells and subsequent tissue invasion.

  3. Key intestinal genes involved in lipoprotein metabolism are downregulated in dyslipidemic men with insulin resistance.

    Science.gov (United States)

    Couture, Patrick; Tremblay, André J; Kelly, Isabelle; Lemelin, Valéry; Droit, Arnaud; Lamarche, Benoît

    2014-01-01

    Insulin resistance (IR) is associated with elevated plasma levels of triglyceride-rich lipoproteins (TRLs) of intestinal origin. However, the mechanisms underlying the overaccumulation of apolipoprotein (apo)B-48-containing TRLs in individuals with IR are not yet fully understood. This study examined the relationships between apoB-48-containing TRL kinetics and the expression of key intestinal genes and proteins involved in lipid/lipoprotein metabolism in 14 obese nondiabetic men with IR compared with 10 insulin-sensitive (IS) men matched for waist circumference. The in vivo kinetics of TRL apoB-48 were assessed using a primed-constant infusion of L-[5,5,5-D₃]leucine for 12 h with the participants in a constantly fed state. The expression of key intestinal genes and proteins involved in lipid/lipoprotein metabolism was assessed by performing real-time PCR quantification and LC-MS/MS on duodenal biopsy specimens. The TRL apoB-48 pool size and production rate were 102% (P < 0.0001) and 87% (P = 0.01) greater, respectively, in the men with IR versus the IS men. On the other hand, intestinal mRNA levels of sterol regulatory element binding factor-2, hepatocyte nuclear factor-4α, and microsomal triglyceride transfer protein were significantly lower in the men with IR than in the IS men. These data indicate that IR is associated with intestinal overproduction of lipoproteins and significant downregulation of key intestinal genes involved in lipid/lipoprotein metabolism.

  4. Reliability of Calculated Low-Density Lipoprotein Cholesterol.

    Science.gov (United States)

    Meeusen, Jeffrey W; Snozek, Christine L; Baumann, Nikola A; Jaffe, Allan S; Saenger, Amy K

    2015-08-15

    Aggressive low-density lipoprotein cholesterol (LDL-C)-lowering strategies are recommended for prevention of cardiovascular events in high-risk populations. Guidelines recommend a 30% to 50% reduction in at-risk patients even when LDL-C concentrations are between 70 and 130 mg/dl (1.8 to 3.4 mmol/L). However, calculation of LDL-C by the Friedewald equation is the primary laboratory method for routine LDL-C measurement. We compared the accuracy and reproducibility of calculated LDL-C <130 mg/dl (3.4 mmol/L) to LDL-C measured by β quantification (considered the gold standard method) in 15,917 patients with fasting triglyceride concentrations <400 mg/dl (4.5 mmol/L). Both variation and bias of calculated LDL-C increased at lower values of measured LDL-C. The 95% confidence intervals for a calculated LDL-C of 70 mg/dl (1.8 mmol/L) and 30 mg/dl (0.8 mmol/L) were 60 to 86 mg/dl (1.6 to 2.2 mmol/L) and 24 to 60 mg/dl (0.6 to 1.6 mmol/L), respectively. Previous recommendations have emphasized the requirement for a fasting sample with triglycerides <400 mg/dl (4.5 mmol/L) to calculate LDL-C by the Friedewald equation. However, no recommendations have addressed the appropriate lower reportable limit for calculated LDL-C. In conclusion, calculated LDL-C <30 mg/dl (0.8 mmol/L) should not be reported because of significant deviation from the gold standard measured LDL-C results, and caution is advised when using calculated LDL-CF values <70 mg/dl (1.8 mmol/L) to make treatment decisions.

  5. 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.

  6. 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...

  7. Progress of cardioprotective effects of high density lipoprotein: function and mechanism

    Directory of Open Access Journals (Sweden)

    Hai-ge SUN

    2015-01-01

    Full Text Available The high density lipoprotein (HDL in human plasma is a heterogeneous lipoprotein consisting of roughly equal contents of lipid and protein in roughly equal content, and it consists of several subtypes. HDL possesses several well-documented functions, including anti-atherosclerosis by promoting reverse cholesterol transport, inhibiting the oxidative modification of low density lipoproteins (LDLs, inhibiting vascular inflammation, preventing thrombosis and apoptosis, and promoting endothelial repair. Recently, more cardiovascular protective functions of HDL have been found, mainly including the ability of suppressing immune inflammatory reaction, inhibiting the proliferation of hematopoietic stem cells, and regulating the plasma glucose level. It is of great importance to understand how different HDL subtypes contribute to the potentially cardioprotective functions. DOI: 10.11855/j.issn.0577-7402.2014.11.13

  8. Lipoprotein(a) concentrations, isoform size, and risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Kamstrup, Pia Rørbæk; Nordestgaard, Børge

    2013-01-01

    BACKGROUND: Low concentrations of lipoprotein(a) in plasma are associated with increased risk of type 2 diabetes, but whether this association is causal is unclear. Variations in the LPA gene affect lipoprotein(a) isoform size and concentrations in plasma. We therefore did a Mendelian randomisation...... study to investigate whether large isoform size, low concentrations in plasma, or both, are causally associated with type 2 diabetes. METHODS: We assessed data for adults from the Danish general population enrolled in the Copenhagen City Heart Study and the Copenhagen General Population Study......, with and without type 2 diabetes. Eligible participants had data for lipoprotein(a) concentrations in plasma, LPA kringle IV type 2 (KIV-2) sums of repeats (affecting both isoform size and plasma concentrations), and carrier status for the LPA single-nucleotide polymorphism rs10455872 (mainly affecting...

  9. Identification of megalin/gp330 as a receptor for lipoprotein(a) in vitro

    DEFF Research Database (Denmark)

    Niemeier, A; Willnow, T; Dieplinger, H;

    1999-01-01

    Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein of unknown physiological function. The mechanism of Lp(a) atherogenicity as well as its catabolic pathways are only incompletely understood at present. In this report, we show that the low density lipoprotein receptor (LDLR) gene family member...... megalin/glycoprotein (gp) 330 is capable of binding and mediating the cellular uptake and degradation of Lp(a) in vitro. A mouse embryonic yolk sac cell line with native expression of megalin/gp330 but genetically deficient in LDLR-related protein (LRP) and a control cell line carrying a double knockout...... unlabeled Lp(a) and LDL suggested that Lp(a) uptake is mediated at least partially by apolipoprotein B100. Binding and uptake of DiI-Lp(a) resulted in strong signals on megalin/gp330-expressing cells versus background only on control cells. In addition, we show that purified megalin/gp330, immobilized...

  10. 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......Apolipoprotein M (apoM) is a novel apolipoprotein found mainly in high-density lipoproteins (HDL). Its function is yet to be defined. ApoM (25 kDa) has a typical lipocalin ss-barrel fold and a hydrophobic pocket. Retinoids bind apoM but with low affinity and may not be the natural ligands. Apo......; possible mechanisms include increased formation of pre-ss HDL, enhanced cholesterol mobilization from foam cells, and increased antioxidant properties....

  11. Lipoprotein apheresis and new therapies for severe familial hypercholesterolemia in adults and children.

    Science.gov (United States)

    Page, Michael M; Bell, Damon A; Hooper, Amanda J; Watts, Gerald F; Burnett, John R

    2014-06-01

    Familial hypercholesterolemia (FH), the most common and severe monogenic form of hypercholesterolemia, is an autosomal co-dominant disease characterized by an increased plasma low density lipoprotein (LDL)-cholesterol concentration and premature coronary heart disease (CHD). The clinical phenotype depends on the gene involved and severity of mutation (or mutations) present. Patients with homozygous or compound heterozygous FH have severe hypercholesterolemia (LDL-cholesterol >13 mmol/L) due to a gene dosing effect and without treatment have accelerated atherosclerotic CHD from birth, and frequently die of CHD before age 30. Cholesterol-lowering therapies have been shown to reduce both mortality and major adverse cardiovascular events in individuals with FH. Lipoprotein apheresis concomitant with lipid-lowering therapy is the treatment of choice for homozygous FH. This article describes the rationale and role of lipoprotein apheresis in the treatment of severe FH and outlines the recent advances in new pharmacotherapies for this condition.

  12. Triglycerides and high-density lipoprotein cholesterol are associated with insulinemia in adolescents

    Directory of Open Access Journals (Sweden)

    Ramírez-López Guadalupe

    2006-01-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the association between lipids and insulin concentration in adolescents. MATERIAL AND METHODS: A cross-sectional study of 350 adolescents aged 14-19 years old from a public high school in Guadalajara, in the state of Jalisco, Mexico, was conducted. Fasting insulin concentration was determined using microparticle enzyme immunoassay; total cholesterol and triglycerides were detected by standard enzymatic procedures; and low- and high-density lipoproteins were found using standard precipitation methods. Statistical analysis included linear multivariate regression. RESULTS: Serum triglycerides were associated positively with insulin fasting (beta= 0.003, p= 0.0001 and high-density lipoprotein cholesterol was negatively associated with insulin fasting in male adolescents 18-19 years old (beta= -0.03, p= 0.012. CONCLUSIONS: The relationships between triglycerides and insulin and between high-density lipoprotein cholesterol and insulin are already present in adolescence.

