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Sample records for apolipoprotein b-containing lipoprotein

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

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    Michael D. Shapiro

    2017-02-01

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

  2. 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...

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

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    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

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

    NARCIS (Netherlands)

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

    1995-01-01

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

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

    Science.gov (United States)

    Oscarsson, Jan; Hurt-Camejo, Eva

    2017-08-10

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

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

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

    1996-03-01

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

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

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

    2004-01-01

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

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

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    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...

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

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    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.

  10. Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family

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    Nilsson, Stefan K; Lookene, Aivar; Beckstead, Jennifer A

    2007-01-01

    Apolipoprotein A-V is a potent modulator of plasma triacylglycerol levels. To investigate the molecular basis for this phenomenon we explored the ability of apolipoprotein A-V, in most experiments complexed to disks of dimyristoylphosphatidylcholine, to interact with two members of the low density...... lipoprotein receptor family, the low density lipoprotein receptor-related protein and the mosaic type-1 receptor, SorLA. Experiments using surface plasmon resonance showed specific binding of both free and lipid-bound apolipoprotein A-V to both receptors. The binding was calcium dependent and was inhibited......, apolipoprotein A-V (Arg210Glu/Lys211Gln), showed decreased binding to heparin and decreased ability to bind the low density lipoprotein receptor-related protein. Association of apolipoprotein A-V with the low density lipoprotein receptor-related protein or SorLA resulted in enhanced binding of human chylomicrons...

  11. 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

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

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

    1997-03-01

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

  13. Lipid, lipoprotein and apolipoprotein profiles in active and sedentary men with tetraplegia

    NARCIS (Netherlands)

    Dallmeijer, A.J.; van der Woude, L.H.V.; Hopman, M.T.E.

    1997-01-01

    Objective: To investigate whether the risk profile of coronary heart disease (CHD) is more favorable in physically active men with tetraplegia compared with sedentary men with tetraplegia. Design: Using a cross-sectional design, the lipid and (apo)lipoprotein concentrations of 11 active and 13

  14. 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

  15. The Association Between Small Dense Low Density Lipoprotein,Apolipoprotein B, Apolipoprotein B/apolipoprotein A1 Ratio and coronary Artery Stenosis

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    Abbas Zavarehee

    2009-05-01

    Full Text Available Background:Recently,small dense low density lipoprotein (sdLDL has been highlighted as a new risk factor for the coronary artery disease(CAD.Small dense LDLs are believed to be atherogenic since these particles are taken up more easily by arterial wall.They are readily oxidized and have reduced affinity for low density lipoprotein (LDL receptor and increased affinity for arterial proteoglicans.LDL cholesterol is only a measure of the cholesterol level in the LDL whereas apolipoprotein B(apo B is a measure of the cholesterol levels of all the atherogenic particles,including very low density lipoprotein, intermediate density, and low density lipoproteins. Therefore,it might be a better marker than other traditional lipids. The aim of the present study was to evaluate the association between serum small dense LDL, apolipoprotein B, apolipoprotein A1 (apo A1 and apoB/apoA1 ratio and the coronary stenosis.Methods: 86 patients with coronary stenosis, 35 patients without coronary stenosis   identified by angiography who were referred to Rajaii Heart Center , and 30 healthy individuals were studied.SdLDL was measured by a direct homogenous LDL-C assay in the supernatant of serum which remained after heparin-magnesium precipitation.Serum apolipoprotein A1 and apolipoprotein B were measured by using immunoturbidimetric method.Results: The results showed that the sdLDL levels were higher in patients with coronary stenosis than patients without coronary stenosis and healthy individuals   (21.54±7.1, 16.88±4.4 and 15.45±5mg/dl, p=0.001, respectively. In addition the level   of apoB (with stenosis: 113.71±21.8, without stenosis:100.88±18.7 and healthy:102.30±9.6, p=0.003 and apoB/apoA1 ratio (with stenosis:1.100±0.24, without stenosis :0.589±0.26 and healthy:0.751±0.16, p=0.001 were significantly higher in patients with coronary stenosis. SdLDL levels were positively correlated with the level of apoB(r=0.589, apoB/apoA1 ratio(r=0.416, triglyceride

  16. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction

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    Langsted, A.; Freiberg, J.J.; Nordestgaard, Børge

    2008-01-01

    to HDL cholesterol, and ratio of apolipoprotein B to apolipoprotein A1 did not change in response to normal food intake. The maximum changes after normal food and fluid intake from fasting levels were -0.2 mmol/L for total cholesterol, -0.2 mmol/L for low-density lipoprotein cholesterol, -0.1 mmol....../L for HDL cholesterol, and 0.3 mmol/L for triglycerides. Highest versus lowest tertile of nonfasting total cholesterol, non-HDL cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, triglycerides, ratio of total cholesterol to HDL cholesterol, and ratio of apolipoprotein B/apolipoprotein A1...... and lowest versus highest tertile of nonfasting HDL cholesterol and apolipoprotein A1 predicted 1.7- to 2.4-fold increased risk of cardiovascular events. CONCLUSIONS: Lipid profiles at most change minimally in response to normal food intake in individuals in the general population. Furthermore, nonfasting...

  17. Apolipoprotein B is a calcium binding protein

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    Dashti, N.; Lee, D.M.; Mok, T.

    1986-05-29

    Human hepatocarcinoma Hep G2 cells were grown in culture medium containing (/sup 45/Ca/sup 2 +/). The secreted lipoproteins of d < 1.063 g/ml and d 1.063-1.21 g/ml were isolated from the culture media and analyzed by 3.3% and 7% SDS-polyacrylamide gel electrophoresis. Radioactivity profiles of (/sup 45/Ca) from the gels showed that the peak of radioactivity corresponded to the apolipoprotein B band. The molar ratio of the incorporated (/sup 45/Ca/sup 2 +/) and apolipoprotein B was close to unity. No radioactivity was found associated with any other secreted apolipoproteins. To confirm these findings, apolipoprotein B-containing lipoproteins were precipitated with anti-apolipoprotein B and high density lipoproteins were precipitated with anti-apolipoprotein A-I. Only the former precipitate was radioactive. These results suggest that apolipoprotein B is a calcium binding protein.

  18. Genetically elevated apolipoprotein A-I, high-density lipoprotein cholesterol levels, and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Lundegaard, Christiane; Tybjærg-Hansen, Anne; Grande, Peer

    2010-01-01

    Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD).......Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD)....

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

    DEFF Research Database (Denmark)

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

    1995-01-01

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

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

    African Journals Online (AJOL)

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

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

    NARCIS (Netherlands)

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

    1996-01-01

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

  2. Relationships of plasma estradiol, testosterone, and sex hormone-binding globulin with lipoproteins, apolipoproteins, and high density lipoprotein subfractions in men.

    Science.gov (United States)

    Stefanick, M L; Williams, P T; Krauss, R M; Terry, R B; Vranizan, K M; Wood, P D

    1987-04-01

    Plasma estradiol, testosterone, and sex hormone-binding globulin (SHBG) were studied in relation to plasma lipoproteins, high density lipoprotein (HDL) subfractions, and apolipoproteins in 73 healthy but sedentary middle-aged men. Among potentially confounding variables, a strong positive association was found between estradiol levels and cigarette use, while testosterone and SHBG correlated negatively with percent body fat and alcohol intake. After adjustment for smoking, percent body fat, and alcohol, plasma estradiol levels correlated negatively with total cholesterol and low density lipoprotein cholesterol, and testosterone levels correlated positively with apolipoprotein B, while SHBG levels correlated positively with HDL2 mass and apolipoprotein A-I. SHBG was also strongly associated with the waist to hip girth ratio (WHR). Adjustment for WHR eliminated the significant associations of SHBG with triglycerides, HDL2 mass, and apolipoprotein A-I. SHBG levels and WHR may reflect tissue sensitivity and the impact of exposure to fluctuating levels of sex hormones for a period of days, or longer. These variables may provide more insight into the role of sex hormones in lipoprotein metabolism than do single samples of circulating hormones. It is also suggested that long term effects of sex hormones on adipose tissue distribution may at least partially underlie sex-related differences in lipoprotein metabolism.

  3. Birth Weight, Cord Blood Lipoprotein and Apolipoprotein Levels in Indian Newborns

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    Simmi Kharb

    2010-01-01

    Full Text Available Objectives: Primordial prevention of chronic disease is of clinical andpublic health importance. Considering the fetal onset of atherosclerosis,we aimed to determine the cord blood level of lipoproteins andapolipoproteins as well as their correlation with birth weight and gestationalage.Methods: This cross-sectional study comprised 100 healthy Indiannewborns. Ten ml. of cord blood was collected from placental end ofumbilical vein. Serum was separated by centrifugation and analyzed onthe same day for lipid profile including total cholesterol (TC, triglycerides(TG, high density lipoprotein- cholesterol (HDL-C, very lowdensity lipoprotein-cholesterol (VLDL and low density lipoproteincholesterol(LDL-C, apolipoproteins A-I and B (ApoA-I, ApoB.Atherogenic index (AI was calculated as the ratio of ApoB to ApoA-I.Results: Cord blood of female newborns had higher TC, HDL-C,LDL-C, Apo A-I, Apo B and AI as compared to male newborns,whereas TG and VLDL-C were higher in male than in female newborns.Significant positive correlation was observed between cordblood Apo A-I and HDL-C (r= 0.45, p0.05.Conclusions: These findings are another confirmatory evidence forthe association of prenatal factors with cord blood lipid profile, andcan serve as starting point for studying lipid transport system changesduring early life.

  4. Lipoprotein and apolipoprotein differences in black and white girls - The National Heart, Lung, and Blood Institute Growth and Health Study

    NARCIS (Netherlands)

    Sprecher, DL; Morrison, JA; Simbartl, LA; Schreiber, GB; Sabry, ZI; Biro, FM; Barton, BA

    Objective: To define racial differences in lipoprotein and apolipoprotein levels in girls aged 9 to 10 years. Design: Baseline analysis of a prospective cohort study. Setting: Three clinical sites. Subjects: A total of 1871 black and white girls, aged 9 to 10 years, with complete maturation data

  5. Familial defective apolipoprotein B-100: low density lipoproteins with abnormal receptor binding

    International Nuclear Information System (INIS)

    Innerarity, T.L.; Weisgraber, K.H.; Arnold, K.S.; Mahley, R.W.; Krauss, R.M.; Vega, G.L.; Grundy, S.M.

    1987-01-01

    Previous in vivo turnover studies suggested that retarded clearance of low density lipoproteins (LDL) from the plasma of some hypercholesterolemic patients is due to LDL with defective receptor binding. The present study examined this postulate directly by receptor binding experiments. The LDL from a hypercholesterolemic patient (G.R.) displayed a reduced ability to bind to the LDL receptors on normal human fibroblasts. The G.R. LDL possessed 32% of normal receptor binding activity. Likewise, the G.R. LDL were much less effective than normal LDL in competing with 125 I-labeled normal LDL for cellular uptake and degradation and in stimulating intracellular cholesteryl ester synthesis. The defect in LDL binding appears to be due to a genetic abnormality of apolipoprotein B-100: two brothers of the proband possess LDL defective in receptor binding, whereas a third brother and the proband's son have normally binding LDL. Further, the defect in receptor binding does not appear to be associated wit an abnormal lipid composition or structure of the LDL. Normal and abnormal LDL subpopulations were partially separated from plasma of two subjects by density-gradient ultracentrifugation, a finding consistent with the presence of a normal and a mutant allele. The affected family members appear to be heterozygous for this disorder, which has been designated familial defective apolipoprotein B-100. These studies indicate that the defective receptor binding results in inefficient clearance of LDL and the hypercholesterolemia observed in these patients

  6. Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

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    García-Arias Carlota

    2009-06-01

    Full Text Available Abstract Background Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. Methods Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases and 31 patients with severe hypertriglyceridaemia (controls were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. Results Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS. Conclusion Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during chilhood.

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

    Science.gov (United States)

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

    2000-10-13

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

  8. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction

    DEFF Research Database (Denmark)

    Langsted, A.; Freiberg, J.J.; Nordestgaard, Børge

    2008-01-01

    BACKGROUND: Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events. METHODS AND RESULTS: We cross-sectionally studied 33 391 individuals 20 to 95...... to HDL cholesterol, and ratio of apolipoprotein B to apolipoprotein A1 did not change in response to normal food intake. The maximum changes after normal food and fluid intake from fasting levels were -0.2 mmol/L for total cholesterol, -0.2 mmol/L for low-density lipoprotein cholesterol, -0.1 mmol...... years of age from the Copenhagen General Population Study. We also studied 9319 individuals 20 to 93 years of age from the Copenhagen City Heart Study, 1166 of whom developed cardiovascular events during 14 years of follow-up. Compared with fasting levels, total cholesterol, low-density lipoprotein...

  9. Lipoprotein (a)--lipid profile and apolipoprotein B in children of young parents with coronary artery disease.

    Science.gov (United States)

    Khalil, Anita; Aggarwal, Amit; Arora, Sarika; Bhattacharya, Jayashree

    2011-01-01

    To evaluate lipoprotein(a), apolipoprotein B and lipid profile in children of young parents with coronary artery disease. Analytical observational study. Tertiary care hospital. The study included 80 children (9-18 years) out of which 40 were children of young parents (one or both) with established coronary artery disease (CAD), while the other 40 were children of parents with no evidence of CAD (controls). All were evaluated for fasting blood glucose, lipid profile, apolipoprotein B and lipoprotein (a) - Lp(a). Two sample 't' test was applied for analysis of continuous variables between study & control group. The study group children had significantly higher levels of total serum cholesterol (p = 0.004), LDL cholesterol (p = 0.002), lipoprotein a (p = 0.001) as compared to children of the control group. A significant difference in apolipoprotein B levels (p = 0.044) was observed in children in the adolescent age group (14-18 years). Both systolic and diastolic blood pressures were significantly higher without any significant difference being observed for weight and body mass index between the two groups. Higher levels of pro-atherogenic factors in children with family history of premature CAD indicate that the combined effects of "nature and nurture" are responsible for development of accelerated atherosclerosis especially in Indians. Tracking of Lp(a) levels from childhood may be a better option than detecting other elements of dyslipidemia which are not fully expressed until middle age.

  10. Apolipoprotein C-III deficiency accelerates triglyceride hydrolysis by lipoprotein lipase in wild-type and apoE knockout mice

    NARCIS (Netherlands)

    Jong, M.C.; Rensen, P.C.N.; Dahlmans, V.E.H.; Boom, H. van der; Berkel, T.J.C. van; Havekes, L.M.

    2001-01-01

    Previous studies with hypertriglyceridemic APOC3 transgenic mice have suggested that apolipoprotein C-III (apoC-III) may inhibit either the apoE-mediated hepatic uptake of TG-rich lipoproteins and/or the lipoprotein lipase (LPL)-mediated hydrolysis of TG. Accordingly, apoC3 knockout (apoC3-/-) mice

  11. On-treatment non-high-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipid ratios in relation to residual vascular risk after treatment with potent statin therapy

    DEFF Research Database (Denmark)

    Mora, Samia; Glynn, Robert J; Boekholdt, S Matthijs

    2012-01-01

    The goal of this study was to determine whether residual risk after high-dose statin therapy for primary prevention individuals with reduced levels of low-density lipoprotein cholesterol (LDL-C) is related to on-treatment apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), tri...

  12. Very low-density lipoprotein apolipoprotein B-100 turnover in glycogen storage disease type Ia (von Gierke disease).

    Science.gov (United States)

    Wierzbicki, A S; Watt, G F; Lynas, J; Winder, A F; Wray, R

    2001-10-01

    Mixed hyperlipidaemia is a common finding in glycogen storage disease type Ia (GSD Ia). Although cross-sectional studies have demonstrated increases in intermediate-density lipoproteins (IDLs) and reductions in lipoprotein lipase activity, no studies have investigated the dynamics of apolipoprotein B-100 (apo B) metabolism in GSD Ia. This study investigated apoB turnover in GSD Ia using an exogenous labelling method in one sib from a kinship with established GSD Ia. The study demonstrated normal hepatic secretion of very low-density lipoprotein (VLDL), but hypocatabolism of VLDL, probably due to lack of lipoprotein lipase activity. The production rate of IDL was slightly increased, but the turnover rate of low-density lipoprotein was normal. The findings suggest that, as well as a corn starch diet and dietary fat restriction, treatment of severe mixed hyperlipidaemia in GSD Ia and its attendant risk of pancreatitis should possibly involve fibrates that activate lipoprotein lipase and may enhance the clearance of IDL, rather than omega-3 fatty acids, which principally suppress hepatic secretion of VLDL.

  13. Gestational hyperlipidemia and acute pancreatitis with underlying partial lipoprotein lipase deficiency and apolipoprotein E3/E2 genotype.

    Science.gov (United States)

    Han, Dong Hee; Moh, In Ho; Kim, Doo-Man; Ihm, Sung Hee; Choi, Moon-Gi; Yoo, Hyung Joon; Hong, Eun-Gyoung

    2013-09-01

    We report the case of a patient who experienced extreme recurrent gestational hyperlipidemia. She was diagnosed with partial lipoprotein lipase (LPL) deficiency but without an associated LPL gene mutation in the presence of the apolipoprotein E3/2 genotype. This is the first reported case of extreme gestational hyperlipidemia with a partial LPL deficiency in the absence of an LPL gene mutation and the apolipoprotein E 3/2 genotype. She was managed with strict dietary control and medicated with omega-3 acid ethyl esters. A patient with extreme hyperlipidemia that is limited to the gestational period should be considered partially LPL-deficient. Extreme instances of hyperlipidemia increase the risk of acute pancreatitis, and the effect of parturition on declining plasma lipid levels can be immediate and dramatic. Therefore, decisions regarding the timing and route of delivery with extreme gestational hyperlipidemia are critical and should be made carefully.

  14. Effects of red grape juice consumption on high density lipoprotein-cholesterol, apolipoprotein AI, apolipoprotein B and homocysteine in healthy human volunteers.

    Science.gov (United States)

    Khadem-Ansari, Mohammad H; Rasmi, Yousef; Ramezani, Fatemeh

    2010-01-01

    It has suggested that grape juice consumption has lipid- lowering effect and it is associated with a decreased risk of heart disease. We aimed to evaluate the effects of red grape juice (RGj) consumption on high density lipoprotein-cholesterol (HDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB) and homocysteine (Hcy) levels in healthy human volunteers. Twenty six healthy and nonsmoking males, aged between 25-60 years, who were under no medication asked to consume 150 ml of RGj twice per day for one month. Serum HDL-C, apoAI, apoB and plasma Hcy levels were measured before and after one month RGj consumption. HDL-C levels after RGj consumption were significantly higher than the corresponding levels before the RGj consumption (41.44 ± 4.50 and 44.37 ± 4.30 mg/dl; P0.05). Hcy levels were decreased after RGj consumption (7.70 ± 2.80 and 6.20 ± 2.30 µmol/l; P<0.001). The present study demonstrates that RGj consumption can significantly increase serum HDL-C levels and decrease Hcy levels. These findings may have important implications for the prevention of atherosclerosis in healthy individuals.

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

    NARCIS (Netherlands)

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

    1996-01-01

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

  16. Plasma lipoproteins in familial dysbetalipoproteinemia associated with apolipoproteins E2 (Arg158 -->Cys), E3-Leiden, and E2 (Lys146-->Gln), and effects of treatment with simvastatin

    NARCIS (Netherlands)

    Zhao, S.P.; Smelt, A.H.; Maagdenberg, A.M. van den; Tol, A. van; Vroom T.F.; Gevers Leuven, J.A.; Frants, R.R.; Havekes, L.M.; Laarse, A. van der; Hooft, F.M. van 't

    1994-01-01

    Using a density-gradient ultracentrifugation technique, we analyzed in detail the plasma lipoprotein profiles of 18 patients with familial dysbetalipoproteinemia (FD) who had apolipoprotein (apo) E2(Arg158-->Cys) homozygosity (the E2-158 variant, n = 6), apoE3-Leiden heterozygosity (the E3-Leiden

  17. 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...

  18. Cinnamon Extract Improves TNF-a Induced Overproduction of Intestinal ApolipoproteinB-48 Lipoproteins

    Science.gov (United States)

    TNF-alpha stimulates the overproduction of intestinal apolipoproteins. We evaluated whether a water extract of cinnamon (Cinnulin PF®) improved the dyslipidemia induced by TNF-alpha in Triton WR-1339 treated hamsters, and whether Cinnulin PF® inhibits the TNF-alpha-induced over the secretion of apoB...

  19. Metabolism of apolipoproteins A-I and A-II in human high-density lipoprotein: a mathematical approach for analysis of their specific activity decay curves

    International Nuclear Information System (INIS)

    Atmeh, R.F.

    1987-01-01

    The differential rate equations describing the compartmental model of human high-density lipoprotein (HDL) were integrated by means of Laplace transforms and an exponential equation was obtained for each of the three compartments. These equations were used to fit the observed plasma decay data and give estimates for the rate constants of the system by means of a written computer program. Furthermore, these estimates were used to calculate the exponential constants of the integrated equations. Consequently, the amount of label in any of the intravascular, extravascular, and urine compartments can be calculated as a fraction of the original dose of label at any time point. This method was tested using data for the (AI)HDL subclass because it contains only apolipoprotein A-I as the major apolipoprotein and does not contain apolipoprotein A-II. The calculated plasma and urine radioactivity data were compared with the experimentally obtained data from two normolipoproteinemic subjects and found to be in good agreement. The significance of this method is its application to the analysis of the decay data of the individual apolipoproteins of (AI + AII) HDL subclass where the urinary radioactivity data resulting from the individual apolipoprotein breakdown on the native particle cannot be measured experimentally at present. Such data are essential for the detailed calculation of the kinetic parameters of these apolipoproteins

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

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Jauhiainen, Matti; Moser, Markus

    2008-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    1993-01-01

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

  3. Effects of dietary maritime pine seed oil on lipoprotein metabolism and atherosclerosis development in mice expressing human apolipoprotein B.

    Science.gov (United States)

    Asset, G; Baugé, E; Wolff, R L; Fruchart, J C; Dallongeville, J

    2001-12-01

    Conifer seeds are used for food preparation in several countries. Aim of the study To assess the lipid-lowering and antiatherogenic properties of maritime pine (Pinuspinaster) seed oil. The effects of maritime pine oil supplementation (20% w/w) for 2 weeks were compared to those of coconut and sunflower oil in mice expressing human apolipoprotein B (hApoB). Atherosclerosis lesion development was measured in hApoB mice fed 1.25% (w/w) cholesterol and 0.05% (w/w) sodium cholate and either coconut, sunflower or maritime pine oil (20% w/w) for 8 weeks. After 2 weeks of dietary treatment, plasma cholesterol (p oil than in those treated with coconut oil. These effects were accounted for by a lowering of LDL-cholesterol, LDL-phospholipids and LDL-triglycerides, as well as a decrease in HDL-cholesterol and HDL-phospholipids. After 8 weeks of dietary treatment cholesterol and cholate, the mean area of aortic lesions was not statistically different between fat groups. Feeding maritime pine oil is associated with major changes of lipid and lipoprotein levels in hApoB mice. However, in the long term, maritime pine oil has no preventive effect on cholesterol-induced aortic lesion development in hApoB mice.

  4. High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Gordon

    2016-09-01

    Full Text Available Apolipoprotein A-I (apoA-I and high-density lipoproteins (HDL mediate reverse cholesterol transport out of cells. Furthermore, HDL has additional protective functions, which include anti-oxidative, anti-inflammatory, anti-apoptotic, and vasoprotective effects. In contrast, HDL can become dysfunctional with a reduction in both cholesterol efflux and anti-inflammatory properties in the setting of disease or the acute phase response. These paradigms are increasingly being recognized to be active in the pulmonary system, where apoA-I and HDL have protective effects in normal lung health, as well as in a variety of disease states, including acute lung injury, asthma, chronic obstructive pulmonary disease, lung cancer, pulmonary arterial hypertension, pulmonary fibrosis, and viral pneumonia. Similar to observations in cardiovascular disease, however, HDL may become dysfunctional and contribute to disease pathogenesis in respiratory disorders. Furthermore, synthetic apoA-I mimetic peptides have been shown to have protective effects in animal models of acute lung injury, asthma, pulmonary hypertension, and influenza pneumonia. These findings provide evidence to support the concept that apoA-I mimetic peptides might be developed into a new treatment that can either prevent or attenuate the manifestations of lung diseases, such as asthma. Thus, the lung is positioned to take a page from the cardiovascular disease playbook and utilize the protective properties of HDL and apoA-I as a novel therapeutic approach.

  5. Magnolol-mediated regulation of plasma triglyceride through affecting lipoprotein lipase activity in apolipoprotein A5 knock-in mice.

    Directory of Open Access Journals (Sweden)

    Chun-Kai Chang

    Full Text Available Hyperlipidemia is a risk factor of arteriosclerosis, stroke, and other coronary heart disease, which has been shown to correlate with single nucleotide polymorphisms of genes essential for lipid metabolism, such as lipoprotein lipase (LPL and apolipoprotein A5 (APOA5. In this study, the effect of magnolol, the main active component extracted from Magnolia officinalis, on LPL activity was investigated. A dose-dependent up-regulation of LPL activity, possibly through increasing LPL mRNA transcription, was observed in mouse 3T3-L1 pre-adipocytes cultured in the presence of magnolol for 6 days. Subsequently, a transgenic knock-in mice carrying APOA5 c.553G>T variant was established and then fed with corn oil with or without magnolol for four days. The baseline plasma triglyceride levels in transgenic knock-in mice were higher than those in wild-type mice, with the highest increase occurred in homozygous transgenic mice (106 mg/dL vs 51 mg/dL, pT variant carrier mice and facilitate the triglyceride metabolism in postprandial hypertriglyceridemia.

  6. Effect of apolipoprotein E-free high density lipoproteins on cholesterol metabolism in cultured pig hepatocytes

    International Nuclear Information System (INIS)

    Bachorik, P.S.; Virgil, D.G.; Kwiterovich, P.O. Jr.

    1987-01-01

    We studied cholesterol synthesis from [ 14 C]acetate, cholesterol esterification from [ 14 C]oleate, and cellular cholesterol and cholesteryl ester levels after incubating cells with apoE-free high density lipoproteins (HDL) or low density lipoproteins (LDL). LDL suppressed synthesis by up to 60%, stimulated esterification by up to 280%, and increased cell cholesteryl ester content about 4-fold. Esterification increased within 2 h, but synthesis was not suppressed until after 6 h. ApoE-free HDL suppressed esterification by about 50% within 2 h. Cholesterol synthesis was changed very little within 6 h, unless esterification was maximally suppressed; synthesis was then stimulated about 4-fold. HDL lowered cellular unesterified cholesterol by 13-20% within 2 h and promoted the removal of newly synthesized cholesterol and cholesteryl esters. These changes were transient; by 24 h, both esterification and cellular unesterified cholesterol returned to control levels, and cholesteryl esters increased 2-3-fold. HDL core lipid was taken up selectively from 125 I-labeled [ 3 H]cholesteryl ester- and ether-labeled HDL. LDL core lipid uptake was proportional to LDL apoprotein uptake. The findings suggest that 1) the cells respond initially to HDL or LDL with changes in esterification, and 2) HDL mediates both the removal of free cholesterol from the cell and the delivery of HDL cholesteryl esters to the cell

  7. Expression of apolipoprotein B in the kidney attenuates renal lipid accumulation

    DEFF Research Database (Denmark)

    Krzystanek, Marcin; Pedersen, Tanja Xenia; Bartels, Emil Daniel

    2010-01-01

    The ability to produce apolipoprotein (apo) B-containing lipoproteins enables hepatocytes, enterocytes, and cardiomyocytes to export triglycerides. In this study, we examined secretion of apoB-containing lipoproteins from mouse kidney and its putative impact on triglyceride accumulation in the tu......The ability to produce apolipoprotein (apo) B-containing lipoproteins enables hepatocytes, enterocytes, and cardiomyocytes to export triglycerides. In this study, we examined secretion of apoB-containing lipoproteins from mouse kidney and its putative impact on triglyceride accumulation...... in the tubular epithelium. Mouse kidney expressed both the apoB and microsomal triglyceride transfer protein genes, which permit lipoprotein formation. To examine de novo lipoprotein secretion, kidneys from human apoB-transgenic mice were minced and placed in medium with (35)S-amino acids. Upon sucrose gradient...... ultracentrifugation of the labeled medium, fractions were analyzed by apoB immunoprecipitation. (35)S-Labeled apoB100 was recovered in approximately 1.03-1.04 g/ml lipoproteins (i.e. similar to the density of plasma low density lipoproteins). Immunohistochemistry of kidney sections suggested that apoB mainly...

  8. Clinical chemistry of common apolipoprotein E isoforms

    NARCIS (Netherlands)

    Brouwer, DAJ; vanDoormaal, JJ; Muskiet, FAJ

    1996-01-01

    Apolipoprotein E plays a central role in clearance of lipoprotein remnants by serving as a ligand for low-density lipoprotein and apolipoprotein E receptors. Three common alleles (apolipoprotein E(2), E(3) and E(4)) give rise to six phenotypes. Apolipoprotein E(3) is the ancestral form. Common

  9. Lipoproteins of slow-growing Mycobacteria carry three fatty acids and are N-acylated by apolipoprotein N-acyltransferase BCG_2070c.

    Science.gov (United States)

    Brülle, Juliane K; Tschumi, Andreas; Sander, Peter

    2013-10-05

    Lipoproteins are virulence factors of Mycobacterium tuberculosis. Bacterial lipoproteins are modified by the consecutive action of preprolipoprotein diacylglyceryl transferase (Lgt), prolipoprotein signal peptidase (LspA) and apolipoprotein N- acyltransferase (Lnt) leading to the formation of mature triacylated lipoproteins. Lnt homologues are found in Gram-negative and high GC-rich Gram-positive, but not in low GC-rich Gram-positive bacteria, although N-acylation is observed. In fast-growing Mycobacterium smegmatis, the molecular structure of the lipid modification of lipoproteins was resolved recently as a diacylglyceryl residue carrying ester-bound palmitic acid and ester-bound tuberculostearic acid and an additional amide-bound palmitic acid. We exploit the vaccine strain Mycobacterium bovis BCG as model organism to investigate lipoprotein modifications in slow-growing mycobacteria. Using Escherichia coli Lnt as a query in BLASTp search, we identified BCG_2070c and BCG_2279c as putative lnt genes in M. bovis BCG. Lipoproteins LprF, LpqH, LpqL and LppX were expressed in M. bovis BCG and BCG_2070c lnt knock-out mutant and lipid modifications were analyzed at molecular level by matrix-assisted laser desorption ionization time-of-flight/time-of-flight analysis. Lipoprotein N-acylation was observed in wildtype but not in BCG_2070c mutants. Lipoprotein N- acylation with palmitoyl and tuberculostearyl residues was observed. Lipoproteins are triacylated in slow-growing mycobacteria. BCG_2070c encodes a functional Lnt in M. bovis BCG. We identified mycobacteria-specific tuberculostearic acid as further substrate for N-acylation in slow-growing mycobacteria.

  10. Conflicting interactions of apolipoprotein A and high density lipoprotein cholesterol with microvascular complications of type 2 diabetes.

    Science.gov (United States)

    Aryan, Zahra; Afarideh, Mohsen; Ghajar, Alireza; Esteghamati, Sadaf; Esteghamati, Alireza; Nakhjavani, Manouchehr

    2017-11-01

    This study is amid at investigating the associations, and interactions of serum lipid biomarkers with microvascular complications of type 2 diabetes (T2D). A nested case-control study was conducted within an ongoing prospective study on patients with T2D. Microvascular complications of T2D including diabetic neuropathy, diabetic retinopathy and diabetic nephropathy were investigated. A total of 444 cases with at least one of the microvascular complications of T2D and 439 age- and gender-matched controls free of any of the chronic microvascular complications of T2D were included. The associations and interactions of a panel of serum lipid biomarkers with the microvascular complications of T2D were investigated. Serum triglyceride had the strongest association with microvascular complications of T2D (crude model: β=0.632, P value=0.045). Each standard deviation increment in serum TG was associated with 3.7 times increased frequency of microvascular complications. Despite high density lipoprotein cholesterol (HDL-C), serum apolipoprotein A1 (Apo A1) was positively associated with the presence of diabetic neuropathy. Each standard deviation increment in serum ApoA1 was associated with increased frequency of diabetic neuropathy (OR, 1.2, 95% CI, (1.1-1.3), P value=0.006). The frequency of diabetic neuropathy was higher in 2nd and 3rd quartiles of serum Lp(a) compared to diabetic patients in the first quartile (OR, 5.52, 95% (1.17-25.8), P value=0.047). ApoA1 but not HDL-C is straightly associated with diabetic neuropathy. Even Slight rise in serum Lp(a) is associated with increased frequency of diabetic retinopathLipid variables could serve as specific predictors of vascular complications in diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. MicroRNA-182 Promotes Lipoprotein Lipase Expression and Atherogenesisby Targeting Histone Deacetylase 9 in Apolipoprotein E-Knockout Mice.

    Science.gov (United States)

    Cheng, Hai-Peng; Gong, Duo; Zhao, Zhen-Wang; He, Ping-Ping; Yu, Xiao-Hua; Ye, Qiong; Huang, Chong; Zhang, Xin; Chen, Ling-Yan; Xie, Wei; Zhang, Min; Li, Liang; Xia, Xiao-Dan; Ouyang, Xin-Ping; Tan, Yu-Lin; Wang, Zong-Bao; Tian, Guo-Ping; Zheng, Xi-Long; Yin, Wei-Dong; Tang, Chao-Ke

    2017-12-25

    Lipoprotein lipase (LPL) expressed in macrophages plays an important role in promoting the development of atherosclerosis or atherogenesis. MicroRNA-182 (miR-182) is involved in the regulation of lipid metabolism and inflammation. However, it remains unclear how miR-182 regulates LPL and atherogenesis.Methods and Results:Using bioinformatics analyses and a dual-luciferase reporter assay, we identified histone deacetylase 9 (HDAC9) as a target gene of miR-182. Moreover, miR-182 upregulated LPL expression by directly targetingHDAC9in THP-1 macrophages. Hematoxylin-eosin (H&E), Oil Red O and Masson's trichrome staining showed that apolipoprotein E (ApoE)-knockout (KO) mice treated with miR-182 exhibited more severe atherosclerotic plaques. Treatment with miR-182 increased CD68 and LPL expression in atherosclerotic lesions in ApoE-KO mice, as indicated by double immunofluorescence staining in the aortic sinus. Increased miR-182-induced increases in LPL expression in ApoE-KO mice was confirmed by real-time quantitative polymerase chain reaction and western blotting analyses. Treatment with miR-182 also increased plasma concentrations of proinflammatory cytokines and lipids in ApoE-KO mice. The results of the present study suggest that miR-182 upregulates LPL expression, promotes lipid accumulation in atherosclerotic lesions, and increases proinflammatory cytokine secretion, likely through targetingHDAC9, leading to an acceleration of atherogenesis in ApoE-KO mice.

  12. Interaction of plasma apolipoproteins with lipid monolayers

    NARCIS (Netherlands)

    Jackson, R.L.; Pattus, F.; Demel, R.A.

    1979-01-01

    The monolayer technique has been used to study the interaction of lipids with plasma apolipoproteins. Apolipoprotein C-II and C-III from human very low density lipoproteins, apolipoprotein A-I from human high density lipoproteins and arginine-rich protein from swine very low density lipoproteins

  13. Disruption of human plasma high-density lipoproteins by streptococcal serum opacity factor requires labile apolipoprotein A-I.

    Science.gov (United States)

    Han, Mikyung; Gillard, Baiba K; Courtney, Harry S; Ward, Kathryn; Rosales, Corina; Khant, Htet; Ludtke, Steven J; Pownall, Henry J

    2009-02-24

    Human plasma high-density lipoproteins (HDL), the primary vehicle for reverse cholesterol transport, are the target of serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes that turns serum opaque. HDL comprise a core of neutral lipidscholesteryl esters and some triglyceridesurrounded by a surface monolayer of cholesterol, phospholipids, and specialized proteins [apolipoproteins (apos) A-I and A-II]. A HDL is an unstable particle residing in a kinetic trap from which it can escape via chaotropic, detergent, or thermal perturbation. Recombinant (r) SOF catalyzes the transfer of nearly all neutral lipids of approximately 100,000 HDL particles (D approximately 8.5 nm) into a single, large cholesteryl ester-rich microemulsion (CERM; D > 100 nm), leaving a new HDL-like particle [neo HDL (D approximately 5.8 nm)] while releasing lipid-free (LF) apo A-I. CERM formation and apo A-I release have similar kinetics, suggesting parallel or rapid consecutive steps. By using complementary physicochemical methods, we have refined the mechanistic model for HDL opacification. According to size exclusion chromatography, a HDL containing nonlabile apo A-I resists rSOF-mediated opacification. On the basis of kinetic cryo-electron microscopy, rSOF (10 nM) catalyzes the conversion of HDL (4 microM) to neo HDL via a stepwise mechanism in which intermediate-sized particles are seen. Kinetic turbidimetry revealed opacification as a rising exponential reaction with a rate constant k of (4.400 +/- 0.004) x 10(-2) min(-1). Analysis of the kinetic data using transition state theory gave an enthalpy (DeltaH()), entropy (DeltaS(++)), and free energy (DeltaG()) of activation of 73.9 kJ/mol, -66.87 J/K, and 94.6 kJ/mol, respectively. The free energy of activation for opacification is nearly identical to that for the displacement of apo A-I from HDL by guanidine hydrochloride. We conclude that apo A-I lability is required for HDL opacification, LF apo A-I desorption is the

  14. Disruption of Human Plasma High Density Lipoproteins by Streptococcal Serum Opacity Factor Requires Labile Apolipoprotein A-I

    Science.gov (United States)

    Han, Mikyung; Gillard, Baiba K.; Courtney, Harry S.; Ward, Kathryn; Rosales, Corina; Khant, Htet; Ludtke, Steven J.; Pownall, Henry J.

    2010-01-01

    Human plasma high density lipoproteins (HDL), the primary vehicle for reverse cholesterol transport, are the target of serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes that turns serum opaque. HDL comprise a core of neutral lipids–cholesteryl esters and some triglyceride–surrounded by a surface monolayer of cholesterol, phospholipids, and specialized proteins–apolipoproteins (apos) A-I and A-II. HDL is an unstable particle residing in a kinetic trap from which it can escape via chaotropic, detergent or thermal perturbation. Recombinant (r) SOF catalyzes the transfer of nearly all neutral lipids of ~100,000 HDL particles (D ~ 8.5 nm) into a single, large cholesteryl ester-rich microemulsion (CERM; D >100 nm) leaving a new HDL-like particle–neo HDL (D ~5.8 nm) while releasing lipid-free (LF) apo A-I. CERM formation and apo A-I release have similar kinetics suggesting parallel or rapid consecutive steps. By using complementary physico-chemical methods, we have refined the mechanistic model for HDL opacification. According to size exclusion chromatography, HDL containing non-labile apo A-I resists rSOF-mediated opacification. Based on kinetic cryo electron microscopy, rSOF (10 nM) catalyzes the conversion of HDL (4 μM) to neo HDL via a step-wise mechanism in which intermediate-size particles are seen. Kinetic turbidimetry revealed opacification as a rising exponential reaction with a rate constant k = (4.400 ± 0.004) × 10−2 min−1. Analysis of the kinetic data using transition state theory gave an enthalpy, entropy and free energy of activation of ΔH‡ = 73.9 kJ/mol, ΔS‡ = −66.87 J/°K, and ΔG‡ = 94.6 kJ/mol respectively. The free energy of activation for opacification is nearly identical to that for the displacement of apo A-I from HDL by guanidine hydrochloride. We conclude that apo A-I lability is required for HDL opacification, LF apo A-I desorption is the rate-limiting step, and nearly all HDL particles contain

  15. Association of the Apolipoprotein B/Apolipoprotein A-I Ratio, Metabolic Syndrome Components, Total Cholesterol, and Low-Density Lipoprotein Cholesterol with Insulin Resistance in the Population of Georgia

    Directory of Open Access Journals (Sweden)

    Zaza Makaridze

    2014-01-01

    Full Text Available The study was designed to assess the association between insulin resistance (IR and apolipoprotein B/apolipoprotein A-I ratio (ApoB/ApoA-I ratio, metabolic syndrome (MetS components, total cholesterol (TC, and low-density lipoprotein cholesterol (LDL-C in the nondiabetic population of Georgia. The subjects were 1522 Georgians of Caucasian origin (mean age = 45 years, 653 women without diabetes who had visited the clinics for a related health checkup between 2012 and 2013. IR was calculated using the computer homeostasis model assessment (HOMA2-IR and was defined as the upper quartile. MetS was diagnosed using the updated ATP-III definition of the metabolic syndrome. Logistic and multiple regression models were used to estimate the association between IR and other components. IR was positively correlated with age, ApoB, ApoB/ApoA-I ratio, MetS components (excluding high-density lipoprotein cholesterol—HDL-C, LDL-C, fasting insulin, and TC and negatively correlated with HDL-C and ApoA-I in both sexes (all P<0.001. In the logistic regression models, gender, age, ApoB/ApoA-I ratio, diastolic pressure, HDL-C, LDL-C, fasting glucose, and triglycerides were the covariates significantly associated with IR (OR: 8.64, 1.03, 17.95, 1.06, 0.13, 1.17, 3.75, and 2.29, resp.; all P<0.05. Multiple regression models demonstrated that these components (except for HDL-C made an independent contribution to the prediction of HOMA2 (all P<0.05.

  16. Measurement of rhesus monkey (Macaca mulatta) apolipoprotein B in serum by radioimmunoassay: comparison of immunoreactivities of rhesus and human low density lipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Karlin, J.B.; Juhn, D.J.; Fless, G.; Scanu, A.M.; Rubenstein, A.H.

    1978-02-01

    A sensitive and specific double antibody radioimmunoassay for the major apolipoprotein (apoB) of rhesus (Macaca mulatta) serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL) is described. The antiserum was raised to LDL (d 1.030 to 1.040 g/ml) and the LDL/sub 2/ (d 1.020 to 1.050 g/ml) was labeled with /sup 125/I by the chloramine-T or iodine monochloride method. The assay, which was sensitive to 0.02 to 0.5 ..mu..g of LDL/sub 2/, had an interassay coefficient of variation of 4.5%. This assay was successfully used to measure apoB in the whole serum and low density lipoproteins of control monkeys maintained on a standard Purina monkey chow (PMC) diet and of three groups of monkeys fed atherogenic diets: an average American diet, a 25% peanut oil and 2% cholesterol-supplemented PMC diet, and a 25% coconut oil and 2% cholesterol-supplemented PMC diet.

  17. Measurement of rhesus monkey (Macaca mulatta) apolipoprotein B in serum by radioimmunoassay: comparison of immunoreactivities of rhesus and human low density lipoproteins

    International Nuclear Information System (INIS)

    Karlin, J.B.; Juhn, D.J.; Fless, G.; Scanu, A.M.; Rubenstein, A.H.

    1978-01-01

    A sensitive and specific double antibody radioimmunoassay for the major apolipoprotein (apoB) of rhesus (Macaca mulatta) serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL) is described. The antiserum was raised to LDL (d 1.030 to 1.040 g/ml) and the LDL 2 (d 1.020 to 1.050 g/ml) was labeled with 125 I by the chloramine-T or iodine monochloride method. The assay, which was sensitive to 0.02 to 0.5 μg of LDL 2 , had an interassay coefficient of variation of 4.5%. This assay was successfully used to measure apoB in the whole serum and low density lipoproteins of control monkeys maintained on a standard Purina monkey chow (PMC) diet and of three groups of monkeys fed atherogenic diets: an average American diet, a 25% peanut oil and 2% cholesterol-supplemented PMC diet, and a 25% coconut oil and 2% cholesterol-supplemented PMC diet

  18. Apolipoprotein E genotype is a determinant of low-density lipoprotein cholesterol and of its response to a low-cholesterol diet in type 1 diabetic patients with elevated urinary albumin excretion

    NARCIS (Netherlands)

    Blaauwwiekel, EE; Beusekamp, BJ; Sluiter, WJ; Hoogenberg, K; Dullaart, RPF

    1998-01-01

    The effect of the apolipoprotein (apo) E genotype on the lipoprotein response to a 1 year low cholesterol diet (200 mg cholesterol per day) was evaluated in 36 patients with Type 1 diabetes mellitus with albuminuria between 10 and 200 mu g min(-1). Apo E genotype was characterized by polymerase

  19. A prominent large high-density lipoprotein at birth enriched in apolipoprotein C-I identifies a new group of infancts of lower birth weight and younger gestational age

    Energy Technology Data Exchange (ETDEWEB)

    Kwiterovich Jr., Peter O.; Cockrill, Steven L.; Virgil, Donna G.; Garrett, Elizabeth; Otvos, James; Knight-Gibson, Carolyn; Alaupovic, Petar; Forte, Trudy; Farwig, Zachlyn N.; Macfarlane, Ronald D.

    2003-10-01

    Because low birth weight is associated with adverse cardiovascular risk and death in adults, lipoprotein heterogeneity at birth was studied. A prominent, large high-density lipoprotein (HDL) subclass enriched in apolipoprotein C-I (apoC-I) was found in 19 percent of infants, who had significantly lower birth weights and younger gestational ages and distinctly different lipoprotein profiles than infants with undetectable, possible or probable amounts of apoC-I-enriched HDL. An elevated amount of an apoC-I-enriched HDL identifies a new group of low birth weight infants.

  20. Common and rare alleles in apolipoprotein B contribute to plasma levels of low-density lipoprotein cholesterol in the general population

    DEFF Research Database (Denmark)

    Benn, M.; Stene, Maria Charlotte Aslaug; Nordestgaard, Børge

    2008-01-01

    demonstrated to affect low-density lipoprotein (LDL) cholesterol levels. Objective: We tested the hypothesis that nonsynonymous SNPs in three important functional domains of APOB and APOB tag SNPs predict levels of LDL cholesterol and apolipoprotein B and risk of ischemic heart disease. Design......: This was a prospective study with 25 yr 100% follow up, The Copenhagen City Heart Study. Setting: The study was conducted in the Danish general population. Participants: Participants included 9185 women and men aged 20-80+ yr. Main Outcome Measures: Levels of LDL cholesterol and apolipoprotein B and risk of ischemic...... (0.21), R3611Q (0.09), E4154K (0.17), and N4311S (0.21). SNPs were associated with increases (T71I, Ivs181708g > t, T2488Tc > t, R3611) or decreases (Ivs4 + 171c > a, A591V, Ivs18 + 379a > c, P2712L, E4154, N4311S) in LDL cholesterol from -4.7 to +8.2% (-0.28 to 0.30 mmol/liter; P

  1. Apolipoprotein M

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Dahlbäck, B; Nielsen, L B

    2006-01-01

    M in the phospholipid moiety of plasma lipoproteins. Recent studies suggest that apoM may affect HDL metabolism and have anti-atherogenic functions. The subfraction of human HDL that contains apoM therefore protects LDL from oxidation and mediates cholesterol efflux more efficiently then HDL without apoM. In addition......ApoM is a novel apolipoprotein mainly present in high-density lipoprotein (HDL). It belongs to the lipocalin protein superfamily and may bind a small but so far unknown lipophilic ligand. It is secreted without cleavage of its hydrophobic signal peptide, which probably anchors apo...... to unravel the potential roles of apoM in lipoprotein metabolism, atherosclerosis and kidney biology....

  2. Apolipoprotein E deficiency increases remnant lipoproteins and accelerates progressive atherosclerosis, but not xanthoma formation, in gene modified minipigs

    DEFF Research Database (Denmark)

    Shim, Jeong; Poulsen, Christian Bo; Hagensen, Mette K.

    2017-01-01

    Summary: Deficiency of apolipoprotein E (APOE) causes familial dysbetalipoproteinemia in humans resulting in a higher risk of atherosclerotic disease. In mice, APOE deficiency results in a severe atherosclerosis phenotype, but it is unknown to what extent this is unique to mice. In this study, APOE...... progressive atherosclerosis but not xanthoma formation. This indicates that remnant lipoproteinemia does not induce early lesions but is atherogenic in pre-existing atherosclerosis....

  3. Apolipoprotein M

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Nielsen, Lars Bo

    2013-01-01

    Purpose of review: The review will address the potential roles of apolipoprotein M (apoM) as a carrier protein and modulator of sphingosine-1-phosphate (S1P) bioactivity. Recent findings: Recombinant apoM can bind small lipids such as retinoic acid, oxidized phospholipids, and S1P. Thus, the effe......Purpose of review: The review will address the potential roles of apolipoprotein M (apoM) as a carrier protein and modulator of sphingosine-1-phosphate (S1P) bioactivity. Recent findings: Recombinant apoM can bind small lipids such as retinoic acid, oxidized phospholipids, and S1P. Thus....... In humans, sepsis that is characterized by impaired endothelial function is associated with low plasma apoM. Summary: Plasma apoM is mainly bound to HDL. The roles of apoM in atherosclerosis and lipoprotein metabolism have been given much attention. New in the field is the discovery of apoM as a chaperone...

  4. Associations of apolipoprotein E and low-density lipoprotein receptor-related protein 5 polymorphisms with dyslipidemia and generalized aggressive periodontitis in a Chinese population.

    Science.gov (United States)

    Gao, H; Tian, Y; Meng, H; Hou, J; Xu, L; Zhang, L; Shi, D; Lu, R; Feng, X; Wang, X; Chen, Z

    2015-08-01

    Dyslipidemia is associated with aggressive periodontitis, a condition characterized by the rapid destruction of the periodontium. Apolipoprotein E (APOE) and low-density lipoprotein receptor-related protein 5 (LRP5) are involved in immunomodulation and inflammatory activity. We evaluated the association of LRP5 and APOE polymorphisms with serum lipid concentrations and generalized aggressive periodontitis within a Chinese population. Mean serum lipid concentrations were compared across LRP5 and APOE polymorphisms, among cases (n = 185) and controls (n = 138). Multivariable logistic regression was used to evaluate the independent and combined associations of LRP5 and APOE polymorphisms with generalized aggressive periodontitis. Compared with controls, individuals with generalized aggressive periodontitis exhibited significantly lower serum total cholesterol (TC) and lower high-density lipoprotein cholesterol (HDL-c). Individuals with LRP5 polymorphisms (rs682429-AA or rs312016-GG) exhibited higher TC, higher HDL-c and decreased odds for generalized aggressive periodontitis. Haplotype (A-G), determined by rs682429 and rs312016, was also associated with decreased odds for generalized aggressive periodontitis. Furthermore, individuals with the combined polymorphisms (LRP5-rs682429-AA and APOE-rs429358-CC/CT) had higher levels of low-density lipoprotein cholesterol, higher levels of TC and decreased odds for generalized aggressive periodontitis. Independently or combined with APOE, LRP5 polymorphisms may lead to dyslipidemia and are associated with generalized aggressive periodontitis. Dyslipidemia may be a risk indicator for generalized aggressive periodontitis in the Chinese population. Furthermore, two LRP5 polymorphisms (rs682429 and rs312016) might be useful for identifying subjects at higher risk of generalized aggressive periodontitis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Effect of Fish Oil on Serum Levels of Lipid Profile, Lipoprotein (a, Apolipoprotein A-1 and B, Fasting Sugar and Insulin, and InsulinResistance in the Elderly Residents of Kahrizak Charity Foundation

    Directory of Open Access Journals (Sweden)

    Hossein Fakhrzadeh

    2010-03-01

    Full Text Available Objectives: This study was performed to investigate the effect of ω-3 fatty acids on lipid profiles, lipoprotein (a, apolipoprotein A-1 and apolipoprotein B, fasting glucose and insulin, and insulin resistance in a group of Iranian elderly subjects. Methods & Materials: In this clinical trial, 124 elderly residents of the KahrizakCharity Foundation, aged 65 and older were divided into two intervention (consumption of 1 gram per day of fish oil and control (consumption of placebo groups. Blood sampling was done at the baseline and at the end of the study. Results: After 6 months, TG and apo A-1 increased significantly (P=0.01 and P=0.02, respectively and high-density lipoprotein cholesterol decreased significantly in the control group (P=0.009. Overall and comparative effects of fish oil were positively significant (P=0.02. Conclusion: fish oil intake can be effective in reduction of serumtriglycerides in elderly.

  6. Changes in apolipoprotein B and oxidized low-density lipoprotein levels in gingival crevicular fluids as a result of periodontal tissue conditions.

    Science.gov (United States)

    Ishizuka, M; Kato, R; Moriya, Y; Noguchi, E; Koide, Y; Inoue, S; Itabe, H; Yamamoto, M

    2017-06-01

    Periodontal disease is a chronic inflammatory disease caused by bacterial infection that can lead to tooth loss. Gingival crevicular fluid can be collected easily and noninvasively. We previously discovered the presence of apolipoprotein B (apoB), the main constituent of low-density lipoprotein, and oxidized low-density lipoprotein (oxLDL) in the gingival crevicular fluid of healthy subjects. In this study, we investigated whether periodontal conditions affect the levels of apoB and oxLDL in gingival crevicular fluid. The study population comprised 11 patients with chronic periodontitis. A pair of gingival crevicular fluid samples was collected from each patient at a healthy site and at a site with periodontitis (baseline samples). Thereafter, gingival crevicular fluid samples were collected from the same patients again at 4 and 8 wk after scaling and root planing (SRP). The levels of apoB, oxLDL, protein and cytokines in gingival crevicular fluid, in addition to gingival crevicular fluid volume, were measured. At baseline, the levels of apoB and oxLDL in gingival crevicular fluid were higher at the sites with periodontitis than at the healthy sites. The levels of apoB and oxLDL at periodontal sites decreased after SRP. The level of oxLDL in gingival crevicular fluid correlated well with the probing pocket depth. The oxLDL : apoB ratio in gingival crevicular fluid was significantly higher than that in plasma. The levels of apoB and oxLDL in gingival crevicular fluid change according to the periodontal tissue conditions. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. The Hypocholesterolemic Effect of Germinated Brown Rice Involves the Upregulation of the Apolipoprotein A1 and Low-Density Lipoprotein Receptor Genes

    Directory of Open Access Journals (Sweden)

    Mustapha Umar Imam

    2013-01-01

    Full Text Available Germinated brown rice (GBR is rich in bioactive compounds, which confer GBR with many functional properties. Evidence of its hypocholesterolemic effects is emerging, but the exact mechanisms of action and bioactive compounds involved have not been fully documented. Using type 2 diabetic rats, we studied the effects of white rice, GBR, and brown rice (BR on lipid profile and on the regulation of selected genes involved in cholesterol metabolism. Our results showed that the upregulation of apolipoprotein A1 and low-density lipoprotein receptor genes was involved in the hypocholesterolemic effects of GBR. Additionally, in vitro studies using HEPG2 cells showed that acylated steryl glycoside, gamma amino butyric acid, and oryzanol and phenolic extracts of GBR contribute to the nutrigenomic regulation of these genes. Transcriptional and nontranscriptional mechanisms are likely involved in the overall hypocholesterolemic effects of GBR suggesting that it may have an impact on the prevention and/or management of hypercholesterolemia due to a wide variety of metabolic perturbations. However, there is need to conduct long-term clinical trials to determine the clinical relevance of the hypocholesterolemic effects of GBR determined through animal studies.

  8. Apolipoprotein B metabolism: tracer kinetics, models, and metabolic studies.

    Science.gov (United States)

    Burnett, John R; Barrett, P Hugh R

    2002-04-01

    The study of apolipoprotein (apo) B metabolism is central to our understanding of lipoprotein metabolism. However, the assembly and secretion of apoB-containing lipoproteins is a complex process. Specialized techniques, developed and applied to in vitro and in vivo studies of apoB metabolism, have provided insights into the mechanisms involved in the regulation of this process. Moreover, these studies have important implications for understanding both the pathophysiology as well as the therapeutic options for the dyslipidemias. The purpose of this review is to examine the role of apoB in lipoprotein metabolism and to explore the applications of kinetic analysis and multicompartmental modeling to the study of apoB metabolism. New developments and significant advances over the last decade are discussed.

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

    Science.gov (United States)

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

    2012-10-01

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

  10. On-Treatment Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, Triglycerides, and Lipid Ratios in Relation to Residual Vascular Risk After Treatment With Potent Statin Therapy JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin)

    NARCIS (Netherlands)

    Mora, Samia; Glynn, Robert J.; Boekholdt, S. Matthijs; Nordestgaard, Børge G.; Kastelein, John J. P.; Ridker, Paul M.

    2012-01-01

    Objectives The goal of this study was to determine whether residual risk after high-dose statin therapy for primary prevention individuals with reduced levels of low-density lipoprotein cholesterol (LDL-C) is related to on-treatment apolipoprotein B, non-high-density lipoprotein cholesterol

  11. MicroRNA-27 Prevents Atherosclerosis by Suppressing Lipoprotein Lipase-Induced Lipid Accumulation and Inflammatory Response in Apolipoprotein E Knockout Mice.

    Directory of Open Access Journals (Sweden)

    Wei Xie

    Full Text Available Atherosclerotic lesions are lipometabolic disorder characterized by chronic progressive inflammation in arterial walls. Previous studies have shown that macrophage-derived lipoprotein lipase (LPL might be a key factor that promotes atherosclerosis by accelerating lipid accumulation and proinflammatory cytokine secretion. Increasing evidence indicates that microRNA-27 (miR-27 has beneficial effects on lipid metabolism and inflammatory response. However, it has not been fully understood whether miR-27 affects the expression of LPL and subsequent development of atherosclerosis in apolipoprotein E knockout (apoE KO mice. To address these questions and its potential mechanisms, oxidized low-density lipoprotein (ox-LDL-treated THP-1 macrophages were transfected with the miR-27 mimics/inhibitors and apoE KO mice fed high-fat diet were given a tail vein injection with miR-27 agomir/antagomir, followed by exploring the potential roles of miR-27. MiR-27 agomir significantly down-regulated LPL expression in aorta and peritoneal macrophages by western blot and real-time PCR analyses. We performed LPL activity assay in the culture media and found that miR-27 reduced LPL activity. ELISA showed that miR-27 reduced inflammatory response as analyzed in vitro and in vivo experiments. Our results showed that miR-27 had an inhibitory effect on the levels of lipid both in plasma and in peritoneal macrophages of apoE KO mice as examined by HPLC. Consistently, miR-27 suppressed the expression of scavenger receptors associated with lipid uptake in ox-LDL-treated THP-1 macrophages. In addition, transfection with LPL siRNA inhibited the miR-27 inhibitor-induced lipid accumulation and proinflammatory cytokines secretion in ox-LDL-treated THP-1 macrophages. Finally, systemic treatment revealed that miR-27 decreased aortic plaque size and lipid content in apoE KO mice. The present results provide evidence that a novel antiatherogenic role of miR-27 was closely related to

  12. Cultured cells of the blood-brain barrier from apolipoprotein B-100 transgenic mice: effects of oxidized low-density lipoprotein treatment.

    Science.gov (United States)

    Lénárt, Nikolett; Walter, Fruzsina R; Bocsik, Alexandra; Sántha, Petra; Tóth, Melinda E; Harazin, András; Tóth, Andrea E; Vizler, Csaba; Török, Zsolt; Pilbat, Ana-Maria; Vígh, László; Puskás, László G; Sántha, Miklós; Deli, Mária A

    2015-07-17

    The apolipoprotein B-100 (ApoB-100) transgenic mouse line is a model of human atherosclerosis. Latest findings suggest the importance of ApoB-100 in the development of neurodegenerative diseases and microvascular/perivascular localization of ApoB-100 protein was demonstrated in the cerebral cortex of ApoB-100 transgenic mice. The aim of the study was to characterize cultured brain endothelial cells, pericytes and glial cells from wild-type and ApoB-100 transgenic mice and to study the effect of oxidized low-density lipoprotein (oxLDL) on these cells. Morphology of cells isolated from brains of wild type and ApoB-100 transgenic mice was characterized by immunohistochemistry and the intensity of immunolabeling was quantified by image analysis. Toxicity of oxLDL treatment was monitored by real-time impedance measurement and lactate dehydrogenase release. Reactive oxygen species and nitric oxide production, barrier permeability in triple co-culture blood-brain barrier model and membrane fluidity were also determined after low-density lipoprotein (LDL) or oxLDL treatment. The presence of ApoB-100 was confirmed in brain endothelial cells, while no morphological change was observed between wild type and transgenic cells. Oxidized but not native LDL exerted dose-dependent toxicity in all three cell types, induced barrier dysfunction and increased reactive oxygen species (ROS) production in both genotypes. A partial protection from oxLDL toxicity was seen in brain endothelial and glial cells from ApoB-100 transgenic mice. Increased membrane rigidity was measured in brain endothelial cells from ApoB-100 transgenic mice and in LDL or oxLDL treated wild type cells. The morphological and functional properties of cultured brain endothelial cells, pericytes and glial cells from ApoB-100 transgenic mice were characterized and compared to wild type cells for the first time. The membrane fluidity changes in ApoB-100 transgenic cells related to brain microvasculature indicate

  13. Arrangement of apolipoprotein A-I in reconstituted high-density lipoprotein disks: an alternative model based on fluorescence resonance energy transfer experiments.

    Science.gov (United States)

    Tricerri, M A; Behling Agree, A K; Sanchez, S A; Bronski, J; Jonas, A

    2001-04-24

    The folding and organization of apolipoprotein A-I (apoA-I) in discoidal, high-density lipoprotein (HDL) complexes with phospholipids are not yet completely resolved. For about 20 years, it was generally accepted that the amphipathic helices of apoA-I lie parallel to the acyl chains of the phospholipids ("picket fence" model). However, based on the X-ray crystal structure of a large, lipid-free fragment of apoA-I, a "belt model" was recently proposed. In this model, the helices of two antiparallel apoA-I molecules are extended in a circular arrangement and lie perpendicular to the phospholipid acyl chains. To obtain conclusive information on the spatial organization of apoA-I in discoidal HDL, we engineered three separate cysteine mutants of apoA-I (D9C, A124C, A232C) for specific labeling with the fluorescence probes ALEXA-488 or ALEXA-546 (fluorescein and rhodamine derivatives). The labeled apoA-I was reconstituted into well-defined HDL complexes containing two molecules of protein and dipalmitoylphosphatidylcholine, and the complexes were used in three quantitative fluorescence resonance energy transfer (FRET) experiments to determine the distances between two specific sites in an HDL particle. Comparison of the distances measured by FRET (4.7-7.8 nm) with those predicted from the existing models indicated that neither the picket fence nor the belt model can account for the experimental results; rather, a hairpin folding of each apoA-I monomer with most helices perpendicular to the phospholipid acyl chains and a random head-to-tail and head-to-head arrangement of the two apoA-I molecules in the HDL particles are strongly suggested by the distance and lifetime data.

  14. Polymorphisms in apolipoprotein B and risk of ischemic stroke

    DEFF Research Database (Denmark)

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

    2007-01-01

    Apolipoprotein B levels associate with risk of ischemic stroke. APOB polymorphisms may influence levels of apolipoprotein B and low-density lipoprotein (LDL), but whether they associate with risk of ischemic stroke is unknown.......Apolipoprotein B levels associate with risk of ischemic stroke. APOB polymorphisms may influence levels of apolipoprotein B and low-density lipoprotein (LDL), but whether they associate with risk of ischemic stroke is unknown....

  15. Apolipoprotein M

    Directory of Open Access Journals (Sweden)

    Nilsson-Ehle Peter

    2004-10-01

    Full Text Available Abstract Apolipoprotein M (apoM is a 26-kDa protein that is mainly associated with high-density lipoprotein (HDL in human plasma, with a small proportion present in triglyceride-rich lipoproteins (TGRLP and low-density lipoproteins (LDL. Human apoM gene is located in p21.31 on chromosome 6 (chromosome 17, in mouse. Human apoM cDNA (734 base pairs encodes 188-amino acid residue-long protein. It belongs to lipocalin protein superfamily. Human tissue expression array study indicates that apoM is only expressed in liver and in kidney and small amounts are found in fetal liver and kidney. In situ apoM mRNA hybridization demonstrates that apoM is exclusively expressed in the hepatocytes and in the tubule epithelial cells in kidney. Expression of apoM could be regulated by platelet activating factor (PAF, transforming growth factors (TGF, insulin-like growth factor (IGF and leptin in vivo and/or in vitro. It has been demonstrated that apoM expression is dramatically decreased in apoA-I deficient mouse. Hepatocyte nuclear factor-1α (HNF-1α is an activator of apoM gene promoter. Deficiency of HNF-1α mouse shows lack of apoM expression. Mutations in HNF-1α (MODY3 have reduced serum apoM levels. Expression of apoM is significantly decreased in leptin deficient (ob/ob mouse or leptin receptor deficient (db/db mouse. ApoM concentration in plasma is positively correlated to leptin level in obese subjects. These may suggest that apoM is related to the initiation and progression of MODY3 and/or obesity.

  16. Plasma Lipoproteins as Mediators of the Oxidative Stress Induced by UV Light in Human Skin: A Review of Biochemical and Biophysical Studies on Mechanisms of Apolipoprotein Alteration, Lipid Peroxidation, and Associated Skin Cell Responses

    Directory of Open Access Journals (Sweden)

    Paulo Filipe

    2013-01-01

    Full Text Available There are numerous studies concerning the effect of UVB light on skin cells but fewer on other skin components such as the interstitial fluid. This review highlights high-density lipoprotein (HDL and low-density lipoprotein (LDL as important targets of UVB in interstitial fluid. Tryptophan residues are the sole apolipoprotein residues absorbing solar UVB. The UVB-induced one-electron oxidation of Trp produces •Trp and O2•- radicals which trigger lipid peroxidation. Immunoblots from buffered solutions or suction blister fluid reveal that propagation of photooxidative damage to other residues such as Tyr or disulfide bonds produces intra- and intermolecular bonds in apolipoproteins A-I, A-II, and B100. Partial repair of phenoxyl tyrosyl radicals (TyrO• by α-tocopherol is observed with LDL and HDL on millisecond or second time scales, whereas limited repair of α-tocopherol by carotenoids occurs in only HDL. More effective repair of Tyr and α-tocopherol is observed with the flavonoid, quercetin, bound to serum albumin, but quercetin is less potent than new synthetic polyphenols in inhibiting LDL lipid peroxidation or restoring α-tocopherol. The systemic consequences of HDL and LDL oxidation and the activation and/or inhibition of signalling pathways by oxidized LDL and their ability to enhance transcription factor DNA binding activity are also reviewed.

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

    Science.gov (United States)

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

    2007-08-17

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

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  19. Suppression of cholesterol synthesis in cultured fibroblasts from a patient with homozygous familial hypercholesterolemia by her own low density lipoprotein density fraction. A possible role of apolipoprotein E

    NARCIS (Netherlands)

    Havekes, L.; Vermeer, B.J.; Wit, E. de

    1980-01-01

    The suppression of cellular cholesterol synthesis by low density lipoprotein (LDL) from a normal and from a homozygous familial hypercholesterolemic subject was measured on normal fibroblasts and on fibroblasts derived from the same homozygous familial hypercholesterolemic patient. On normal

  20. The role of fatty acid saturation on plasma lipids, lipoproteins, and apolipoproteins: I. Effects of whole food diets high in cocoa butter, olive oil, soybean oil, dairy butter, and milk chocolate on the plasma lipids of young men.

    Science.gov (United States)

    Kris-Etherton, P M; Derr, J; Mitchell, D C; Mustad, V A; Russell, M E; McDonnell, E T; Salabsky, D; Pearson, T A

    1993-01-01

    The present studies were conducted to evaluate the cholesterolemic effects of whole-food diets high in stearic acid. In study no. 1, normocholesterolemic young men were fed diets high in stearic acid provided by cocoa butter (CB); oleic acid provided by olive oil (OO); linoleic acid provided by soybean oil (SO); and myristic acid (and lauric acid) provided by dairy butter (B). In study no. 2, different subjects with similar baseline characteristics were fed diets high in stearic acid provided by milk chocolate (C), CB, CB+B (4:1, MIX), and myristic (and lauric) acid provided by B. Both studies used a randomized, crossover, double-blind experimental design, and experimental subjects (n = 18 for study no. 1 and n = 15 for study no. 2) in each study consumed every diet for 26 days with a 1-month wash-out period between each experimental period. The diets provided 37% of calories from fat, of which 81% was provided by the test fat. Ten ounces (280 g) C was provided daily by the C diet. In study no. 1, the B diet was hypercholesterolemic, whereas the SO diet was hypocholesterolemic, compared with the other diets. The OO and SO diets were hypocholesterolemic compared with the CB diet. Low-density lipoprotein (LDL) cholesterol levels, in general, paralleled the changes in plasma total cholesterol levels. SO significantly decreased apolipoprotein (apo) B levels compared with the other diets. Plasma very-low density lipoprotein (VLDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apo A-I levels were unaffected by the experimental diets.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Apolipoprotein A-V Deficiency Results in MarkedHypertriglyceridemia Attributable to Decreased Lipolysis ofTriglyceride-Rich Lipoproteins and Removal of Their Remnants

    Energy Technology Data Exchange (ETDEWEB)

    Grosskopf, Itamar; Baroukh, Nadine; Lee, Sung-Joon; Kamari,Yehuda; Harats, Dror; Rubin, Edward M.; Pennacchio, Len A.; Cooper, AllenD.

    2005-09-01

    Objective--ApoAV, a newly discovered apoprotein, affectsplasma triglyceride level. To determine how this occurs, we studiedtriglyceride-rich lipoprotein (TRL) metabolism in mice deficient inapoAV. Methods and Results No significant difference in triglycerideproduction rate was found between apoa5_/_ mice and controls. Thepresence or absence of apoAV affected TRL catabolism. After the injectionof 14C-palmitate and 3H-cholesterol labeled chylomicrons and 125I-labeledchylomicron remnants, the disappearance of 14C, 3H, and 125I wassignificantly slower in apoa5_/_ mice relative to controls. This wasbecause of diminished lipolysis of TRL and the reduced rate of uptake oftheir remnants in apoa5_/_ mice. Observed elevated cholesterol level wascaused by increased high-density lipoprotein (HDL) cholesterol inapoa5_/_ mice. VLDL from apoa5_/_ mice were poor substrate forlipoprotein lipase, and did not bind to the low-density lipoprotein (LDL)receptor as well as normal very-low-density lipoprotein (VLDL). LDLreceptor levels were slightly elevated in apoa5_/_ mice consistent withlower remnant uptake rates. These alterations may be the result of thelower apoE-to-apoC ratio found in VLDL isolated from apoa5_/_mice.Conclusions These results support the hypothesis that the absence ofapoAV slows lipolysis of TRL and the removal of their remnants byregulating their apoproteins content after secretion.

  2. Secondary radicals derived from chloramines of apolipoprotein B-100 contribute to HOCl-induced lipid peroxidation of low-density lipoproteins

    DEFF Research Database (Denmark)

    Hazell, L J; Davies, Michael Jonathan; Stocker, R

    1999-01-01

    Oxidation of low-density lipoproteins (LDL) is thought to contribute to atherogenesis. Although there is increasing evidence for a role of myeloperoxidase-derived oxidants such as hypochlorite (HOCl), the mechanism by which HOCl modifies LDL remains controversial. Some studies report the protein...... by an extended period of lipid peroxidation during which further protein oxidation does not occur. The secondary lipid peroxidation process involves EPR-detectable radicals, is attenuated by a radical trap or treatment of HOCl-oxidized LDL with methionine, and occurs less rapidly when the lipoprotein...... component to be the major site of attack, whereas others describe extensive lipid peroxidation. The present study addresses this controversy. The results obtained are consistent with the hypothesis that radical-induced oxidation of LDL's lipids by HOCl is a secondary reaction, with most HOCl consumed via...

  3. Revisiting the gram-negative lipoprotein paradigm

    Science.gov (United States)

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

  4. Disturbances of lipoprotein metabolism in metabolic syndro

    Directory of Open Access Journals (Sweden)

    Marta Czyżewska

    2010-01-01

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

  5. The Apolipoprotein C-I Content of Very-Low-Density Lipoproteins Is Associated with Fasting Triglycerides, Postprandial Lipemia, and Carotid Atherosclerosis

    Directory of Open Access Journals (Sweden)

    John-Bjarne Hansen

    2011-01-01

    Full Text Available Background. Experimental studies in animals suggest that apolipoprotein (apo C-I is an important regulator of triglycerides in fasting and postprandial conditions and associated with carotid atherosclerosis. Methods. A cross-sectional study was conducted with 81 subjects, aged 56–80 years recruited from a population health survey. The participants underwent a fat tolerance test (1 g fat per Kg body weight and carotid atherosclerosis was determined by ultrasound examination. VLDL particles, Sf 20–400, were isolated and their lipid composition and apoC-I content determined. Results. The carotid plaque area increased linearly with the number of apoC-I molecules per VLDL particles (P=0.048 under fasting conditions. Fasting triglycerides increased across tertiles of apoC-I per VLDL particle in analyses adjusted for apoC-II and -C-III, apoE genotype and traditional cardiovascular risk factors (P=0.011. The relation between apoC-I in VLDL and serum triglycerides was conveyed by triglyceride enrichment of VLDL particles (P for trend <0.001. The amount of apoC-I molecules per VLDL was correlated with the total (r=0.41, P<0.0001 and incremental (r=0.35, P<0.001 area under the postprandial triglyceride curve. Conclusions. Our findings support the concept that the content of apoC-I per VLDL particle is an important regulator of triglyceride metabolism in the fasting and postprandial state and associated with carotid athrosclerosis.

  6. Reversal of hypercholesterolemia in apolipoprotein E2 and apolipoprotein E3-Leiden transgenic mice by adenovirus-mediated gene transfer of the VLDL receptor

    NARCIS (Netherlands)

    Dijk, K.W. van; Vlijmen, B.J.M. van; Zee, A. van der; Hof, B. van 't; Boom, H. van der; Kobayashi, K.; Chan, L.; Havekes, L.M.; Hofker, M.H.