  13. The role of lipoprotein processing by signal peptidase II in the Gram-positive eubacterium Bacillus subtilis : Signal peptidase II is required for the efficient secretion of alpha-amylase, a non-lipoprotein

    NARCIS (Netherlands)

    Tjalsma, H; Kontinen, VP; Pragai, Z; Meima, R; Venema, G; Bron, S; Sarvas, M; van Dijl, JM

    1999-01-01

    Computer-assisted analyses indicate that Bacillus subtilis contains approximately 300 genes for exported proteins with an amino-terminal signal peptide. About 114 of these are lipoproteins, which are retained in the cytoplasmic membrane. We have investigated the importance of lipoprotein processing

  14. 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 OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

  15. Lipids, lipoproteins, fibrinogen and fibrinolytic activity in angiographically assessed coronary heart disease.

    Science.gov (United States)

    Lipinska, I; Gurewich, V; Meriam, C M; Kosowsky, B D; Ramaswamy, K; Philbin, E; Losordo, D

    1987-01-01

    Plasma lipids, lipoproteins, fibrinogen and fibrinolytic activity (FA) were measured in 202 consecutive patients undergoing coronary angiography. Twenty-one patients, 13 men and 8 women with a mean age of 52.8 years and 56.7 years respectively, were found to be angiographically free of coronary artery disease (CAD) and served as the principal control group. Since this group contained a disproportionate number of subjects with risk factors such as family history, hypertension and smoking, a second control group of clinically healthy subjects selected for age was also tested. Their laboratory results were not used in the statistical calculations. The group with angiographic CAD consisted of 130 men (mean age 57.6 years) and 51 women (mean age 61.5 years). Abnormal angiograms were graded according to the number of major vessels with more than 50% stenosis involved. The laboratory variables which were significantly (p less than .01-.001) associated with the presence of CAD were: High density lipoprotein (HDL) when determined by polyacrylamide gel electrophoresis (PAGE) and expressed as a percentage of total lipoproteins rather than concentration, presence of Intermediate Density Lipoprotein (IDL), percent of Very Low Density Lipoprotein (VLDL), fibrinogen concentration and FA. The HDL2 subfraction was significantly inversely correlated only in women. The total plasma cholesterol was normal and virtually identical in both groups. Within the CAD group, only two of the laboratory results were significantly correlated with the extent of disease. By univariate analysis, the FA showed the closest association with the score for severity of CAD (p less than .001) followed by the presence of IDL (p less than .01). In conclusion, lipoprotein analysis by a method which measures not only HDL, but also LDL, VLDL and IDL, together with the determination of fibrinogen and FA provides information useful in the identification of individuals at risk for CAD.

  16. 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.

  17. 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.

  18. Changes in epitope exposition of apolipoprotein A-I on the surface of high density lipoproteins after phospholipase A2 treatment.

    Science.gov (United States)

    Menschikowski, M; Hempel, U; Dinnebier, G; Lattke, P; Wenzel, K W; Jaross, W

    1995-10-01

    The immunoreactivity of high density lipoprotein (HDL) modified by treatment with porcine pancreatic phospholipase A2 (PLA2) was studied in a competitive radioimmunoassay using 6 different monoclonal apolipoprotein (apo) A-I antibodies. The competition tests have shown that after PLA2 treatment the immunoreactivity of selected epitopes of apo A-I changed in different ways. While the binding behavior of two epitopes remained unchanged, three epitopes exhibited decreased immunoreactivities after phospholipids hydrolysis. In contrast to the latter epitopes, the immunoreactivity of an epitope located on the cyanogen bromide fragment 4 of apo A-I increased with the degree of lipolysis. A loss of apo A-I from HDL as a consequence of PLA2-treatment did not occur as shown by the determination of the apo A-I concentration in HDL before and after treatment with PLA2. Using overlapped synthetic decapeptides it could be shown that the epitope increasingly exposed on the particle surface of PLA2-modified HDL consists of the amino acid residues 162-173 and 212-229. These residues are characterized by high hydrophobic indices as determined by hydropathy analysis. Furthermore, these regions belong partially to the proposed receptor-binding domain of apo A-I. Thus, an increased exposition of this epitope might result in elevated cellular binding affinities of HDL occurring after modification of lipoproteins by PLA2-treatment.

  19. Reduced adipose tissue lipoprotein lipase responses, postprandial lipemia, and low high-density lipoprotein-2 subspecies levels in older athletes with silent myocardial ischemia.

    Science.gov (United States)

    Katzel, L I; Busby-Whitehead, M J; Rogus, E M; Krauss, R M; Goldberg, A P

    1994-02-01

    Healthy older (64 +/- 1 years, mean +/- SEM) athletic (maximal oxygen consumption [VO2max] > 40 mL/kg/min) normocholesterolemic men with no prior history of coronary artery disease (CAD) were recruited for cardiovascular and metabolic studies. Thirty-three percent had asymptomatic exercise-induced ST segment depression on their exercise electrocardiogram (ECG), consistent with silent myocardial ischemia (SI). We hypothesized that abnormalities in high-density lipoprotein (HDL) and postprandial triglyceride (TG) metabolism may increase their risk for CAD. Compared with 12 nonischemic controls of comparable age, percent body fat, and VO2max, the 13 men with SI had decreased fasting HDL cholesterol ([HDL-C] 41 +/- 2 v 50 +/- 2 mg/dL, P postprandial plasma TG, chylomicron-TG, and very-low-density lipoprotein (VLDL)-TG levels and postprandial areas were higher in men with SI (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

  20. 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

  1. Darapladib, a lipoprotein-associated phospholipase A2 inhibitor, in diabetic macular edema

    DEFF Research Database (Denmark)

    Staurenghi, Giovanni; Ye, Li; Magee, Mindy H;

    2015-01-01

    PURPOSE: To investigate the potential of lipoprotein-associated phospholipase A2 inhibition as a novel mechanism to reduce edema and improve vision in center-involved diabetic macular edema (DME). DESIGN: Prospective, multicenter, randomized, double-masked, placebo-controlled phase IIa study...... (AEs) and nonocular AEs were similar between treatment groups. CONCLUSIONS: Once-daily oral darapladib administered for 3 months demonstrated modest improvements in vision and macular edema that warrant additional investigation of this novel lipoprotein-associated phospholipase A2 inhibitory mechanism...

  2. Electrophoretic demonstration of glycoproteins, lipoproteins, and phosphoproteins in human and bovine enamel

    DEFF Research Database (Denmark)

    Kirkeby, S; Moe, D; Bøg-Hansen, T C;

    1990-01-01

    Enamel proteins from fully mineralized human molars and from bovine tooth germs were separated by electrophoresis. The gels were stained for detection of glycoproteins, lipoproteins, and phosphoproteins. Glycoproteins were shown by periodic acid-Schiff staining and lectin blotting. In mature human...... enamel a number of high molecular weight proteins could be demonstrated after ethylenediaminetetra-acetic acid demineralization and subsequent Triton X-100 extraction. These proteins are suggested to be lipoproteins. Phosphoproteins could only be visualized in enamel matrix from the tooth germs....

  3. 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

    2016-07-27

    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.

  4. Relationship between two common lipoprotein lipase variants and the metabolic syndrome and its individual components

    DEFF Research Database (Denmark)

    Vishram, Julie K. K.; Hansen, Tine W.; Torp-Pedersen, Christian

    2016-01-01

    BACKGROUND: Common lipoprotein lipase (LPL) variants are important determinants of triglycerides (TG) and high-density lipoprotein (HDL) cholesterol (C) concentrations. High TG/low HDL-C tend to cluster with hypertension, glucose intolerance, and abdominal obesity and comprise the metabolic...... syndrome (MetS). The role of LPL variants as a cause of MetS is unclear. This study investigated the relationship between two common LPL variants and the presence of MetS and its individual components. METHODS: Cross-sectional study, including 2348 Danish women (50.7%) and men, age 41-72 years, without...

  5. Particle physics

    CERN Document Server

    Kennedy, Eugene

    2012-01-01

    Stimulated by the Large Hadron Collider and the search for the elusive Higgs Boson, interest in particle physics continues at a high level among scientists and the general public. This book includes theoretical aspects, with chapters outlining the generation model and a charged Higgs boson model as alternative scenarios to the Standard Model. An introduction is provided to postulated axion photon interactions and associated photon dispersion in magnetized media. The complexity of particle physics research requiring the synergistic combination of theory, hardware and computation is described in terms of the e-science paradigm. The book concludes with a chapter tackling potential radiation hazards associated with extremely weakly interacting neutrinos if produced in copious amounts with future high-energy muon-collider facilities.