    1998-01-01

    We have investigated the interaction of apolipoprotein E2(Arg158- Cys) (apoE2) and apolipoprotein E3Leiden (apoE3-Leiden) with the very low density lipoprotein (VLDL) receptor in vivo and in vitro to define the possible role of this receptor in lipoprotein metabolism and atherosclerosis. The in vivo

  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. Lipoprotein(a) and HIV: Allele-Specific Apolipoprotein(a) Levels Predict Carotid Intima-Media Thickness in HIV-Infected Young Women in the Women's Interagency HIV Study.

    Science.gov (United States)

    Enkhmaa, Byambaa; Anuurad, Erdembileg; Zhang, Wei; Li, Chin-Shang; Kaplan, Robert; Lazar, Jason; Merenstein, Dan; Karim, Roksana; Aouizerat, Brad; Cohen, Mardge; Butler, Kenneth; Pahwa, Savita; Ofotokun, Igho; Adimora, Adaora A; Golub, Elizabeth; Berglund, Lars

    2017-05-01

    In the general population, lipoprotein(a) [Lp(a)] has been established as an independent causal risk factor for cardiovascular disease. Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a) [apo(a)] gene. The roles of Lp(a)/apo(a) in human immunodeficiency virus (HIV)-related elevated cardiovascular disease risk remain unclear. The associations between total plasma Lp(a) level, allele-specific apo(a) level, an Lp(a) level carried by individual apo(a) alleles, and common carotid artery intima-media thickness were assessed in 150 HIV-infected and 100 HIV-uninfected women in the WIHS (Women's Interagency HIV Study). Linear regression analyses with and without adjustments were used. The cohort was young (mean age, ≈31 years), with the majority being Blacks (≈70%). The prevalence of a small size apo(a) (≤22 Kringle repeats) or a high Lp(a) level (≥30 mg/dL) was similar by HIV status. Total plasma Lp(a) level ( P =0.029) and allele-specific apo(a) level carried by the smaller apo(a) sizes ( P =0.022) were significantly associated with carotid artery intima-media thickness in the HIV-infected women only. After accounting for confounders (age, race, smoking, body mass index, blood pressure, hepatitis C virus coinfection, menopause, plasma lipids, treatment status, CD4 + T cell count, and HIV/RNA viral load), the association remained significant for both Lp(a) ( P =0.035) and allele-specific apo(a) level carried by the smaller apo(a) sizes ( P =0.010) in the HIV-infected women. Notably, none of the other lipids/lipoproteins was associated with carotid artery intima-media thickness. Lp(a) and allele-specific apo(a) levels predict carotid artery intima-media thickness in HIV-infected young women. Further research is needed to identify underlying mechanisms of an increased Lp(a) atherogenicity in HIV infection. © 2017 American Heart Association, Inc.

  9. Effects of arotinolol on serum lipid and apolipoprotein levels in patients with mild essential hypertension.

    Science.gov (United States)

    Sasaki, J; Handa, K; Arakawa, K

    1989-01-01

    Nineteen patients with mild essential hypertension received 20 mg of arotinolol daily for 12 weeks. The patients' systolic and diastolic blood pressures and pulse rate decreased significantly after arotinolol. The ratio of apolipoprotein B to apolipoprotein A-I decreased significantly after treatment. No significant changes were observed in serum and lipoprotein lipid levels, apolipoprotein levels, or in the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol. The results indicate that arotinolol is an effective antihypertensive agent with favorable effect on apolipoproteins.

  10. Apolipoprotein CII

    Science.gov (United States)

    ... lipoprotein ( VLDL ), which is made up of mostly triglycerides (a type of fat in your blood). This ... gov/pubmed/23257303 . Semenkovich CF. Disorders of lipid metabolism. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

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

    Science.gov (United States)

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

    2004-09-01

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

  12. Apolipoprotein E and cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Adriana Moreno Valladares

    2006-01-01

    Full Text Available Apolipoprotein E is a polymorphic glycoprotein who interacts with the lipoprotein receptors (LRP-Receptor Related Protein and the receptors for low density lipoproteins of (LDL receptors. When lipoproteins bring up the receptors begins lipids captation and degradation which allows cholesterol utilization, taking place an intracellular auto regulation. The three isoforms of greater importance: Apo E2, E3 and E4 are product of three alleles e2, e3, e4 of one only gene. This factor is related with the amount of lipoproteins that contains ApoE for E/B receptors. A low concentration of lipoproteins with ApoE can increase the activity of LDL receptors and consequently downward the circulating LDL. In the other hand particles with Apo E3 or Apo E4, can cause a downward regulation of LDL and in this way produces a LDL plasma elevation. Many studies in human populations have concluded that this polymorphism of apoE and the plasma variation of lipoproteins are associated with cardiovascular risk. Cardiovascular disease is the result of different interaction between factors which are genetic factor specially ApoE polymorphism e4 allelic of ApoE can explain, in some degree, the greater frequency of cardiovascular disease in those who carries it.

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

    Science.gov (United States)

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

    2016-06-01

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

  14. Overexpression of apolipoprotein O does not impact on plasma HDL levels or functionality in human apolipoprotein A-I transgenic mice

    NARCIS (Netherlands)

    Nijstad, Niels; de Boer, Jan Freark; Lagor, William R.; Toelle, Markus; Usher, David; Annema, Wijtske; van der Giet, Markus; Rader, Daniel J.; Tietge, Uwe J. F.

    Apolipoprotein (apo) O is a newly discovered apolipoprotein preferentially contained within HDL; however, currently, no data are available on the (patho)physiological effects of apoO. Therefore, the present study assessed the impact of apoO overexpression on (i) plasma lipids and lipoproteins as

  15. Plasma markers of cholesterol homeostasis and apolipoprotein B-100 kinetics in the metabolic syndrome.

    Science.gov (United States)

    Chan, Dick C; Watts, Gerald F; Barrett, P Hugh R; O'Neill, Frans H; Thompson, Gilbert R

    2003-04-01

    The metabolic syndrome is characterized by defective hepatic apolipoprotein B-100 (apoB) metabolism. Hepato-intestinal cholesterol metabolism may contribute to this abnormality. We examined the association of cholesterol absorption and synthesis with the kinetics of apoB in 35 obese subjects with the metabolic syndrome. Plasma ratios of campesterol and lathosterol to cholesterol were used to estimate cholesterol absorption and synthesis, respectively. Very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein apoB kinetics were studied using stable isotopy and mass spectrometry. Kinetic parameters were derived using multicompartmental modeling. Compared with controls, the obese subjects had significantly lower plasma ratios of campesterol, but higher plasma ratios of lathosterol (p < 0.05 in both). This was associated with elevated VLDL-apoB secretion rate (p < 0.05) and delayed fractional catabolism of IDL and low-density lipoprotein-apoB (p < 0.01). In the obese group, plasma ratios of campesterol correlated inversely with VLDL-apoB secretion (r = -0.359, p < 0.05), VLDL-apoB (r = -0.513, p < 0.01) and IDL-apoB (r = -0.511, p < 0.01) pool size, and plasma lathosterol ratio (r = -0.366, p < 0.05). Subjects with low cholesterol absorption had significantly higher VLDL-apoB secretion, VLDL-apoB and IDL-apoB pool size, and plasma lathosterol ratio (p < 0.05 in both) than those with high cholesterol absorption. Subjects with the metabolic syndrome have oversecretion of VLDL-apoB and decreased catabolism of apoB-containing particles and low absorption and high synthesis rates of cholesterol. These changes in cholesterol homeostasis may contribute to the kinetic defects in apoB metabolism in the metabolic syndrome.

  16. 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.

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

    Science.gov (United States)

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

    1998-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-03-01

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

  19. In search of new structural states of exchangeable apolipoproteins

    International Nuclear Information System (INIS)

    Xicohtencatl-Cortes, J.; Castillo, R.; Mas-Oliva, J.

    2004-01-01

    Based upon state of the art biophysical experimentation, this article focuses on the different structural arrangements exchangeable apolipoproteins achieve when placed on Langmuir monolayers and subjected to changes in lateral pressure. We have studied the monolayers of apolipoproteins CI, CIII, AI, AII, and E that show as secondary structure a high percentage of amphipathic α-helix. This has been achieved employing techniques such as Brewster angle microscopy, synchrotron X-ray diffraction, and surface pressure measurements. In addition, the lateral order of protein arrays has been also studied by atomic force microscopy. These monolayers show that a phase transition from a two-dimensional disorder fluid to an ordered state is detected at relatively high lateral pressure, where unusual one-dimensional solid phases are discovered. While several helices that conform the apolipoprotein are confined to the interface, others are uniformly tilted toward the hydrophobic air or the phospholipid fatty acid chains. Our results suggest that a similar ordering might also occur when these apolipoproteins are attached to a lipoprotein particle such as a high density lipoprotein (HDL) particle. Therefore, changes from a nascent or discoidal HDL to a mature spherical HDL might in parallel involve structural changes as those described in our Langmuir interfaces. Current experimentation is being carried out in order to elucidate if the structural states already found are related to the efficiency of lipid transfer between lipoprotein particles or lipoproteins and the plasma membrane of cells, as well as receptor ligand recognition

  20. Molecules that mimic apolipoprotein A-I: potential agents for treating atherosclerosis.

    Science.gov (United States)

    Leman, Luke J; Maryanoff, Bruce E; Ghadiri, M Reza

    2014-03-27

    Certain amphipathic α-helical peptides can functionally mimic many of the properties of full-length apolipoproteins, thereby offering an approach to modulate high-density lipoprotein (HDL) for combating atherosclerosis. In this Perspective, we summarize the key findings and advances over the past 25 years in the development of peptides that mimic apolipoproteins, especially apolipoprotein A-I (apoA-I). This assemblage of information provides a reasonably clear picture of the state of the art in the apolipoprotein mimetic field, an appreciation of the potential for such agents in pharmacotherapy, and a sense of the opportunities for optimizing the functional properties of HDL.

  1. Effects of fenofibrate on hyperlipidemia and postprandial triglyceride metabolism in human apolipoprotein C1 transgenic mice

    NARCIS (Netherlands)

    Jong, M.C.; Dahlmans, V.E.H.; Princen, H.M.G.; Hofker, M.H.; Havekes, L.M.

    1998-01-01

    To study the in vivo role of apolipoprotein (apo) C1 in lipoprotein metabolism, we have generated transgenic mice expressing the human apo C1 gene. Apo C1 is a small 6.6 kDa protein that is primarily synthesized by the liver and is present on chylomicrons, very low density lipoproteins (VLDL) and

  2. Analysis of structure--function relationships in human apolipoprotein(a)

    NARCIS (Netherlands)

    van der Hoek, Y. Y.; Kastelein, J. J.; Koschinsky, M. L.

    1994-01-01

    Elevated levels of lipoprotein(a) (Lp(a)) have been strongly correlated with the development of atherosclerosis in human populations. Lp(a) is distinguishable from low density lipoprotein by the presence of the unique protein component apolipoprotein(a) (apo(a)), which contains repeated domains that

  3. Apolipoprotein C3 polymorphism is associated with cognitive function in Caribbean Hispanics

    Science.gov (United States)

    Background: Apolipoprotein C3(APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired ...

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

    Directory of Open Access Journals (Sweden)

    Raul Cavalcante Maranhão

    2014-07-01

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

  5. Relationship between depression and apolipoproteins A and B: a case-control study

    Directory of Open Access Journals (Sweden)

    Masoumeh Sadeghi

    2011-01-01

    Full Text Available OBJECTIVE: To investigate the relation between major depressive disorder and metabolic risk factors of coronary heart disease. INTRODUCTION: Little evidence is available indicating a relationship between major depressive disorder and metabolic risk factors of coronary heart disease such as lipoprotein and apolipoprotein. METHODS: This case-control study included 153 patients with major depressive disorder who fulfilled the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV, and 147 healthy individuals. All participants completed a demographic questionnaire and Hamilton rating scale for depression. Anthropometric characteristics were recorded. Blood samples were taken and total cholesterol, high-and low-density lipoproteins and apolipoproteins A and B were measured. To analyze the data, t-test, χ2 test, Pearson correlation test and linear regression were applied. RESULTS: Depression was a negative predictor of apolipoprotein A (β = -0.328, p<0.01 and positive predictor of apolipoprotein B (β = 0.290, p<0.05. Apolipoprotein A was inversely predicted by total cholesterol (β = -0.269, p<0.05 and positively predicted by high-density lipoprotein (β = 0.401, p<0.01. Also, low-density lipoprotein was a predictor of apolipoprotein B (β = 0.340, p<0.01. The severity of depression was correlated with the increment in serum apolipoprotein B levels and the decrement in serum apolipoprotein A level. CONCLUSION: In view of the relationship between apolipoproteins A and B and depression, it would seem that screening of these metabolic risk factors besides psychological interventions is necessary in depressed patients

  6. Remnant lipoproteins

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G.

    2017-01-01

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

  7. Thyrotropin interaction with high-density lipoproteins.

    Science.gov (United States)

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

    1985-07-09

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

  8. Influence of apolipoprotein-E gene on lipid profile, physical activity and body fat relationship

    Directory of Open Access Journals (Sweden)

    Thales Boaventura Rachid Nascimento

    2012-03-01

    Full Text Available Physical activity and body fat modify lipemia, and this effect seems to be influenced by apolipoprotein-E (APOE gene polymorphism. Thus, the purpose of this article was to review main results of studies that have analyzed the relation of APOE gene with physical activity and body fat on triglycerides, total cholesterol and low (LDL and high density lipoprotein (HDL concentrations. The Scientific Electronic Library Online – SciELO, Web of Science and PubMed database were used to locate the articles. The keywords used in combination were: apoe genotype, apolipoprotein-E polymorphism, physical exercise, physical activity, aerobic exercise, body fat and obesity. Originals scientific investigations performed with humans were included, and excluded those ones which involved samples with diseases, except obesity and/or lipemic disorders. It was observed a trend, that ε2 allele carriers are the ones with the greater improvements on lipemia from physical exercise. In addition, the body fat impact on the elevation of triglycerides and LDL are stronger in carriers of the ε2 and ε4 allele, respectively. Considering the small number of originals scientific investigations and their divergent results, reliable inferences can not be made about the APOE gene polymorphism influences on physical activity and body fat effect on lipemia. Thus, further studies with others populations and more volunteers for allele, as well as others exercise modalities and intensities, are necessary.

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

    DEFF Research Database (Denmark)

    Roeseler, Eberhard; Julius, Ulrich; Heigl, Franz

    2016-01-01

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

  10. Lipoprotein(a) accelerates atherosclerosis in uremic mice

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  11. Effect of lipid composition and packing on the adsorption of apolipoproteins to lipid monolayers

    International Nuclear Information System (INIS)

    Ibdah, J.A.; Lund-Katz, S.; Phillips, M.C.

    1987-01-01

    The monolayer system has been used to study the effects of lipoprotein surface lipid composition and packing on the affinities of apolipoproteins for the surfaces of lipoprotein particles. The adsorption of apolipoproteins injected beneath lipid monolayers prepared with pure lipids or lipoprotein surface lipids is evaluated by monitoring the surface pressure of the film and the surface concentration (Gamma) of 14 C-labelled apolipoprotein. At a given initial film pressure (π/sub i/) there is a higher adsorption of human apo A-I to unsaturated phosphatidylcholine (PC) monolayers compared to saturated PC monolayers (e.g., at π/sub i/ = 10 mN/m, Gamma = 0.35 and 0.06 mg/m 2 for egg PC and distearoyl PC, respectively, with 3 x 10 -4 mg/ml apo A-I in the subphase). In addition, adsorption of apo A-I is less to an egg sphingomyelin monolayer than to an egg PC monolayer. The adsorption of apo A-I to PC monolayers is decreased by addition of cholesterol. Generally, apo A-I adsorption diminishes as the lipid molecular area decreases. Apo A-I adsorbs more to monolayers prepared with HDL 3 surface lipids than with LDL surface lipids. These studies suggest that lipoprotein surface lipid composition and packing are crucial factors influencing the transfer and exchange of apolipoproteins among various lipoprotein classes during metabolism of lipoprotein particles

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

    NARCIS (Netherlands)

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

    2003-01-01

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

  13. Intracellular role of exchangeable apolipoproteins in energy homeostasis, obesity and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Wu, Chen-Lu; Zhao, Shui-Ping; Yu, Bi-Lian

    2015-05-01

    Exchangeable apolipoproteins play an important role in systemic lipid metabolism, especially for lipoproteins with which they are associated. Recently, emerging evidence has suggested that exchangeable apolipoproteins, such as apolipoprotein A4 (apoA4), apolipoprotein A5 (apoA5), apolipoprotein C3 (apoC3) and apolipoprotein E (apoE), also exert important effects on intracellular lipid homeostasis. There is a close link between lipid metabolism in adipose tissue and liver because the latter behaves as the metabolic sensor of dysfunctional adipose tissue and is a main target of lipotoxicity. Given that the energy balance between these two major lipogenic organs is intimately involved in the pathogenesis of obesity and non-alcoholic fatty liver disease (NAFLD), we here review recent findings concerning the intracellular function of exchangeable apolipoproteins in triglyceride metabolism in adipocytes and hepatocytes. These apolipoproteins may act as mediators of crosstalk between adipose tissue and liver, thus influencing development of obesity and hepatosteatosis. This review provides new insights into the physiological role of exchangeable apolipoproteins and identifies latent targets for therapeutic intervention of obesity and its related disorders. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

  14. Caffeine Increases Apolipoprotein A-1 and Paraoxonase-1 but not Paraoxonase-3 Protein Levels in Human-Derived Liver (HepG2) Cells

    OpenAIRE

    Sayılan Özgün, Gülben; Özgün, Eray; Tabakçıoğlu, Kıymet; Süer Gökmen, Selma; Eskiocak, Sevgi; Çakır, Erol

    2017-01-01

    Background: Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 are antioxidant and anti-atherosclerotic structural high-density lipoprotein proteins that are mainly synthesized by the liver. No study has ever been performed to specifically examine the effects of caffeine on paraoxonase enzymes and on liver apolipoprotein A-1 protein levels. Aims: To investigate the dose-dependent effects of caffeine on liver apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels. Study Design: In...

  15. Caffeine Increases Apolipoprotein A-1 and Paraoxonase-1 but not Paraoxonase-3 Protein Levels in Human-Derived Liver (HepG2) Cells

    OpenAIRE

    Gülben Sayılan Özgün; Eray Özgün; Kıymet Tabakçıoğlu; Selma Süer Gökmen; Sevgi Eskiocak; Erol Çakır

    2017-01-01

    Background: Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 are antioxidant and anti-atherosclerotic structural high-density lipoprotein proteins that are mainly synthesized by the liver. No study has ever been performed to specifically examine the effects of caffeine on paraoxonase enzymes and on liver apolipoprotein A-1 protein levels. Aims: To investigate the dose-dependent effects of caffeine on liver apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels. Study De...

  16. Effect of apolipoprotein E variants on plasma lipids and apolipoproteins in the Orang Asli ('aborigines') of Malaysia.

    Science.gov (United States)

    Gajra, B; Candlish, J K; Saha, N; Mak, J W; Tay, J S

    1994-01-01

    Members of the Semai group of Orang Asli ('aborigines') in peninsular Malaysia were examined for apolipoprotein E (apo E) variants in relation to plasma total cholesterol (TC), high density lipoprotein cholesterol, low density lipoprotein cholesterol (LDLC), triglycerides (TG), apolipoprotein AI and apolipoprotein B (apo B). The e2 and e4 alleles were found to be higher than in most other groups as reported. The sample as a whole was normotriglyceridaemic (mean plasma TG, 1.5 mmol/l) and very markedly hypocholesterolaemic (mean plasma TC 1.7 mmol/l). The distribution of apo E variants was not related to any of the plasma lipids or apolipoprotein fractions using results from all subjects, but if a distinctly hypertriglyceridaemic sub-section was omitted (TG > 1.7 mmol/l) then apo E variants were determinants of plasma TC, LDLC, and apo B concentrations, the lower values of these being associated with the 2-2 and 2-3 genotypes, and the higher with 3-4, and 4-4.

  17. Anti-infective activity of apolipoprotein domain derived peptides in vitro: identification of novel antimicrobial peptides related to apolipoprotein B with anti-HIV activity

    Directory of Open Access Journals (Sweden)

    McKnight Áine

    2010-03-01

    Full Text Available Abstract Background Previous reports have shown that peptides derived from the apolipoprotein E receptor binding region and the amphipathic α-helical domains of apolipoprotein AI have broad anti-infective activity and antiviral activity respectively. Lipoproteins and viruses share a similar cell biological niche, being of overlapping size and displaying similar interactions with mammalian cells and receptors, which may have led to other antiviral sequences arising within apolipoproteins, in addition to those previously reported. We therefore designed a series of peptides based around either apolipoprotein receptor binding regions, or amphipathic α-helical domains, and tested these for antiviral and antibacterial activity. Results Of the nineteen new peptides tested, seven showed some anti-infective activity, with two of these being derived from two apolipoproteins not previously used to derive anti-infective sequences. Apolipoprotein J (151-170 - based on a predicted amphipathic alpha-helical domain from apolipoprotein J - had measurable anti-HSV1 activity, as did apolipoprotein B (3359-3367 dp (apoBdp, the latter being derived from the LDL receptor binding domain B of apolipoprotein B. The more active peptide - apoBdp - showed similarity to the previously reported apoE derived anti-infective peptide, and further modification of the apoBdp sequence to align the charge distribution more closely to that of apoEdp or to introduce aromatic residues resulted in increased breadth and potency of activity. The most active peptide of this type showed similar potent anti-HIV activity, comparable to that we previously reported for the apoE derived peptide apoEdpL-W. Conclusions These data suggest that further antimicrobial peptides may be obtained using human apolipoprotein sequences, selecting regions with either amphipathic α-helical structure, or those linked to receptor-binding regions. The finding that an amphipathic α-helical region of

  18. Revisiting the Gram-negative lipoprotein paradigm.

    Science.gov (United States)

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

    2015-05-01

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

  19. Increased oxidizability of low-density lipoproteins in hypothyroidism

    NARCIS (Netherlands)

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

    1998-01-01

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

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

    African Journals Online (AJOL)

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

  1. 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.

  2. Sortilins: new players in lipoprotein metabolism

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  3. Apolipoprotein M - a new biomarker in sepsis

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Nielsen, Lars Bo

    2012-01-01

    ABSTRACT: Sepsis is one of the leading causes of mortality in non-cardiac intensive care units, and the need for markers of progression and severity are high. Also, treatment of sepsis is highly debated and potential new targets of treatment are of great interest. In the previous issue of Critical...... Care Kumaraswamy and colleagues have investigated whether plasma apolipoprotein M (apoM) is affected during different grades of sepsis, septic shock and systemic inflammatory response syndrome. Interestingly, plasma apoM was significantly decreased in all groups of patients with a relationship...... to severity of disease. This identifies apoM as a potential new biomarker in sepsis. It also underscores the possibility that altered high-density lipoprotein in sepsis patients can affect the course of disease. Thus, since apoM is the carrier of Sphingosine-1-P (S1P), a molecule with great influence...

  4. Plasma levels of apolipoprotein E and risk of ischemic heart disease in the general population

    DEFF Research Database (Denmark)

    Rasmussen, Katrine L.; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2016-01-01

    BACKGROUND AND AIMS: Triglyceride-rich lipoproteins are causally associated with high risk of ischemic heart disease (IHD), and apolipoprotein E (apoE) has a central role in their plasma clearance. While both quantitative and qualitative changes of apoE are established causes of rare dyslipidemia...

  5. Trimerization of apolipoprotein A-I retards plasma clearance and preserves antiatherosclerotic properties

    DEFF Research Database (Denmark)

    Graversen, Jonas Heilskov; Laurberg, Jacob Marsvin; Andersen, Mikkel Holmen

    2008-01-01

    An increased plasma level of the major high-density lipoprotein (HDL) component, apolipoprotein A-I (apoA-I) is the aim of several therapeutic strategies for combating atherosclerotic disease. HDL therapy by direct intravenous administration of apoA-I is a plausible way; however, a fast renal...

  6. Association of LDL Cholesterol, Non-HDL Cholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events Among Patients Treated With Statins A Meta-analysis

    NARCIS (Netherlands)

    Boekholdt, S. Matthijs; Arsenault, Benoit J.; Mora, Samia; Pedersen, Terje R.; LaRosa, John C.; Nestel, Paul J.; Simes, R. John; Durrington, Paul; Hitman, Graham A.; Welch, K. M. A.; Demicco, David A.; Zwinderman, Aeilko H.; Clearfield, Michael B.; Downs, John R.; Tonkin, Andrew M.; Colhoun, Helen M.; Gotto, Antonio M.; Ridker, Paul M.; Kastelein, John J. P.

    2012-01-01

    Context The associations of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (apoB) levels with the risk of cardiovascular events among patients treated with statin therapy have not been reliably documented. Objective To evaluate

  7. Levels and changes of HDL cholesterol and apolipoprotein A-I in relation to risk of cardiovascular events among statin-treated patients: a meta-analysis

    NARCIS (Netherlands)

    Boekholdt, S. Matthijs; Arsenault, Benoit J.; Hovingh, G. Kees; Mora, Samia; Pedersen, Terje R.; LaRosa, John C.; Welch, K. M. A.; Amarenco, Pierre; Demicco, David A.; Tonkin, Andrew M.; Sullivan, David R.; Kirby, Adrienne; Colhoun, Helen M.; Hitman, Graham A.; Betteridge, D. John; Durrington, Paul N.; Clearfield, Michael B.; Downs, John R.; Gotto, Antonio M.; Ridker, Paul M.; Kastelein, John J. P.

    2013-01-01

    It is unclear whether levels of high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I (apoA-I) remain inversely associated with cardiovascular risk among patients who achieve very low levels of low-density lipoprotein cholesterol on statin therapy. It is also unknown whether a rise in

  8. Effects of apolipoproteins on the kinetics of cholesterol exchange

    International Nuclear Information System (INIS)

    Letizia, J.Y.; Phillips, M.C.

    1991-01-01

    The effects of apolipoproteins on the kinetics of cholesterol exchange have been investigated by monitoring the transfer of [ 14 C]cholesterol from donor phospholipid/cholesterol complexes containing human apolipoproteins A, B, or C. Negatively charged discoidal and vesicular particles containing purified apolipoproteins complexed with lipid and a trace of [ 14 C]cholesterol were incubated with a 10-fold excess of neutral, acceptor, small unilamellar vesicles. The donor and acceptor particles were separated by chromatogrphy of DEAE-Sepharose, and the rate of movement of labeled cholesterol was analyzed as a first-order exchange process. The kinetics of exchange of cholesterol from both vesicular and discoidal complexes that contain apoproteins are consistent with an aqueous diffusion mechanism, as has been established previously for PC/cholesterol SUV. Apolipoproteins A-I, A-II, reduced and carboxymethylated A-11, and B-100 present in SUV at the same lipid/protein (w/w) ratio all enhance the rate of cholesterol exchange to about the same degree. Cholesterol molecules exchange more rapidly from discoidal complexes. Generally, as the diameter of apoprotein/phospholipid/cholesterol discs decreases, t 1/2 for cholesterol exchange decreases. Since small bilayer discs have a relatively high ratio of boundary to face surface area, cholesterol molecules desorb more rapidly than from larger discs. The modulation of lipid packing by the apoprotein molecules present at the surface of lipoprotein particles affects the rate of cholesterol exchange from such particles

  9. Postprandial Hyperlipidemia and Remnant Lipoproteins

    Science.gov (United States)

    Yamashita, Shizuya

    2017-01-01

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

  10. Major lipids, apolipoproteins, and risk of vascular disease

    DEFF Research Database (Denmark)

    Collaboration, Emerging Risk Factors; Di Angelantonio, Emanuele; Sarwar, Nadeem

    2009-01-01

    CONTEXT: Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified. OBJECTIVE: To assess major lipids and apolipoproteins in vascular risk. DESIGN, SETTING, AND PARTICIPANTS: Individual records were supplied on 302,430 people without...... initial vascular disease from 68 long-term prospective studies, mostly in Europe and North America. During 2.79 million person-years of follow-up, there were 8857 nonfatal myocardial infarctions, 3928 coronary heart disease [CHD] deaths, 2534 ischemic strokes, 513 hemorrhagic strokes, and 2536...... mg/dL directly measured low-density lipoprotein cholesterol (LDL-C). Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. RESULTS: The rates of CHD per 1000 person-years in the bottom and top thirds of baseline lipid distributions, respectively...

  11. Apolipoprotein Mimetic Peptides: A New Approach for the Treatment of Asthma

    Directory of Open Access Journals (Sweden)

    Xianglan eYao

    2012-03-01

    Full Text Available New treatments are needed for severe asthmatics to improve disease control and avoid severe toxicities associated with oral corticosteroids. We have used a murine model of house dust mite (HDM-induced asthma to identify steroid-unresponsive genes that might represent targets for new therapeutic approaches for severe asthma. This strategy identified apolipoprotein E as a steroid-unresponsive gene with increased mRNA expression in the lungs of HDM-challenged mice. Furthermore, apolipoprotein E functioned as an endogenous negative regulator of airway hyperreactivity and goblet cell hyperplasia in experimental HDM-induced asthma. The ability of apolipoprotein E, which is expressed by lung macrophages, to attenuate AHR and goblet cell hyperplasia is mediated by low density lipoprotein (LDL receptors expressed by airway epithelial cells. Consistent with this, administration of an apolipoprotein E mimetic peptide, corresponding to amino acids 130 to 149 of the LDL receptor-binding domain of the holo-apoE protein, significantly reduced AHR and goblet cell hyperplasia in HDM-challenged apoE-/- mice. These findings identified the apolipoprotein E - LDL receptor pathway as a new druggable target for asthma that can be activated by administration of apoE mimetic peptides. Similarly, apolipoprotein A-I may have therapeutic potential in asthma based upon its anti-inflammatory, anti-oxidative and anti-fibrotic properties. Furthermore, administration of apolipoprotein A-I mimetic peptides has attenuated airway inflammation, airway remodeling and airway hyperreactivity in murine models of experimental asthma. Thus, site-directed delivery of inhaled apolipoprotein E or apolipoprotein A-I mimetic peptides may represent novel treatment approaches that can be developed for asthma, including severe disease.

  12. Apolipoprotein nanodiscs with telodendrimer

    Science.gov (United States)

    Luo, Juntao; He, Wei; Lam, Kit S.; Henderson, Paul; Coleman, Matthew; Cheng, R. Holland; Xing, Li

    2017-05-09

    The present invention provides a nanodisc with a membrane scaffold protein. The nanodisc includes a membrane scaffold protein, a telodendrimer and a lipid. The membrane scaffold protein can be apolipoprotein. The telodendrimer has the general formula PEG-L-D-(R).sub.n, wherein D is a dendritic polymer; L is a bond or a linker linked to the focal point group of the dendritic polymer; each PEG is a poly(ethylene glycol) polymer; each R is and end group of the dendritic polymer, or and end group with a covalently bound hydrophobic group, hydrophilic group, amphiphilic compound, or drug; and subscript n is an integer from 2 to 20. Cell free methods of making the nanodiscs are also provided.

  13. Characterization of Lipoprotein Lipases interactions with Sortilin and SorLA

    DEFF Research Database (Denmark)

    Klinger, Stine Christensen

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

  14. Overexpression of LolCDE allows deletion of the Escherichia coli gene encoding apolipoprotein N-acyltransferase.

    Science.gov (United States)

    Narita, Shin-ichiro; Tokuda, Hajime

    2011-09-01

    Bacterial lipoproteins represent a subset of membrane-associated proteins that are covalently modified with lipids at the N-terminal cysteine. The final step of lipoprotein modification, N-acylation of apolipoproteins, is mediated by apolipoprotein N-acyltransferase (Lnt). Examinations with reconstituted proteoliposomes and a conditional mutant previously indicated that N-acylation of lipoproteins is required for their efficient release from the inner membrane catalyzed by LolA and LolCDE, the lipoprotein-specific chaperone and ABC transporter, respectively. Because Lnt is essential for Escherichia coli, a mutant lacking Lnt activity has not been isolated. However, we report here that lnt-null strains can be constructed when LolCDE is overproduced in strains lacking either the major outer membrane lipoprotein Lpp or transpeptidases that cross-link Lpp with peptidoglycan. Lipoproteins purified from the lnt-null strain exhibited increased mobility on SDS-PAGE compared to those from wild-type cells and could be sequenced by Edman degradation, indicating that lipoproteins in this mutant exist as apolipoproteins that lack N-acylation. Overexpression of Lpp in the lnt-null strain resulted in the accumulation of apoLpp in the inner membrane and caused growth arrest. In contrast to the release of mature Lpp in the presence of LolA and LolCDE, that of apoLpp from the inner membrane was significantly retarded. Furthermore, the amount of lipoproteins copurified with LolCDE was significantly reduced in the lnt-null strain. These results indicate that the affinity of LolCDE for apolipoprotein is very low, and therefore, overexpression of LolCDE is required for its release and sorting to the outer membrane. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

  15. Overexpression of LolCDE Allows Deletion of the Escherichia coli Gene Encoding Apolipoprotein N-Acyltransferase ▿

    Science.gov (United States)

    Narita, Shin-ichiro; Tokuda, Hajime

    2011-01-01

    Bacterial lipoproteins represent a subset of membrane-associated proteins that are covalently modified with lipids at the N-terminal cysteine. The final step of lipoprotein modification, N-acylation of apolipoproteins, is mediated by apolipoprotein N-acyltransferase (Lnt). Examinations with reconstituted proteoliposomes and a conditional mutant previously indicated that N-acylation of lipoproteins is required for their efficient release from the inner membrane catalyzed by LolA and LolCDE, the lipoprotein-specific chaperone and ABC transporter, respectively. Because Lnt is essential for Escherichia coli, a mutant lacking Lnt activity has not been isolated. However, we report here that lnt-null strains can be constructed when LolCDE is overproduced in strains lacking either the major outer membrane lipoprotein Lpp or transpeptidases that cross-link Lpp with peptidoglycan. Lipoproteins purified from the lnt-null strain exhibited increased mobility on SDS-PAGE compared to those from wild-type cells and could be sequenced by Edman degradation, indicating that lipoproteins in this mutant exist as apolipoproteins that lack N-acylation. Overexpression of Lpp in the lnt-null strain resulted in the accumulation of apoLpp in the inner membrane and caused growth arrest. In contrast to the release of mature Lpp in the presence of LolA and LolCDE, that of apoLpp from the inner membrane was significantly retarded. Furthermore, the amount of lipoproteins copurified with LolCDE was significantly reduced in the lnt-null strain. These results indicate that the affinity of LolCDE for apolipoprotein is very low, and therefore, overexpression of LolCDE is required for its release and sorting to the outer membrane. PMID:21742870

  16. Association Between Lipoprotein(A) and Small Apo(A) Phenotypes and Coronary Heart Disease in Sudanese Diabetic Patients

    International Nuclear Information System (INIS)

    Ahmed, A.M.; Elabid, B.E.H.; Addalla, M.A.

    2013-01-01

    Background:Recent studies indicate an independent association of apolipoprotein(a) small phenotypes with the diabetes and the onset of coronary heart disease.Apolipoprotein(a)small phenotypes when used together with Lipoprotein(a) levels make powerful markers in assessing the actual risk of developing coronary heart disease in diabetic patients. Objectives: Evaluation of clinical and diagnostic significant of Lipoprotein(a) levels and apolipoprotein(a) small phenotypes and its relation to coronary heart disease in Sudanese diabetic patients. Setting and duration of study: Diabetic patients attending hospitals and medical centers from May 2011-December 2012, in Khartoum, Sudan. Patients and Methods: This was a case control, hospital based study done on 138 Sudanese diabetic patients attending hospitals and medical centers in Khartoum. Patients were divided into 2 groups. One group had diabetic cases with coronary heart disease and the other were diabetic patients without coronary heart disease. Controls were age and gender matched. Blood samples were collected from both groups(patients and controls) and were run for apolipoproteins, lipoproteins and apolipoprotein(a) small phenotype,low-density lipoprotein,high-density lipoprotein and trigeminal ganglia. Results: The levels of Lipoprotein(a) of patients were significantly higher than controls (p<0.05). Apolipoprotein(a)small phenotype distribution showed a significant difference when compared between patients of both groups (diabetics with and without coronary heart disease) and controls (p<0.05). Both low-density lipoprotein and high-density lipoprotein cholesterol showed significant difference in both patient groups and controls (p<0.05). Total cholesterol and triglyceride levels showed no significant difference between patients and controls. Apolipoprotein(a) small phenotypes showed significant distribution in diabetic patients when compared with coronary heart disease patients (more than one low molecular weight

  17. Effect of an isoenergetic traditional Mediterranean diet on apolipoprotein A-I kinetic in men with metabolic syndrome

    Science.gov (United States)

    The impact of the Mediterranean diet (MedDiet) on high-density lipoprotein (HDL) kinetics has not been studied to date. The objective of this study was therefore to investigate the effect of the MedDiet in the absence of changes in body weight on apolipoprotein (apo) A-I kinetic in men with metaboli...

  18. Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic apolipoprotein E*3-Leiden transgenic mice

    NARCIS (Netherlands)

    Vlijmen, B.J.M. van; Mensink, R.P.; Hof, H.B. van 't; Offermans, R.F.G.; Hofker, M.H.; Havekes, L.M.

    1998-01-01

    Studying the effects of dietary fish oil on VLDL metabolism in humans is subject to both large intra- and interindividual variability. In the present study we therefore used hyperlipidentic apolipoprotein (APO) E*3-Leiden mice, which have impaired chylomicron and very low density lipoprotein (VDL)

  19. Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100

    International Nuclear Information System (INIS)

    Soria, L.F.; Ludwig, E.H.; Clarke, H.R.G.; McCarthy, B.J.; Vega, G.L.; Grundy, S.M.

    1989-01-01

    Familial defective apolipoprotein (apo) B-100 is a genetic disease that leads to hypercholesterolemia and to an increased serum concentration of low density lipoproteins that bind defectively to the apoB,E(LDL) receptor. The disorder appears to result from a mutation in the gene for apoB-100. Extensive sequence analysis of the two alleles of one subject heterozygous for the disorder has revealed a previously unreported mutation in the codon for amino acid 3500 that results in the substitution of glutamine for arginine. This same mutant allele occurs in six other, unrelated subjects and in eight affected relatives in two of these families. A partial haplotype of this mutant apoB-100 allele was constructed by sequence analysis and restriction enzyme digestion at positions where variations in the apoB-100 are known to occur. This haplotype is the same in three probands and four affected members of one family and lacks a polymorphic Xba I site whose presence has been correlated with high cholesterol levels. Thus, it appears that the mutation in the codon for amino acid 3500 (CGG → CAG), a CG mutational hot spot, defines a minor apoB-100 allele associated with defective low density lipoproteins and hypercholesterolemia

  20. Expression of very low density lipoprotein receptor in the vascular wall. Analysis of human tissues by in situ hybridization and immunohistochemistry

    DEFF Research Database (Denmark)

    Multhaupt, H A; Gåfvels, M E; Kariko, K

    1996-01-01

    The recently cloned very low density lipoprotein (VLDL) receptor binds triglyceride-rich, apolipoprotein-E-containing lipoproteins with high affinity. The observation that VLDL receptor mRNA is abundantly expressed in extracts of tissues such as skeletal muscle and heart, but not liver, has led t...

  1. Effects of lipid composition and packing on the adsorption of apolipoprotein A-I to lipid monolayers

    International Nuclear Information System (INIS)

    Ibdah, J.A.; Phillips, M.C.

    1988-01-01

    To better understand the factors controlling the binding of apolipoprotein molecules at the surfaces of serum lipoprotein particles, the adsorption of human apolipoprotein A-I to phospholipid monolayers has been studied. The influence of lipid packing was investigated by spreading the monolayers at various initial surface pressures (π/sub i/) and by using various types of lipid. The adsorption of 14 C-methylated apolipoprotein A-I was monitored by simultaneously following the surface radioactivity and the change in surface pressure (Δπ). In general, increasing the π/sub i/ of lipid monolayers reduces the adsorption of apolipoprotein A-I. The degree of adsorption of the apolipoprotein is also influenced by the physical state of the lipid monolayers. Addition of cholesterol generally decreases the adsorption of apolipoprotein A-I to egg PC monolayers. Analysis of the adsorption data suggests that the lateral compressibility of a lipid monolayer is a major determinant of the extent to which apolipoprotein A-I adsorbs. The protein penetrates into the interface to occupy space made available by the concomitant compression of phospholipid molecules so Gamma is higher for relatively compressible lipid monolayers. Lipid-protein interactions appear to influence the degree of adsorption to only a minor degree

  2. Plasma lipids and apolipoproteins in a population of Orang Asli ('aborigines') from West Malaysia.

    Science.gov (United States)

    Candlish, J K; Saha, N; Mak, J W

    1997-02-28

    Plasma total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDLC) and apolipoproteins Al (apo Al) and B (apo B) were measured in a sample of subjects from the Semai tribe of Orang Asli in peninsular Malaysia. They appeared to exhibit the lowest TC ever recorded (1.6 for males and 1.9 mmol/l for females) and relatively high TG (1.4 mmol/l for males and 1.5 mmol/l for females)(means for the whole sample). There was little apparent aging gradient in any of the plasma analytes. but the group of men aged 21-40 had lower HDLC than the corresponding female group. Both low density lipoprotein cholesterol (LDLC) (calculated) and HDLC as well as their corresponding apolipoproteins were correspondingly very low. There was a significant correlation between apo AI and HDLC in both sexes.

  3. Genetics of Lipid and Lipoprotein Disorders and Traits.

    Science.gov (United States)

    Dron, Jacqueline S; Hegele, Robert A

    2016-01-01

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

  4. The Apolipoprotein M/S1P Axis Controls Triglyceride Metabolism and Brown Fat Activity

    Directory of Open Access Journals (Sweden)

    Christina Christoffersen

    2018-01-01

    Full Text Available Summary: Apolipoprotein M (apoM is the carrier of sphingosine-1-phosphate (S1P in plasma high-density lipoproteins. S1P is a bioactive lipid interacting with five receptors (S1P1–5. We show that lack of apoM in mice increases the amount of brown adipose tissue (BAT, accelerates the clearance of postprandial triglycerides, and protects against diet-induced obesity (i.e., a phenotype similar to that induced by cold exposure or β3-adrenergic stimulation. Moreover, the data suggest that the phenotype of apoM-deficient mice is S1P dependent and reflects diminished S1P1 stimulation. The results reveal a link between the apoM/S1P axis and energy metabolism. : Apolipoprotein M (apoM is the carrier of sphingosine-1-phosphate (S1P in lipoproteins. Christoffersen et al. show that lack of apoM in mice increases the amount of brown adipose tissue, accelerates the turnover of fat, and protects against obesity. The results reveal a link between the apoM/S1P axis and energy metabolism. Keywords: apolipoproteins, sphingolipids, sphingosine-1-phosphate, lipoproteins, lipid metabolism, triglyceride, brown adipose tissue, apoM

  5. Apolipoprotein E and familial longevity

    DEFF Research Database (Denmark)

    Schupf, Nicole; Barral, Sandra; Perls, Thomas

    2013-01-01

    Exceptional longevity is associated with substantial heritability. The ε4 allele in apolipoprotein E and the linked G allele in rs2075650 of TOMM40 have been associated with increased mortality and the ε2 allele with decreased mortality, although inconsistently. Offspring from long-lived families...

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

    NARCIS (Netherlands)

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

    1990-01-01

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

  7. Both serum apolipoprotein B and the apolipoprotein B/apolipoprotein A-I ratio are associated with carotid intima-media thickness.

    Directory of Open Access Journals (Sweden)

    Fei Huang

    Full Text Available BACKGROUND: Previous studies indicated that apolipoprotein measurements predicted cardiovascular disease (CVD risk; however, associations between apolipoproteins and carotid intima-media thickness (CIMT were less explored. METHODOLOGY AND PRINCIPAL FINDINGS: The cross-sectional study included 6069 participants aged 40 years or older with NGT from Shanghai, China. Serum fasting traditional lipids (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG], apoA-I and apoB were assessed. A high-resolution B-mode ultrasonography was performed to measure CIMT. We found CIMT increased progressively across the quartiles of serum apoB (p for trend <0.0001. In logistic regression, concentrations of apoB (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.18-1.36, TC (OR 1.23, 95% CI 1.14-1.32, LDL-C (OR 1.25, 95% CI 1.16-1.34 and TG (OR 1.11, 95% CI 1.04-1.20 were significantly related to elevated CIMT after adjusted for age and sex. Meanwhile, the apoB/apoA-I ratio (OR 1.25, 95% CI 1.17-1.34 related to elevated CIMT. ApoB (OR 1.23, 95% CI 1.00-1.51 and the apoB/apoA-I ratio (OR 1.19, 95% CI 1.04-1.36 remained significantly associated with elevated CIMT, after adjusted for the traditional CVD risk factors including traditional lipids. CONCLUSIONS AND SIGNIFICANCE: There were significant associations between serum apoB, the apoB/apoA-I ratio and elevated CIMT. Serum apoB and the apoB/apoA-I ratio might be independent predictors of early atherosclerosis in NGT.

  8. Multiple system atrophy and apolipoprotein E.

    Science.gov (United States)

    Ogaki, Kotaro; Martens, Yuka A; Heckman, Michael G; Koga, Shunsuke; Labbé, Catherine; Lorenzo-Betancor, Oswaldo; Wernick, Anna I; Walton, Ronald L; Soto, Alexandra I; Vargas, Emily R; Nielsen, Henrietta M; Fujioka, Shinsuke; Kanekiyo, Takahisa; Uitti, Ryan J; van Gerpen, Jay A; Cheshire, William P; Wszolek, Zbigniew K; Low, Phillip A; Singer, Wolfgang; Dickson, Dennis W; Bu, Guojun; Ross, Owen A

    2018-02-14

    Dysregulation of the specialized lipid metabolism involved in myelin synthesis and maintenance by oligodendrocytes has been associated with the unique neuropathology of MSA. We hypothesized that apolipoprotein E, which is associated with neurodegeneration, may also play a role in the pathogenesis of MSA. This study evaluated genetic associations of Apolipoprotein E alleles with risk of MSA and α-synuclein pathology, and also examined whether apolipoprotein E isoforms differentially affect α-synuclein uptake in a oligodendrocyte cell. One hundred sixty-eight pathologically confirmed MSA patients, 89 clinically diagnosed MSA patients, and 1,277 control subjects were genotyped for Apolipoprotein E. Human oligodendrocyte cell lines were incubated with α-synuclein and recombinant human apolipoprotein E, with internalized α-synuclein imaged by confocal microscopy and cells analyzed by flow cytometry. No significant association with risk of MSA or was observed for either Apolipoprotein E ɛ2 or ɛ4. α-Synuclein burden was also not associated with Apolipoprotein E alleles in the pathologically confirmed patients. Interestingly, in our cell assays, apolipoprotein E ɛ4 significantly reduced α-synuclein uptake in the oligodendrocytic cell line. Despite differential effects of apolipoprotein E isoforms on α-synuclein uptake in a human oligodendrocytic cell, we did not observe a significant association at the Apolipoprotein E locus with risk of MSA or α-synuclein pathology. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

  9. Influence of apolipoprotein-E gene on lipid profile, physical activity and body fat relationship. DOI:10.5007/1980-0037.2012v14n2p221

    Directory of Open Access Journals (Sweden)

    Thales Boaventura Rachid Nascimento

    2012-02-01

    Full Text Available Physical activity and body fat modify lipemia, and this effect seems to be influenced by apolipoprotein-E (APOE gene polymorphism. Thus, the purpose of this article was to review main results of studies that have analyzed the relation of APOE gene with physical activity and body fat on triglycerides, total cholesterol and low (LDL and high density lipoprotein (HDL concentrations. The Scientific Electronic Library Online – SciELO, Web of Science and PubMed database were used to locate the articles. The keywords used in combination were: apoe genotype, apolipoprotein-E polymorphism, physical exercise, physical activity, aerobic exercise, body fat and obesity. Originals scientific investigations performed with humans were included, and excluded those ones which involved samples with diseases, except obesity and/or lipemic disorders. It was observed a trend, that ε2 allele carriers are the ones with the greater improvements on lipemia from physical exercise. In addition, the body fat impact on the elevation of triglycerides and LDL are stronger in carriers of the ε2 and ε4 allele, respectively. Considering the small number of originals scientific investigations and their divergent results, reliable inferences can not be made about the APOE gene polymorphism influences on physical activity and body fat effect on lipemia. Thus, further studies with others populations and more volunteers for allele, as well as others exercise modalities and intensities, are necessary.

  10. THE ESSENTIAL E. COLI APOLIPOPROTEIN N-ACYLTRANSFERASE (LNT) EXISTS AS AN EXTRACYTOPLASMIC THIOESTER ACYL-ENZYME INTERMEDIATE‡

    OpenAIRE

    Buddelmeijer, Nienke; Young, Ry

    2010-01-01

    Escherichia coli apolipoprotein N-acyltransferase (Lnt) transfers an acyl group from sn-1-glycerolphospholipid to the free α-amino group of the N-terminal cysteine of apolipoproteins, resulting in mature triacylated lipoprotein. Here we report that the Lnt reaction proceeds through an acyl enzyme intermediate in which a palmitoyl group forms a thioester bond with the thiol of active site residue C387 that was cleaved by neutral hydroxylamine. Lnt(C387S) also formed a fatty acyl intermediate t...

  11. Lipoprotein(a)

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    1995-01-01

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

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

    DEFF Research Database (Denmark)

    Kamstrup, P.R.

    2010-01-01

    and animal studies in support of pathophysiological effects of the risk factor, and preferably evidence from randomized clinical trials documenting reduced morbidity in response to interventions targeting the risk factor. Elevated and in particular extreme lipoprotein(a) levels have in prospective studies...... atherosclerosis and thrombosis, including accumulation of lipoprotein(a) in atherosclerotic plaques and attenuation of t-PA mediated plasminogen activation. No randomized clinical trial of the effect of lowering lipoprotein(a) levels on IHD prevention has ever been conducted. Lacking evidence from randomized...... clinical trials, genetic studies, such as Mendelian randomization studies, can also support claims of causality. Levels of lipoprotein(a) are primarily determined by variation in the LPA gene coding for the apolipoprotein(a) moiety of lipoprotein(a), and genetic epidemiologic studies have documented...

  14. The Association between Apolipoprotein A-II and Metabolic Syndrome in Korean Adults: A Comparison Study of Apolipoprotein A-I and Apolipoprotein B

    Directory of Open Access Journals (Sweden)

    Dong Won Yi

    2012-02-01

    Full Text Available BackgroundApolipoprotein A-II (apoA-II is the second-most abundant apolipoprotein in human high-density lipoprotein and its role in cardio metabolic risk is not entirely clear. It has been suggested to have poor anti-atherogenic or even pro-atherogenic properties, but there are few studies on the possible role of apoA-II in Asian populations. The aim of this study is to evaluate the role of apoA-II in metabolic syndrome (MetS compared with apolipoprotein A-I (apoA-I and apolipoprotein B (apoB in Korean adults.MethodsWe analyzed data from 244 adults who visited the Center for Health Promotion in Pusan National University Yangsan Hospital for routine health examinations.ResultsThe mean apoB level was significantly higher, and the mean apoA-I level was significantly lower, in MetS; however, there was no significant difference in apoA-II levels (30.5±4.6 mg/dL vs. 31.2±4.6 mg/dL, P=0.261. ApoA-II levels were more positively correlated with apoA-I levels than apoB levels. ApoA-II levels were less negatively correlated with homocysteine and high sensitivity C-reactive protein levels than apoA-I levels. The differences in MetS prevalence from the lowest to highest quartile of apoA-II were not significant (9.0%, 5.7%, 4.9%, and 6.6%, P=0.279. The relative risk of the highest quartile of apoA-II compared with the lowest quartile also was not significantly different (odds ratio, 0.96; 95% confidence interval, 0.95 to 1.04; P=0.956.ConclusionCompared with apoA-I (negative association with MetS and apoB (positive association with MetS levels, apoA-II levels did not show any association with MetS in this study involving Korean adults. However, apoA-II may have both anti-atherogenic and pro-atherogenic properties.

  15. Plasma lipid oxidation predicts atherosclerotic status better than cholesterol in diabetic apolipoprotein E deficient mice

    DEFF Research Database (Denmark)

    Petersen, Karen Ekkelund; Lykkesfeldt, Jens; Raun, Kirsten

    2017-01-01

    Increased levels of oxidative stress have been suggested to play a detrimental role in the development of diabetes-related vascular complications. Here, we investigated whether the concentration of malondialdehyde, a marker of lipid oxidation correlated to the degree of aortic plaque lesions...... in a proatherogenic diabetic mouse model. Three groups of apolipoprotein E knockout mice were studied for 20 weeks, a control, a streptozotocin-induced diabetic, and a diabetic enalapril-treated group. Enalapril was hypothesized to lower oxidative stress level and thus the plaque burden. Both diabetic groups were...... significantly different from the control group as they had higher blood glucose, HbA1c, total cholesterol, low-density lipoprotein, very low-density lipoprotein, together with a lower high-density lipoprotein concentration and body weight. Animals in the diabetic group had significantly higher plaque area...

  16. Monoclonal antibodies to apolipoprotein AI: generation and characterization.

    Science.gov (United States)

    Falero, G; Rodriguez, I; Rojas, A

    1993-01-01

    BALB/c mice were immunized with apolipoprotein (apo AI)--high density lipoprotein (HDL) conjugate. By polyethylene glycol-induced fusion of isolated spleen cells with the myeloma cell line P3 X63 Ag8 6.5.3, three different hybridomas were obtained and characterized. Two of them were found to secrete antibodies of the IgG2a subclass, whereas the third produced antibodies of the IgG1 type. Binding capacities to 125I-apo AI and 125I-HDL were higher than 90% in all cases. The isolated antibodies recognize independent epitopes on the apo AI molecule and bind isolated HDL and serum-HDL with different affinities.

  17. Serum concentrations of cholesterol, apolipoprotein A-I and apolipoprotein B in a total of 1694 meat-eaters, fish-eaters, vegetarians and vegans.

    Science.gov (United States)

    Bradbury, K E; Crowe, F L; Appleby, P N; Schmidt, J A; Travis, R C; Key, T J

    2014-02-01

    The objective of this study was to describe serum lipid concentrations, including apolipoproteins A-I and B, in different diet groups. A cross-sectional analysis of a sample of 424 meat-eaters, 425 fish-eaters, 423 vegetarians and 422 vegans, matched on sex and age, from the European Prospective Investigation into Cancer and Nutrition-Oxford cohort. Serum concentrations of total, and high-density lipoprotein (HDL) cholesterol, as well as apolipoproteins A-I and B were measured, and serum non-HDL cholesterol was calculated. Vegans had the lowest body mass index (BMI) and the highest and lowest intakes of polyunsaturated and saturated fat, respectively. After adjustment for age, alcohol and physical activity, compared with meat-eaters, fish-eaters and vegetarians, serum concentrations of total and non-HDL cholesterol and apolipoprotein B were significantly lower in vegans. Serum apolipoprotein A-I concentrations did not differ between the diet groups. In males, the mean serum total cholesterol concentration was 0.87 mmol/l lower in vegans than in meat-eaters; after further adjustment for BMI this difference was 0.76 mmol/l. In females, the difference in total cholesterol between these two groups was 0.6 mmol/l, and after further adjustment for BMI was 0.55 mmol/l. [corrected]. In this study, which included a large number of vegans, serum total cholesterol and apolipoprotein B concentrations were lower in vegans compared with meat-eaters, fish-eaters and vegetarians. A small proportion of the observed differences in serum lipid concentrations was explained by differences in BMI, but a large proportion is most likely due to diet.

  18. 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.

  19. The multiligand α2-macroglobulin receptor/low density lipoprotein receptor-related protein

    DEFF Research Database (Denmark)

    Gliemann, Jørgen; Nykjær, Anders; Petersen, Claus Munck

    1994-01-01

    ), was cloned by Herz et al. in 1988.'Evidence was provided demonstrating that LRP can function as a receptor for chylomicron remnants@-migrating very low density lipoproteins (P-VLDL) rich in apolipoprotein E (apoE)?' The a2-macroglobulin (a2M) receptor (a2MR) was purified from rat livep and human p l a~e n t...

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

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

    Science.gov (United States)

    Stieb, Stefanie; Hoeger, Ulrich; Schenk, Sven

    2008-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Cornish Marion L

    2007-12-01

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

  3. Suppressive effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Natsume, Midori; Baba, Seigo

    2014-01-01

    Previous studies in humans have shown that the cacao polyphenols, (-)-epicatechin and its oligomers, prevent in vitro and ex vivo low-density lipoprotein oxidation mediated by free radical generators and metal ions and also reduce plasma LDL-cholesterol levels. The aim of this study was to examine the effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice. Mice aged 8 weeks (n = 90) were randomized into three groups, and fed either normal mouse chow (controls) or chow supplemented with 0.25 or 0.40 % cacao polyphenols for 16 weeks. The mean plaque area in cross-sections of the brachiocephalic trunk was measured and found to be lower in the 0.25 % cacao polyphenol group than in the control group (p cacao polyphenol group (p cacao polyphenols inhibit the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice by reducing oxidative stress and inflammatory responses.

  4. Palm and partially hydrogenated soybean oils adversely alter lipoprotein profiles compared with soybean and canola oils in moderately hyperlipidemic subjects.

    Science.gov (United States)

    Vega-López, Sonia; Ausman, Lynne M; Jalbert, Susan M; Erkkilä, Arja T; Lichtenstein, Alice H

    2006-07-01

    Partially hydrogenated fat has an unfavorable effect on cardiovascular disease risk. Palm oil is a potential substitute because of favorable physical characteristics. We assessed the effect of palm oil on lipoprotein profiles compared with the effects of both partially hydrogenated fat and oils high in monounsaturated or polyunsaturated fatty acids. Fifteen volunteers aged > or =50 y with LDL cholesterol > or =130 mg/dL were provided with food for each of 4 diets (35 d/phase) varying in type of fat (partially hydrogenated soybean, soybean, palm, or canola; two-thirds fat, 20% of energy). Plasma fatty acid profiles, lipids, lipoproteins, apolipoprotein A-I, apolipoprotein B, lipoprotein(a), glucose, insulin, HDL subfractions, and indicators of lipoprotein metabolism (HDL-cholesterol fractional esterification rate, cholesteryl ester transfer protein, phospholipid transfer protein, and paraoxonase activities) were measured at the end of each phase. Plasma fatty acid profiles reflected the main source of dietary fat. Partially hydrogenated soybean and palm oils resulted in higher LDL-cholesterol concentrations than did soybean (12% and 14%, respectively; P oils. Apolipoprotein B (P palm oil compared with the other dietary fats. HDL3 cholesterol was higher after palm oil than after partially hydrogenated and soybean oils (P Palm and partially hydrogenated soybean oils, compared with soybean and canola oils, adversely altered the lipoprotein profile in moderately hyperlipidemic subjects without significantly affecting HDL intravascular processing markers.

  5. Cacao polyphenols influence the regulation of apolipoprotein in HepG2 and Caco2 cells.

    Science.gov (United States)

    Yasuda, Akiko; Natsume, Midori; Osakabe, Naomi; Kawahata, Keiko; Koga, Jinichiro

    2011-02-23

    Cocoa powder is rich in polyphenols, such as catechins and procyanidins, and has been shown to inhibit low-density lipoprotein (LDL) oxidation and atherogenesis in a variety of models. Human studies have also shown daily intake of cocoa increases plasma high-density lipoprotein (HDL) and decreases LDL levels. However, the mechanisms responsible for these effects of cocoa on cholesterol metabolism have yet to be fully elucidated. The present study investigated the effects of cacao polyphenols on the production of apolipoproteins A1 and B in human hepatoma HepG2 and intestinal Caco2 cell lines. The cultured HepG2 cells or Caco2 cells were incubated for 24 h in the presence of cacao polyphenols such as (-)-epicatechin, (+)-catechin, procyanidin B2, procyanidin C1, and cinnamtannin A2. The concentration of apolipoproteins in the cell culture media was quantified using an enzyme-linked immunoassay, and the mRNA expression was quantified by RT-PCR. Cacao polyphenols increased apolipoprotein A1 protein levels and mRNA expression, even though apolipoprotein B protein and the mRNA expression were slightly decreased in both HepG2 cells and Caco2 cells. In addition, cacao polyphenols increased sterol regulatory element binding proteins (SREBPs) and activated LDL receptors in HepG2 cells. These results suggest that cacao polyphenols may increase the production of mature form SREBPs and LDL receptor activity, thereby increasing ApoA1 and decreasing ApoB levels. These results elucidate a novel mechanism by which HDL cholesterol levels become elevated with daily cocoa intake.

  6. [Fundamental evaluation of apolipoprotein B-48 by chemiluminescence enzyme immunoassay--identification of apolipoprotein B-48 with immunoblotting].

    Science.gov (United States)

    Sato, Itsuko; Fujioka, Yoshio; Hayashi, Fujio; Mukai, Masahiko; Kawano, Seiji; Ishikawa, Yuichi; Yamashita, Shizuya; Kumagai, Shunichi

    2007-06-01

    Apolipoprotein B-48 (apo B-48) is a constituent of chylomicrons and chylomicron remnants, and its fasting concentration has been reported to be a marker of postprandial hyperlipidemia, which is thought to be a risk factor of atherosclerosis. We evaluated the serum apo B-48 concentrations by chemiluminescence enzyme immunoassay (CLEIA), which was recently introduced as Lumipulse f fully automated immunosaasy analyzer by Fujirebio Inc (Tokyo, Japan), and performed immunoblotting on agarose gel electrophoresis with anti-apo B-48 antibody. Apo B-48 assay was intra-assay reproducible (CVs: 1.9-3.1%) and inter-assay reproducible (CVs: 2.2-4.4%). The assay range for apo B-48 was from 0.2 to 40.0 microg/ml. The effects of interfering substances such as free/conjugated birirubin, hemoglobin, Intrafat, ascorbic acid and rheumatoid factor were negligible. For storage, it was preferable to freeze, and to avoid frozen-thaw process as much as possible. Anti-apo B-48 antibody was reactive over a wide range from origin to the position of very-low-density lipoproteins in immunoblotting after agarose gel electrophoresis. Apo B-48 measurement by CLEIA was feasible to clinical use for the assessment of lipoprotein metabolism.

  7. Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders.

    Science.gov (United States)

    Mahley, Robert W

    2016-07-01

    Apolipoprotein (apo) E was initially described as a lipid transport protein and major ligand for low density lipoprotein (LDL) receptors with a role in cholesterol metabolism and cardiovascular disease. It has since emerged as a major risk factor (causative gene) for Alzheimer's disease and other neurodegenerative disorders. Detailed understanding of the structural features of the three isoforms (apoE2, apoE3, and apoE4), which differ by only a single amino acid interchange, has elucidated their unique functions. ApoE2 and apoE4 increase the risk for heart disease: apoE2 increases atherogenic lipoprotein levels (it binds poorly to LDL receptors), and apoE4 increases LDL levels (it binds preferentially to triglyceride-rich, very low density lipoproteins, leading to downregulation of LDL receptors). ApoE4 also increases the risk for neurodegenerative diseases, decreases their age of onset, or alters their progression. ApoE4 likely causes neurodegeneration secondary to its abnormal structure, caused by an interaction between its carboxyl- and amino-terminal domains, called domain interaction. When neurons are stressed or injured, they synthesize apoE to redistribute cholesterol for neuronal repair or remodeling. However, because of its altered structure, neuronal apoE4 undergoes neuron-specific proteolysis, generating neurotoxic fragments (12-29 kDa) that escape the secretory pathway and cause mitochondrial dysfunction and cytoskeletal alterations, including tau phosphorylation. ApoE4-associated pathology can be prevented by small-molecule structure correctors that block domain interaction by converting apoE4 to a molecule that resembles apoE3 both structurally and functionally. Structure correctors are a potential therapeutic approach to reduce apoE4 pathology in both cardiovascular and neurological disorders.

  8. Plasma apolipoprotein M responses to statin and fibrate administration in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Kappelle, Paul J W H; Ahnström, Josefin; Dikkeschei, Bert D

    2010-01-01

    by statin or fibrate administration in patients with diabetes mellitus. Methods: Fourteen type 2 diabetic patients participated in a placebo-controlled crossover study which included three 8-week treatment periods with simvastatin (40mg daily), bezafibrate (400mg daily), and their combination. Results: Apo......M was decreased by 7% in response to simvastatin (P administration. Plasma apoM concentrations correlated positively with apoB-containing lipoprotein measures at baseline and during placebo (P

  9. 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.

  10. Caffeine Increases Apolipoprotein A-1 and Paraoxonase-1 but not Paraoxonase-3 Protein Levels in Human-Derived Liver (HepG2) Cells.

    Science.gov (United States)

    Sayılan Özgün, Gülben; Özgün, Eray; Tabakçıoğlu, Kıymet; Süer Gökmen, Selma; Eskiocak, Sevgi; Çakır, Erol

    2017-12-01

    Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 are antioxidant and anti-atherosclerotic structural high-density lipoprotein proteins that are mainly synthesized by the liver. No study has ever been performed to specifically examine the effects of caffeine on paraoxonase enzymes and on liver apolipoprotein A-1 protein levels. To investigate the dose-dependent effects of caffeine on liver apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels. In vitro experimental study. HepG2 cells were incubated with 0 (control), 10, 50 and 200 μM of caffeine for 24 hours. Cell viability was evaluated by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels were measured by western blotting. We observed a significant increase on apolipoprotein A-1 and paraoxonase-1 protein levels in the cells incubated with 50 µM of caffeine and a significant increase on paraoxonase-1 protein level in the cells incubated with 200 µM of caffeine. Our study showed that caffeine does not change paraoxonase-3 protein level, but the higher doses used in our study do cause an increase in both apolipoprotein A-1 and paraoxonase-1 protein levels in liver cells.

  11. In vivo regulation of scavenger receptor BI and the selective uptake of high density lipoprotein cholesteryl esters in rat liver parenchymal and Kupffer cells

    NARCIS (Netherlands)

    Fluiter, K.; van der Westhuijzen, D. R.; van Berkel, T. J.

    1998-01-01

    High density lipoprotein cholesteryl esters (HDL-CE) are selectively taken up by liver parenchymal cells without parallel apolipoprotein uptake. This selective uptake route forms an important step in the so-called reverse cholesterol transport. Scavenger receptor BI (SR-BI) is the only known HDL

  12. Sex steroids and lipoprotein metabolism

    NARCIS (Netherlands)

    Gevers Leuven, J.A.

    1994-01-01

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

  13. 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.

  14. 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

  15. Hypercholesterolemia and apolipoprotein B expression: Regulation by selenium status

    Directory of Open Access Journals (Sweden)

    Bansal Mohinder P

    2005-11-01

    Full Text Available Abstract Background Apolipoprotein B (apoB contains ligand-binding domain for the binding of LDL to LDL-R site, which enables the removal of LDL from circulation. Our recent data showed that selenium (Se is involved in the lipid metabolism. The present study was aimed to understand the effect of Se deficiency (0.02 ppm and selenium supplementation (1 ppm on apoB expression in liver during hypercholesterolemia in male Sprague Dawley rats. Animals were fed with control and high cholesterol diet (2% for 1 and 2 months. ApoB levels by ELISA and protein expression by western blot was done. Hepatic LDL receptor (LDL-R activity (in vivo and mRNA expression by RT-PCR was monitored. Results In selenium deficiency and on high cholesterol diet (HCD feeding apoB levels increased and LDL-R expression decreased significantly after 2 months. On 1 ppm selenium supplementation apoB expression significantly decreased and LDL-R expression increased after 2 months. But after one month of treatment there was no significant change observed in apoB and LDL-R expression. Conclusion So the present study demonstrates that Se deficiency leads to up regulation of apoB expression during experimental hypercholesterolemia. Selenium supplementation upto 1 ppm leads to downregulation of apoB expression. Further, this study will highlight the nutritional value of Se supplementation in lipid metabolism.

  16. Apolipoprotein C-III Levels and Incident Coronary Artery Disease Risk: The EPIC-Norfolk Prospective Population Study.

    Science.gov (United States)

    van Capelleveen, Julian C; Bernelot Moens, Sophie J; Yang, Xiaohong; Kastelein, John J P; Wareham, Nicholas J; Zwinderman, Aeilko H; Stroes, Erik S G; Witztum, Joseph L; Hovingh, G Kees; Khaw, Kay-Tee; Boekholdt, S Matthijs; Tsimikas, Sotirios

    2017-06-01

    Apolipoprotein C-III (apoC-III) is a key regulator of triglyceride metabolism. Elevated triglyceride-rich lipoproteins and apoC-III levels are causally linked to coronary artery disease (CAD) risk. The mechanism(s) through which apoC-III increases CAD risk remains largely unknown. The aim was to confirm the association between apoC-III plasma levels and CAD risk and to explore which lipoprotein subfractions contribute to this relationship between apoC-III and CAD risk. Plasma apoC-III levels were measured in baseline samples from a nested case-control study in the European Prospective Investigation of Cancer (EPIC)-Norfolk study. The study comprised 2711 apparently healthy study participants, of whom 832 subsequently developed CAD. We studied the association of baseline apoC-III levels with incident CAD risk, lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy and inflammatory biomarkers. ApoC-III levels were significantly associated with CAD risk (odds ratio, 1.91; 95% confidence interval, 1.48-2.48 for highest compared with lowest quintile), retaining significance after adjustment for traditional CAD risk factors (odds ratio, 1.47; 95% confidence interval, 1.11-1.94). ApoC-III levels were positively correlated with triglyceride levels, ( r =0.39), particle numbers of very-low-density lipoprotein ( r =0.25), intermediate-density lipoprotein ( r =0.23), small dense low-density lipoprotein ( r =0.26), and high-sensitivity C-reactive protein ( r =0.15), whereas an inverse correlation was observed with large low-density lipoprotein particle number ( r =-0.11), P C-reactive protein. ApoC-III levels are significantly associated with incident CAD risk. Elevated levels of remnant lipoproteins, small dense low-density lipoprotein, and low-grade inflammation may explain this association. © 2017 American Heart Association, Inc.

  17. Heritabilities of Apolipoprotein and Lipid Levels in Three Countries

    NARCIS (Netherlands)

    Beekman, A.J.; Heijmans, B.T.; Martin, N.G.; Pedersen, N.L.; Whitfield, J.B.; DeFaire, U.; van Baal, G.C.M.; Snieder, H.; Vogler, G.P.; Slagboom, P.E.; Boomsma, D.I.

    2002-01-01

    This study investigated the influence of genes and environment on the variation of apolipoprotein and lipid levels, which are important intermediate phenotypes in the pathways toward cardiovascular disease. Heritability estimates are presented, including those for apolipoprotein E and All levels

  18. Different associations of apolipoprotein E polymorphism with metabolic syndrome by sex in an elderly Chinese population.

    Science.gov (United States)

    Tao, Meng Hua; Liu, Jian Wei; LaMonte, Michael J; Liu, Jing; Wang, Lei; He, Yao; Li, Xiao Ying; Wang, Lu Ning; Ye, Ling

    2011-10-01

    The metabolic syndrome (MetS) is characterized by a cluster of metabolic disorders including abnormal lipid and lipoprotein metabolism. Apolipoprotein E (ApoE) is involved in the regulation of the metabolism of cholesterol, lipoproteins, and triglycerides. The common ApoE polymorphism has been found to be associated with cardiovascular disease and diabetes. This study evaluated the ApoE genetic polymorphism and its relation to MetS defined by the modified National Cholesterol Education Program and International Diabetes Federation criteria in a population-based cross-sectional survey of an elderly Chinese population in Beijing, China. Genotypes of 937 men and 1385 women were included in the study. All participants were measured for blood pressure, anthropometric measurements, and fasting concentrations of glucose, triglycerides, cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. We applied a logistic regression model to derive adjusted odds ratios (ORs) and their 95% confidence intervals. In this Chinese population, the ɛ2, ɛ3, and ɛ4 allele frequencies were 8.3%, 83.4%, and 8.3% for men and 8.7%, 82.9%, and 8.4% for women, respectively. In men, concentrations of fasting triglycerides were higher among the APOE2 and E4 subjects; and a lower level of high-density lipoprotein cholesterol was observed in the APOE4 group. There were approximately linear associations of low-density lipoprotein cholesterol levels with APOE genotype groups in both men and women. We observed that the ɛ4 allele was associated with a significantly increased OR of MetS defined by the modified National Cholesterol Education Program criteria in men (OR, 1.75; 95% confidence interval, 1.17-2.63). In summary, our data show that common polymorphism of ApoE gene is associated with the presence of MetS in an elderly Chinese population. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Gil Atzmon

    2006-04-01

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

  20. 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.

  1. Skeletal muscle apolipoprotein B expression reduces muscular triglyceride accumulation

    DEFF Research Database (Denmark)

    Bartels, Emil D; Ploug, Thorkil; Størling, Joachim

    2014-01-01

    Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design....... In this study, we investigated whether expression of a human apoB transgene affects triglyceride accumulation and insulin sensitivity in skeletal muscle in fat fed obese mice. Results. Expression of apoB and MTP mRNA and the human apoB transgene was seen in skeletal muscle of the transgene mice. Human apo......B transgenic mice accumulated 28% less triglycerides in skeletal myocytes after one year of fat-feeding as compared with WT mice (32 ± 5, n = 10 vs. 44 ± 4 nmol/mg ww, n = 13, p = 0.04). Moreover, expression of human apoB in fat-fed mice was associated with 32% (p = 0.02) and 37% (p = 0.01) lower plasma...