  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. Particle astrophysics

    CERN Document Server

    Krauss, Lawrence M

    1997-01-01

    Astrophysics and cosmology provide fundamental testing grounds for many ideas in elementary particle physics, and include potential probes which are well beyond the range of current or even planned accelerators. In this series of 3 lectures, I will give and overview of existing constraints, and a discussion of the potential for the future. I will attempt whenever possible to demonstrate the connection between accelerator-based physics and astrophysicas/cosmology. The format of the kectures will be to examine observables from astrophysics, and explore how these can be used to constrain particle physics. Tentatively, lecture 1 will focus on the age and mass density of the universe and galaxy. Lecture 2 will focus on stars, stellar evolution, and the abundance of light elements. Lecture 3 will focus on various cosmic diffuse backgrounds, including possibly matter, photons, neutrinos and gravitational waves.

  8. Particle encapsulation

    OpenAIRE

    Sun, Xiaobin

    2000-01-01

    Several engineering processes are powder based, ranging from food processing to engineering ceramic and composite production. In most of these processes, powders of different composition are mixed together in order to produce the final product, and this combining of powders of different density, shape, and surface properties is often very difficult. Mixtures may be quite inhomogeneous. This research focuses on a method of avoiding such problems, by coating individual particles of one material...

  9. ApoA-I enhances generation of HDL-like lipoproteins through interaction between ABCA1 and phospholipase Cγ in rat astrocytes.

    Science.gov (United States)

    Ito, Jin-ichi; Nagayasu, Yuko; Kheirollah, Alireza; Abe-Dohmae, Sumiko; Yokoyama, Shinji

    2011-12-01

    In the previous paper, we reported that apolipoprotein (apo) A-I enhances generation of HDL-like lipoproteins in rat astrocytes to be accompanied with both increase in tyrosine phosphorylation of phospholipase Cγ (PL-Cγ) and PL-Cγ translocation to cytosolic lipid-protein particles (CLPP) fraction. In this paper, we studied the interaction between apoA-I and ATP-binding cassette transporter A1 (ABCA1) to relate with PL-Cγ function for generation of HDL-like lipoproteins in the apoA-I-stimulated astrocytes. ABCA1 co-migrated with exogenous apoA-I with apparent molecular weight over 260kDa on SDS-PAGE when rat astrocytes were treated with apoA-I and then with a cross-linker, BS3. The solubilized ABCA1 of rat astrocytes was associated with the apoA-I-immobilized Affi-Gel 15. An LXR agonist, To901317, increased the cellular level of ABCA1, association of apoA-I with ABCA1 and apoA-I-mediated lipid release in rat astrocytoma GA-1/Mock cells where ABCA1 expression at baseline is very low. PL-Cγ was co-isolated by apoA-I-immobilized Affi-Gel 15 and co-immunoprecipitated by anti-ABCA1 antibody along with ABCA1 from the solubilized membrane fraction of rat astrocytes. The SiRNA of ABCA1 suppressed not only the PL-Cγ binding to ABCA1 but also the tyrosine phosphorylation of PL-Cγ. A PL-C inhibitor, U73122, prevented generation of apoA-I-mediated HDL-like lipoproteins in rat astrocytes. To901317 increased the association of PL-Cγ with ABCA1 in GA-1/Mock cells dependently on the increase of cellular level of ABCA1 without changing that of PL-Cγ. These findings suggest that the exogenous apoA-I augments the interaction between PL-Cγ and ABCA1 to stimulate tyrosine phosphorylation and activation of PL-Cγ for generation of HDL-like lipoproteins in astrocytes.

  10. Serum apolipoprotein(a) levels and its effect on the measured values of low density lipoprotein cholesterol.

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    Serum low density lipoprotein cholesterl (LDL-C) and lipoprotein(a)[Lp(a)]levels were analyzed in 1032 sequential cases on routine physical check up, with special attention to the effect of Lp(a) on the LDL-C values. Since the determination of LDL-C by various

  11. 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 ...

  12. Plasma levels of HDL subpopulations and remnant lipoproteins predict the extent of angiographically defined disease in post-menopausal women

    Science.gov (United States)

    The association of coronary heart disease (CHD) with subpopulations of triglyceride (TG)-rich lipoproteins and high-density lipoproteins (HDL) is established in men, but has not been well characterized in women. Plasma HDL subpopulation concentrations, quantified by 2-dimensional gel electrophoresis...

  13. Surface-associated lipoprotein PpmA of Streptococcus pneumoniae is involved in colonization in a strain-specific manner.

    NARCIS (Netherlands)

    Cron, L.E.; Bootsma, H.J.; Noske, N.; Burghout, P.J.; Hammerschmidt, S.; Hermans, P.W.M.

    2009-01-01

    Streptococcus pneumoniae produces two surface-associated lipoproteins that share homology with two distinct families of peptidyl-prolyl isomerases (PPIases), the streptococcal lipoprotein rotamase A (SlrA) and the putative proteinase maturation protein A (PpmA). Previously, we have demonstrated that

  14. 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

    receptor for apolipoprotein (apo) B100. It interacts with apoB100 in the Golgi and facilitates the formation and hepatic export of apoB100-containing lipoproteins, thereby regulating plasma low-density lipoprotein (LDL) cholesterol. Absence of sortilin in gene-targeted mice reduces secretion...

  15. [The alternative view on diagnostic of hyperlipoproteinemia, cholesterol lipoproteins of low density and effect of statins: a lecture].

    Science.gov (United States)

    Tupoleva, T A; Tikhomirov, D S; Grumbkova, L O; Ignatova, E N; Romanova, T Iu; Filatov, F P; Garanzha, T A

    2015-01-01

    The effect of statins occur in several stages: 1) inhibition in hepatocytes of synthesis of functionally specific pool of spirit cholesterol, polar mono-layer of lipoproteins of very low density; 2) activation of hydrolysis of triglycerides in lipoproteins of very low density, formation of apoE/B-100-ligand and absorption of lipoproteins of very low density by insulin-depended cells; 3) decreasing of content of and spirit cholesterol-lipoproteins of very low density in blood plasma; 4) activation of hydrolysis of triglycerides in lipoproteins of low density, formation of apoB-100-ligand and absorption of lipoproteins of low density by insulin-independent cells; 5) decreasing of level of and increasing of content of lipoproteins of high density. During first weeks of effect of statins occurs decreasing of concentration of triglycerides and unesterified spirit cholesterol-lipoproteins of very low density in blood plasma. Then, slower and more durational decreasing of level of spirit cholesterol-lipoproteins of low density occurs. The value of spirit cholesterol-lipoproteins of low density is primarily determined by content of palmitic saturated fatty acid in food, its endogenous synthesis from glucose and concentration of palmitic triglycerides and lipoproteins of very low density of the same name in blood plasma. The effect of preparations is biologically valid and corresponds to alternative hypolipidemic preparations. All these preparations have an effect following a common algorithm: they activate, using different mechanisms, receptor absorption of lipoproteins of very low density or lipoproteins of low density by cells. The level of spirit cholesterol-lipoproteins of low density in full measure depends on content of triglycerides in blood. The concentration of spirit cholesterol in blood plasma has a reliable diagnostic significance only under physiological content of triglycerides. The main criterion of diagnostic and control of hypolipidemic therapy

  16. 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.

  17. An ABCA1-independent pathway for recycling a poorly lipidated 8.1 nm apolipoprotein E particle from glia

    Science.gov (United States)

    Fan, Jianjia; Stukas, Sophie; Wong, Charmaine; Chan, Jennifer; May, Sharon; DeValle, Nicole; Hirsch-Reinshagen, Veronica; Wilkinson, Anna; Oda, Michael N.; Wellington, Cheryl L.

    2011-01-01

    Lipid transport in the brain is coordinated by glial-derived lipoproteins that contain apolipoprotein E (apoE) as their primary protein. Here we show that apoE is secreted from wild-type (WT) primary murine mixed glia as nascent lipoprotein subspecies ranging from 7.5 to 17 nm in diameter. Negative-staining electron microscropy (EM) revealed rouleaux, suggesting a discoidal structure. Potassium bromide (KBr) density gradient ultracentrifugation showed that all subspecies, except an 8.1 nm particle, were lipidated. Glia lacking the cholesterol transporter ABCA1 secreted only 8.1 nm particles, which were poorly lipidated and nondiscoidal but could accept lipids to form the full repertoire of WT apoE particles. Receptor-associated-protein (RAP)-mediated inhibition of apoE receptor function blocked appearance of the 8.1 nm species, suggesting that this particle may arise through apoE recycling. Selective deletion of the LDL receptor (LDLR) reduced the level of 8.1 nm particle production by approximately 90%, suggesting that apoE is preferentially recycled through the LDLR. Finally, apoA-I stimulated secretion of 8.1 nm particles in a dose-dependent manner. These results suggest that nascent glial apoE lipoproteins are secreted through multiple pathways and that a greater understanding of these mechanisms may be relevant to several neurological disorders. PMID:21705806

  18. A Safe, Versatile and Translation-prone Strategy for Using Circulating Lipoproteins as Endogenous Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Mahshid Foroozesh

    2010-10-01

    Full Text Available "nLipoproteins (LPs, the endogenous lipid-protein micro- and nanostructures involved in lipid metabolism, have attracted a high degree of interest in recent years for being used as novel drug delivery systems. Numerous diagnostic and therapeutic agents (in particular anti-cancer agents have been studied using native and (semisynthetic LPs as both prolonged and targeted drug delivery systems. Since all reported loading methods are basically in vitro or ex vivo procedures with related limitations, an idea has been raised for finding a completely new loading paradigm to overcome the limitations in using native particles as drug vehicles. The basis for this hypothesis is that we are able to load native and circulating LPs without extracting them from body via using specific monoclonal antibodies (MAb, already linked to desired drugs or to be linked to drug via proper linker system such as avidin-biotin bridges actively-targeted against specialized Apos available on the surface of all LPs. Obviously, by choosing the right anti-Apo antibody (preferably single chain variable fragment; scFv, we can select the right circulating LP subpopulation (i.e., LDL, HDL, VLDL, or CM. By considering all parameters and using the most appropriate strategy, this novel, safe, versatile, industrializable, and clinically translation-prone  paradigm could be used for both prolonged and (LP receptor- and non-LP receptor- targeted drug delivery purposes.