  2. Impact of psychological stress on the associations between apolipoprotein E variants and metabolic traits: findings in an American sample of caregivers and controls

    DEFF Research Database (Denmark)

    Kring, Sofia Iqbal; Brummett, Beverly H; Barefoot, John

    2010-01-01

    To examine the association between apolipoprotein E (APOE) gene variants and waist circumference, fasting plasma glucose, serum insulin, serum high-density lipoprotein cholesterol, and serum triglycerides, all metabolic traits known as cardiovascular disease (CVD) endophenotypes, in a population ...... of stressed individuals and controls. Abdominal obesity, insulin resistance, elevated serum lipid concentration, and APOE polymorphisms have been associated with CVD risk. Current evidence supports the hypothesis that gene-environment interactions modulate serum lipid concentrations....

  3. Effects of short-term niacin treatment on plasma lipoprotein concentrations in African green monkeys (Chlorocebus aethiops)

    KAUST Repository

    Chauke, Chesa G.

    2014-01-22

    Niacin is the most effective drug available for raising levels of high-density lipoprotein (HDL) cholesterol. To evaluate its effects on plasma lipid concentrations, the authors administered a low dose of niacin to healthy, adult, female African green monkeys for 3 months. In the treated monkeys, low-density lipoprotein cholesterol concentrations decreased by 43% from baseline, whereas concentrations of HDL cholesterol and apolipoprotein A-I increased by 49% and 34%, respectively. The results suggest that in this primate model, a low dose of niacin can effectively increase concentrations of HDL cholesterol.©2014 Nature America, Inc. All rights reserved.

  4. Laboratory-based assessment of plasma lipids and lipoproteins for the classification of familial hypercholesterolemic and hypertriglyceridemic states.

    Science.gov (United States)

    Demacker, Pierre N M

    2004-02-01

    Laboratory-based coronary heart disease risk assessment classically involves measurement of lipids and lipoproteins. In this review, information is provided on the methods commonly used in laboratories for the diagnosis of hyperlipidemia, including aspects of precision and accuracy. The latter, when fulfilled, allows the use of uniform reference values. Special attention is paid to the risk estimation using apolipoprotein B and lipoprotein(a) measurement. The overall aim of this review is to simplify the laboratory-based risk estimation for coronary heart disease and to provide help in interpreting the results for effective prevention and treatment of this complex disease.

  5. Dietary squalene increases high density lipoprotein-cholesterol and paraoxonase 1 and decreases oxidative stress in mice.

    Directory of Open Access Journals (Sweden)

    Clara Gabás-Rivera

    Full Text Available BACKGROUND AND PURPOSE: Squalene, the main hydrocarbon in the unsaponifiable fraction of virgin olive oil, is involved in cholesterol synthesis and it has been reported to own antiatherosclerotic and antiesteatosic effects. However, the squalene's role on lipid plasma parameters and the influence of genotype on this effect need to be addressed. EXPERIMENTAL APPROACHES: Three male mouse models (wild-type, Apoa1- and Apoe- deficient were fed chow semisynthetic diets enriched in squalene to provide a dose of 1 g/kg during 11 weeks. After this period, their plasma parameters and lipoprotein profiles were analyzed. KEY RESULTS: Squalene administration at a dose of 1 g/kg showed decreased reactive oxygen species in lipoprotein fractions independently of the animal background and caused an specific increase in high density lipoprotein (HDL-cholesterol levels, accompanied by an increase in phosphatidylcholine and paraoxonase 1 and no changes in apolipoproteins A1 and A4 in wild-type mice. In these mice, the cholesterol increase was due to its esterified form and associated with an increased hepatic expression of Lcat. These effects were not observed in absence of apolipoprotein A1. The increases in HDL- paraoxonase 1 were translated into decreased plasma malondialdehyde levels depending on the presence of Apolipoprotein A1. CONCLUSIONS AND IMPLICATIONS: Dietary squalene promotes changes in HDL- cholesterol and paraoxonase 1 and decreases reactive oxygen species in lipoproteins and plasma malondialdehyde levels, providing new benefits of its intake that might contribute to explain the properties of virgin olive oil, although the phenotype related to apolipoproteins A1 and E may be particularly relevant.

  6. Apolipoprotein gene variants and susceptibility to essential ...

    African Journals Online (AJOL)

    Apolipoprotein gene variants and susceptibility to essential hypertension in Cameroon. ... Results: Whereas advanced age, SBP, DBP, lack of exercise and family history constituted risk factors of EH, sex, body mass index (BMI), Fasting blood sugar (FBS), lipid profile, smoking, excessive alcohol consumption did not.

  7. Spirochetal Lipoproteins and Immune Evasion

    Science.gov (United States)

    Christodoulides, Alexei; Boyadjian, Ani; Kelesidis, Theodoros

    2017-01-01

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

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  9. Temporal changes in concentrations of lipids and apolipoprotein B among adults with diagnosed and undiagnosed diabetes, prediabetes, and normoglycemia: findings from the National Health and Nutrition Examination Survey 1988–1991 to 2005–2008

    Directory of Open Access Journals (Sweden)

    Ford Earl S

    2013-01-01

    Full Text Available Abstract Background Diabetes is characterized by profound lipid abnormalities. The objective of this study was to examine changes in concentrations of lipids and apolipoprotein B among participants stratified by glycemic status (diabetes, undiagnosed diabetes, prediabetes, and normoglycemia in the United States from 1988–1991 to 2005–2008. Methods We used data from 3202 participants aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES III (1988–1991 and 3949 participants aged ≥20 years from NHANES 2005–2008. Results Among participants of all four groups, unadjusted and adjusted mean concentrations of total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B, but not triglycerides, decreased significantly. Among participants with prediabetes and normoglycemia, unadjusted and adjusted mean concentrations of high-density lipoprotein cholesterol increased significantly. Adjusted mean log-transformed concentrations of triglycerides decreased in adults with undiagnosed diabetes and prediabetes. During 2005–2008, unadjusted concentrations of apolipoprotein B ≥80 mg/dl were observed in 72.8% of participants with diagnosed diabetes, 87.9% of participants with undiagnosed diabetes, 86.6% of participants with prediabetes, and 77.2% of participants with normoglycemia. The unadjusted use of cholesterol-lowering medications rose rapidly, especially among participants with diabetes (from ~1% to ~49%, P Conclusion Lipid profiles of adults with diabetes improved during the approximately 16-year study period. Nevertheless, large percentages of adults continue to have elevated concentrations of apolipoprotein B.

  10. 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.

  11. 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.

  12. Genome-wide search for QTLs for apolipoprotein A-I level in elderly Swedish DZ twins: evidence of female-specific locus on 15q11-13.

    Science.gov (United States)

    Magnusson, Patrik K E; Boman, Marcus; de Faire, Ulf; Perola, Markus; Peltonen, Leena; Pedersen, Nancy L

    2008-09-01

    The effect of genetic variants underlying atherosclerosis is thought to be mediated through intermediate phenotypes such as serum cholesterol levels. Localization of quantitative trait loci influencing levels of serum lipids and (apo)lipoproteins may aid in the search for determinants of susceptibility to atherosclerotic diseases. Since apolipoprotein A-I is the primary protein constituent of high-density lipoprotein, it is considered to be critical for the antiatherogenic effect of high-density lipoproteins. We describe here an effort to map loci influencing apolipoprotein A-I levels. Measurements of apolipoprotein A-I levels and genome scans with more than 1000 microsatellite markers were successfully performed in both members of 501 pairs of fraternal twins from Sweden. Variance component linkage analysis was undertaken to map quantitative trait loci. In the total study sample, two loci showed comparable suggestive evidence of linkage, 6p21-12 (LOD=2.4) and 12q23 (LOD=2.4). Sex-limited analyses revealed significant female-specific linkage at marker D15S156 on 15q11-13 (LOD=4.1). The loci on 12q and 15q in the present study confirm previously reported loci for apolipoprotein A-I, while the peak on chromosome 6p lends further support to a locus influencing several phenotypes related to atherosclerosis. Intriguingly, the presence of genes belonging to the phospholipase A2 superfamily under three out of four observed linkage peaks would lend some support to the view that this group of genes might collectively represent candidates as apolipoprotein A-I level regulators.

  13. Targeting Apolipoproteins in Magnetic Resonance Imaging

    Science.gov (United States)

    Sriram, Renuka; Lagerstedt, Jens O.; Samardzic, Haris; Kreutzer, Ulrike; Petrolova, Jitka; Xie, Hongtao; Kaysen, George A.; Voss, John C.; Desreux, Jean F.; Jue, Thomas

    Maintaining normal physiological homeostasis depends upon a coordinated metabolism of both water-soluble and -insoluble substrates. In humans the body derives these molecules — such as glucose, amino acids, and fatty acids — from complex food matter. Water-soluble substrates can circulate readily in blood, while water-insoluble molecules — such as fatty acid, triacylglycerol, and cholesterol — require ampiphathic carriers to transport them from the site of biosynthesis (liver and intestine) to the target tissue. For fatty acid, albumin serves as the major transporter. For triacylglycerol and cholesterol, however, macromolecular complexes aggregate the hydrophobic molecules into the core and cover the surface with amphiphatic proteins and phospholipids to solubilize the particles in the lymphatic and circulatory systems. These macromolecules belong to a class of proteins, plasma lipoproteins, with specific functions and cellular targets. In the clinic these lipoproteins prognosticate the risk of cardiovascular disease (CVD). Lipoproteins divide usually into five major types: chylomicron, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Each lipoprotein type exhibits characteristic density, size, and composition. As implied in the name, the density varies from the low-density chylomicron (<0.95 g/ml) to the high-density HDL (1.2 g/ml). Size also varies. The chylomicron has the largest diameter (75-1,200 nm), and HDL has the smallest (5-12 nm). The physical property variation arises from each lipoprotein's distinct composition. In a chylomicron, cholesterol, triacylglycerol, and phospholipid predominate and constitute about 90% of the particle. Protein constitutes only about 10%. In contrast, the smaller HDL has less cholesterol, triacylglycerol, and phospholipid (65% of the particle) but more protein (over 30%).

  14. Antiretroviral Effects on Host Lipoproteins Are Associated With Changes in Hepatitis C Virus (HCV) RNA Levels in Human Immunodeficiency Virus/HCV Coinfected Individuals

    Science.gov (United States)

    Naggie, Susanna; Patel, Keyur; Yang, Lan-Yan; Chow, Shein-Chung; Johnson, Victoria; Guyton, John R.; Muir, Andrew J.; Sulkowski, Mark; Hicks, Charles

    2015-01-01

    We evaluated the impact of antiretroviral-induced dyslipidemia on hepatitis C virus (HCV) biogenesis in human immunodeficiency virus (HIV)/HCV coinfected patients. This study used serum samples from antiretroviral-naive HIV/HCV patients initiating their first regimen as part of AIDS Clinical Trials Group study protocols (A5142, A5202). Initiation of antiretrovirals increased most lipoproteins and apolipoproteins. In the multivariable model, changes in apolipoproteins were associated with changes in log10 HCV RNA from baseline to week-24 of therapy. Off-target lipogenic changes need to be considered in the context of liver and other metabolic disease in HIV/HCV patients. PMID:26110167

  15. Genetics of non-conventional lipoprotein fractions

    Science.gov (United States)

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

  16. Apical secretion of apolipoproteins from enterocytes

    DEFF Research Database (Denmark)

    Danielsen, E M; Hansen, Gert Helge; Poulsen, Mona Dam

    1993-01-01

    Synthesis and secretion of apolipoproteins in pig small intestine was studied by pulse-chase labeling of jejunal segments, kept in organ culture. Apo A-1 and apo B-48 were the two major proteins released, constituting 25 and 10%, respectively, of the total amount of labeled protein in the mucosal...... in the soluble fraction, suggesting a basolateral secretion into the intercellular space, and both this accumulation and the release to the medium was prevented by culture at 20 degrees C. The specific radioactivity of apo A-1 and apo B-48 released to the medium was significantly higher than...... that enterocytes release most of their newly made free apo A-1 and a significant portion of apo B-48 by exocytosis via the brush border membrane into the intestinal lumen. Fat absorption reduced apolipoprotein secretion to the medium and induced the formation of chylomicrons, containing apo A-1 at their surface...

  17. Nonfasting lipids, lipoproteins, and apolipoproteins in individuals with and without diabetes

    DEFF Research Database (Denmark)

    Langsted, Anne; Nordestgaard, Børge G

    2011-01-01

    Whether lipid profiles should be collected from fasting or nonfasting individuals is controversial, particularly in the diabetic population. We examined the influence of normal food intake on lipid profiles in diabetic and nondiabetic individuals.......Whether lipid profiles should be collected from fasting or nonfasting individuals is controversial, particularly in the diabetic population. We examined the influence of normal food intake on lipid profiles in diabetic and nondiabetic individuals....

  18. Association of apolipoprotein M with high-density lipoprotein kinetics in overweight-obese men

    DEFF Research Database (Denmark)

    Ooi, Esther M M; Watts, Gerald F; Chan, Dick C

    2009-01-01

    OBJECTIVE: The aim of this study was to investigate associations between plasma apoM concentration and HDL apoA-I and apoA-II kinetics in 60 overweight-obese, insulin resistant men. METHODS: Plasma apoM concentration was determined using a sandwich ELISA with two monoclonal antibodies (CV....01, respectively) and negatively associated with HDL apoA-I and apoA-II fractional catabolic rate (FCR) (r=-0.291, p=0.03 and r=-0.291, p=0.026, respectively). No significant associations were observed between plasma apoM and HDL apoA-I and apoA-II production rate. In multivariate regression models, both plasma...

  19. Effect of Synthetic Truncated Apolipoprotein C-I Peptide on Plasma Lipoprotein Cholesterol in Nonhuman Primates

    Directory of Open Access Journals (Sweden)

    Rampratap S. Kushwaha

    2004-01-01

    Full Text Available The present studies were conducted to determine whether a synthetic truncated apoC-I peptide that inhibits CETP activity in baboons would raise plasma HDL cholesterol levels in nonhuman primates with low HDL levels. We used 2 cynomolgus monkeys and 3 baboons fed a cholesterol- and fat-enriched diet. In cynomolgus monkeys, we injected synthetic truncated apoC-I inhibitor peptide at a dose of 20 mg/kg and, in baboons, at doses of 10, 15, and 20 mg/kg at weekly intervals. Blood samples were collected 3 times a week and VLDL + LDL and HDL cholesterol concentrations were measured. In cynomolgus monkeys, administration of the inhibitor peptide caused a rapid decrease in VLDL + LDL cholesterol concentrations (30%–60% and an increase in HDL cholesterol concentrations (10%–20%. VLDL + LDL cholesterol concentrations returned to baseline levels in approximately 15 days. In baboons, administration of the synthetic inhibitor peptide caused a decrease in VLDL + LDL cholesterol (20%–60% and an increase in HDL cholesterol (10%–20%. VLDL + LDL cholesterol returned to baseline levels by day 21, whereas HDL cholesterol concentrations remained elevated for up to 26 days. ApoA-I concentrations increased, whereas apoE and triglyceride concentrations decreased. Subcutaneous and intravenous administrations of the inhibitor peptide had similar effects on LDL and HDL cholesterol concentrations. There was no change in body weight, food consumption, or plasma IgG levels of any baboon during the study. These studies suggest that the truncated apoC-I peptide can be used to raise HDL in humans.

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

    Science.gov (United States)

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

    2012-01-01

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

  1. 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.

  2. Apolipoprotein A5 in health and disease

    Czech Academy of Sciences Publication Activity Database

    Hubáček, J. A.; Adámková, V.; Vrablík, M.; Kadlecová, Michaela; Zicha, Josef; Kuneš, Jaroslav; Piťha, J.; Suchánek, P.; Poledne, R.

    2009-01-01

    Roč. 58, Suppl.2 (2009), S101-S109 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Grant - others:IKEM(CZ) 00023001; GA MŠk(CZ) MEB060808; GA MZd(CZ) NR8895; GAMZd(CZ) NR9393 Institutional research plan: CEZ:AV0Z50110509 Keywords : apolipoprotein A5 * plasma triglycerides * myocardial infarction Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.430, year: 2009

  3. 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

  4. Phytosterols, Phytostanols, and Lipoprotein Metabolism.

    Science.gov (United States)

    Gylling, Helena; Simonen, Piia

    2015-09-17

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

  5. Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lasrich, Dorothee; Bartelt, Alexander [Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Grewal, Thomas, E-mail: thomas.grewal@sydney.edu.au [Faculty of Pharmacy A15, The University of Sydney, Sydney, NSW 2006 (Australia); Heeren, Joerg, E-mail: heeren@uke.de [Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany)

    2015-09-10

    Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid accumulation and adipogenic differentiation in adipose tissue. However, little is yet known if APOE functions in a similar manner in human adipocytes. This prompted us to compare lipid loading and expression of adipocyte differentiation markers in APOE-deficient and control adipocytes using the differentiated human mesenchymal stem cell line hMSC-Tert as well as primary human and mouse adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with or without siRNA targeting APOE while murine adipocytes were isolated from wild type and Apoe knockout mice. Human APOE knockdown hMSC-Tert adipocytes accumulated markedly less triglycerides compared to control cells. This correlated with strongly decreased gene expression levels of adipocyte markers such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as the key transcription factor driving adipocyte differentiation, peroxisome proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform. Similarly, differentiation of murine Apoe-deficient adipocytes was characterized by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3-overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL) partially restored triglyceride accumulation, but were unable to induce adipocyte differentiation, as judged by expression of adipocyte markers. Taken together, depletion of endogenous APOE in human adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation. - Highlights: • Immortalized human mesenchymal stem cells were used to study adipocyte development. • Knockdown of endogenous APOE lead to impaired lipid accumulation and adipogenesis. • APOE supplementation partially restored lipid accumulation but not differentiation.

  6. Effects of obesity and body fat distribution on lipids and lipoproteins in nondiabetic American Indians: The Strong Heart Study.

    Science.gov (United States)

    Hu, D; Hannah, J; Gray, R S; Jablonski, K A; Henderson, J A; Robbins, D C; Lee, E T; Welty, T K; Howard, B V

    2000-09-01

    To examine the relationship between obesity and lipoprotein profiles and compare the effects of total obesity and central adiposity on lipids/lipoproteins in American Indians. Participants were 773 nondiabetic American Indian women and 739 men aged 45 to 74 years participating in the Strong Heart Study. Total obesity was estimated using body mass index (BMI). Central obesity was measured as waist circumference. Lipoprotein measures included triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein AI (apoAI), and apolipoprotein B (apoB). Partial and canonical correlation analyses were used to examine the associations between obesity and lipids/ lipoproteins. Women were more obese than men in Arizona (median BMI 32.1 vs. 29.2 kg/m2) and South Dakota and North Dakota (28.3 vs. 28.0 kg/m2), but there was no sex difference in waist circumference. Men had higher apoB and lower apoAI levels than did women. In women, when adjusted for center, gender, and age, BMI was significantly related to HDL cholesterol (r = -0.24, p HDL cholesterol (r = -0.23, p correlated with triglycerides (r = 0.30, p correlated with HDL cholesterol (r = -0.35, p HDL cholesterol decreased with waist circumference (r = -0.36, p correlation analysis, waist circumference received a greater weight (0.86) than did BMI (0.17) in women. However, the canonical weights were similar for waist (0.46) and BMI (0.56) in men. Only HDL cholesterol (-1.02) carried greater weight in women, whereas in men, triglycerides (0.50), and HDL cholesterol (-0.64) carried a large amount of weight. All the correlation coefficients between BMI, waist circumference, and the first canonical variable of lipids/lipoproteins or between the individual lipid/lipoprotein variables and the first canonical variable of obesity were smaller in women than in men. Triglycerides and HDL cholesterol showed clinically meaningful changes with BMI and waist circumference in men. All

  7. Apolipoprotein(a) in insulin-dependent diabetic patients with and without diabetic nephropathy

    DEFF Research Database (Denmark)

    Gall, M A; Rossing, P; Hommel, E

    1992-01-01

    to the increased risk of ischaemic heart disease, apo(a) was determined in 50 insulin-dependent diabetic patients with diabetic nephropathy (group 1), in 50 insulin-dependent diabetic patients with microalbuminuria (group 2), in 50 insulin-dependent diabetic patients with normoalbuminuria (group 3), and in 50......Insulin-dependent diabetic patients with diabetic nephropathy have a highly increased morbidity and mortality from cardiovascular diseases. To determine whether altered levels of apolipoprotein(a) (apo(a)), the glycoprotein of the potentially atherogenic lipoprotein(a) (Lp(a)), contribute...... healthy subjects (group 4). The groups were matched with regard to sex, age and body mass index. The diabetic groups were also matched with regard to diabetes duration. The level of apo(a) was approximately the same in the four groups, being: 122 (x/ divided by 4.2) U l-1, 63 (x/ divided by 4.4) U l-1...

  8. Post-transcriptional regulation of lipoprotein receptors by the E3-ubiquitin ligase inducible degrader of the low-density lipoprotein receptor.

    Science.gov (United States)

    Sorrentino, Vincenzo; Zelcer, Noam

    2012-06-01

    The hepatic low-density lipoprotein receptor (LDLR) pathway is essential for clearing circulating LDL and is an important therapeutic target for treating cardiovascular disease. Abundance of the LDLR is subject to both transcriptional and nontranscriptional control. Here, we highlight a new post-transcriptional mechanism for controlling LDLR function via ubiquitination of the receptor by the E3-ubiquitin ligase inducible degrader of the LDLR (IDOL). IDOL is a recently identified transcriptional target of the liver X receptors. Acting as an E3-ubiquitin ligase IDOL promotes ubiquitination of the LDLR, thereby marking it for lysosomal degradation. The determinants required for degradation of the LDLR by IDOL have been largely identified. IDOL also targets two related lipoprotein receptors, the very low-density lipoprotein receptor and apolipoprotein E receptor 2. Despite several similarities, the IDOL, and PCSK9 pathways for controlling LDLR abundance seem independent of each other. Genome-wide association studies have recently identified IDOL as a locus influencing variability in circulating levels of LDL, thereby highlighting the possible role of IDOL in human lipoprotein metabolism. Transcriptional induction of IDOL by liver X receptor defines a new post-transcriptional pathway for controlling LDLR abundance and LDL uptake independent of sterol regulatory element binding proteins. Targeting IDOL activity may offer a novel therapeutic approach complementary to statins for treating cardiovascular disease.

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

    Science.gov (United States)

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

    2014-01-01

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

  10. 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.

  11. Apolipoprotein C3 polymorphisms, cognitive function and diabetes in Caribbean origin Hispanics.

    Directory of Open Access Journals (Sweden)

    Caren E Smith

    Full Text Available Apolipoprotein C3 (APOC3 modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired glucose metabolism are linked to cognitive decline, and all three conditions may decrease lifespan. Associations between apolipoprotein C3 (APOC3 gene polymorphisms and impaired lipid and glucose metabolism are well-established, but potential connections between APOC3 polymorphisms, cognitive decline and diabetes deserve further attention.We examined whether APOC3 single nucleotide polymorphisms (SNPs m482 (rs2854117 and 3u386 (rs5128 were related to cognitive measures, whether the associations between cognitive differences and genotype were related to metabolic differences, and how diabetes status affected these associations. Study subjects were Hispanics of Caribbean origin (n = 991, aged 45-74 living in the Boston metropolitan area.Cognitive and metabolic measures differed substantially by type II diabetes status. In multivariate regression models, APOC3 m482 AA subjects with diabetes exhibited lower executive function (P = 0.009, Stroop color naming score (P = 0.014 and Stroop color-word score (P = 0.022 compared to AG/GG subjects. APOC3 m482 AA subjects with diabetes exhibited significantly higher glucose (P = 0.032 and total cholesterol (P = 0.028 compared to AG/GG subjects. APOC3 3u386 GC/GG subjects with diabetes exhibited significantly higher triglyceride (P = 0.004, total cholesterol (P = 0.003 and glucose (P = 0.016 compared to CC subjects.In summary, we identified significant associations between APOC3 polymorphisms, impaired cognition and metabolic dysregulation in Caribbean Hispanics with diabetes. Further research investigating these relationships in other populations is warranted.

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

    Directory of Open Access Journals (Sweden)

    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

  13. 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

  14. Association of four apolipoprotein B polymorphisms with lipid profile ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 91; Issue 1. Association of four apolipoprotein B polymorphisms with lipid profile and stenosis in Tunisian coronary patients. Rebhi Lamia Omezzine Asma Kacem Slim Rejeb Jihène ... Keywords. apolipoprotein B; coronary artery disease; Gensini score; haplotype; lipid; stenosis.

  15. Laryngeal Presentation of Systemic Apolipoprotein A-I-Derived Amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Aldert J. C.; Dikkers, Frederik G.; Hawkins, Philip N.; Bijzet, Johan; Rowczenio, Dorota; Gilbertson, Janet; Posthumus, Marcel D.; Leijsma, Martha K.; Hazenberg, Bouke P. C.

    Objective: To study the clinical and pathological characteristics of two patients with laryngeal apolipoprotein A-I (apoA-I)-derived (AApoAI) amyloidosis with the apolipoprotein A-I variants Leu174Ser and Leu178Pro, respectively. The latter variant has not been associated with amyloid before. Study

  16. Apolipoprotein CI knock-out mice display impaired memory functions

    NARCIS (Netherlands)

    Berbée, J.F.P.; Abildayeva, K.; Blokland, A.; Jansen, P.J.; Lütjohann, D.; Gautier, T.; Sijbrands, E.; Prickaerts, J.; Hadfoune, M.; Ramaekers, F.C.S.; Kuipers, F.; Rensen, P.C.N.

    2011-01-01

    The e4 allele of apolipoprotein E (APOE4), which is a well established genetic risk factor for development of Alzheimer's disease (AD), is in genetic disequilibrium with the H2 allele of apolipoprotein C1 (APOC1), giving rise to increased expression of apoC-I. This raises the possibility that the H2

  17. Apolipoprotein CI Knock-Out Mice Display Impaired Memory Functions

    NARCIS (Netherlands)

    Berbee, Jimmy F. P.; Vanmierlo, Tim; Abildayeva, Karlygash; Blokland, Arjan; Jansen, Paula J.; Luetjohann, Dieter; Gautier, Thomas; Sijbrands, Eric; Prickaerts, Jos; Hadfoune, M'hamed; Ramaekers, Frans C. S.; Kuipers, Folkert; Rensen, Patrick C. N.; Mulder, Monique

    2011-01-01

    The epsilon 4 allele of apolipoprotein E (APOE4), which is a well established genetic risk factor for development of Alzheimer's disease (AD), is in genetic disequilibrium with the H2 allele of apolipoprotein C1 (APOC1), giving rise to increased expression of apoC-I. This raises the possibility that

  18. The common polymorphism of apolipoprotein E

    DEFF Research Database (Denmark)

    Gerdes, Ulrik

    2003-01-01

    Apolipoprotein E (apoE) has important functions in systemic and local lipid transport, but also has other functions. The gene (APOE) shows a common polymorphism with three alleles--APOE*2, APOE*3, and APOE*4. Their frequencies vary substantially around the world, but APOE*3 is the most common...... from only 10-15% in southern Europe to 40-50% in the north. The gradient may be a trace of the demic expansion of agriculture that began about 10,000 years ago, but it may also reflect the possibility that APOE*4 carriers are less likely to develop vitamin D deficiency. The common APOE polymorphism...

  19. Apolipoproteins modulate the inflammatory response to lipopolysaccharide

    NARCIS (Netherlands)

    Berbée, J.F.P.; Havekes, L.M.; Rensen, P.C.N.

    2005-01-01

    An increasing body of evidence demonstrates a close interplay between lipoprotein metabolism and sepsis. Sepsis results in an increase of plasma triglycerides within VLDL as a consequence of an enhanced hepatic VLDL production and/or inhibited peripheral and hepatic VLDL clearance. In contrast,

  20. 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.

  1. Embryo lipoproteins and yolk lipovitellin consumption during embryogenesis in Macrobrachium borellii (Crustacea: Palaemonidae).

    Science.gov (United States)

    García, F; Cunningham, M L; Garda, H; Heras, H

    2008-11-01

    The prawn Macrobrachium borellii has lecithotrophic eggs with highly-abbreviated development. The major yolk component is lipovitellin (LV), a lipoprotein with 30% lipids (by weight). LV consumption during embryogenesis was followed by ELISA and Western blot analysis using an anti-LV polyclonal antibody. No cross-reacting proteins were observed and LV-like lipoproteins were strongly recognized by the antibody in hemolymph (vitellogenin), yolk (LV) and embryos (LVe), as determined by Western Blot analysis. LV decreased significantly along development from 9.4 to 1.1 microg/mg egg. Consumption rate of LV was slow in early embryogenesis, followed by a rapid utilization in late embryonic stages. Significant LVe amounts were still present at hatching. LV apolipoproteins were selectively degraded during embryo development, being the highest molecular weight subunit the most affected. Comparison among in vitro, in vivo and theoretical proteolysis suggested that trypsin may be involved in LV degradation during late embryogenesis. Embryo lipoprotein (HDLe) synthesis was first detected at stage 6. HDLe shared the same density, MW and subunit composition as adult hemolymph HDL(1) and did not cross-react with LV-like lipoproteins. Though expressed at low concentration, it fulfilled embryo needs for lipid transport among organs.

  2. IQ, educational attainment, memory and plasma lipids: associations with apolipoprotein E genotype in 5995 children.

    Science.gov (United States)

    Taylor, Amy E; Guthrie, Philip A I; Smith, George Davey; Golding, Jean; Sattar, Naveed; Hingorani, Aroon D; Deanfield, John E; Day, Ian N M

    2011-07-15

    Apolipoprotein E (APOE) genotype (ε2/ε3/ε4: rs429358 ε4 allele; rs7412 ε2 allele) is strongly associated with both lipid levels and Alzheimer's disease. Although there is also evidence of milder cognitive impairment in later life in carriers of the APOE ε4 allele, there have been few studies investigating the impact of APOE genotype on cognitive function in children. We determined APOE genotype in 5995 children from the Avon Longitudinal Study of Parents and Children and investigated associations between APOE genotype and plasma lipids (at age 9), IQ (at age 8), memory (at ages 8 and 10), and performance in school attainment tests (at ages 7, 11, and 14). Observed genotype group counts were consistent with Hardy-Weinberg equilibrium (χ(2)p value = .84). There were strong relationships between APOE genotype and low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides, which follow the same patterns as in adults. There was no strong evidence to suggest that APOE genotype was associated with IQ (all p values ≥ .46), memory function (p ≥ .35), or school attainment test results (p ≥ .28). Although APOE genotype does have strong associations with lipid levels in childhood, there does not seem to be meaningful effects on cognitive performance, suggesting that any detrimental effects of the ε4 allele on cognitive function are not important until later life. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Intermittent cold stress enhances features of atherosclerotic plaque instability in apolipoprotein E‑deficient mice.

    Science.gov (United States)

    Zheng, Xi; Wang, Qiang; Zhang, Yan; Yang, Dachun; Li, De; Tang, Bing; Li, Xiuchuan; Yang, Yongjian; Ma, Shuangtao

    2014-10-01

    The cold weather is associated with an increased occurrence of acute coronary events. However, the mechanisms underlying cold‑induced myocardial infarctions have not yet been fully elucidated. In the present study, 20 male, eight week‑old, apolipoprotein E (ApoE)‑deficient mice were subjected to either control conditions or intermittent cold exposure for eight weeks. Mice in the cold group were placed in a cold room at 4˚C for 4 h per day, while the mice in the control group were kept in a room at 24˚C. Cold‑exposed mice did not significantly differ from control mice in body weight, fasting glucose concentration and plasma lipid levels, including triglyceride, total cholesterol, low‑density lipoprotein and high‑density lipoprotein. The hematoxylin and eosin‑stained sections of the aortic root demonstrated increased plaque size in the cold group compared with the control group (Pinstability. Additionally, the protein expression of matrix metalloproteinase (MMP)‑2, MMP‑9 and MMP‑14 were significantly increased (Pinstability in ApoE‑deficient mice by altering the balance of MMPs and TIMPs. These findings may provide mechanistic insights into sudden cardiac death in cold environments.

  4. Mechanism of lipid lowering in mice expressing human apolipoprotein A5

    Energy Technology Data Exchange (ETDEWEB)

    Fruchart-Najib, Jamila; Bauge, Eric; Niculescu, Loredan-Stefan; Pham, Tatiana; Thomas, Benoit; Rommens, Corinne; Majd, Zouher; Brewer, Bryan; Rubin, Edward M.; Pennacchio, Len A.; Fruchart, Jean-Charles

    2004-01-15

    Recently, we reported that apoAV plays key role in triglycerides lowering. Here, we attempted to determine the mechanism underlying this hypotriglyceridemic effect. We showed that triglyceride turnover is faster in hAPOA5 transgenic compared to wild type mice. Moreover, both apoB and apoCIII are decreased and LPL activity is increased in postheparin plasma of hAPOA5 transgenic mice. These data suggest a decrease in size and number of VLDL. To further investigate the mechanism of hAPOA5 in hyperlipidemic background, we intercrossed hAPOA5 and hAPOC3 transgenic mice. The effect resulted in a marked decreased of VLDL triglyceride, cholesterol, apolipoproteins B and CIII. In postprandial state, the triglyceride response is abolished in hAPOA5 transgenic mice. We demonstrated that in response to the fat load in hAPOA5XhAPOC3 mice, apoAV shifted from HDL to VLDL, probably to limit the elevation of triglycerides. In vitro, apoAV activates lipoprotein lipase. However, apoAV does not interact with LPL but interacts physically with apoCIII. This interaction does not seem to displace apoCIII from VLDL but may induce conformational change in apoCIII and consequently change in its function leading the activation of lipoprotein lipase.

  5. Evolutionary analysis of apolipoprotein E by Maximum Likelihood and complex network methods

    Directory of Open Access Journals (Sweden)

    Leandro de Jesus Benevides

    Full Text Available Abstract Apolipoprotein E (apo E is a human glycoprotein with 299 amino acids, and it is a major component of very low density lipoproteins (VLDL and a group of high-density lipoproteins (HDL. Phylogenetic studies are important to clarify how various apo E proteins are related in groups of organisms and whether they evolved from a common ancestor. Here, we aimed at performing a phylogenetic study on apo E carrying organisms. We employed a classical and robust method, such as Maximum Likelihood (ML, and compared the results using a more recent approach based on complex networks. Thirty-two apo E amino acid sequences were downloaded from NCBI. A clear separation could be observed among three major groups: mammals, fish and amphibians. The results obtained from ML method, as well as from the constructed networks showed two different groups: one with mammals only (C1 and another with fish (C2, and a single node with the single sequence available for an amphibian. The accordance in results from the different methods shows that the complex networks approach is effective in phylogenetic studies. Furthermore, our results revealed the conservation of apo E among animal groups.

  6. Role of apolipoprotein E in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Giau VV

    2015-07-01

    Full Text Available Vo Van Giau,1 Eva Bagyinszky,1 Seong Soo A An,1 SangYun Kim2 1Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Seongnam, South Korea; 2Department of Neurology, Seoul National University College of Medicine in Seoul National Bundang Hospital, Seoul, South Korea Abstract: Apolipoprotein E (APOE is a lipid-transport protein abundantly expressed in most neurons in the central nervous system. APOE-dependent alterations of the endocytic pathway can affect different functions. APOE binds to cell-surface receptors to deliver lipids and to the hydrophobic amyloid-β peptide, regulating amyloid-β aggregations and clearances in the brain. Several APOE isoforms with major structural differences were discovered and shown to influence the brain lipid transport, glucose metabolism, neuronal signaling, neuroinflammation, and mitochondrial function. This review will summarize the updated research progress on APOE functions and its role in Alzheimer’s disease, Parkinson’s disease, cardiovascular diseases, multiple sclerosis, type 2 diabetes mellitus, Type III hyperlipoproteinemia, vascular dementia, and ischemic stroke. Understanding the mutations in APOE, their structural properties, and their isoforms is important to determine its role in various diseases and to advance the development of therapeutic strategies. Targeting APOE may be a potential approach for diagnosis, risk assessment, prevention, and treatment of various neurodegenerative and cardiovascular diseases in humans. Keywords: apolipoprotein E, pathogenesis, diseases

  7. Aerosol preparation of intact lipoproteins

    Science.gov (United States)

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

    2012-01-17

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

  8. Transendothelial lipoprotein exchange and microalbuminuria

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  9. A receptor-based biosensor for lipoprotein docking at the endothelial surface and vascular matrix.

    Science.gov (United States)

    Siegel, G; Malmsten, M; Klüssendorf, D; Michel, F

    2001-12-01

    Proteoheparan sulfate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution, representing a receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques showing that HDL has a high binding affinity to the receptor and a protective effect on interfacial heparan sulfate proteoglycan layers, with respect to LDL and Ca(2+) complexation. LDL was found to deposit strongly at the proteoheparan sulfate, particularly in the presence of Ca(2+), thus creating the complex formation "proteoglycan-low density lipoprotein-calcium". This ternary complex build-up may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. On the other hand, HDL bound to heparan sulfate proteoglycan protected against LDL docking and completely suppressed calcification of the proteoglycan-lipoprotein complex. In addition, HDL and aqueous garlic extract were able to reduce the ternary complex deposition and to disintegrate HS-PG/LDL/Ca(2+) aggregates. Although much remains unclear regarding the mechanism of lipoprotein depositions at proteoglycan-coated surfaces, it seems clear that the use of such systems offers possibilities for investigating lipoprotein deposition at a "nanoscopic" level under close to physiological conditions. In particular, Ca(2+)-promoted LDL deposition and the protective effect of HDL, even at high Ca(2+) and LDL concentrations, agree well with previous clinical observations regarding risk and beneficial factors for early stages of atherosclerosis. Therefore, we believe that the system can be of some use in investigations, e.g. of the interplay between different lipoproteins in arteriosclerotic

  10. [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

  11. Prebeta-migrating high density lipoprotein: quantitation in normal and hyperlipidemic plasma by solid phase radioimmunoassay following electrophoretic transfer

    International Nuclear Information System (INIS)

    Ishida, B.Y.; Frolich, J.; Fielding, C.J.

    1987-01-01

    A quantitative solid phase immunoassay has been developed for the determination of the mass of electrophoretically separated prebeta apolipoprotein A-I (apoA-I) in human plasma. Conditions have been identified for the quantitative transfer and immunoblotting of the apolipoprotein in the absence of organic solvents or detergents. In normolipidemic plasma, the prebeta-migrating fraction of apoA-I represented 4.2 +/- 1.8% of total apoA-I (61 +/- 26 micrograms of apoA-I per ml of plasma). Significantly higher levels were found in hypercholesterolemia of genetic origin, in primary and secondary hypertriglyceridemia, and in congenital lecithin:cholesterol acyltransferase deficiency. In all cases prebeta-migrating apoA-I consisted in large part of low molecular weight lipoprotein species, compared to the size of the major, alpha-migrating apoA-I fraction

  12. Apolipoprotein E polymorphism in Omani dyslipidemic patients with and without coronary artery disease.

    Science.gov (United States)

    Al-Yahyaee, Said Ali S; Ganguly, Shyam Sundar; Al Kindi, Mohammed Nasser; Al-Bahrani, Ali Ihassan

    2007-02-01

    Apolipoprotein E (APOE) polymorphism is a predictor of interindividual variability in plasma levels of lipids and lipoproteins and a predictor of risk of coronary artery disease (CAD). We studied the relationship between APOE polymorphism and lipid profiles and risk of CAD in Omani dyslipidemic patients. This retrospective study included 244 dyslipidemic patients, of whom 67 had CAD. Fasting blood glucose, lipids, and plasma lipoprotein levels were measured using standard methods, and APOE genotypes were detected by PCR-RFLP. The dyslipidemic patients had the following APOE allele frequencies: APOE*2, 0.030; APOE*3, 0.894; and APOE*4, 0.076. APOE allele frequencies between patients with and without CAD showed no significant differences. Compared to APOE*3/*3 homozygotes, APOE*4 allele patients had higher mean levels of low-density lipoprotein (LDL) cholesterol (p = 0.014), apoB (p = 0.031), lower mean levels of apoA1 (p = 0.043), and a trend of higher mean level of total cholesterol (p = 0.084). Thirty-one percent of patients with CAD had the APOE*4 allele compared to 26% with the APOE*3 allele, but this difference was not significant. Compared with APOE*3/*3 homozygotes, patients with the APOE*4 allele had 1.3 times higher risk for CAD after ignoring dyslipidemia, but this risk was modified after adjusting for dyslipidemia. In conclusion, among dyslipidemic patients, carriers of APOE*4 compared to homozygous carriers of APOE*3 had significantly higher levels of LDL cholesterol and apoB, but no relationship with CAD was found.

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

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    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

  14. Intralipid decreases apolipoprotein M levels and insulin sensitivity in rats.

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    Lu Zheng

    Full Text Available BACKGROUND: Apolipoprotein M (ApoM is a constituent of high-density lipoproteins (HDL. It plays a crucial role in HDL-mediated reverse cholesterol transport. Insulin resistance is associated with decreased ApoM levels. AIMS: To assess the effects of increased free fatty acids (FFAs levels after short-term Intralipid infusion on insulin sensitivity and hepatic ApoM gene expression. METHODS: Adult male Sprague-Dawley (SD rats infused with 20% Intralipid solution for 6 h. Glucose infusion rates (GIR were determined by hyperinsulinemic-euglycemic clamp during Intralipid infusion and plasma FFA levels were measured by colorimetry. Rats were sacrificed after Intralipid treatment and livers were sampled. Human embryonic kidney 293T cells were transfected with a lentivirus mediated human apoM overexpression system. Goto-Kakizaki (GK rats were injected with the lentiviral vector and insulin tolerance was assessed. Gene expression was assessed by real-time RT-PCR and PCR array. RESULTS: Intralipid increased FFAs by 17.6 folds and GIR was decreased by 27.1% compared to the control group. ApoM gene expression was decreased by 40.4% after Intralipid infusion. PPARβ/δ expression was not changed by Intralipid. Whereas the mRNA levels of Acaca, Acox1, Akt1, V-raf murine sarcoma 3611 viral oncogene homolog, G6pc, Irs2, Ldlr, Map2k1, pyruvate kinase and RBC were significantly increased in rat liver after Intralipid infusion. The Mitogen-activated protein kinase 8 (MAPK8 was significantly down-regulated in 293T cells overexpressing ApoM. Overexpression of human ApoM in GK rats could enhance the glucose-lowering effect of exogenous insulin. CONCLUSION: These results suggest that Intralipid could decrease hepatic ApoM levels. ApoM overexpression may have a potential role in improving insulin resistance in vivo and modulating apoM expression might be a future therapeutic strategy against insulin resistance in type 2 diabetes.

  15. 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

  16. Effects of apolipoprotein M in uremic atherosclerosis

    DEFF Research Database (Denmark)

    Bosteen, Markus Høybye; Madsen Svarrer, Eva Martha; Bisgaard, Line Stattau

    2017-01-01

    BACKGROUND AND AIMS: Chronic kidney disease is characterized by uremia and causes premature death, partly due to accelerated atherosclerosis. Apolipoprotein (apo) M is a plasma carrier protein for the lipid sphingosine-1-phosphate (S1P). The Apom-S1P complex associates with HDL, and may contribute...... to its anti-atherosclerotic effects. The role of Apom/S1P in atherosclerosis is presently controversial and has not been explored in a uremic setting. We aimed to explore whether plasma concentrations of Apom/S1P are altered by uremia and whether Apom overexpression or deficiency affects classical...... and uremic atherosclerosis. METHODS: Mild to moderate uremia was induced by subtotal nephrectomy (NX) in 86-92 Apoe-deficient mice that were either Apom-wild type, Apom-deficient, or overexpressed Apom (∼10 fold). The effects of uremia on plasma Apom/S1P and atherosclerosis were evaluated and compared to non...

  17. Independent effects of apolipoprotein AV and apolipoprotein CIII on plasma triglyceride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Baroukh, Nadine N.; Bauge, Eric; Akiyama, Jennifer; Chang, Jessie; Fruchart, Jean-Charles; Rubin, Edward M.; Fruchart, Jamila; Pennacchio, Len A.

    2003-08-15

    Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered triglycerides. To overcome these confounding factors and address their relationship, we generated independent lines of mice that either over-expressed (''double transgenic'') or completely lacked (''double knockout'') both apolipoprotein genes. We report that both ''double transgenic'' and ''double knockout'' mice display intermedia tetriglyceride concentrations compared to over-expression or deletion of either gene alone. Furthermore, we find that human ApoAV plasma protein levels in the ''double transgenic'' mice are approximately 500-fold lower than human ApoCIII levels, supporting Apo

  18. Lifestyle and Dietary Determinants of Serum Apolipoprotein A1 and Apolipoprotein B Concentrations: Cross-Sectional Analyses within a Swedish Cohort of 24,984 Individuals

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    Kasper Frondelius

    2017-02-01

    Full Text Available Low serum apolipoprotein (Apo A1 concentrations and high serum ApoB concentrations may be better markers of the risk of cardiovascular disease than high-density lipoprotein (HDL and low-density lipoprotein (LDL. However, the associations between modifiable lifestyle factors and Apo concentrations have not been investigated in detail. Therefore, this study investigated the associations between Apo concentrations and education, lifestyle factors and dietary intake (macronutrients and 34 food groups. These cross-sectional associations were examined among 24,984 individuals in a Swedish population-based cohort. Baseline examinations of the cohort were conducted between 1991 and 1996. Dietary intake was assessed using a modified diet history method. The main determinants of high ApoA1 concentrations (r between 0.05 and 0.25 were high alcohol consumption, high physical activity, non-smoking, and a low body mass index (BMI, and the main determinants of high ApoB concentrations were smoking and a high BMI. The intake of sucrose and food products containing added sugar (such as pastries, sweets, chocolate, jam/sugar and sugar-sweetened beverages was negatively correlated with ApoA1 concentrations and positively correlated with ApoB concentrations and the ApoB/ApoA1 ratio, whereas the intake of fermented dairy products, such as fermented milk and cheese, was positively correlated with ApoA1 concentrations and negatively correlated with the ApoB/ApoA1 ratio. These results indicate that smoking, obesity, low physical activity, low alcohol consumption and a diet high in sugar and low in fermented dairy products are correlated with an unfavorable Apo profile.

  19. Long term effects on human plasma lipoproteins of a formulation enriched in butter milk polar lipid

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    Nilsson Åke

    2009-10-01

    Full Text Available Abstract Background Sphingolipids (SL, in particular sphingomyelin (SM are important components of milk fat polar lipids. Dietary SM inhibits cholesterol absorption in rats (Nyberg et al. J Nutr Biochem. 2000 and SLs decrease both cholesterol and TG concentrations in lipid- and cholesterol fed APOE*3Leiden mice (Duivenvoorden et al. Am J Clin Nutr. 2006. This human study examines effects of a butter milk formulation enriched in milk fat globule membrane material, and thereby in SLs, on blood lipids in healthy volunteers. In a four week parallel group study with 33 men and 15 women we examined the effects of an SL-enriched butter milk formulation (A and an equivalent control formulation (B on plasma lipid levels. Plasma concentrations of HDL and LDL cholesterol, triacylglycerols (TG, apolipoproteins AI and B, and lipoprotein (a were measured. The daily dose of SL in A was 975 mg of which 700 mg was SM. The participants registered food and drink intake four days before introducing the test formula and the last four days of the test period. Results A daily increase of SL intake did not significantly influence fasting plasma lipids or lipoproteins. In group B TG, cholesterol, LDL, HDL and apolipoprotein B concentrations increased, however, but not in group A after four weeks. The difference in LDL cholesterol was seen primarily in women and difference in TG primarily in men. No significant side effects were observed. Conclusion The study did not show any significant decrease on plasma lipids or lipoprotein levels of an SL-enriched formulation containing 2-3 times more SL than the normal dietary intake on cholesterol, other plasma lipids or on energy intake. The formulation A may, however, have counteracted the trend towards increased blood lipid concentrations caused by increased energy intake that was seen with the B formulation.

  20. Apolipoprotein M promotes mobilization of cellular cholesterol in vivo

    DEFF Research Database (Denmark)

    Elsøe, Sara; Christoffersen, Christina; Luchoomun, Jayraz

    2013-01-01

    The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice.......The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice....

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

    Science.gov (United States)

    Shearer, Gregory C.; Newman, John W.

    2009-01-01

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

  2. 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...

  3. Balanced high fat diet reduces cardiovascular risk in obese women although changes in adipose tissue, lipoproteins, and insulin resistance differ by race.

    Science.gov (United States)

    Niswender, Kevin D; Fazio, Sergio; Gower, Barbara A; Silver, Heidi J

    2018-05-01

    We previously reported that consuming a balanced high fat diet (BHFD) wherein total saturated fat was reduced and total unsaturated fat increased by proportionately balancing the type of fat (1/3 saturated, 1/3 monounsaturated, 1/3 polyunsaturated) led to significant improvements in inflammatory burden, blood pressure, and vascular function in obese premenopausal European American (EA) and African American (AA) women. Here we compared changes in adipose tissue, lipoproteins, insulin resistance, and cardiovascular risk between EA and AA women. Dietary intakes, plasma fatty acids, lipids, apolipoproteins, lipoproteins, HOMA-IR and ASCVD risk was measured in 144 women who consumed BHFD for 16 weeks. Generalized linear modeling was performed while controlling for change in body weight. EA women had greater reductions in visceral adipose tissue. Only EA women had significant reductions in fasting insulin levels (↓24.8%) and HOMA-IR (↓29%) scores. In EA women, the most significant improvements occurred in VLDL particle size (↑), apolipoprotein B levels (↑), serum TG (↓), number of plasma LDL particles (↓), and serum LDL-cholesterol (↓). In AA women, significant improvements occurred in HDL particle size (↑), number of large HDL particles (↑), and apolipoprotein AI levels (↑). Consequently, both groups had improved ASCVD risk scores (↓5.5%). Consuming the balanced high fat diet led to significant reduction in cardiovascular risk factors in both groups. However, the pattern of response to BHFD differed with EA women responding more in components of the apolipoprotein B pathway versus AA women responding more in components of the apolipoprotein AI pathway. Published by Elsevier Inc.

  4. Comparison of Serum Apolipoprotein Levels of Diabetic Children and Healthy Children with or without Diabetic Parents

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    Mohammad Hashemi

    2012-01-01

    Full Text Available Introduction. The association of diabetes and atherosclerosis with disorders of lipids and lipoproteins, notably high apolipoprotein B (apoB and low apolipoprotein A1(apoA1 is well established. Because of the beginning of the atherosclerosis' process from early life, in this study, the plasma levels of apoA1 and apoB were compared in diabetic children with type I diabetes mellitus(DM, healthy children with diabetic parents (HDPs,and healthy children with nondiabetic parents (HNDPs. Methods. This case-control study was conducted among 90 children aged 9–18 years. Serum levels of apoA and apoB were compared among 30 diabetic children (DM, 30 healthy children with diabetic parents (HDPs, and 30 healthy children with nondiabetic parents (HNDP. Results. The mean serum apoA1 was higher in DM (153±69 mg/dL followed by HNDPs (138±58 mg/dL and HDPs (128±56 mg/dl, but the difference was not statistically significant. The mean apoB value in HNDPs was significantly lower than DM and HDPs (90±21 mg/dL versus 127±47 and 128±38 mg/dL, P0.05. Conclusions. Diabetic children and healthy children with diabetic parent(s are at higher risk of dyslipidemia and atherosclerosis. Thus for primordial and primary prevention of atherosclerosis, we suggest screening these children for low plasma apoA1 and high plasma apoB levels.

  5. Effects of hormones on lipids and lipoproteins

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    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.

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

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    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.

  7. Lipoprotein(a: Cellular Effects and Molecular Mechanisms

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    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.

  8. Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages

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    Dana Atrahimovich

    2016-01-01

    Full Text Available High levels of circulating low-density lipoprotein (LDL are a primary initiating event in the development of atherosclerosis. Recently, the antiatherogenic effect of polyphenols has been shown to be exerted via a mechanism unrelated to their antioxidant capacity and to stem from their interaction with specific intracellular or plasma proteins. In this study, we investigated the interaction of the main polyphenol in pomegranate, punicalagin, with apolipoprotein B-100 (ApoB100 that surrounds LDL. Punicalagin bound to ApoB100 at low concentrations (0.25–4 μM. Upon binding, it induced LDL influx to macrophages in a concentration-dependent manner, up to 2.5-fold. In contrast, another polyphenol which binds to ApoB100, glabridin, did not affect LDL influx. We further showed that LDL influx occurs specifically through the LDL receptor, with LDL then accumulating in the cell cytoplasm. Taken together with the findings of Aviram et al., 2000, that pomegranate juice and punicalagin induce plasma LDL removal and inhibit macrophage cholesterol synthesis and accumulation, our results suggest that, upon binding, punicalagin stimulates LDL influx to macrophages, thus reducing circulating cholesterol levels.

  9. Biogenesis and Membrane Targeting of Lipoproteins.

    Science.gov (United States)

    Narita, Shin-Ichiro; Tokuda, Hajime

    2010-09-01

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

  10. Vascular lesions in patient with Takayasu arteritis and massive elevated lipoprotein(a) levels. Residual involvement or premature aterosclerosis?

    Science.gov (United States)

    Alarcón García, José Carlos; Rodríguez Suárez, Santiago; Muñiz Grijalvo, Ovidio; García Morillo, Salvador

    Lipoprotein (a) [Lp(a)] is a lipoprotein defined by presenting a specific apolipoprotein, ApoA, linked to the ApoB-100 by different types of chemical bonds, including a disulfide bridge. Despite their atherogenic mechanism is not fully understood, its importance has been demonstrated in the development of premature aterosclerosis. Multiple studies have shown its role as a cardiovascular risk factor associated with heart disease and stroke. We report the case of a patient with a diagnosis of Takayasu arteritis in which a massive elevation of Lp(a) was detected. We emphasize its diagnostic and therapeutic implications. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

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

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    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.

  12. Low-Density Lipoprotein Modified by Myeloperoxidase in Inflammatory Pathways and Clinical Studies

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    Cédric Delporte

    2013-01-01

    Full Text Available Oxidation of low-density lipoprotein (LDL has a key role in atherogenesis. Among the different models of oxidation that have been studied, the one using myeloperoxidase (MPO is thought to be more physiopathologically relevant. Apolipoprotein B-100 is the unique protein of LDL and is the major target of MPO. Furthermore, MPO rapidly adsorbs at the surface of LDL, promoting oxidation of amino acid residues and formation of oxidized lipoproteins that are commonly named Mox-LDL. The latter is not recognized by the LDL receptor and is accumulated by macrophages. In the context of atherogenesis, Mox-LDL accumulates in macrophages leading to foam cell formation. Furthermore, Mox-LDL seems to have specific effects and triggers inflammation. Indeed, those oxidized lipoproteins activate endothelial cells and monocytes/macrophages and induce proinflammatory molecules such as TNFα and IL-8. Mox-LDL may also inhibit fibrinolysis mediated via endothelial cells and consecutively increase the risk of thrombus formation. Finally, Mox-LDL has been involved in the physiopathology of several diseases linked to atherosclerosis such as kidney failure and consequent hemodialysis therapy, erectile dysfunction, and sleep restriction. All these issues show that the investigations of MPO-dependent LDL oxidation are of importance to better understand the inflammatory context of atherosclerosis.

  13. Endoplasmic Reticulum Stress Caused by Lipoprotein Accumulation Suppresses Immunity against Bacterial Pathogens and Contributes to Immunosenescence

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    Jogender Singh

    2017-05-01

    Full Text Available The unfolded protein response (UPR is a stress response pathway that is activated upon increased unfolded and/or misfolded proteins in the endoplasmic reticulum (ER, and enhanced ER stress response prolongs life span and improves immunity. However, the mechanism by which ER stress affects immunity remains poorly understood. Using the nematode Caenorhabditis elegans, we show that mutations in the lipoproteins vitellogenins, which are homologs of human apolipoprotein B-100, resulted in upregulation of the UPR. Lipoprotein accumulation in the intestine adversely affects the immune response and the life span of the organism, suggesting that it could be a contributing factor to immunosenescence. We show that lipoprotein accumulation inhibited the expression of several immune genes encoding proteins secreted by the intestinal cells in an IRE-1-independent manner. Our studies provide a mechanistic explanation for adverse effects caused by protein aggregation and ER stress on immunity and highlight the role of an IRE-1-independent pathway in the suppression of the expression of genes encoding secreted proteins.

  14. The essential Escherichia coli apolipoprotein N-acyltransferase (Lnt) exists as an extracytoplasmic thioester acyl-enzyme intermediate.

    Science.gov (United States)

    Buddelmeijer, Nienke; Young, Ry

    2010-01-19

    Escherichia coli apolipoprotein N-acyltransferase (Lnt) transfers an acyl group from sn-1-glycerophospholipid to the free alpha-amino group of the N-terminal cysteine of apolipoproteins, resulting in mature triacylated lipoprotein. Here we report that the Lnt reaction proceeds through an acyl-enzyme intermediate in which a palmitoyl group forms a thioester bond with the thiol of the active site residue C387 that was cleaved by neutral hydroxylamine. Lnt(C387S) also formed a fatty acyl intermediate that was resistant to neutral hydroxylamine treatment, consistent with formation of an oxygen-ester linkage. Lnt(C387A) did not form an acyl-enzyme intermediate and, like Lnt(C387S), did not have any detectable Lnt activity, indicating that acylation cannot occur at other positions in the catalytic domain. The existence of this thioacyl-enzyme intermediate allowed us to determine whether essential residues in the catalytic domain of Lnt affect the first step of the reaction, the formation of the acyl-enzyme intermediate, or the second step in which the acyl chain is transferred to the apolipoprotein substrate. In the catalytic triad, E267 is required for the formation of the acyl-enzyme intermediate, indicating its role in enhancing the nucleophilicity of C387. E343 is also involved in the first step but is not in close proximity to the active site. W237, Y388, and E389 play a role in the second step of the reaction since acyl-Lnt is formed but N-acylation does not occur. The data presented allow discrimination between the functions of essential Lnt residues in catalytic activity and substrate recognition.

  15. THE ESSENTIAL E. COLI APOLIPOPROTEIN N-ACYLTRANSFERASE (LNT) EXISTS AS AN EXTRACYTOPLASMIC THIOESTER ACYL-ENZYME INTERMEDIATE‡

    Science.gov (United States)

    Buddelmeijer, Nienke; Young, Ry

    2011-01-01

    Escherichia coli apolipoprotein N-acyltransferase (Lnt) transfers an acyl group from sn-1-glycerolphospholipid to the free α-amino group of the N-terminal cysteine of apolipoproteins, resulting in mature triacylated lipoprotein. Here we report that the Lnt reaction proceeds through an acyl enzyme intermediate in which a palmitoyl group forms a thioester bond with the thiol of active site residue C387 that was cleaved by neutral hydroxylamine. Lnt(C387S) also formed a fatty acyl intermediate that was resistant to neutral hydroxylamine treatment, consistent with formation of an oxygen-ester linkage. Lnt(C387A) did not form an acyl enzyme intermediate and, like Lnt(C387S), did not have any detectable Lnt activity, indicating that acylation can not occur at other positions in the catalytic domain. The existence of this thioacyl-enzyme intermediate allowed us to determine whether essential residues in the catalytic domain of Lnt affect the first step of the reaction, the formation of the acyl enzyme intermediate, or the second step in which the acyl chain is transferred to apolipoprotein substrate. In the catalytic triad, E267 is required for the formation of the acyl-enzyme intermediate, indicating its role in enhancing the nucleophilicity of C387. E343 is also involved in the first step but is not in close proximity to the active site. W237, Y388 and E389 play a role in the second step of the reaction since acyl-Lnt is formed but N-acylation does not occur. The data presented allow discrimination between the functions of essential Lnt residues in catalytic activity and substrate recognition. PMID:20000742

  16. Common and Rare Alleles in Apolipoprotein B Contribute to Plasma Levels of LDL Cholesterol in the General Population

    DEFF Research Database (Denmark)

    Benn, M; Stene, MC; Nordestgaard, BG

    2008-01-01

    demonstrated to affect low-density lipoprotein (LDL) cholesterol levels. OBJECTIVE: We tested the hypothesis that nonsynonymous SNPs in three important functional domains of APOB and APOB tag SNPs predict levels of LDL cholesterol and apolipoprotein B and risk of ischemic heart disease. DESIGN......: This was a prospective study with 25 yr 100% follow up, The Copenhagen City Heart Study. SETTING: The study was conducted in the Danish general population. PARTICIPANTS: Participants included 9185 women and men aged 20-80+ yr. MAIN OUTCOME MEASURES: Levels of LDL cholesterol and apolipoprotein B and risk of ischemic......Q (0.09), E4154K (0.17), and N4311S (0.21). SNPs were associated with increases (T71I, Ivs181708g>t, T2488Tc>t, R3611) or decreases (Ivs4+171c>a, A591V, Ivs18+379a>c, P2712L, E4154, N4311S) in LDL cholesterol from -4.7 to +8.2% (-0.28 to 0.30 mmol/liter; P

  17. Study on the correlation between the concentration of plasma lipoprotein-associated phospholipase A2 and coronary heart disease.

    Science.gov (United States)

    Cen, Jin-Ming; Cheng, Jie; Xiong, Qing-Yuan; Mei, Bai-Qiang; Cai, Wei-Biao; Yang, Xi-Li

    2015-06-01

    This study explores the correlation between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) and coronary heart disease (CHD) by comparing the level of plasma Lp-PLA2 in the plasma of patients with different types of CHD. Blood samples were collected from 56 patients diagnosed with CHD by the Department of Cardiology of the First People's Hospital of Foshan and 34 healthy subjects from February 2013 to January 2014. We measured the concentration of plasma Lp-PLA2 and determined the levels of total cholesterol (Tch), triglyceride (TG), apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), high density lipoprotein-cholesterol (HDL-c), low density lipoprotein-cholesterol (LDL-c), lipoprotein a (Lp(a)), glucose (Glu), and high-sensitivity C-reactive protein (hs-CRP). The concentration of plasma Lp-PLA2 in the healthy control group and each subgroup of CHD patients were compared and analyzed for correlations of plasma Lp-PLA2 between the patients in different CHD subgroups and several laboratory indicators. The concentration of plasma Lp-PLA2 in each subgroup of CHD was significantly higher than in the control group ( P  A1, Apo-B, HDL-c, LDL-c, Lp(a) and Glu did not. The concentration of plasma Lp-PLA2 in patients with CHD was higher than that in the control group. The concentration of plasma Lp-PLA2 in the subgroups of CHD patients varied greatly from each other. The inflammatory response of atherosclerosis might be resulted from the synergy of plasma Lp-PLA2 and hs-CRP.

  18. Clinical chemistry of atherosclerosis : Contribution to apolipoprotein-E analysis, public Health and nutricion

    NARCIS (Netherlands)

    Brouwer, Dineke Aletta Johanna

    1999-01-01

    Chapter 1 is meant as a general introduction to atherosclerosis and the ensuing coronary artery disease (CAD). It gives special attention to atherogenesis, lipoprotein metabolism and nutritional factors. The chapter opens with the presentation of an integrated model of atherogenesis with a central

  19. Plasma levels of apolipoprotein-E in residents of the European North of Russia.

    Science.gov (United States)

    Kaneva, Anastasiya M; Bojko, Evgeny R; Potolitsyna, Natalya N; Odland, Jon O

    2013-03-27

    Apolipoprotein-E (apoE) is one of the metabolically active apoproteins and plays an important role in lipid metabolism. However, there are no data on levels of apoE in residents of the North in spite of the fact that specific features of lipid metabolism in the northerners are described. The present work was designed to study plasma levels of apoE in residents of the European North of Russia. A total of 937 native residents of the European North of Russia (463 men and 474 women) aged 13-60 years were included in the study. ApoE concentrations in the blood plasma were measured by immunoturbidimetric method. Plasma levels of apoE in residents of the European North of Russia were low. ApoE concentrations below the defined normal values were detected in 57.0% of the men and in 59.2% of the women. The mean plasma levels of apoE did not significantly differ in men and women (2.80 mg/dl vs 2.87 mg/dl). Plasma apoE concentrations in residents of the European North of Russia changed with age. Plasma levels of apoE decreased from 13 to 21 years in men and from 13 to 35 years in women and then increased in both sexes (p Russia shift towards lower values. Plasma levels of apoE below normal values were observed in approximately half of investigation subjects.

  20. Charged Residues in the C-Terminal Domain of Apolipoprotein A-I Modulate Oligomerization.

    Science.gov (United States)

    Fuentes, Lukas A; Beck, Wendy H J; Tsujita, Maki; Weers, Paul M M

    2018-04-03

    Charged residues of the C-terminal domain of human apolipoprotein A-I (apoA-I) were targeted by site-directed mutagenesis. A series of mutant proteins was engineered in which lysine residues (Lys 195, 206, 208, 226, 238, and 239) or glutamate residues (Glu 234 and 235) were replaced by glutamine. The amino acid substitutions did not result in changes in secondary structure content or protein stability. Cross-linking and size-exclusion chromatography showed that the mutations resulted in reduced self-association, generating a predominantly monomeric apoA-I when five or six lysine residues were substituted. The rate of phosphatidylcholine vesicle solubilization was enhanced for all variants, with approximately a threefold rate enhancement for apoA-I lacking Lys 206, 208, 238, and 239, or Glu 234 and 235. Single or double mutations did not change the ability to protect lipolyzed low density lipoprotein from aggregation, but variants lacking >4 lysine residues were less effective in preventing lipoprotein aggregation. ApoA-I mediated cellular lipid efflux from wild-type mice macrophage foam cells was decreased for the variant with five lysine mutations. However, this protein was more effective in releasing cellular phosphatidylcholine and sphingomyelin from Abca1-null mice macrophage foam cells. This suggests that the mutations caused changes in the interaction with ABCA1 transporters and that membrane microsolubilization was primarily responsible for lipid efflux in cells lacking ABCA1. Taken together, this study indicates that ionic interactions in the C-terminal domain of apoA-I favor self-association and that monomeric apoA-I is more active in solubilizing phospholipid bilayers.

  1. Apolipoprotein CIII polymorphism and triglyceride levels of a Japanese population living in Southern Brazil

    Directory of Open Access Journals (Sweden)

    L. Parzianello

    2008-06-01

    Full Text Available Apolipoprotein CIII (apo-CIII participates in the regulation of triglyceride-rich lipoprotein metabolism. Several polymorphic sites have been detected within and around the apo-CIII gene. Here, we examined the relationship between apo-CIII SstI polymorphism (CC, CG, GG genotypes and plasma triglyceride (TG levels in a group of 159 Japanese individuals living in Southern Brazil. The sample was divided into a group of Japanese descendants (N = 51 with high TG (HTG; >200 mg/dL and a group of Japanese descendants (N = 108 with normal TG (NTG; <200 mg/dL. TG and total cholesterol levels were analyzed by an enzymatic method using the Labtest-Diagnostic kit and high- and low-density lipoproteins by a direct method using the Labtest-Diagnostic kit and DiaSys Diagnostic System International kit, respectively. A 428-bp sequence of apo-CIII gene was amplified using oligonucleotide primers 5' GGT GAC CGA TGG CTT CAG TTC CCT GA 3' and 5' CAG AAG GTG GAT AGA GCG CTG GCC T 3'. The PCR products were digested with a restriction endonuclease SstI. Rare G allele was highly prevalent in our study population (0.416 compared to Caucasians (0.00-0.11. G allele was almost two times more prevalent in the HTG group compared to the NTG group (P < 0.001. The genotype distribution was consistent with the Hardy-Weinberg equilibrium. There was a significant association between rare G allele and HTG in Japanese individuals living in Southern Brazil as indicated by one-way ANOVA, P < 0.05.

  2. The intravenous injection of oxidized LDL- or Apolipoprotein B100 – Coupled splenocytes promotes Th1 polarization in wildtype and Apolipoprotein E – Deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Steinmetz, Martin, E-mail: martin.steinmetz@ukb.uni-bonn.de [INSERM, Unit 970, Paris Cardiovascular Research Center, 75015 Paris (France); Internal Medicine II, University Hospital Bonn, 53105 Bonn (Germany); Ponnuswamy, Padmapriya; Laurans, Ludivine; Esposito, Bruno; Tedgui, Alain [INSERM, Unit 970, Paris Cardiovascular Research Center, 75015 Paris (France); Mallat, Ziad [INSERM, Unit 970, Paris Cardiovascular Research Center, 75015 Paris (France); Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke' s Hospital, Cambridge, CB2 2QQ (United Kingdom)

    2015-08-14

    Background: Th1 responses in atherosclerosis are mainly associated with the aggravation of atherosclerotic plaques, whereas Th2 responses lead to a less pronounced disease in mouse models. The fixation of antigens on cells by means of ethylene carbodiimide (ECDI), and subsequent injection of these antigen-coupled splenocytes (Ag-SP) to induce tolerance against the attached antigens, has been successfully used to treat murine type 1 diabetes or encephalomyelitis in. We analyzed this approach in a mouse model for atherosclerosis. Methods and results: OTII-transgenic mice that were treated with a single dose of 5 × 10{sup 7} OVA-coupled splenocytes (OVA-SP), had decreased splenocyte proliferation, and lower IFNγ production in vitro upon antigen recall. However, in vivo CD4 cell activation was increased. To try lipoprotein-derived, “atherosclerosis-associated” antigens, we first tested human oxidized LDL. In wild type mice, an increase of IFNγ production upon in vitro recall was detected in the oxLDL-SP group. In Apolipoprotein E − deficient (ApoE−/−) mice that received oxLDL-SP every 5 weeks for 20 weeks, we did not find any difference of atherosclerotic plaque burden, but again increased IFNγ production. To overcome xenogenous limitations, we then examined the effects of mouse Apolipoprotein B100 peptides P3 and P6. ApoB100-SP treatment again promoted a more IFNγ pronounced response upon in vitro recall. Flow cytometry analysis of cytokine secreting spleen cells revealed CD4 positive T cells to be mainly the source for IFNγ. In ApoE−/− mice that were administered ApoB100-SP during 20 weeks, the atherosclerotic plaque burden in aortic roots as well as total aorta was unchanged compared to PBS treated controls. Splenocyte proliferation upon antigen recall was not significantly altered in ApoB100-SP treated ApoE−/− mice. Conclusion: Although we did not observe a relevant anti-atherosclerotic benefit, the treatment with antigen

  3. The intravenous injection of oxidized LDL- or Apolipoprotein B100 – Coupled splenocytes promotes Th1 polarization in wildtype and Apolipoprotein E – Deficient mice

    International Nuclear Information System (INIS)

    Steinmetz, Martin; Ponnuswamy, Padmapriya; Laurans, Ludivine; Esposito, Bruno; Tedgui, Alain; Mallat, Ziad

    2015-01-01

    Background: Th1 responses in atherosclerosis are mainly associated with the aggravation of atherosclerotic plaques, whereas Th2 responses lead to a less pronounced disease in mouse models. The fixation of antigens on cells by means of ethylene carbodiimide (ECDI), and subsequent injection of these antigen-coupled splenocytes (Ag-SP) to induce tolerance against the attached antigens, has been successfully used to treat murine type 1 diabetes or encephalomyelitis in. We analyzed this approach in a mouse model for atherosclerosis. Methods and results: OTII-transgenic mice that were treated with a single dose of 5 × 10 7 OVA-coupled splenocytes (OVA-SP), had decreased splenocyte proliferation, and lower IFNγ production in vitro upon antigen recall. However, in vivo CD4 cell activation was increased. To try lipoprotein-derived, “atherosclerosis-associated” antigens, we first tested human oxidized LDL. In wild type mice, an increase of IFNγ production upon in vitro recall was detected in the oxLDL-SP group. In Apolipoprotein E − deficient (ApoE−/−) mice that received oxLDL-SP every 5 weeks for 20 weeks, we did not find any difference of atherosclerotic plaque burden, but again increased IFNγ production. To overcome xenogenous limitations, we then examined the effects of mouse Apolipoprotein B100 peptides P3 and P6. ApoB100-SP treatment again promoted a more IFNγ pronounced response upon in vitro recall. Flow cytometry analysis of cytokine secreting spleen cells revealed CD4 positive T cells to be mainly the source for IFNγ. In ApoE−/− mice that were administered ApoB100-SP during 20 weeks, the atherosclerotic plaque burden in aortic roots as well as total aorta was unchanged compared to PBS treated controls. Splenocyte proliferation upon antigen recall was not significantly altered in ApoB100-SP treated ApoE−/− mice. Conclusion: Although we did not observe a relevant anti-atherosclerotic benefit, the treatment with antigen

  4. A More Flexible Lipoprotein Sorting Pathway

    Science.gov (United States)

    Chahales, Peter

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-08-12

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

  6. Serum high-density lipoprotein is associated with better cognitive function in a cross-sectional study of aging women.

    Science.gov (United States)

    Bates, Kristyn A; Sohrabi, Hamid R; Rainey-Smith, Stephanie R; Weinborn, Michael; Bucks, Romola S; Rodrigues, Mark; Beilby, John; Howard, Matthew; Taddei, Kevin; Martins, Georgia; Paton, Athena; Shah, Tejal; Dhaliwal, Satvinder S; Foster, Jonathan K; Martins, Ian J; Lautenschlager, Nicola T; Mastaglia, Frank L; Gandy, Samuel E; Martins, Ralph N

    2017-03-01

    Purpose/Aim of the study: Poor cardiovascular health, including obesity and altered lipid profiles at mid-life, are linked to increased risk of Alzheimer's disease (AD). The biological mechanisms linking cardiovascular health and cognitive function are unclear though are likely to be multifactorial. This study examined the association between various lipoproteins and cognitive functioning in ageing women. We investigated the relationship between readily available biomarkers (i.e. serum lipoprotein) and cognitive decline in domains associated with increased risk of AD (e.g. episodic verbal memory performance and subjective memory complaint). We report cross-sectional data investigating the relationship between serum total cholesterol, triglycerides, high-density lipoprotein (HDL-C) and low-density lipoprotein with verbal memory and learning ability in 130 women with and without memory complaints (n = 71 and 59, respectively) drawn from a study investigating cognitively healthy Western Australians (average age 62.5 years old). After statistical modelling that controlled for the effects of age, depression and apolipoprotein E genotype, HDL-C was significantly associated with better verbal learning and memory performance, specifically short and long delay-free recalls (F = 3.062; p ageing. Further exploration of the protective effect of HDL-C on cognitive function in ageing is warranted through follow-up, longitudinal studies.