  19. Design and evaluation of lipoprotein resembling curcumin-encapsulated protein-free nanostructured lipid carrier for brain targeting.

    Science.gov (United States)

    Meng, Fanfei; Asghar, Sajid; Xu, Yurui; Wang, Jianping; Jin, Xin; Wang, Zhilin; Wang, Jing; Ping, Qineng; Zhou, Jianping; Xiao, Yanyu

    2016-06-15

    Many nanoparticle matrixes have been demonstrated to be efficient in brain targeting, but there are still certain limitations for them. To overcome the shortcomings of the existing nanoparticulate systems for brain-targeted delivery, a lipoprotein resembling protein-free nanostructured lipid carrier (PS80-NLC) loaded with curcumin was constructed and assessed for in vitro and in vivo performance. Firstly, single factor at a time approach was employed to investigate the effects of various formulation factors. Mean particle sizes of ≤100nm, high entrapment efficiency (EE, about 95%) and drug loading (DL, >3%) were obtained for the optimized formulations. In vitro release studies in the presence of plasma indicated stability of the formulation under physiological condition. Compared with NLC, PS80-NLC showed noticeably higher affinity for bEnd.3 cells (1.56 folds greater than NLC) but with lower uptake in macrophages. The brain coronal sections showed strong and widely distributed fluorescence intensity of PS80-NLC than that of NLC in the cortex. Ex vivo imaging studies further confirmed that PS80-NLC could effectively permeate BBB and preferentially accumulate in the brain (2.38 times greater than NLC). The considerable in vitro and in vivo performance of the safe and biocompatible PS80-NLC makes it a suitable option for further investigations in brain targeted drug delivery.

  20. 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.

  1. Catalytic stimulation by restrained active-site floppiness--the case of high density lipoprotein-bound serum paraoxonase-1.

    Science.gov (United States)

    Ben-David, Moshe; Sussman, Joel L; Maxwell, Christopher I; Szeler, Klaudia; Kamerlin, Shina C L; Tawfik, Dan S

    2015-03-27

    Despite the abundance of membrane-associated enzymes, the mechanism by which membrane binding stabilizes these enzymes and stimulates their catalysis remains largely unknown. Serum paraoxonase-1 (PON1) is a lipophilic lactonase whose stability and enzymatic activity are dramatically stimulated when associated with high-density lipoprotein (HDL) particles. Our mutational and structural analyses, combined with empirical valence bond simulations, reveal a network of hydrogen bonds that connect HDL binding residues with Asn168--a key catalytic residue residing >15Å from the HDL contacting interface. This network ensures precise alignment of N168, which, in turn, ligates PON1's catalytic calcium and aligns the lactone substrate for catalysis. HDL binding restrains the overall motion of the active site and particularly of N168, thus reducing the catalytic activation energy barrier. We demonstrate herein that disturbance of this network, even at its most far-reaching periphery, undermines PON1's activity. Membrane binding thus immobilizes long-range interactions via second- and third-shell residues that reduce the active site's floppiness and pre-organize the catalytic residues. Although this network is critical for efficient catalysis, as demonstrated here, unraveling these long-rage interaction networks is challenging, let alone their implementation in artificial enzyme design.

  2. Model of mouth-to-mouth transfer of bacterial lipoproteins through inner membrane LolC, periplasmic LolA, and outer membrane LolB

    OpenAIRE

    Okuda, Suguru; Tokuda, Hajime

    2009-01-01

    Outer membrane-specific lipoproteins in Escherichia coli are released from the inner membrane by an ATP-binding cassette transporter, the LolCDE complex, which causes the formation of a soluble complex with a periplasmic molecular chaperone, LolA. LolA then transports lipoproteins to the outer membrane where an outer membrane receptor, LolB, incorporates lipoproteins into the outer membrane. The molecular mechanisms underlying the Lol-dependent lipoprotein sorting have been clarified in detai...

  3. Low-density lipoprotein receptor-related protein-1 facilitates heme scavenging after intracerebral hemorrhage in mice.

    Science.gov (United States)

    Wang, Gaiqing; Manaenko, Anatol; Shao, Anwen; Ou, Yibo; Yang, Peng; Budbazar, Enkhjargal; Nowrangi, Derek; Zhang, John H; Tang, Jiping

    2016-06-17

    Heme-degradation after erythrocyte lysis plays an important role in the pathophysiology of intracerebral hemorrhage. Low-density lipoprotein receptor-related protein-1 is a receptor expressed predominately at the neurovascular interface, which facilitates the clearance of the hemopexin and heme complex. In the present study, we investigated the role of low-density lipoprotein receptor-related protein-1 in heme removal and neuroprotection in a mouse model of intracerebral hemorrhage. Endogenous low-density lipoprotein receptor-related protein-1 and hemopexin were increased in ipsilateral brain after intracerebral hemorrhage, accompanied by increased hemoglobin levels, brain water content, blood-brain barrier permeability and neurological deficits. Exogenous human recombinant low-density lipoprotein receptor-related protein-1 protein reduced hematoma volume, brain water content surrounding hematoma, blood-brain barrier permeability and improved neurological function three days after intracerebral hemorrhage. The expression of malondialdehyde, fluoro-Jade C positive cells and cleaved caspase 3 was increased three days after intracerebral hemorrhage in the ipsilateral brain tissues and decreased with recombinant low-density lipoprotein receptor-related protein-1. Intracerebral hemorrhage decreased and recombinant low-density lipoprotein receptor-related protein-1 increased the levels of superoxide dismutase 1. Low-density lipoprotein receptor-related protein-1 siRNA reduced the effect of human recombinant low-density lipoprotein receptor-related protein-1 on all outcomes measured. Collectively, our findings suggest that low-density lipoprotein receptor-related protein-1 contributed to heme clearance and blood-brain barrier protection after intracerebral hemorrhage. The use of low-density lipoprotein receptor-related protein-1 as supplement provides a novel approach to ameliorating intracerebral hemorrhage brain injury via its pleiotropic neuroprotective effects.

  4. 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

  5. Blood-brain barrier (BBB) toxicity and permeability assessment after L-(4-¹⁰Boronophenyl)alanine, a conventional B-containing drug for boron neutron capture therapy, using an in vitro BBB model.

    Science.gov (United States)

    Roda, E; Nion, S; Bernocchi, G; Coccini, T

    2014-10-01

    Since brain tumours are the primary candidates for treatment by Boron Neutron Capture Therapy, one major challenge in the selective drug delivery to CNS is the crossing of the blood-brain barrier (BBB). The present pilot study investigated (i) the transport of a conventional B-containing product (i.e., L-(4-(10)Boronophenyl)alanine, L-(10)BPA), already used in medicine but still not fully characterized regarding its CNS interactions, as well as (ii) the effects of the L-(10)BPA on the BBB integrity using an in vitro model, consisting of brain capillary endothelial cells co-cultured with glial cells, closely mimicking the in vivo conditions. The multi-step experimental strategy (i.e. Integrity test, Filter study, Transport assay) checked L-(10)BPA toxicity at 80 µg Boron equivalent/ml, and its ability to cross the BBB, additionally by characterizing the cytoskeletal and TJ's proteins by immunocytochemistry and immunoblotting. In conclusion, a lack of toxic effects of L-(10)BPA was demonstrated, nevertheless accompanied by cellular stress phenomena (e.g. vimentin expression modification), paralleled by a low permeability coefficient (0.39 ± 0.01 × 10(-3)cm min(-1)), corroborating the scarce probability that L-(10)BPA would reach therapeutically effective cerebral concentration. These findings emphasized the need for novel strategies aimed at optimizing boron delivery to brain tumours, trying to ameliorate the compound uptake or developing new targeted products suitable to safely and effectively treat head cancer. Thus, the use of in vitro BBB model for screening studies may provide a useful early safety assessment for new effective compounds.

  6. 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.

  7. Moderate alcohol consumption and lipoprotein-associated phospholipase A2 activity

    NARCIS (Netherlands)

    Beulens, J.W.J.; Berg, van den R.; Kok, F.J.; Helander, A.; Vermunt, S.H.F.; Hendriks, H.F.J.