  7. DMPD: Regulation of endogenous apolipoprotein E secretion by macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18388328 Regulation of endogenous apolipoprotein E secretion by macrophages. Kockx ...svg) (.html) (.csml) Show Regulation of endogenous apolipoprotein E secretion by macrophages. PubmedID 18388...328 Title Regulation of endogenous apolipoprotein E secretion by macrophages. Aut

  8. The effect of preoperative serum triglycerides and high-density lipoprotein-cholesterol levels on the prognosis of breast cancer.

    Science.gov (United States)

    Li, Xing; Tang, Hailin; Wang, Jin; Xie, Xinhua; Liu, Peng; Kong, Yanan; Ye, Feng; Shuang, Zeyu; Xie, Zeming; Xie, Xiaoming

    2017-04-01

    Although dyslipidemia has been documented to be associated with several types of cancer including breast cancer, it remains uncertainty the prognostic value of serum lipid in breast cancer. The purpose of this study is to evaluate the association between the preoperative plasma lipid profile and the prognostic of breast cancer patients. The levels of preoperative serum lipid profile (including cholesterol [CHO], Triglycerides [TG], high-density lipoprotein-cholesterol [HDL-C], low-density lipoprotein-cholesterol [LDL-C], apolipoprotein A-I [ApoAI], and apolipoprotein B [ApoB]) and the clinical data were retrospectively collected and reviewed in 1044 breast cancer patients undergoing operation. Kaplan-Meier method and the Cox proportional hazards regression model were used in analyzing the overall survival [OS] and disease-free survival [DFS]. Combining the receiver-operating characteristic and Kaplan-Meier analysis, we found that preoperative lower TG and HDL-C level were risk factors of breast cancer patients. In multivariate analyses, a decreased HDL-C level showed significant association with worse OS (HR: 0.528; 95% CI: 0.302-0.923; P = 0.025), whereas a decreased TG level showed significant association with worse DFS (HR: 0.569; 95% CI: 0.370-0.873; P = 0.010). Preoperative serum levels of TG and HDL-C may be independent factor to predict outcome in breast cancer patient. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. SPONTANEOUS LIPOPROTEIN GLOMERULOPATHY-LIKE NEPHROPATHY IN A SQUIRREL (SCIURUS VULGARIS).

    Science.gov (United States)

    Kobayashi, Ryosuke; Chambers, James K; Yoshida, Keiko; Nakamura, Takashi; Yasuno, Kyohei; Uchida, Kazuyuki; Kamiie, Junichi; Shirota, Kinji

    2016-06-01

    Lipoprotein glomerulopathy (LPG) is a rare human glomerular disease caused by abnormal lipid metabolism. Naturally occurring LPG has not been reported in animals. We describe the histopathological characterization of spontaneous LPG-like nephropathy in a captive squirrel ( Sciurus vulgaris ). Macroscopically, swollen glomeruli were distinctively identified as fine white granules in the renal cortex. Histologically, most glomeruli were markedly enlarged with distended capillaries containing faintly eosinophilic and amorphous materials. The amorphous material was negative using the periodic acid-Schiff reaction, periodic acid-methenamine silver stain, or Masson's trichrome stain. Sudan III staining revealed lipid in the materials, and immunohistochemistry demonstrated that the material additionally contained apolipoprotein E. Electron microscopy showed numerous lipid granules and vacuoles of various sizes in the capillary lumina associated with foot process effacement of podocytes. These pathological characteristics bear some resemblance to those of human LPG.

  10. A role for Apolipoprotein A-I in the pathogenesis of multiple sclerosis.

    Science.gov (United States)

    Meyers, Lindsay; Groover, Chassidy J; Douglas, Joshua; Lee, Sangmin; Brand, David; Levin, Michael C; Gardner, Lidia A

    2014-12-15

    Apolipoprotein A1 (Apo A-I), the most abundant component of high-density lipoprotein (HDL), is an anti-inflammatory molecule, yet its potential role in the pathogenesis of multiple sclerosis (MS) has not been fully investigated. In this study, Western blot analyses of human plasma showed differential Apo A-I expression in healthy controls compared to MS patients. Further, primary progressive MS patients had less plasma Apo A-I than other forms of MS. Using experimental allergic encephalomyelitis (EAE) as a model for MS, Apo A-I deficient mice exhibited worse clinical disease and more neurodegeneration concurrent with increased levels of pro-inflammatory cytokines compared to wild-type animals. These data suggest that Apo A-I plays a role in the pathogenesis of EAE, a model for MS, creating the possibility for agents that increase Apo A-I levels as potential therapies for MS. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Human plasma lipid modulation in schistosomiasis mansoni depends on apolipoprotein E polymorphism.

    Directory of Open Access Journals (Sweden)

    Caíque Silveira Martins da Fonseca

    Full Text Available Schistosomiasis mansoni is a parasitic liver disease, which causes several metabolic disturbances. Here, we evaluate the influence of Apolipoprotein E (APOE gene polymorphism, a known modulator of lipid metabolism, on plasma lipid levels in patients with hepatosplenic schistosomiasis.Blood samples were used for APOE genotyping and to measure total cholesterol (TC, LDL-C, HDL-C and triglycerides. Schistosomiasis patients had reduced TC, LDL-C and triglycerides (25%, 38% and 32% lower, respectively; Pε3>ε4 was absent in patients (ε2 or ε4>ε3, and the increase in HDL-C of ε2 or ε4 patients compared to ε3 patients was not seen in the control groups.We confirm that human schistosomiasis causes dyslipidemia and report for the first time that certain changes in plasma lipid and lipoprotein levels depend on APOE gene polymorphism. Importantly, we also concluded that S. mansoni disrupts the expected regulation of plasma lipids by the different ApoE isoforms. This finding suggests ways to identify new metabolic pathways affected by schistosomiasis and also potential molecular targets to treat associated morbidities.

  12. The protective effect of apolipoprotein in models of trophoblast invasion and preeclampsia.

    Science.gov (United States)

    Charlton, Francesca; Bobek, Gabriele; Stait-Gardner, Tim; Price, William S; Mirabito Colafella, Katrina M; Xu, Bei; Makris, Angela; Rye, Kerry-Anne; Hennessy, Annemarie

    2017-01-01

    Preeclampsia is a hypertensive disorder of pregnancy. It is associated with abnormal placentation via poor placental invasion of the uterine vasculature by trophoblast cells, leading to poor placental perfusion, oxidative stress, and inflammation, all of which are implicated in its pathogenesis. A dyslipidemia characterized by low plasma levels of high-density lipoproteins (HDL) and elevated triglycerides has been described in preeclampsia. Apolipoprotein A-I (apoA-I), a constituent of HDL is an anti-inflammatory agent. This study investigated whether apoA-I protects against hypertension and adverse placental changes in a proinflammatory cytokine (TNF-α)-induced model of preeclampsia. Further, this study investigated whether apoA-I protects against the inhibitory effect of TNF-α in a human in vitro model of trophoblast invasion. Administration of apoA-I to pregnant mice before infusion with TNF-α resulted in a significant reduction in the cytokine-induced increase in systolic blood pressure. MRI measurement of T 2 relaxation, a parameter that is tissue specific and sensitive to physiological changes within tissues, showed a reversal of TNF-α-induced placental changes. Preincubation of endothelial cells with apoA-I protected against the TNF-α-induced inhibition of HTR-8/SVneo (trophoblast) cell integration into endothelial (UtMVEC) networks. These data suggest that a healthy lipid profile may affect pregnancy outcomes by priming endothelial cells in preparation for trophoblast invasion. Copyright © 2017 the American Physiological Society.

  13. Taurine reduces the secretion of apolipoprotein B100 and lipids in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Nagao Koji

    2008-10-01

    Full Text Available Abstract Background Higher concentrations of serum lipids and apolipoprotein B100 (apoB are major individual risk factors of atherosclerosis and coronary heart disease. Therefore ameliorative effects of food components against the diseases are being paid attention in the affluent countries. The present study was undertaken to investigate the effect of taurine on apoB secretion and lipid metabolism in human liver model HepG2 cells. Results The results demonstrated that an addition of taurine to the culture media reduces triacylglycerol (TG-mass in the cells and the medium. Similarly, cellular cholesterol-mass was decreased. Taurine inhibited the incorporation of [14C] oleate into cellular and medium TG, suggesting the inhibition of TG synthesis. In addition, taurine reduced the synthesis of cellular cholesterol ester and its secretion, suggesting the inhibition of acyl-coenzyme A:cholesterol acyltransferase activity. Furthermore, taurine reduced the secretion of apoB, which is a major protein component of very low-density lipoprotein. Conclusion This is a first report to demonstrate that taurine inhibits the secretion of apoB from HepG2 cells.

  14. Relation of apolipoprotein E polymorphism to lipid metabolism in obese children.

    Science.gov (United States)

    Parlier, G; Thomas, G; Bereziat, G; Fontaine, J L; Girardet, J P

    1997-05-01

    To determine whether the risk of obesity-associated dyslipidemia in children is influenced by apolipoprotein E (apoE) polymorphism, we studied 137 obese, nongenetically related children aged 2.2-14.4 y (mean age, 9.9 +/- 3.1 y) with a weight-for-height excess of 43.7 +/- 17.9%. The apoE genotype was determined by studying specific DNA restriction patterns. Total cholesterol, HDL-cholesterol, and triglycerides were assayed in plasma before dietary treatment initiation. ApoE allele and phenotype distributions were comparable to those reported in the Caucasian population at large. Fifty-five children (41%) had elevated lipid levels. Compared with obese children with the epsilon3 or epsilon4 allele, those with the epsilon2 allele were more likely to have hypertriglyceridemia (19.5% versus 52.9%, p < 0.05) and had a higher mean triglyceride level: children with the epsilon4 allele were more likely to have a LDL-cholesterol elevation (34.7% versus 13.4%, p < 0.05). Our data demonstrate that, even in childhood, obesity is associated with a marked increase in the risk of lipoprotein abnormalities and that the latter are influenced by apoE polymorphism.

  15. Obesity occurring in apolipoprotein E-knockout mice has mild effects on fertility.

    Science.gov (United States)

    Zhang, Ting; Dai, Pengyuan; Cheng, Dong; Zhang, Liang; Chen, Zijiang; Meng, Xiaoqian; Zhang, Fumiao; Han, Xiaoying; Liu, Jianwei; Pan, Jie; Yang, Guiwen; Zhang, Cong

    2014-02-01

    The Apolipoprotein (Apo) family is implicated in lipid metabolism. There are five types of Apo: Apoa, Apob, Apoc, Apod, and Apoe. Apoe has been demonstrated to play a central role in lipoprotein metabolism and to be essential for efficient receptor-mediated plasma clearance of chylomicron remnants and VLDL remnant particles by the liver. Apoe-deficient (Apoe(-/-)) mice develop atherosclerotic plaques spontaneously, followed by obesity. In this study, we investigated whether lipid deposition caused by Apoe knockout affects reproduction in female mice. The results demonstrated that Apoe(-/-) mice were severely hypercholesterolemic, with their cholesterol metabolism disordered, and lipid accumulating in the ovaries causing the ovaries to be heavier compared with the WT counterparts. In addition, estrogen and progesterone decreased significantly at D 100. Quantitative PCR analysis demonstrated that at D 100 the expression of cytochromeP450 aromatase (Cyp19a1), 3β-hydroxysteroid dehydrogenase (Hsd3b), mechanistic target of rapamycin (Mtor), and nuclear factor-κB (Nfkb) decreased significantly, while that of BCL2-associated agonist of cell death (Bad) and tuberous sclerosis complex 2 (Tsc2) increased significantly in the Apoe(-/-) mice. However, there was no difference in the fertility rates of the Apoe(-/-) and WT mice; that is, obesity induced by Apoe knockout has no significant effect on reproduction. However, the deletion of Apoe increased the number of ovarian follicles and the ratio of ovarian follicle atresia and apoptosis. We believe that this work will augment our understanding of the role of Apoe in reproduction.

  16. Orphan nuclear receptor Nur77 participates in human apolipoprotein A5 gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Song, Kwang-Hoon, E-mail: ksong@kiom.re.kr [Korea Institute of Oriental Medicine, Daejeon 305-811 (Korea, Republic of)

    2010-01-29

    The orphan nuclear receptor Nur77 (NR4A1) has been reported to play a crucial role in the modulation of diverse metabolic processes in liver. Here, we reported the identification of human apolipoprotein A5 (ApoA5), which implicated in lowering plasma triglyceride levels, as a novel target gene of Nur77. Nur77 induced the human ApoA5 promoter activity. Using 5'-deletion and mutagenesis of human ApoA5 promoter analysis and chromatin immunoprecipitation assays, it was shown that Nur77 directly regulated human ApoA5 gene expression by binding to a Nur77 response element (AAAGGTCA) located in the proximal human ApoA5 promoter region. In addition, we demonstrated that blocking of Nur77 transcriptional activity via overexpression of dominant negative Nur77 suppressed human ApoA5 promoter activity and mRNA expression in human hepatoma cells, HepG2. Taken together, our results demonstrated that Nur77 is a novel regulator of human ApoA5 gene expression and provide a new insight into the role of this orphan nuclear receptor in lipoprotein metabolism and triglyceride homeostasis.

  17. Orphan nuclear receptor Nur77 participates in human apolipoprotein A5 gene expression

    International Nuclear Information System (INIS)

    Song, Kwang-Hoon

    2010-01-01

    The orphan nuclear receptor Nur77 (NR4A1) has been reported to play a crucial role in the modulation of diverse metabolic processes in liver. Here, we reported the identification of human apolipoprotein A5 (ApoA5), which implicated in lowering plasma triglyceride levels, as a novel target gene of Nur77. Nur77 induced the human ApoA5 promoter activity. Using 5'-deletion and mutagenesis of human ApoA5 promoter analysis and chromatin immunoprecipitation assays, it was shown that Nur77 directly regulated human ApoA5 gene expression by binding to a Nur77 response element (AAAGGTCA) located in the proximal human ApoA5 promoter region. In addition, we demonstrated that blocking of Nur77 transcriptional activity via overexpression of dominant negative Nur77 suppressed human ApoA5 promoter activity and mRNA expression in human hepatoma cells, HepG2. Taken together, our results demonstrated that Nur77 is a novel regulator of human ApoA5 gene expression and provide a new insight into the role of this orphan nuclear receptor in lipoprotein metabolism and triglyceride homeostasis.

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

    Science.gov (United States)

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

    2017-01-01

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

  19. Structural basis for the pathophysiology of lipoprotein(a in the athero-thrombotic process

    Directory of Open Access Journals (Sweden)

    E. Anglés-Cano

    1997-11-01

    Full Text Available Lipoprotein Lp(a is a major and independent genetic risk factor for atherosclerosis and cardiovascular disease. The essential difference between Lp(a and low density lipoproteins (LDL is apolipoprotein apo(a, a glycoprotein structurally similar to plasminogen, the precursor of plasmin, the fibrinolytic enzyme. This structural homology endows Lp(a with the capacity to bind to fibrin and to membrane proteins of endothelial cells and monocytes, and thereby to inhibit plasminogen binding and plasmin generation. The inhibition of plasmin generation and the accumulation of Lp(a on the surface of fibrin and cell membranes favor fibrin and cholesterol deposition at sites of vascular injury. Moreover, insufficient activation of TGF-ß due to low plasmin activity may result in migration and proliferation of smooth muscle cells into the vascular intima. These mechanisms may constitute the basis of the athero-thrombogenic mode of action of Lp(a. It is currently accepted that this effect of Lp(a is linked to its concentration in plasma. An inverse relationship between Lp(a concentration and apo(a isoform size, which is under genetic control, has been documented. Recently, it has been shown that inhibition of plasminogen binding to fibrin by apo(a is also inversely associated with isoform size. Specific point mutations may also affect the lysine-binding function of apo(a. These results support the existence of functional heterogeneity in apolipoprotein(a isoforms and suggest that the predictive value of Lp(a as a risk factor for vascular occlusive disease would depend on the relative concentration of the isoform with the highest affinity for fibrin

  20. Effects of a Dipeptidyl Peptidase 4 Inhibitor Sitagliptin on Glycemic Control and Lipoprotein Metabolism in Patients with Type 2 Diabetes Mellitus (GLORIA Trial).

    Science.gov (United States)

    Masuda, Daisaku; Kobayashi, Takuya; Sairyou, Masami; Hanada, Hiroyuki; Ohama, Tohru; Koseki, Masahiro; Nishida, Makoto; Maeda, Norikazu; Kihara, Shinji; Minami, Tatsuya; Yanagi, Koji; Sakata, Yasushi; Yamashita, Shizuya

    2017-12-02

    The morbidity of cardiovascular disease in patients with type 2 diabetes mellitus (DM) deteriorates in combination with dyslipidemia. The accumulation of remnant lipoproteins in patients with fasting and postprandial hypertriglyceridemia is highly atherogenic. The current study investigated whether the dipeptidyl peptidase-4 inhibitor sitagliptin ameliorates dyslipidemia and hyperglycemia. We enrolled 38 patients with type 2 DM (20 males and 18 females, 65.7±9.9 years old, HbA1c levels <8.4%), and all patients gave written informed consent. Sitagliptin (50 mg/day) was added to current antidiabetic treatments and increased to 100 mg/day to achieve low HbA1c levels (<7.4%). Glucose and lipoprotein metabolism profiles were analyzed at 0, 4, and 12 weeks after sitagliptin administration. Sitagliptin significantly decreased fasting levels of triglyceride (TG) (161±90 vs. 130±66 mg/dl, p<0.01) and non-HDL-C (129±29 vs. 116±20 mg/dl, p<0.01) in combination with glucose (150±47 vs. 129±27 mg/dl, p<0.01) and HbA1c (7.1±0.6 vs. 6.6±0.7 mg/dl, p<0.001). Sitagliptin also significantly decreased the fasting levels of apolipoprotein (apo) B-48 (7.8±6.7 vs. 5.6±4.0 µg/ml, p<0.01), remnant lipoprotein cholesterol (15.3±9.5 vs. 12.0±7.9 mg/dl, p<0.05) and other apolipoproteins, such as apoB, apoC-II, apoC-III, and apoE. Analyses of the lipoprotein profiles of fasting sera revealed that sitagliptin significantly decreased cholesterol and TG levels of lipoprotein fractions in the size of very low density lipoprotein and low density lipoprotein. These findings indicated that sitagliptin administration ameliorated the lipid and lipoprotein profiles in patients with diabetes, which may be due to the decrease in atherogenic remnant lipoproteins (UMIN#000013218).

  1. Lipoprotein(a-Associated Molecules Are Prominent Components in Plasma and Valve Leaflets in Calcific Aortic Valve Stenosis

    Directory of Open Access Journals (Sweden)

    Michael Torzewski, MD

    2017-06-01

    Full Text Available Summary: The LPA gene is the only monogenetic risk factor for calcific aortic valve stenosis (CAVS. Oxidized phospholipids (OxPL and lysophosphatidic acid generated by autotaxin (ATX from OxPL are pro-inflammatory. Aortic valve leaflets categorized pathologically from both ATX–apolipoprotein B and ATX–apolipoprotein(a were measureable in plasma. Lipoprotein(a (Lp[a], ATX, OxPL, and malondialdehyde epitopes progressively increased in immunostaining (p < 0.001 for all. Six species of OxPL and lysophosphatidic acid were identified after extraction from valve leaflets. The presence of a constellation of pathologically linked, Lp(a-associated molecules in plasma and in aortic valve leaflets of patients with CAVS suggest that Lp(a is a key etiologic factor in CAVS. Key Words: aortic valve stenosis, autotaxin, inflammation, Lp(a, oxidation-specific epitopes

  2. Whole Body Vibration Retards Progression of Atherosclerosis via Insulin-Like Growth Factor 1 in Apolipoprotein E-Deficient Mice

    Directory of Open Access Journals (Sweden)

    He Wu

    2018-01-01

    Full Text Available Whole body vibration (WBV has a marked impact on lipid metabolism and the endocrine system, which is related to the progression of atherosclerosis (AS. To investigate the effects of WBV, we measured the atherosclerotic plaque area of apolipoprotein E-knockout (ApoE−/− AS mice, which were trained by WBV (15 Hz, 30 min for 12 weeks. Simultaneously, serum levels of lipids, insulin-like growth factor 1 (IGF-1, insulin-like growth factor 1 receptor (IGF-1R, interleukin 6 (IL-6, and the mRNA and protein levels of the same in the aorta were compared between the control and WBV groups. The results indicated that WBV significantly reduced the atherosclerotic plaque area with lower very low-density lipoprotein (VLDL and oxidized low-density lipoprotein (ox-LDL in the blood. Moreover, the levels of IGF-1 in serum and expression of IL-6, IGF-1R, and p-IGF-1R protein in the mice aorta decreased significantly in the WBV group. In addition, we found that serum IGF-1 in mice increased to the highest concentration in 30 min after WBV for 10, 30, 60, and 120 minutes. These results suggested that appropriate WBV may delay the progression of AS, which was associated with acutely elevated serum IGF-1 and lower levels of IGF-1 and IL-6 in the aorta for long-term treatment.

  3. Whole Body Vibration Retards Progression of Atherosclerosis via Insulin-Like Growth Factor 1 in Apolipoprotein E-Deficient Mice.

    Science.gov (United States)

    Wu, He; Zhang, Yibo; Yang, Xuan; Li, Xian; Shao, Zhenya; Zhou, Zipeng; Li, Yuanlong; Pan, Shuwen; Liu, Chang

    2018-01-01

    Whole body vibration (WBV) has a marked impact on lipid metabolism and the endocrine system, which is related to the progression of atherosclerosis (AS). To investigate the effects of WBV, we measured the atherosclerotic plaque area of apolipoprotein E-knockout (ApoE -/- ) AS mice, which were trained by WBV (15 Hz, 30 min) for 12 weeks. Simultaneously, serum levels of lipids, insulin-like growth factor 1 (IGF-1), insulin-like growth factor 1 receptor (IGF-1R), interleukin 6 (IL-6), and the mRNA and protein levels of the same in the aorta were compared between the control and WBV groups. The results indicated that WBV significantly reduced the atherosclerotic plaque area with lower very low-density lipoprotein (VLDL) and oxidized low-density lipoprotein (ox-LDL) in the blood. Moreover, the levels of IGF-1 in serum and expression of IL-6, IGF-1R, and p-IGF-1R protein in the mice aorta decreased significantly in the WBV group. In addition, we found that serum IGF-1 in mice increased to the highest concentration in 30 min after WBV for 10, 30, 60, and 120 minutes. These results suggested that appropriate WBV may delay the progression of AS, which was associated with acutely elevated serum IGF-1 and lower levels of IGF-1 and IL-6 in the aorta for long-term treatment.

  4. Proteomic analysis of high-density lipoprotein

    NARCIS (Netherlands)

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

    2006-01-01

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

  5. 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

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

    Science.gov (United States)

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

    2012-03-15

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    1979-11-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  10. Acrolein Modification Impairs Key Functional Features of Rat Apolipoprotein E: Identification of Modified Sites by Mass Spectrometry

    Science.gov (United States)

    Tran, Tuyen N.; Kosaraju, Malathi G.; Tamamizu-Kato, Shiori; Akintunde, Olayemi; Zheng, Ying; Bielicki, John K.; Pinkerton, Kent; Uchida, Koji; Lee, Yuan Yu; Narayanaswami, Vasanthy

    2014-01-01

    Apolipoprotein E (apoE), an anti-atherogenic apolipoprotein, plays a significant role in the metabolism of lipoproteins. It lowers plasma lipid levels by acting as a ligand for low-density lipoprotein receptor (LDLr) family of proteins, in addition to playing a role in promoting macrophage cholesterol efflux in atherosclerotic lesions. The objective of this study is to examine the effect of acrolein modification on the structure and function of rat apoE and to determine sites and nature of modification by mass spectrometry. Acrolein is a highly reactive aldehyde, which is generated endogenously as one of the products of lipid peroxidation and is present in the environment in pollutants such as tobacco smoke and heated oils. In initial studies, acrolein-modified apoE was identified by immunoprecipitation using an acrolein-lysine specific antibody, in the plasma of ten-week old male rats that were exposed to filtered air (FA) or low doses of environmental tobacco smoke (ETS). While both groups displayed acrolein-modified apoE in the lipoprotein fraction, the ETS group had higher levels in lipid-free fraction compared to the FA group. This observation provided the rationale to further investigate the effect of acrolein modification on rat apoE at a molecular level. Treatment of recombinant rat apoE with a 10-fold molar excess of acrolein resulted in: (i) a significant decrease in lipid-binding and cholesterol efflux abilities, (ii) impairment in the LDLr- and heparin-binding capabilities, and (iii) significant alterations in the overall stability of the protein. The disruption in the functional abilities is attributed directly or indirectly to acrolein modification yielding: an aldimine adduct at K149 and K155 (+38); a propanal adduct at K135 and K138 (+56); an Nε-(3-methylpyridinium)lysine (MP-lysine) at K64, K67 and K254 (+76), and Nε-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine) derivative at position K68 (+94), as determined by Matrix-Assisted Laser

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

    Directory of Open Access Journals (Sweden)

    Jakob Von Engelhardt

    2009-10-01

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

  12. The apolipoprotein AV gene and diurnal triglyceridaemia in normolipidaemic subjects

    NARCIS (Netherlands)

    Masana, L; Ribalta, J; Salazar, J; Fernandez-Ballart, J; Joven, J; Cabezas, MC

    2003-01-01

    The newly recognised apolipoprotein (apo) AV gene (APOAV) has been linked to fasting plasma triglyceride (TG) concentrations with some polymorphisms associated with elevated fasting TGs. Since fasting plasma TGs are mainly determined by the hepatic production of TGrich particles (very low density

  13. Apolipoprotein E gene polymorphism in Egyptian acute coronary ...

    African Journals Online (AJOL)

    Background: Apolipoprotein E (apo E) gene polymorphism was found to be associated with coronary artery disease in several studies. In this investigation, we aimed to study the association between apo E gene polymorphism and acute coronary syndrome in Egyptian population. Subjects and methods: The study included ...

  14. Apolipoprotein E gene and sporadic frontal lobe dementia.

    NARCIS (Netherlands)

    M. Stevens (Martijn); C.M. van Duijn (Cornelia); P. de Knijff (Peter); B.A. Oostra (Ben); M.F. Niermeijer (Martinus); J.C. van Swieten (John); P. Heutink (Peter); C. van Broeckhoven (Christine)

    1997-01-01

    textabstractThe apolipoprotein E gene has been associated with various types of dementia. We studied the connection between the APOE gene and the risk and onset of disease in 34 patients with clinically diagnosed frontal lobe dementia (FLD) derived from a population-based study in the Netherlands. A

  15. Demonstration Of An Abnormality Of Apolipoprotein Ciii And Genetic ...

    African Journals Online (AJOL)

    ... HDL at the same manner (p < 0.01). So it could be concluded that rare S2 allele of APOC3 gene may be represent a risk factor of developing coronary artery disease in Egyptians Keywords: Apolipoprotein CIII, genetic polymorphism, gout, hypertriglyceridemia. Egyptian Journal of Biochemistry and Molecular Biology Vol.

  16. Circulating Apolipoprotein A1, Haptoglobin and Α2 Macroglobulin ...

    African Journals Online (AJOL)

    α2-MG), Apolipoprotein A1 (Apo-1) and Haptoglobin (HP) as non-invasive index of the presence of cirrhosis in chronic hepatitis C patients in relation to the histopathological findings. Subjects and Methods: The study was carried out on 20 ...

  17. Role of apolipoprotein CI in lipid metabolism and bacterial sepsis

    NARCIS (Netherlands)

    Berbée, Jimmy Fransiscus Paulus

    2007-01-01

    The research described in this thesis focussed on the role of apolipoproteins in lipid metabolism, inflammation and bacterial sepsis, with specific emphasis on apoCI. From studies in human APOC1¬-transgenic and apoc1-/- mice, we were able to identify apoCI as a potent inhibitor of triglyceride

  18. Familial defective apolipoprotein-B is rare in hypercholesterolaemic ...

    African Journals Online (AJOL)

    The frequency of familial defective apolipoprotein B-100. (FOB) was assessed among hypercholesterolaemic. Afrikaners, coloureds and Indians. Patients selected for screening did not carry any of the founder or common. LOL-receptor mutations known to be associated with these groups. No FOB was detected and the ...

  19. Apolipoprotein a5 and hypertriglyceridemia in prague hypertriglyceridemic rats

    Czech Academy of Sciences Publication Activity Database

    Kadlecová, Michaela; Hojná, Silvie; Bohuslavová, R.; Hubáček, J. A.; Zicha, Josef; Kuneš, Jaroslav

    2006-01-01

    Roč. 55, č. 4 (2006), s. 373-379 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/03/0769 Institutional research plan: CEZ:AV0Z50110509 Keywords : metabolic syndrome * apolipoprotein A5 * rat Subject RIV: ED - Physiology Impact factor: 2.093, year: 2006

  20. Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke

    DEFF Research Database (Denmark)

    Khan, Tauseef A; Shah, Tina; Prieto, David

    2013-01-01

    At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less c...

  1. Association of four apolipoprotein B polymorphisms with lipid profile ...

    Indian Academy of Sciences (India)

    Sahloul University Hospital, 4054 Sousse, Tunisia. [Lamia R., Asma O., Slim K., Jihène R., Imen B., Ibtihel B. H., Kaouther K., Radhia B., Nabila B. R., Naoufel N., Ahmed B. A., Essia B. and Ali B. 2012 Association of four apolipoprotein B polymorphisms with lipid profile and stenosis in Tunisian coronary patients. J. Genet.

  2. MicroRNA-134 Promotes the Development of Atherosclerosis Via the ANGPTL4/LPL Pathway in Apolipoprotein E Knockout Mice.

    Science.gov (United States)

    Ye, Qiong; Tian, Guo-Ping; Cheng, Hai-Peng; Zhang, Xin; Ou, Xiang; Yu, Xiao-Hua; Tan, Ru-Qi; Yang, Feng-Yun; Gong, Duo; Huang, Chong; Pan, Yan-Jun; Zhang, Jie; Chen, Ling-Yan; Zhao, Zhen-Wang; Xie, Wei; Li, Liang; Zhang, Min; Xia, Xiao-Dan; Zheng, Xi-Long; Tang, Chao-Ke

    2018-03-01

    Atherosclerosis is the most common cause of cardiovascular disease, such as myocardial infarction and stroke. Previous study revealed that microRNA (miR)-134 promotes lipid accumulation and proinflammatory cytokine secretion through angiopoietin-like 4 (ANGPTL4)/lipid lipoprotein (LPL) signaling in THP-1 macrophages. ApoE KO male mice on a C57BL/6 background were fed a high-fat/high-cholesterol Western diet, from 8 to 16 weeks of age. Mice were divided into four groups, and received a tail vein injection of miR-134 agomir, miR-134 antagomir, or one of the corresponding controls, respectively, once every 2 weeks after starting the Western diet. After 8 weeks we measured aortic atherosclerosis, LPL Activity, mRNA and protein levels of ANGPTL4 and LPL, LPL/ low-density lipoprotein receptor related protein 1 Complex Formation, proinflammatory cytokine secretion and lipid levels. Despite this finding, the influence of miR-134 on atherosclerosis in vivo remains to be determined. Using the well-characterized mouse atherosclerosis model of apolipoprotein E knockout, we found that systemic delivery of miR-134 agomir markedly enhanced the atherosclerotic lesion size, together with a significant increase in proinflammatory cytokine secretion and peritoneal macrophages lipid contents. Moreover, overexpression of miR-134 decreased ANGPTL4 expression but increased LPL expression and activity in both aortic tissues and peritoneal macrophages, which was accompanied by increased formation of LPL/low-density lipoprotein receptor-related protein 1 complexes in peritoneal macrophages. However, an opposite effect was observed in response to miR-134 antagomir. These findings suggest that miR-134 accelerates atherogenesis by promoting lipid accumulation and proinflammatory cytokine secretion via the ANGPTL4/LPL pathway. Therefore, targeting miR-134 may offer a promising strategy for the prevention and treatment of atherosclerotic cardiovascular disease.

  3. Effects of lutein-enriched egg yolk in buttermilk or skimmed milk on serum lipids & lipoproteins of mildly hypercholesterolemic subjects.

    Science.gov (United States)

    Severins, N; Mensink, R P; Plat, J

    2015-02-01

    Earlier studies in our group suggested that traditionally prepared buttermilk influences cholesterol metabolism. We therefore designed a study to evaluate whether traditionally prepared buttermilk lowers serum low-density lipoprotein cholesterol (LDL-C) and/or prevents the LDL-C raising effect of egg yolks. Mildly hypercholesterolemic subjects were randomly allocated to one of four diet groups consuming daily at lunch 80 ml skimmed milk with (n = 23) or without (n = 25) lutein-enriched egg yolk (28 g from 1.5 eggs providing 323 mg cholesterol) or traditionally prepared buttermilk with (n = 23) or without (n = 21) lutein-enriched egg yolk during a 12 week period. Fasting blood samples were taken to measure concentrations of serum lipids, (apo)lipoproteins, liver and kidney function markers, and plasma lutein, zeaxanthin and high-sensitive C-reactive protein (hsCRP). Egg yolk consumption significantly increased serum total cholesterol (total-C) (p = 0.035) and LDL-C concentrations (p = 0.022). Buttermilk did not change the effects of egg yolk on serum lipids and (apo)lipoproteins. There was a trend towards significant lower total-C (p = 0.077), but not LDL-C (p = 0.204) concentrations in the buttermilk groups. Plasma lutein and zeaxanthin concentrations increased significantly (p egg yolk groups. In mildly hypercholesterolemic subjects, daily consumption of traditionally prepared buttermilk for 12 weeks did not lower serum total-C or LDL-C concentrations, nor did it prevent the serum total-C and LDL-C raising effect of daily egg yolk consumption. This study is registered at www.clinicaltrials.gov as NCT01566305. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Narita, Shin-Ichiro; Tokuda, Hajime

    2017-11-01

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

  5. A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol

    DEFF Research Database (Denmark)

    Surakka, Ida; Whitfield, John B; Perola, Markus

    2012-01-01

    in serum lipid and apolipoprotein levels. We report data for 1,720 monozygotic female twin-pairs from GenomEUtwin project with 2.5 million SNPs, imputed or genotyped, and measured serum lipid fractions for both twins. We found one locus associated with intra-pair differences in high-density lipoprotein......Genome-wide association analysis on monozygotic twin-pairs offers a route to discovery of gene-environment interactions through testing for variability loci associated with sensitivity to individual environment/lifestyle. We present a genome-wide scan of loci associated with intra-pair differences...

  6. Apolipoprotein-E forms dimers in human frontal cortex and hippocampus

    Directory of Open Access Journals (Sweden)

    Halliday Glenda M

    2010-02-01

    Full Text Available Abstract Background Apolipoprotein-E (apoE plays important roles in neurobiology and the apoE4 isoform increases risk for Alzheimer's disease (AD. ApoE3 and apoE2 are known to form disulphide-linked dimers in plasma and cerebrospinal fluid whereas apoE4 cannot form these dimers as it lacks a cysteine residue. Previous in vitro research indicates dimerisation of apoE3 has a significant impact on its functions related to cholesterol homeostasis and amyloid-beta peptide degradation. The possible occurrence of apoE dimers in cortical tissues has not been examined and was therefore assessed. Human frontal cortex and hippocampus from control and AD post-mortem samples were homogenised and analysed for apoE by western blotting under both reducing and non-reducing conditions. Results In apoE3 homozygous samples, ~12% of apoE was present as a homodimer and ~2% was detected as a 43 kDa heterodimer. The level of dimerisation was not significantly different when control and AD samples were compared. As expected, these dimerised forms of apoE were not detected in apoE4 homozygous samples but were detected in apoE3/4 heterozygotes at a level approximately 60% lower than seen in the apoE3 homozygous samples. Similar apoE3 dimers were also detected in lysates of SK-N-SH neuroblastoma cells and in freshly prepared rabbit brain homogenates. The addition of the thiol trapping agent, iodoacetamide, to block reactive thiols during both human and rabbit brain sample homogenisation and processing did not reduce the amount of apoE homodimer recovered. These data indicate that the apoE dimers we detected in the human brain are not likely to be post-mortem artefacts. Conclusion The identification of disulphide-linked apoE dimers in human cortical and hippocampal tissues represents a distinct structural difference between the apoE3 and apoE4 isoforms that may have functional consequences.

  7. A more flexible lipoprotein sorting pathway.

    Science.gov (United States)

    Chahales, Peter; Thanassi, David G

    2015-05-01

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

  8. [Alterations in the protein content and dysfunction of high-density lipoproteins from hyperhomocysteinemic mice].