    2008-01-01

    Background and aims To investigate the effect of moderate alcohol consumption on lipoprotein-associated phospholipase A2 activity, markers of inflammation and oxidative stress and whether these effects are modified by BMI. Methods and results Eleven lean (BMI: 18.5¿25 kg/m2) and 9 overweight (BMI &g

  8. Changes in the triglyceride-rich lipoproteins and the response to dietary cholesterol in man.

    NARCIS (Netherlands)

    Demacker, P.N.M.; Glatz, J.F.C.; Katan, M.B.

    1988-01-01

    The effect of a cholesterol-enriched diet was studied in nine healthy volunteers with special emphasis to the changes which occurred in the triglyceride-rich lipoproteins (d<1.019 g/ml). Compared to the habitual diet, a moderately increased intake of cholesterol (from 300–900 mg/day) resulted in cha

  9. Mutation in apolipoprotein B associated with hypobetalipoproteinemia despite decreased binding to the low density lipoprotein receptor

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Jan Skov;

    2005-01-01

    Mutations in apolipoprotein B (APOB) may reduce binding of low density lipoprotein (LDL) to the LDL receptor and cause hypercholesterolemia. We showed that heterozygotes for a new mutation in APOB have hypobetalipoproteinemia, despite a reduced binding of LDL to the LDL receptor. APOB R3480P hete...

  10. 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 seden

  11. High-density lipoproteins and coronary artery disease: a single-center cohort study

    NARCIS (Netherlands)

    Schaffer, A.; Verdoia, M.; Barbieri, L.; Aprami, T.M.; Suryapranata, H.; Marino, P.; Luca, G.D.

    2014-01-01

    Our goal was to estimate the role of high-density lipoprotein cholesterol (HDL-C) in predicting the prevalence and extent of coronary artery disease (CAD) in 3280 patients undergoing coronary angiography. Predictors of lower HDL levels (<32 mg/dL) were male gender (P < .001), diabetes mellitus

  12. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Low-density lipoprotein immunological test system. 866.5600 Section 866.5600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... serum may aid in the diagnosis of disorders of lipid (fat) metabolism and help to identify young...

  13. Impact of lipids and lipoproteins on hepatitis C virus infection and virus neutralization.

    Science.gov (United States)

    Vercauteren, Koen; Mesalam, Ahmed Atef; Leroux-Roels, Geert; Meuleman, Philip

    2014-11-21

    Hepatitis C virus (HCV) infections represent a major global health problem. End-stage liver disease caused by chronic HCV infection is a major indication for liver transplantation. However, after transplantation the engrafted liver inevitably becomes infected by the circulating virus. Direct acting antivirals are not yet approved for use in liver transplant patients, and limited efficacy and severe side effects hamper the use of pegylated interferon combined with ribavirin in a post-transplant setting. Therefore, alternative therapeutic options need to be explored. Viral entry represents an attractive target for such therapeutic intervention. Understanding the mechanisms of viral entry is essential to define the viral and cellular factors involved. The HCV life cycle is dependent of and associated with lipoprotein physiology and the presence of lipoproteins has been correlated with altered antiviral efficacy of entry inhibitors. In this review, we summarise the current knowledge on how lipoprotein physiology influences the HCV life cycle. We focus especially on the influence of lipoproteins on antibodies that target HCV envelope proteins or antibodies that target the cellular receptors of the virus. This information can be particularly relevant for the prevention of HCV re-infection after liver transplantation.

  14. Method-dependent increase in lipoprotein(a) in insulin-dependent diabetes mellitus during pregnancy

    NARCIS (Netherlands)

    Pekelharing, HLM; Aalders, NL; Visser, GHA; vanDoormaal, JJ; Kleinveld, HA; vanRijn, HJM; Bouma, Bonno N.

    1995-01-01

    The current prevalent view is that plasma lipoprotein(a) [Lp(a)] concentrations are under strong genetic control. Most dietary and drug interventions seem to have little or no effect on plasma Lp(a) levels. However, evidence for a possible regulatory role of hormones is accumulating, for instance, f

  15. Lipoprotein-associated phospholipase A2 and coronary calcification - The Rotterdam coronary calcification study

    NARCIS (Netherlands)

    Kardys, Isabella; Oei, Hok-Hay S.; Hofman, Albert; Oudkerk, Matthijs; Witteman, Jacqueline C. M.

    2007-01-01

    Objectives: Although several studies have recently suggested that lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent predictor of coronary events, only one study has examined the association between Lp-PLA2 and coronary calcification, using young adults. We investigated the associat

  16. Genetic analysis of long-lived families reveals novel variants influencing high density-lipoprotein cholesterol

    DEFF Research Database (Denmark)

    Feitosa, Mary F; Wojczynski, Mary K; Straka, Robert

    2014-01-01

    The plasma levels of high-density lipoprotein cholesterol (HDL) have an inverse relationship to the risks of atherosclerosis and cardiovascular disease (CVD), and have also been associated with longevity. We sought to identify novel loci for HDL that could potentially provide new insights...

  17. Association of lipoprotein levels with mortality in subjects aged 50 + without previous diabetes or cardiovascular disease

    DEFF Research Database (Denmark)

    Bathum, Lise; Depont Christensen, René; Engers Pedersen, Lars

    2013-01-01

    This study aimed to investigate the association of lipoprotein and triglyceride levels with all-cause mortality in a population free from diabetes and cardiovascular disease (CVD) at baseline. The European Guidelines on cardiovascular disease prevention state that in general total cholesterol (TC...

  18. The HDL hypothesis : does high-density lipoprotein protect from atherosclerosis?

    NARCIS (Netherlands)

    Vergeer, Menno; Holleboom, Adriaan G; Kastelein, John J P; Kuivenhoven, Jan Albert

    2010-01-01

    There is unequivocal evidence of an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentrations and the risk of cardiovascular disease, a finding that has led to the hypothesis that HDL protects from atherosclerosis. This review details the experimental evidence for

  19. Cigarette smoking and its association with serum lipid/lipoprotein among Chinese nonagenarians/centenarians

    Directory of Open Access Journals (Sweden)

    Yan-Ling Zhang

    2012-07-01

    Full Text Available Abstract Objective Cigarette smoking had been confirmed as an increased risk for dyslipidemia, but none of the evidence was from long-lived population. In present study, we detected relationship between cigarette smoking habits and serum lipid/lipoprotein (serum Triglyceride (TG, Total cholesterol (TC, Low-density lipoprotein (LDL and high-density lipoprotein (HDL among Chinese Nonagenarians/Centenarian. Methods The present study analyzed data from the survey that was conducted on all residents aged 90 years or more in a district, there were 2,311,709 inhabitants in 2005. Unpaired Student’s t test, χ2 test, and multiple logistic regression were used to analyze datas. Results The individuals included in the statistical analysis were 216 men and 445 women. Current smokers had lower level of TC (4.05 ± 0.81 vs. 4.21 ± 0.87, t = 2.403, P = 0.017 and lower prevalence of hypercholesteremia (9.62% vs. 15.13%, χ2 = 3.018,P = 0.049 than nonsmokers. Unadjusted and adjusted multiple logistic regressions showed that cigarette smoking was not associated with risk for abnormal serum lipid/lipoprotein. Conclusions In summary, we found that among Chinese nonagenarians/centenarians, cigarette smoking habits were not associated with increased risk for dyslipidemia, which was different from the association of smoking habits with dyslipidemia in general population.

  20. Gold Nanoparticles Enhanced Microchip Capillary Electrophoresis for Detection of Serum Lipoprotein

    Institute of Scientific and Technical Information of China (English)

    WANG Hua; WANG DaXin; CAO Li; CHEN Xia

    2009-01-01

    @@ We describe here the use of gold nanoparticles (AuNPs) in conjunction with chip-based capillary electrophoresis (CE) to improve the selectivity between lipoprotein fractions and increase the efficiency of the separation.AuNPs were added into the running buffer to manipulate solution and control the electroosmotic flow (EOF).

  1. 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

    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....

  2. Evaluation of the immediate vascular stability of lipoprotein lipase-generated 2-monoacylglycerol in mice

    DEFF Research Database (Denmark)

    Kleberg, Karen; Nielsen, Louise Lundeman; Stuhr-Hansen, Nicolai;

    2014-01-01

    2-Monoacylglycerols are gaining increasing interest as signaling lipids, beyond endocannabinoids, for example, as ligands for the receptor GPR119 and as mediators of insulin secretion. In the vascular system, they are formed by the action of lipoprotein lipase (LPL); however, their further dispos...

  3. Effect of a Marathon Run on Serum Lipoproteins, Creatine Kinase, and Lactate Dehydrogenase in Recreational Runners

    Science.gov (United States)

    Kobayashi, Yoshio; Takeuchi, Toshiko; Hosoi, Teruo; Yoshizaki, Hidekiyo; Loeppky, Jack A.

    2005-01-01

    The objective of this study was to determine the effect of a marathon run on serum lipid and lipoprotein concentrations and serum muscle enzyme activities and follow their recovery after the run. These blood concentrations were measured before, immediately after, and serially after a marathon run in 15 male recreational runners. The triglyceride…

  4. 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

  5. Direct Low Density Lipoprotein Cholesterol and Glycated Albumin Levels in Type 2 Diabetes Mellitus

    Science.gov (United States)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) have been associated with a decreased risk of these complications. The aim in this st...

  6. Glycated albumin and direct low density lipoprotein cholesterol levels in type 2 diabetes mellitus

    Science.gov (United States)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) has been associated with a decreased risk of these complications. We evaluated the ut...

  7. Familial lipoprotein lipase-activity deficiency: study of total body fatness and subcutaneous fat tissue distribution.

    Science.gov (United States)

    Brun, L D; Gagné, C; Julien, P; Tremblay, A; Moorjani, S; Bouchard, C; Lupien, P J

    1989-10-01

    Total body fatness and subcutaneous fat tissue distribution were evaluated in 19 hyperchylomicronemic patients. Eleven were males, aged 10 to 57 years, and eight were females, aged 13 to 46 years. Familial lipoprotein-lipase-activity deficiency was diagnosed by the absence of lipoprotein-lipase activity in the plasma withdrawn ten and 20 minutes after intravenous injection of ten units of heparin per kilogram of body weight. The 19 patients had skin-fold measurements for evaluation of subcutaneous fat distribution. Fifteen also underwent body density measurements by underwater weighing. Percent body fat was calculated from body density. These anthropometric data were plotted against the regression curves of 1638 normal controls of both sexes (aged 10 to 54 years) for fat tissue weight, percent body fat, subcutaneous fat/total fat mass ratio and trunk/extremity skin-fold ratio. Impairments in the process of building fat tissue reserves could not be shown in the 19 hyperchylomicronemic patients, in spite of the absence of lipoprotein-lipase activity in their postheparin plasma. It is hypothesized that normal fat tissue mass in these patients could be due partly to de novo synthesis of fatty acids by adipocytes, hydrolysis of plasma triglycerides by hepatic lipase, and/or contribution of a specific fat-tissue lipase to the catabolism of plasma triglyceride-rich lipoproteins.

  8. The relationship between lipoprotein lipase-447C/G genepolymorphism and cerebral infarction in the elderly

    Institute of Scientific and Technical Information of China (English)

    胡晓雁

    2013-01-01

    Objective To explore the relationship between the lipoprotein lipase(LPL)-447C/G gene polymorphism and cerebral infarction in the elderly. Methods This was a case-control study,which enrolled 206 cases with cerebral infarction in the elderly and 203 elderly

  9. Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population

    DEFF Research Database (Denmark)

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

    2014-01-01

    OBJECTIVES: The purpose of this study was to determine whether elevated lipoprotein(a) levels and corresponding LPA risk genotypes (rs10455872, rs3798220, kringle IV type 2 repeat polymorphism) prospectively associate with increased risk of aortic valve stenosis (AVS). BACKGROUND: The etiologic...

  10. Comparison of Total Antioxidant Capacity Oxidative Stress and Blood Lipoprotein Parameters in Volleyball Players and Sedentary

    Science.gov (United States)

    Gokhan, Ismail

    2013-01-01

    This study aims to measure, then compare sedentary blood lipoproteins, oxidant- antioxidant state and oxidative stress index in volleyball players. The experimental group of the research consists of regularly practising 20 boys between the ages of 12 and 17, and the control group comprises 32 children practising no particular sports branch, 12 of…

  11. Palmitic acid and linoleic acid metabolism in Caco-2 cells: Different triglyceride synthesis and lipoprotein secretion

    NARCIS (Netherlands)

    van Greevenbroek, M.M.J.; Voorhout, W.F.; Erkelens, D.W.; van Meer, G.; de Bruin, T.W.A.

    1995-01-01

    Polarized monolayers of intestinal Caco-2 cells were used to study the effects of saturated palmitic acid (16:0) and polyunsaturated linoleic acid (18:2) on triglyceride synthesis and lipoprotein secretion. Monolayers were incubated for 24 h, at the apical or lumenal side, with palmitic acid (16:0)

  12. Low-density lipoprotein-lowering strategies: target versus maximalist versus population percentile.

    NARCIS (Netherlands)

    Sniderman, A.D.; Graaf, J. de; Couture, P.

    2012-01-01

    PURPOSE OF REVIEW: Maximalist low-density lipoprotein (LDL)-lowering strategies such as lowering LDL as much as possible or, alternatively, using the most potent LDL-lowering regimens have become increasingly popular. Almost all attention has focused on the potential advantages of these approaches w

  13. Low density lipoprotein : structure, dynamics, and interactions of apoB-100 with lipids

    NARCIS (Netherlands)

    Murtola, Teemu; Vuorela, Timo A.; Hyvonen, Marja T.; Marrink, Siewert-Jan; Karttunen, Mikko; Vattulainen, Ilpo

    2011-01-01

    Low-density lipoprotein (LDL) transports cholesterol in the bloodstream and plays an important role in the development of cardiovascular diseases, in particular atherosclerosis. Despite its importance to health, the structure of LDL is not known in detail. This is worrying since the lack of LDL's st

  14. Phenotype of heterozygotes for low-density lipoprotein receptor mutations identified in different background populations

    DEFF Research Database (Denmark)

    Tybjaerg-Hansen, Anne; Jensen, Henrik Kjaerulf; Benn, Marianne;

    2005-01-01

    The effect of mutations on phenotype is often overestimated because of ascertainment bias. We determined the effect of background population on cholesterol phenotype associated with specific mutations in the low-density lipoprotein (LDL) receptor and the relative importance of background population...

  15. Low density lipoprotein receptor related protein 1 variant interacts with saturated fatty acids in Puerto Ricans

    Science.gov (United States)

    Low density lipoprotein related receptor protein 1 (LRP1) is a multi-functional endocytic receptor that is highly expressed in adipocytes and the hypothalamus. Animal models and in vitro studies support a role for LRP1 in adipocyte metabolism and leptin signaling, but genetic polymorphisms have not ...

  16. Effect of dietary cis and trans fatty acids on serum lipoprotein(a) levels in humans.

    NARCIS (Netherlands)

    Mensink, R.P.; Zock, P.L.; Katan, M.B.; Hornstra, G.

    1992-01-01

    Serum lipoprotein[a] (Lp[a]) is a strong risk factor for coronary heart disease. We therefore examined the effect of dietary fatty acid composition on serum Lp[a] levels in three strictly controlled experiments with healthy normocholesterolemic men and women. In Expt. I, 58 subjects consumed a contr

  17. Lipoprotein glomerulopathy: a case report of a rare disease in a brazilian child

    Directory of Open Access Journals (Sweden)

    Karla Lais Pegas

    2014-03-01

    Full Text Available Lipoprotein glomerulopathy (LPG is a rare autosomal recessive glomerulopathy associated with the deposition of lipoprotein thrombi in the capillary lumina due to apoE gene mutations. Abnormal plasma lipoprotein profile and marked increase in serum apoliprotein E (apoE are characteristic clinical data. The compromised patients can present nephrotic syndrome, hematuria, and progressive renal failure. Herein, the authors present the first described case of LPG in a Brazilian male patient, 11 years, who presented with a steroid-resistant nephrotic syndrome. Renal function was normal. Kidney biopsy showed markedly enlarged glomerulus, with dilated capillary loops and weak eosinophilic lipoprotein thrombi in the capillary lumina. Interstitium, tubules, arteries, and veins showed normal histologic aspect. Genotypic study for the apoE gene showed the presence of the alleles E3 and E4. The diagnosis of LPG was then performed. The patient received lipid-lowering treatment. After 2 years of follow-up, renal function is gradually decreasing, with persisting heavy proteinuria, despite a marked decrease in serum cholesterol and triglycerides levels.

  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

    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...

  19. Low density lipoprotein induces upregulation of vasoconstrictive endothelin type B receptor expression

    DEFF Research Database (Denmark)

    Xu, Cang-Bao; Zheng, Jian-Pu; Zhang, Wei

    2014-01-01

    Vasoconstrictive endothelin type B (ET(B)) receptors promote vasospasm and ischemic cerebro- and cardiovascular diseases. The present study was designed to examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive ET(B) receptor expression and if extracellular signal...

  20. Ganglioside embedded in reconstituted lipoprotein binds cholera toxin with elevated affinity.

    Science.gov (United States)

    Bricarello, Daniel A; Mills, Emily J; Petrlova, Jitka; Voss, John C; Parikh, Atul N

    2010-09-01

    The ability to exogenously present cell-surface receptors in high-affinity conformations in a synthetic system offers an opportunity to provide host cells with protection from pathogenic toxins. This strategy requires improvement of the synthetic receptor binding affinity against its native counterpart, particularly with polyvalent toxins where clustering of membrane receptors can hinder binding. Here we demonstrate that reconstituted lipoprotein, nanometer-sized discoidal lipid bilayers bounded by apolipoprotein and functionalized by incorporation of pathogen receptors, provides a means to enhance toxin-receptor binding through molecular-level control over the receptor microenvironment (specifically, its rigidity, composition, and heterogeneity). Using a Foerster Resonance Energy Transfer (FRET)-based assay, we found that reconstituted lipoprotein incorporating low concentrations of ganglioside monosialotetrahexosylganglioside (GM1) binds polymeric cholera toxin with significantly higher affinity than liposomes or supported lipid bilayers, most likely a result of the enhanced control over receptor clustering provided by the lipoprotein platform. Using wide-area epifluorescence, we found that this enhanced binding capacity can be effectively utilized to divert cholera toxin away from populations of healthy mammalian cells. In summary, we found that reconstitutions of high-density lipoprotein can be engineered to include specific pathogen receptors; that their pathogen binding affinity is altered, presumably due to attenuation of receptor aggregation; and that these assemblies are effective at protecting cells from biological toxins.

  1. Active lipoprotein precursors in the gram-positive eubacterium Lactococcus lactis

    NARCIS (Netherlands)

    Venema, R; Tjalsma, H; van Dijl, J.M; Leenhouts, K.; Buist, G; Venema, G

    2003-01-01

    Lipid-modified proteins play important roles at the interface between eubacterial cells and their environment. The importance of lipoprotein processing by signal peptidase II (SPase II) is underscored by the fact that this enzyme is essential for viability of the Gram-negative eubacterium Escherichi

  2. High-Density Lipoprotein Modulates Glucose Metabolism in Patients With Type 2 Diabetes Mellitus

    NARCIS (Netherlands)

    Drew, Brian G.; Duffy, Stephen J.; Formosa, Melissa F.; Natoli, Alaina K.; Henstridge, Darren C.; Penfold, Sally A.; Thomas, Walter G.; Mukhamedova, Nigora; de Courten, Barbora; Forbes, Josephine M.; Yap, Felicia Y.; Kaye, David M.; van Hall, Gerrit; Febbraio, Mark A.; Kemp, Bruce E.; Sviridov, Dmitri; Steinberg, Gregory R.; Kingwell, Bronwyn A.

    2009-01-01

    Background-Low plasma high-density lipoprotein (HDL) is associated with elevated cardiovascular risk and aspects of the metabolic syndrome. We hypothesized that HDL modulates glucose metabolism via elevation of plasma insulin and through activation of the key metabolic regulatory enzyme, AMP-activat

  3. Moderate alcohol consumption and lipoprotein-associated phospholipase A2 activity

    NARCIS (Netherlands)

    Beulens, J.W.J.; Berg, R. van den; Kok, F.J.; Helander, A.; Vermunt, S.H.F.; Hendriks, H.F.J.

    2008-01-01

    Background and aims: To investigate the effect of moderate alcohol consumption on lipoprotein-associated phospholipase A2 activity, markers of inflammation and oxidative stress and whether these effects are modified by BMI. Methods and results: Eleven lean (BMI: 18.5-25 kg/m2) and 9 overweight (BMI

  4. Increased Antioxidant Quality Versus Lower Quantity Of High Density Lipoprotein In Benign Prostatic Hyperplasia

    Directory of Open Access Journals (Sweden)

    Aydin Ozgur

    2015-10-01

    Full Text Available Background: Oxidative stress may be involved in the pathogenesis of every human disease. To understand its possible role in benign prostatic hyperplasia (BPH, we measured the overall oxidative status of patients with BPH and the serum activity of the high density lipoprotein (HDL-related antioxidant enzymes paraoxonase 1 (PON1 and arylesterase (ARE.

  5. Effect of methylglyoxal on the physico-chemical and biological properties of low-density lipoprotein

    NARCIS (Netherlands)

    Schalkwijk, C.G.; Vermeer, M.A.; Stehouwer, C.D.A.; Koppele, J. te; Princen, H.M.G.; Hinsbergh, V.W.M. van

    1998-01-01

    In patients with diabetes, non-enzymatic glycation of low-density lipoprotein (LDL) has been suggested to be involved in the development of atherosclerosis. α-Dicarbonyl compounds were identified as intermediates in the non-enzymatic glycation and increased levels were reported in patients with diab

  6. High-density lipoprotein attenuates inflammation and coagulation response on endotoxin challenge in humans

    NARCIS (Netherlands)

    Birjmohun, Rakesh S; van Leuven, Sander I; Levels, Johannes H M; van 't Veer, Cornelis; Kuivenhoven, Jan Albert; Meijers, Joost C M; Levi, Marcel; Kastelein, John J P; van der Poll, Tom; Stroes, Erik S G

    2007-01-01

    OBJECTIVE: Low high-density lipoprotein (HDL) cholesterol is a strong independent cardiovascular risk factor, which has been attributed to its role in reverse cholesterol transport. Whereas HDL also has potent antiinflammatory effects, the relevance of this property remains to be established in huma

  7. 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 we

  8. Phenotype of heterozygotes for low-density lipoprotein receptor mutations identified in different background populations

    DEFF Research Database (Denmark)

    Tybjaerg-Hansen, Anne; Jensen, Henrik Kjaerulf; Benn, Marianne

    2005-01-01

    The effect of mutations on phenotype is often overestimated because of ascertainment bias. We determined the effect of background population on cholesterol phenotype associated with specific mutations in the low-density lipoprotein (LDL) receptor and the relative importance of background population...... and type of mutation (LDL receptor [LDLR] or APOB R3500Q) for cholesterol phenotype....

  9. Association of low density lipoprotein levels and glycaemic control in type-2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Yathish TR.

    2010-01-01

    Full Text Available Earlier diabetes mellitus (DM was thought to be a disease of carbohydrate metabolism. Looking at the effects of insulin deficiency on carbohydrate and lipid metabolism, diabetes mellitus is now being called more a disease of lipid metabolism than carbohydrate metabolism. A cross-sectional study was conducted during March 2005 to March 2006 to study the low-density lipoproteins (LDL levels in diabetes mellitus and its relation to glycaemic control. LDL levels were estimated. Comparison of lipid levels were made between group of diabetic patients with glycated hemoglobin less than 8.0% and a group of diabetic patients with glycated hemoglobin more than 8.0% and the controls. The lipid fractions i.e. total cholesterol (TC, triglycerides (TG, and low-density lipoprotein (LDL levels were higher in the poorly controlled diabetes patients as compared to well controlled diabetic patients and nondiabetic patients. Increased levels of low-density lipoprotein may be a contributory factor to the high risk of atherosclerosis induced coronary artery disease observed in diabetes mellitus patients. Reduction of blood glucose levels is likely to reduce low density lipoprotein levels and the risk of complication, with the lowest risk being in those with glycosylated hemoglobin values in the normal range ie. Less than 8.0%

  10. [Hormonal regulation of lipoprotein metabolism: the role in pathogenesis of coronary heart disease].

    Science.gov (United States)

    Sokolov, E I; Metel'skaia, V A; Perova, N V; Shchukina, G N

    2006-01-01

    The character and role of hormonal dysregulation of lipoprotein metabolism during postprandial hyperlipemia were studied in patients with coronary heart disease (CHD) and hyperthyroidism as compared with healthy subjects. Pronounced hypertriglyceridemia alongside with the decreased high density lipoprotein cholesterol (HDL C) after standard fat load were associated with increased level of insulin and decreased level of cortisol. Moreover, in CHD patients fasting hyperinsulinemia becoming even stronger postprandially resulted in prevalence of antilipolytic action of insulin over lipid-mobilizing effect of cortisol; and an extended postprandial hypertriglyceridemia took place. Patients with hyperthyroidism and low cholesterol level both in atherogenic LDL and antiatherogenic HDL, demonstrated decreased level of apo AI (as in CHD patients) and apo B (three times lower than in CHD patients). Very low ratio of apo B/AI in patients with hyperthyroidism both in fasting and postprandial state was a clear indication of their lipoprotein profile antiatherogeneity. Thus, in patients with hyperthyroidism despite of low HDL C and apo AI levels, antiatherogenic properties of lipoprotein profile are probably determined by very low apo B/AI ratio induced by thyroid hormones, and might be explained by the influence of thyroid hormones on the expression of genes coding these apoproteins.

  11. Apolipoprotein A5 and lipoprotein lipase interact to modulate anthropometric measures in Hispanics of Caribbean origin

    Science.gov (United States)

    Apolipoprotein A5 (APOA5) and lipoprotein lipase (LPL) proteins interact functionally to regulate lipid metabolism, and single nucleotide polymorphisms (SNPs) for each gene have also been associated independently with obesity risk. Evaluating gene combinations may be more effective than single SNP a...

  12. Mechanism underlying the inner membrane retention of Escherichia coli lipoproteins caused by Lol avoidance signals.

    Science.gov (United States)

    Hara, Takashi; Matsuyama, Shin-ichi; Tokuda, Hajime

    2003-10-10

    Escherichia coli lipoproteins are localized to either the inner or outer membrane depending on the residue at position 2. The inner membrane retention signal, Asp at position 2 in combination with certain residues at position 3, functions as a Lol avoidance signal, i.e. the signal inhibits the recognition of lipoproteins by LolCDE that releases lipoproteins from the inner membrane. To understand the role of the residue at position 2, outer membrane-specific lipoproteins with Cys at position 2 were subjected to chemical modification followed by the release reaction in reconstituted proteoliposomes. Sulfhydryl-specific introduction of nonprotein molecules or a negative charge to Cys did not inhibit the LolCDE-dependent release. In contrast, oxidation of Cys to cysteic acid resulted in generation of the Lol avoidance signal, indicating that the Lol avoidance signal requires a critical length of negative charge at the second residue. Furthermore, not only modification of the carboxylic acid of Asp at position 2 but also that of the amine of phosphatidylethanolamine abolished the Lol avoidance function. Based on these results, the Lol avoidance mechanism is discussed.

  13. 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...

  14. Variability in lipoprotein concentrations in serum after prolonged storage at -20°C.

    NARCIS (Netherlands)

    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 a

  15. 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.

  16. High density lipoprotein as a source of cholesterol for adrenal steroidogenesis : A study in individuals with low plasma HDL-C

    NARCIS (Netherlands)

    Bochem, Andrea E.; Holleboom, Adriaan G.; Romijn, Johannes A.; Hoekstra, Menno; Dallinga-Thie, Geesje M.; Motazacker, Mahdi M.; Hovingh, G. Kees; Kuivenhoven, Jan A.; Stroes, Erik S. G.

    2013-01-01

    Few studies have addressed the delivery of lipoprotein-derived cholesterol to the adrenals for steroid production in humans. While there is evidence against a role for low-density lipoprotein (LDL), it is unresolved whether high density lipoprotein (HDL) contributes to adrenal steroidogenesis. To st

  17. A Pressure-dependent Model for the Regulation of Lipoprotein Lipase by Apolipoprotein C-II*

    Science.gov (United States)

    Meyers, Nathan L.; Larsson, Mikael; Olivecrona, Gunilla; Small, Donald M.

    2015-01-01

    Apolipoprotein C-II (apoC-II) is the co-factor for lipoprotein lipase (LPL) at the surface of triacylglycerol-rich lipoproteins. LPL hydrolyzes triacylglycerol, which increases local surface pressure as surface area decreases and amphipathic products transiently accumulate at the lipoprotein surface. To understand how apoC-II adapts to these pressure changes, we characterized the behavior of apoC-II at multiple lipid/water interfaces. ApoC-II adsorption to a triacylglycerol/water interface resulted in large increases in surface pressure. ApoC-II was exchangeable at this interface and desorbed on interfacial compressions. These compressions increase surface pressure and mimic the action of LPL. Analysis of gradual compressions showed that apoC-II undergoes a two-step desorption, which indicates that lipid-bound apoC-II can exhibit at least two conformations. We characterized apoC-II at phospholipid/triacylglycerol/water interfaces, which more closely mimic lipoprotein surfaces. ApoC-II had a large exclusion pressure, similar to that of apoC-I and apoC-III. However, apoC-II desorbed at retention pressures higher than those seen with the other apoCs. This suggests that it is unlikely that apoC-I and apoC-III inhibit LPL via displacement of apoC-II from the lipoprotein surface. Upon rapid compressions and re-expansions, re-adsorption of apoC-II increased pressure by lower amounts than its initial adsorption. This indicates that apoC-II removed phospholipid from the interface upon desorption. These results suggest that apoC-II regulates the activity of LPL in a pressure-dependent manner. ApoC-II is provided as a component of triacylglycerol-rich lipoproteins and is the co-factor for LPL as pressure increases. Above its retention pressure, apoC-II desorbs and removes phospholipid. This triggers release of LPL from lipoproteins. PMID:26026161

  18. Particle Physics

    Science.gov (United States)

    Cooper, Necia Grant; West, Geoffrey B.

    1988-06-01

    Preface; Introduction; Part I. Theoretical Framework: 1. Scale and dimension - From animals to quarks Geoffrey B. West; 2. Particle physics and the standard model Stuart Raby, Richard C. Slansky and Geoffrey B. West; QCD on a Cray: the masses of elementary particles Gerald Guralnik, Tony Warnock and Charles Zemach; Lecture Notes - From simple field theories to the standard model; 3. Toward a unified theory: an essay on the role of supergravity in the search for unification Richard C. Slansky; 4. Supersymmetry at 100 GeV Stuart Raby; 5. The family problem T. Goldman and Michael Martin Nieto; Part II. Experimental Developments: 6. Experiments to test unification schemes Gary H. Sanders; 7. The march toward higher energies S. Peter Rosen; LAMPF II and the High-Intensity Frontier Henry A. Thiessen; The SSC - An engineering challenge Mahlon T. Wilson; 8. Science underground - the search for rare events L. M. Simmons, Jr; Part III. Personal Perspectives: 9. Quarks and quirks among friends Peter A. Carruthers, Stuart Raby, Richard C. Slansky, Geoffrey B. West and George Zweig; Index.

  19. Up-regulation of hepatic low-density lipoprotein receptor-related protein 1: a possible novel mechanism of antiatherogenic activity of hydroxymethylglutaryl-coenzyme A reductase inhibitor Atorvastatin and hepatic LRP1 expression.

    Science.gov (United States)

    Moon, Jae Hoon; Kang, Saet Byol; Park, Jong Suk; Lee, Byung Wan; Kang, Eun Seok; Ahn, Chul Woo; Lee, Hyun Chul; Cha, Bong Soo

    2011-07-01

    Low-density lipoprotein receptor-related protein 1 (LRP1) binds to apolipoprotein E and serves as a receptor for remnant lipoproteins in the liver, thus playing an important role in clearing these atherogenic particles. In this study, we investigated the effect of atorvastatin, a hydroxymethylglutaryl-coenzyme A reductase inhibitor, on hepatic LRP1 expression. We used HepG2 and Hep3B cells for in vitro study, and Otsuka Long-Evans Tokushima fatty and Sprague-Dawley rats for in vivo study. We used relatively high pharmacologic dose of atorvastatin in this study (in vitro, 0.5 μmol/L in culture media, for 48 hours; in vivo, 20 mg/[kg d], for 6 weeks). Atorvastatin increased LRP1 and low-density lipoprotein (LDL) receptor expression in HepG2 and Hep3B cells and induced hepatic LRP1 and LDL receptor expression in chow diet-fed Sprague-Dawley rats and high-fat diet-fed Otsuka Long-Evans Tokushima fatty rats. Atorvastatin decreased intracellular sterol level and increased the amount of the nuclear form of sterol response element-binding protein-2 (SREBP-2) in both HepG2 and Hep3B cells as well as in two animal models. Treatment of HepG2 cells with LDL increased intracellular sterol level and reduced LRP1, LDL receptor, and SREBP-2. When SREBP-2 in HepG2 cells was knocked down by small interfering RNA, the induction of LRP1 expression by atorvastatin did not take place. In conclusion, up-regulation of hepatic LRP1 might be a novel mechanism by which statin treatment decreases remnant lipoproteins. In addition, SREBP-2 acts as a mediator of atorvastatin-induced up-regulation of hepatic LRP1. Future studies using standard doses of atorvastatin in humans are needed to elucidate clinical relevance of these findings.

  20. Very-low-density lipoprotein (VLDL)-producing and hepatitis C virus-replicating HepG2 cells secrete no more lipoviroparticles than VLDL-deficient Huh7.5 cells.

    Science.gov (United States)

    Jammart, Baptiste; Michelet, Maud; Pécheur, Eve-Isabelle; Parent, Romain; Bartosch, Birke; Zoulim, Fabien; Durantel, David

    2013-05-01

    In the plasma samples of hepatitis C virus (HCV)-infected patients, lipoviroparticles (LVPs), defined as (very-) low-density viral particles immunoprecipitated with anti-β-lipoproteins antibodies are observed. This HCV-lipoprotein association has major implications with respect to our understanding of HCV assembly, secretion, and entry. However, cell culture-grown HCV (HCVcc) virions produced in Huh7 cells, which are deficient for very-low-density lipoprotein (VLDL) secretion, are only associated with and dependent on apolipoprotein E (apoE), not apolipoprotein B (apoB), for assembly and infectivity. In contrast to Huh7, HepG2 cells can be stimulated to produce VLDL by both oleic acid treatment and inhibition of the MEK/extracellular signal-regulated kinase (ERK) pathway but are not permissive for persistent HCV replication. Here, we developed a new HCV cell culture model to study the interaction between HCV and lipoproteins, based on engineered HepG2 cells stably replicating a blasticidin-tagged HCV JFH1 strain (JB). Control Huh7.5-JB as well as HepG2-JB cell lines persistently replicated viral RNA and expressed viral proteins with a subcellular colocalization of double-stranded RNA (dsRNA), core, gpE2, and NS5A compatible with virion assembly. The intracellular RNA replication level was increased in HepG2-JB cells upon dimethyl sulfoxide (DMSO) treatment, MEK/ERK inhibition, and NS5A overexpression to a level similar to that observed in Huh7.5-JB cells. Both cell culture systems produced infectious virions, which were surprisingly biophysically and biochemically similar. They floated at similar densities on gradients, contained mainly apoE but not apoB, and were not neutralized by anti-apoB antibodies. This suggests that there is no correlation between the ability of cells to simultaneously replicate HCV as well as secrete VLDL and their capacity to produce LVPs.