    Science.gov (United States)

    Julve, Josep; Errico, Teresa Laura; Chen, Xiangyu; Santos, David; Freixa, Júlia; Porcel, Inmaculada; Cubero, Esther; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

    2013-01-01

    The aim of this study was to evaluate the proteic changes in high-density lipoproteins (HDL) induced by methionine-induced hyperhomocysteinemia in mice and its relationship with two of their main antiatherogenic properties. The oral administration of methionine resulted in an elevation (~8 times) in the plasma concentration of homocysteine. Hyperhomocysteinemia was inversely correlated with the plasma concentration of HDL cholesterol and its main protein component of HDL, apolipoprotein (apo) A-I, respectively. The cholesterol efflux in vivo from macrophages to HDL was decreased in hyperhomocysteinemic mice compared with the control mice. However, the reverse cholesterol transport from macrophages to feces remained unchanged. On the other hand, the ability of HDL from hyperhomocysteinemic mice to prevent the oxidative modification of low-density lipoproteins (LDL) was found decreased and associated with a concomitant reduction in the plasma activity of paraoxonase-1 (PON1) and the plasma concentration of apoA-I, and with a relative reduction in the apoA-IV content (~1.5 times) in the hyperhomocysteinemic HDL, respectively. The decrease in the ability of HDL from hyperhomocysteinemic mice to prevent LDL from oxidation was associated with a decrease in the apoA-I, PON1 and apoA-IV. Copyright © 2013 Elsevier España, S.L. and SEA. All rights reserved.

  9. Ethanol consumption affects lipoprotein lipase gene expression in C57BL/6 mice.

    Science.gov (United States)

    Mudráková, E; Kovár, J

    2007-01-01

    The activity of lipoprotein lipase (LPL) is increased after alcohol consumption and can contribute to an increased level of HDL-cholesterol, which is considered to play a key role in the ethanol-mediated protective effect against cardiovascular disease. The increase in HDL-cholesterol concentration can be also due to an ethanol-enhanced synthesis and secretion of apolipoprotein A-I (apo A-I) from hepatocytes. Therefore, the hypothesis that ethanol consumption affects the LPL and apo A-I gene (LPL and APOA1, respectively) expression was tested in male C57BL/6 mice drinking 5 % ethanol or water and fed a standard chow or high-fat (HF) diet for 4 weeks. The LPL expression was determined in the heart, epididymal and dorsolumbal adipose tissues, the APOA1 expression in the liver. Alcohol consumption did not affect lipid and lipoprotein concentrations in the serum. The LPL expression was increased in the heart of mice given ethanol and HF diet compared to mice on chow and ethanol (pconsumption. Our data suggest that ethanol consumption upregulates LPL expression in a tissue- and diet-dependent manner.

  10. CAT‐2003: A novel sterol regulatory element‐binding protein inhibitor that reduces steatohepatitis, plasma lipids, and atherosclerosis in apolipoprotein E*3‐Leiden mice

    Science.gov (United States)

    Bista, Pradeep; Benson, Ericka L.; Lee, Diana Y.; Liu, Feng; Picarella, Dominic; Vega, Rick B.; Vu, Chi B.; Yeager, Maisy; Ding, Min; Liang, Guosheng; Horton, Jay D.; Kleemann, Robert; Kooistra, Teake; Morrison, Martine C.; Wielinga, Peter Y.; Milne, Jill C.; Jirousek, Michael R.; Nichols, Andrew J.

    2017-01-01

    CAT‐2003 is a novel conjugate of eicosapentaenoic acid (EPA) and niacin designed to be hydrolyzed by fatty acid amide hydrolase to release EPA inside cells at the endoplasmic reticulum. In cultured liver cells, CAT‐2003 blocked the maturation of sterol regulatory element‐binding protein (SREBP)‐1 and SREBP‐2 proteins and decreased the expression of multiple SREBP target genes, including HMGCR and PCSK9. Consistent with proprotein convertase subtilisin/kexin type 9 (PCSK9) reduction, both low‐density lipoprotein receptor protein at the cell surface and low‐density lipoprotein particle uptake were increased. In apolipoprotein E*3‐Leiden mice fed a cholesterol‐containing western diet, CAT‐2003 decreased hepatic inflammation and steatosis as evidenced by fewer inflammatory cell aggregates in histopathologic sections, decreased nuclear factor kappa B activity in liver lysates, reduced inflammatory gene expression, reduced intrahepatic cholesteryl ester and triglyceride levels, and decreased liver mass. Plasma PCSK9 was reduced and hepatic low‐density lipoprotein receptor protein expression was increased; plasma cholesterol and triglyceride levels were lowered. Aortic root segments showed reduction of several atherosclerotic markers, including lesion size, number, and severity. CAT‐2003, when dosed in combination with atorvastatin, further lowered plasma cholesterol levels and decreased hepatic expression of SREBP target genes. Conclusion: SREBP inhibition is a promising new strategy for the prevention and treatment of diseases associated with abnormal lipid metabolism, such as atherosclerosis and nonalcoholic steatohepatitis. (Hepatology Communications 2017;1:311–325) PMID:29404461

  11. Common variants of apolipoprotein E and cholesteryl ester transport protein genes in male patients with coronary heart disease and variable body mass index.

    Science.gov (United States)

    Kolovou, Genovefa D; Panagiotakos, Demosthenes B; Kolovou, Vana; Vasiliadis, Ioannis; Giannakopoulou, Vasiliki; Diakoumakou, Olga; Katsiki, Niki; Mavrogeni, Sophie

    2015-02-01

    Plasma lipids are major risk factors for coronary heart disease (CHD). Cholesteryl ester transfer protein (CETP) and apolipoprotein (apo) E genes are involved in lipoprotein metabolism, thus affecting plasma lipid and lipoproteins levels. Furthermore, such polymorphisms have been associated with susceptibility to CHD and obesity. We evaluated the influence of the gene polymorphisms of CETP TaqIB (B1, B2) and I405V (V, I) and apo E (∊2,∊3,∊4) on lipid levels, according to body mass index (BMI) in Greek men with CHD. The TaqIB (B1, B2) polymorphism affected plasma low-density lipoprotein cholesterol levels in overweight men with CHD, whereas the I405V (V, I) polymorphism affected triglyceride concentrations in normal weight men. No correlation was found between BMI and apo E polymorphisms. Large prospective studies are required to investigate the relationships of CETP and apo E polymorphisms with lipids, BMI, and CHD susceptibility. © The Author(s) 2014.

  12. Effect of two oral contraceptives containing ethinyl estradiol and gestodene or norgestimate on different lipid and lipoprotein parameters.

    Science.gov (United States)

    Wiegratz, I; Jung-Hoffmann, C; Gross, W; Kuhl, H

    1998-08-01

    The effect of a triphasic oral contraceptive containing ethinyl estradiol and gestodene (EE/GSD) on various lipid and lipoprotein parameters was compared with that of a monophasic formulation containing 35 micrograms ethinyl estradiol and 250 micrograms norgestimate (EE/NGM). Blood samples were collected from 46 women on days 2, 11, and 21 of the preceding control cycle and of the third, sixth, and twelfth treatment cycles. There was no significant difference between formulations with regard to the influence on any measured parameter. As compared with controls, a significant increase was observed in the plasma levels of total triglycerides (24-78%), total phospholipids (7-20%), very low density lipoprotein (VLDL) triglycerides (61-76%), VLDL-phospholipids (14-60%), low density lipoprotein (LDL) triglycerides (8-35%), LDL-phospholipids (28-30%), high density lipoprotein (HDL) cholesterol (8-16%), HDL 3-cholesterol (11-20%), HDL-triglycerides (17-66%), HDL-phospholipids, HDL 3-phospholipids (7-11%), apolipoprotein (apo) A-I (5-20%) and apo A-II (10-40%) during treatment with both formulations. In contrast, the LDL-cholesterol levels were significantly decreased. These changes in lipid metabolism appear to reflect a predominance of the effect of the estrogen component. The results indicate that both low dose oral contraceptives containing different progestins and different amounts of EE do not exert a deleterious effect on lipoprotein metabolism, as high HDL-cholesterol and low LDL-cholesterol levels are known as low risk factors of cardiovascular disease. In contrast to endogenous hypertriglyceridemia, an EE-induced rise in triglyceride levels does not appear to increase cardiovascular risk if LDL is not increased.

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

    Science.gov (United States)

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

    2015-12-08

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

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

    Science.gov (United States)

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

    2013-01-01

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

  15. Study on the correlation between the concentration of plasma lipoprotein-associated phospholipase A2 and coronary heart disease

    Directory of Open Access Journals (Sweden)

    Jin-Ming Cen

    2015-06-01

    Full Text Available Objective: This study explores the correlation between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2 and coronary heart disease (CHD by comparing the level of plasma Lp-PLA2 in the plasma of patients with different types of CHD. Methods: Blood samples were collected from 56 patients diagnosed with CHD by the Department of Cardiology of the First People's Hospital of Foshan and 34 healthy subjects from February 2013 to January 2014. We measured the concentration of plasma Lp-PLA2 and determined the levels of total cholesterol (Tch, triglyceride (TG, apolipoprotein A1 (Apo-A1, apolipoprotein B (Apo-B, high density lipoprotein-cholesterol (HDL-c, low density lipoprotein-cholesterol (LDL-c, lipoprotein a (Lp(a, glucose (Glu, and high-sensitivity C-reactive protein (hs-CRP. The concentration of plasma Lp-PLA2 in the healthy control group and each subgroup of CHD patients were compared and analyzed for correlations of plasma Lp-PLA2 between the patients in different CHD subgroups and several laboratory indicators. Results: The concentration of plasma Lp-PLA2 in each subgroup of CHD was significantly higher than in the control group (P < 0.05. The concentration of Lp-PLA2 in the unstable angina pectoris (UAP group and acute myocardial infarction (AMI group were significantly higher than in the stable angina pectoris (SAP group (P < 0.05, and the concentration of plasma Lp-PLA2 in the AMI group was significantly higher than in the UAP group (P < 0.05. The concentration of plasma Lp-PLA2 in the CHD group merely showed a positive correlation (r = 0.493, P < 0.05 with the hs-CRP group, but the levels of Tch, TG, Apo-A1, Apo-B, HDL-c, LDL-c, Lp(a and Glu did not. Conclusions: The concentration of plasma Lp-PLA2 in patients with CHD was higher than that in the control group. The concentration of plasma Lp-PLA2 in the subgroups of CHD patients varied greatly from each other. The inflammatory response of atherosclerosis might be resulted

  16. Aspects on lipoprotein lipase and atherosclerosis

    OpenAIRE

    Neuger, Lucyna

    2005-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yano Takahisa

    2011-01-01

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

  18. Effects of coconut oil, butter, and safflower oil on lipids and lipoproteins in persons with moderately elevated cholesterol levels.

    Science.gov (United States)

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

    1995-08-01

    The physiological effects of coconut oil, butter, and safflower oil on lipids and lipoproteins have been compared in moderately hypercholesterolemic individuals. Twenty eight participants (13 men, 15 women) followed three 6-week experimental diets of similar macronutrient distribution with the different test fats providing 50% total dietary fat. Total cholesterol and low density lipoprotein cholesterol were significantly higher (P coconut oil diet (6.4 +/- 0.8; 4.2 +/- 0.7 mmol/l) when levels were significantly higher (P coconut oil (157 +/- 17 mg/dl) and on butter (141 +/- 23 mg/dl) than on safflower oil (132 +/- 22 mg/dl). Apolipoprotein B was also higher on butter (86 +/- 20 mg/dl) and coconut oil (91 +/- 32 mg/dl) than on safflower oil (77 +/- 19 mg/dl). However gender differences were apparent. In the group as a whole, high density lipoprotein did not differ significantly on the three diets whereas levels in women on the butter and coconut oil diet were significantly higher than on the safflower oil diet. Triacylglycerol was higher on the butter diet than on the safflower and coconut oil diets but the difference only reached statistical significance in women. Cholesteryl ester transfer activity was significantly higher on butter than safflower oil in the group as a whole and in women.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Receptor-mediated uptake of low density lipoprotein stimulates bile acid synthesis by cultured rat hepatocytes

    International Nuclear Information System (INIS)

    Junker, L.H.; Davis, R.A.

    1989-01-01

    The cellular mechanisms responsible for the lipoprotein-mediated stimulation of bile acid synthesis in cultured rat hepatocytes were investigated. Adding 280 micrograms/ml of cholesterol in the form of human or rat low density lipoprotein (LDL) to the culture medium increased bile acid synthesis by 1.8- and 1.6-fold, respectively. As a result of the uptake of LDL, the synthesis of [14C]cholesterol from [2-14C]acetate was decreased and cellular cholesteryl ester mass was increased. Further studies demonstrated that rat apoE-free LDL and apoE-rich high density lipoprotein (HDL) both stimulated bile acid synthesis 1.5-fold, as well as inhibited the formation of [14C]cholesterol from [2-14C]acetate. Reductive methylation of LDL blocked the inhibition of cholesterol synthesis, as well as the stimulation of bile acid synthesis, suggesting that these processes require receptor-mediated uptake. To identify the receptors responsible, competitive binding studies using 125I-labeled apoE-free LDL and 125I-labeled apoE-rich HDL were performed. Both apoE-free LDL and apoE-rich HDL displayed an equal ability to compete for binding of the other, suggesting that a receptor or a group of receptors that recognizes both apolipoproteins is involved. Additional studies show that hepatocytes from cholestyramine-treated rats displayed 2.2- and 3.4-fold increases in the binding of apoE-free LDL and apoE-rich HDL, respectively. These data show for the first time that receptor-mediated uptake of LDL by the liver is intimately linked to processes activating bile acid synthesis

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

    Directory of Open Access Journals (Sweden)

    Valentin eGogonea

    2016-01-01

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

  1. Effect of TNF{alpha} on activities of different promoters of human apolipoprotein A-I gene

    Energy Technology Data Exchange (ETDEWEB)

    Orlov, Sergey V., E-mail: serge@iem.sp.ru [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Mogilenko, Denis A. [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Shavva, Vladimir S. [Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Dizhe, Ella B.; Ignatovich, Irina A. [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Perevozchikov, Andrej P., E-mail: app@iem.sp.ru [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation)

    2010-07-23

    Research highlights: {yields} TNF{alpha} stimulates the distal alternative promoter of human apoA-I gene. {yields} TNF{alpha} acts by weakening of promoter competition within apoA-I gene (promoter switching). {yields} MEK1/2 and nuclear receptors PPAR{alpha} and LXRs take part in apoA-I promoter switching. -- Abstract: Human apolipoprotein A-I (ApoA-I) is a major structural and functional protein component of high-density lipoproteins. The expression of the apolipoprotein A-I gene (apoA-I) in hepatocytes is repressed by pro-inflammatory cytokines such as IL-1{beta} and TNF{alpha}. Recently, two novel additional (alternative) promoters for human apoA-I gene have been identified. Nothing is known about the role of alternative promoters in TNF{alpha}-mediated downregulation of apoA-I gene. In this article we report for the first time about the different effects of TNF{alpha} on two alternative promoters of human apoA-I gene. Stimulation of HepG2 cells by TNF{alpha} leads to activation of the distal alternative apoA-I promoter and downregulation of the proximal alternative and the canonical apoA-I promoters. This effect is mediated by weakening of the promoter competition within human apoA-I 5'-regulatory region (apoA-I promoter switching) in the cells treated by TNF{alpha}. The MEK1/2-ERK1/2 cascade and nuclear receptors PPAR{alpha} and LXRs are important for TNF{alpha}-mediated apoA-I promoter switching.

  2. Metabolic heterogeneity of apolipoprotein B in the rat

    International Nuclear Information System (INIS)

    Sparks, C.E.; Marsh, J.B.

    1981-01-01

    Triglyceride-rich lipoprotein apoprotein catabolism was studied in rats from 5 to 60 min after intravenous injection of 125 I-labeled lipoproteins. The plasma and liver labeled apoprotein content was analyzed by gel filtration column chromatography using an elution buffer containing 1% sodium dodecyl sulfate. The method resolved two B apoproteins of lower (apo B1) and higher (apo Bh) molecular weight. Total apoprotein B disappeared from plasma faster than either apo E or apo C and the smaller sized apo B1 had the most rapid disappearance, with 90% being lost after 60 min. The larger sized apo Bh disappeared rapidly from the plasma in the first 15 min but between 15 and 60 min 40% of the apo Bh remained in the plasma, associated with low density lipoprotein. Apoprotein analysis of liver homogenates was consistent with the plasma results. There was 28% of apo B1 compared to 16% of apo Bh present in the liver 5 min after injection, expressed as percent of initial injected radioactivity in each fraction. Apo B1 and apo Bh were the predominant liver apoproteins up to 30 min but by 60 min there was little of either apo B in the liver. In contrast to apo B, there was a relatively constant amount of apo E and apo C, about 10%, associated with the liver over 60 min. Plasma apo E declined progressively to 68% and apo C to 86% of initial concentration by 60 min. These findings suggest that there is differential hepatic catabolism of a subpopulation of triglyceride-rich lipoproteins containing apo B1. A population of triglyceride-rich lipoproteins containing apo Bh preferentially enters the low density lipoprotein pool with a slower catabolism. The results are consistent with an hypothesis that apo B1 mediates binding and rapid hepatic catabolism of its associated lipoproteins. Metabolic heterogeneity of the triglyceride-rich lipoproteins may be explained by the molecular heterogeneity of apoprotein B

  3. Apolipoprotein M mediates sphingosine-1-phosphate efflux from erythrocytes

    DEFF Research Database (Denmark)

    Christensen, Pernille M.; Bosteen, Markus H.; Hajny, Stefan

    2017-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive lipid implicated in e.g. angiogenesis, lymphocyte trafficking, and endothelial barrier function. Erythrocytes are a main source of plasma S1P together with platelets and endothelial cells. Apolipoprotein M (apoM) in HDL carries 70% of plasma S1P, where...... of ABCB1 or ATPase. Thus, ABCC1 could be involved in export of S1P from erythrocytes to apoM....

  4. 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)....

  5. Postmenopausal hypertension, abdominal obesity, apolipoprotein and insulin resistance.

    Science.gov (United States)

    Ben Ali, Samir; Belfki-Benali, Hanen; Ahmed, Decy Ben; Haddad, Najet; Jmal, Awatef; Abdennebi, Monia; Romdhane, Habiba Ben

    This study aimed to evaluate the association of abdominal obesity, apolipoprotein and insulin resistance (IR) with the risk of hypertension in postmenopausal women. We analyzed a total of 242 women aged between 35 and 70 years. Blood pressure (BP), anthropometric indices, lipid profile, fasting glucose, insulin, C-reactive protein (CRP) and apolipoprotein concentrations were measured. Homeostasis model assessment (HOMA) was used to assess IR. Hypertension was defined as a systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg or current treatment with antihypertensive drugs. Women with hypertension showed significantly higher mean values of age, SBP and DBP, waist circumference (WC), fasting plasma glucose (FPG), insulin, HOMAIR and the apolipoprotein B (apoB). When analyses were done according to the menopausal status, higher prevalence of hypertension was observed in postmenopausal women (72.8% vs. 26.0%, p menopause (p = 0.008) were significantly associated with higher risk for hypertension. These results suggest that changes in WC, apoB and IR accompanying menopause lead to a greater prevalence of hypertension in postmenopausal women.

  6. Smoking, apolipoprotein E genotypes, and mortality (the Ludwigshafen RIsk and Cardiovascular Health study).

    Science.gov (United States)

    Grammer, Tanja B; Hoffmann, Michael M; Scharnagl, Hubert; Kleber, Marcus E; Silbernagel, Günther; Pilz, Stefan; Tomaschitz, Andreas; Lerchbaum, Elisabeth; Siekmeier, Rüdiger; März, Winfried

    2013-05-01

    The genetic polymorphism of apolipoprotein E (APOE) has been suggested to modify the effect of smoking on the development of coronary artery disease (CAD) in apparently healthy persons. The interaction of these factors in persons undergoing coronary angiography is not known. We analysed the association between the APOE-genotype, smoking, angiographic CAD, and mortality in 3263 participants of the LUdwigshafen RIsk and Cardiovascular Health study. APOE-genotypes were associated with CAD [ε22 or ε23: odds ratio (OR) 0.56, 95% confidence interval (CI) 0.43-0.71; ε24 or ε34 or ε44: OR 1.10, 95% CI 0.89-1.37 compared with ε33] and moderately with cardiovascular mortality [ε22 or ε23: hazard ratio (HR) 0.71, 95% CI 0.51-0.99; ε33: HR 0.92, 95% CI 0.75-1.14 compared with ε24 or ε34 or ε44]. HRs for total mortality were 1.39 (95% CI 0.39-0.1.67), 2.29 (95% CI 1.85-2.83), 2.07 (95% CI 1.64-2.62), and 2.95 (95% CI 2.10-4.17) in ex-smokers, current smokers, current smokers without, or current smokers with one ε4 allele, respectively, compared with never-smokers. Carrying ε4 increased mortality in current, but not in ex-smokers (HR 1.66, 95% CI 1.04-2.64 for interaction). These findings applied to cardiovascular mortality, were robust against adjustment for cardiovascular risk factors, and consistent across subgroups. No interaction of smoking and ε4 was seen regarding non-cardiovascular mortality. Smokers with ε4 had reduced average low-density lipoprotein (LDL) diameters, elevated oxidized LDL, and lipoprotein-associated phospholipase A2. In persons undergoing coronary angiography, there is a significant interaction between APOE-genotype and smoking. The presence of the ε4 allele in current smokers increases cardiovascular and all-cause mortality.

  7. Apolipoprotein E gene polymorphism and risk of type 2 diabetes and cardiovascular disease.

    Science.gov (United States)

    El-Lebedy, Dalia; Raslan, Hala M; Mohammed, Asmaa M

    2016-01-22

    Lipoprotein-related mechanisms have been associated with damage to the cardiovascular system in diabetic patients. Apolipoprotein E gene which affects the clearance of lipoproteins and consequently the lipid profile in our body is one of the most studied candidate genes and recently has been reported to be associated with T2DM and CAD. In this work, we studied the association of apoE gene polymorphism with T2DM and CVD and its effect on plasma lipids profile. Our study was conducted on 284 subjects categorized into 100 patients with T2DM, 100 patients with T2DM complicated with CVD and 84 normal control subjects. ApoE gene polymorphism was genotyped by real-time PCR using TaqMan(®) SNP Genotyping Assay. ApoE E3/E3 genotype was the most common in our subjects. The frequencies of E3/E4 genotype and ε4 allele were increased in both T2DM patients and CVD patients as compared with controls, but were significant only in CVD patients (p = 0.004 and 0.007, respectively). Diabetic patients who carried E3/E4 genotype were at 2.4-fold increased risk to develop CVD (95 % CI 1.14-5.19, P = 0.02) and the ε4 allele associated with 2.23-fold higher CVD risk (95 % CI 1.09-4.59, P = 0.02). After adjustment for other established risk factors, E3/E4 genotype was an independent risk factor for CVD (OR = 2.3, p = 0.009) but not for T2DM (OR = 1.7, p = 0.28), while ε4 allele was an independent risk factor for both T2DM (OR = 2.2, p = 0.04) and CVD (OR = 3.0, p = 0.018) with 5.9-fold increased risk to develop CVD in T2DM patients (p = 0.019). E3/E4 genotype associated with significantly higher levels of TC and non HDL-C in all groups and with significantly higher levels of LDL-C in both T2DM and CVD patients. ApoE gene polymorphisms associate with CVD and affect the lipid profile. The ε4 allele is an independent risk factor for both T2DM and CVD. Further genetic studies to add information beyond the traditional cardiovascular risk factors in T2DM and to identify risk genotypes will

  8. Apolipoprotein E isoform dependently affects Tat-mediated HIV-1 LTR transactivation.

    Science.gov (United States)

    Khan, Nabab; Datta, Gaurav; Geiger, Jonathan D; Chen, Xuesong

    2018-03-20

    Apolipoprotein E (ApoE) is the major carrier protein that mediates the transport and delivery of cholesterol and other lipids in the brain. Three isoforms of ApoE (ApoE2, ApoE3, ApoE4) exist in humans, and their relative expression levels impact HIV-1 infection, HIV-1/AIDS disease progression, and cognitive decline associated with HIV-1-associated neurocognitive disorder. Because HIV-1 Tat, a viral protein essential for HIV-1 replication, can bind to low-density lipoprotein receptor-related protein 1 (LRP1) that controls ApoE uptake in the brain, we determined the extent to which different isoforms of ApoE affected Tat-mediated HIV-1 LTR transactivation. Using U87MG glioblastoma cells expressing LTR-driven luciferase, we determined the extent to which LRP1 as well as ApoE2, ApoE3, and ApoE4 affected Tat-mediated HIV-1 LTR transactivation. A specific LRP1 antagonist and siRNA knockdown of LRP1 both restricted significantly Tat-mediated LTR transactivation. Of the three ApoEs, ApoE4 was the least potent and effective at preventing HIV-1 Tat internalization and at decreasing Tat-mediated HIV-1 LTR transactivation. Further, Tat-mediated LTR transactivation was attenuated by an ApoE mimetic peptide, and ApoE4-induced restriction of Tat-mediated LTR transactivation was potentiated by an ApoE4 structure modulator that changes ApoE4 into an ApoE3-like phenotype. These findings help explain observed differential effects of ApoEs on HIV-1 infectivity and the prevalence of HAND in people living with HIV-1 infection and suggest that ApoE mimetic peptides and ApoE4 structure modulator might be used as a therapeutic strategy against HIV-1 infection and associated neurocognitive disorders.

  9. Analysis of apolipoprotein A-I as a substrate for matrix metalloproteinase-14

    International Nuclear Information System (INIS)

    Park, Jun Hyoung; Park, Sung-Min; Park, Ki-Hoon; Cho, Kyung-Hyun; Lee, Seung-Taek

    2011-01-01

    Highlights: → MMP-14 degrades apoA-I more efficiently than other tested MMPs. → Lipid-free apoA-I is more susceptible to MMPs than lipid-bound apoA-I. → MMP-14 cleavage sites on apoA-I have been determined. → Cleavage of apoA-I by MMP-14 impairs its ability to form HDL. -- Abstract: Substrates for matrix metalloproteinase (MMP)-14 were previously identified in human plasma using proteomic techniques. One putative MMP-14 substrate was apolipoprotein A-I (apoA-I), a major component of high-density lipoprotein (HDL). In vitro cleavage assays showed that lipid-free apoA-I is a more accessible substrate for MMP-14 compared to lipid-bound apoA-I, and that MMP-14 is more prone to digest apoA-I than MMP-3. The 28-kDa apoA-I was cleaved into smaller fragments of 27, 26, 25, 22, and 14-kDa by MMP-14. ApoA-I sites cleaved by MMP-14 were determined by isotope labeling of C-termini derived from the cleavage and analysis of the labeled peptides by mass spectrometry, along with N-terminal sequencing of the fragments. Cleavage of apoA-I by MMP-14 resulted in a loss of ability to form HDL. Our results suggest that cleavage of lipid-free apoA-I by MMP-14 may contribute to reduced HDL formation, and this may be occurring during the development of various vascular diseases as lipid metabolism is disrupted.

  10. Differential action of glucocorticoids on apolipoprotein E gene expression in macrophages and hepatocytes.

    Science.gov (United States)

    Trusca, Violeta Georgeta; Fuior, Elena Valeria; Fenyo, Ioana Madalina; Kardassis, Dimitris; Simionescu, Maya; Gafencu, Anca Violeta

    2017-01-01

    Apolipoprotein E (apoE) has anti-atherosclerotic properties, being involved in the transport and clearance of cholesterol-rich lipoproteins as well as in cholesterol efflux from cells. We hypothesized that glucocorticoids may exert anti-inflammatory properties by increasing the level of macrophage-derived apoE. Our data showed that glucocorticoids increased apoE expression in macrophages in vitro as well as in vivo. Dexamethasone increased ~6 fold apoE mRNA levels in cultured peritoneal macrophages and RAW 264.7 cells. Administered to C57BL/6J mice, dexamethasone induced a two-fold increase in apoE expression in peritoneal macrophages. By contrast, glucocorticoids did not influence apoE expression in hepatocytes, in vitro and in vivo. Moreover, dexamethasone enhanced apoE promoter transcriptional activity in RAW 264.7 macrophages, but not in HepG2 cells, as tested by transient transfections. Analysis of apoE proximal promoter deletion mutants, complemented by protein-DNA interaction assays demonstrated the functionality of a putative glucocorticoid receptors (GR) binding site predicted by in silico analysis in the -111/-104 region of the human apoE promoter. In hepatocytes, GR can bind to their specific site within apoE promoter but are not able to modulate the gene expression. The modulatory blockade in hepatocytes is a consequence of partial involvement of transcription factors and other signaling molecules activated through MEK1/2 and PLA2/PLC pathways. In conclusion, our study indicates that glucocorticoids (1) differentially target apoE gene expression; (2) induce a significant increase in apoE level specifically in macrophages. The local increase of apoE gene expression in macrophages at the level of the atheromatous plaque may have therapeutic implications in atherosclerosis.

  11. Differential action of glucocorticoids on apolipoprotein E gene expression in macrophages and hepatocytes.

    Directory of Open Access Journals (Sweden)

    Violeta Georgeta Trusca

    Full Text Available Apolipoprotein E (apoE has anti-atherosclerotic properties, being involved in the transport and clearance of cholesterol-rich lipoproteins as well as in cholesterol efflux from cells. We hypothesized that glucocorticoids may exert anti-inflammatory properties by increasing the level of macrophage-derived apoE. Our data showed that glucocorticoids increased apoE expression in macrophages in vitro as well as in vivo. Dexamethasone increased ~6 fold apoE mRNA levels in cultured peritoneal macrophages and RAW 264.7 cells. Administered to C57BL/6J mice, dexamethasone induced a two-fold increase in apoE expression in peritoneal macrophages. By contrast, glucocorticoids did not influence apoE expression in hepatocytes, in vitro and in vivo. Moreover, dexamethasone enhanced apoE promoter transcriptional activity in RAW 264.7 macrophages, but not in HepG2 cells, as tested by transient transfections. Analysis of apoE proximal promoter deletion mutants, complemented by protein-DNA interaction assays demonstrated the functionality of a putative glucocorticoid receptors (GR binding site predicted by in silico analysis in the -111/-104 region of the human apoE promoter. In hepatocytes, GR can bind to their specific site within apoE promoter but are not able to modulate the gene expression. The modulatory blockade in hepatocytes is a consequence of partial involvement of transcription factors and other signaling molecules activated through MEK1/2 and PLA2/PLC pathways. In conclusion, our study indicates that glucocorticoids (1 differentially target apoE gene expression; (2 induce a significant increase in apoE level specifically in macrophages. The local increase of apoE gene expression in macrophages at the level of the atheromatous plaque may have therapeutic implications in atherosclerosis.

  12. Apolipoprotein(a Kringle-IV Type 2 Copy Number Variation Is Associated with Venous Thromboembolism.

    Directory of Open Access Journals (Sweden)

    Elena Sticchi

    Full Text Available In addition to the established association between high lipoprotein(a [Lp(a] concentrations and coronary artery disease, an association between Lp(a and venous thromboembolism (VTE has also been described. Lp(a is controlled by genetic variants in LPA gene, coding for apolipoprotein(a, including the kringle-IV type 2 (KIV-2 size polymorphism. Aim of the study was to investigate the role of LPA gene KIV-2 size polymorphism and single nucleotide polymorphisms (SNPs (rs1853021, rs1800769, rs3798220, rs10455872 in modulating VTE susceptibility. Five hundred and sixteen patients with VTE without hereditary and acquired thrombophilia and 1117 healthy control subjects, comparable for age and sex, were investigated. LPA KIV-2 polymorphism, rs3798220 and rs10455872 SNPs were genotyped by TaqMan technology. Concerning rs1853021 and rs1800769 SNPs, PCR-RFLP assay was used. LPA KIV-2 repeat number was significantly lower in patients than in controls [median (interquartile range 11(6-17 vs 15(9-25, p<0.0001]. A significantly higher prevalence of KIV-2 repeat number ≤7 was observed in patients than in controls (33.5% vs 15.5%, p<0.0001. KIV-2 repeat number was independently associated with VTE (p = 4.36 x10-9, as evidenced by the general linear model analysis adjusted for transient risk factors. No significant difference in allele frequency for all SNPs investigated was observed. Haplotype analysis showed that LPA haplotypes rather than individual SNPs influenced disease susceptibility. Receiver operating characteristic curves analysis showed that a combined risk prediction model, including KIV-2 size polymorphism and clinical variables, had a higher performance in identifying subjects at VTE risk than a clinical-only model, also separately in men and women.

  13. Exogenous supplement of N-acetylneuraminic acid ameliorates atherosclerosis in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Guo, Shoudong; Tian, Hua; Dong, Rongrong; Yang, Nana; Zhang, Ying; Yao, Shutong; Li, Yongjun; Zhou, Yawei; Si, Yanhong; Qin, Shucun

    2016-08-01

    Previous studies investigating the correlation between plasma sialic acid and the severity of atherosclerosis present conflicting results. In atherosclerosis patients, plasma levels of N-acetylneuraminic acid (NANA) are increased; however, the underlying mechanisms have not yet been clarified. We assume the increased NANA level may be a compensatory mechanism due to oxidative stress and/or inflammation. The aim of this study is to investigate whether supplementation of NANA could attenuate the progression of atherosclerosis. Exogenous NANA was used to determine its effect on apolipoprotein E-deficient (apoE(-/-)) mice taking natural quercetin as a positive control. The effect of NANA on lipid lowering, antioxidant activity and anti-inflammation was investigated by methods of molecular biology. 1) NANA administration decreased 18.9% of the atherosclerotic plaque formation in the aorta and 26.7% of the lipid deposition in the liver of high-fat diet apoE(-/-) mice; 2) notably, NANA treatment reduced 62.6% of the triglyceride by improving lipoprotein lipase activity; 3) NANA lowered 17.5% of the plasma total cholesterol by up-regulating reverse cholesterol transport (RCT)-related protein expression such as ATP-binding cassette transporter (ABC) G1 and ABCG5 in liver or small intestine; 4) NANA administration notably decreased oxidative stress by increasing antioxidant enzymes activity and protein expression of paraoxonase 1 and 2; 5) NANA markedly reduced tumour necrosis factor-α and intercellular adhesion molecule-1 expression in aorta and liver. NANA exhibited triglyceride lowering, anti-oxidation, and RCT promoting activities, and therefore NANA supplementation may be a new strategy for prevention and treatment of atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Current situation of lipoprotein apheresis in Saxony.

    Science.gov (United States)

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

    2013-01-01

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

  15. Expression of very low density lipoprotein receptor in the vascular wall. Analysis of human tissues by in situ hybridization and immunohistochemistry.

    Science.gov (United States)

    Multhaupt, H A; Gåfvels, M E; Kariko, K; Jin, H; Arenas-Elliot, C; Goldman, B I; Strauss, J F; Angelin, B; Warhol, M J; McCrae, K R

    1996-06-01

    The recently cloned very low density lipoprotein (VLDL) receptor binds triglyceride-rich, apolipoprotein-E-containing lipoproteins with high affinity. The observation that VLDL receptor mRNA is abundantly expressed in extracts of tissues such as skeletal muscle and heart, but not liver, has led to the hypothesis that this receptor may facilitate the peripheral uptake of triglyceride-rich lipoproteins. However, little information is available concerning the types of cells that express this receptor in vivo. As expression of the VLDL receptor in the vascular wall might have important implications for the uptake and transport of triglyceride-rich lipoproteins, and perhaps facilitate the development of atherosclerosis in hypertriglyceridemic individuals, we used in situ hybridization and immunohistochemistry to determine whether VLDL receptor mRNA and protein was expressed in human vascular tissue. We observed expression of the receptor by both endothelial and smooth muscle cells within normal arteries and veins, as well as within atherosclerotic plaques. In the latter, the VLDL receptor was also expressed by macrophage-derived foam cells. The widespread distribution of the VLDL receptor in vascular tissue suggests a potentially important role for this receptor in normal and pathophysiological vascular processes.

  16. Impact of corpulence parameters and haemoglobin A1c on metabolic control in type 2 diabetic patients: comparison of apolipoprotein B/A-I ratio with fasting and postprandial conventional lipid ratios.

    Science.gov (United States)

    Diaf, Mustapha; Khaled, Boumediene M; Sellam, Fériel

    2015-01-01

    The incidence of diabetes co-morbidities could probably be better assessed by studying its associations with major corpulence parameters and glycaemic control indicators. We assessed the utility of body mass index (BMI), waist circumference (WC), and glycosylated haemoglobin (HbA1c) levels in metabolic control for type 2 diabetic patients. Fasting and postprandial blood samples were collected from 238 type 2 diabetic patients aged 57.4±11.9 years. The sera were analysed for glucose, HbA1c, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and apolipoproteins (apoA-I and apoB). Ratios of lipids and apolipoproteins were calculated and their associations with BMI, WC, and HbA1c levels were analysed. Our investigation showed increases in most fasting and postprandial lipid parameters according to BMI and WC. In men, postprandial HDL-c and TG levels were significantly higher (ppostprandial TC levels were significantly higher (ppostprandial lipid ratios in both men and women. The apoB/apoA-I ratio was more correlated with postprandial TC/HDL and LDL-c/HDL-c ratios in men and with postprandial TG/HDL-c in women. The apoB/apoA-I ratio is helpful in assessing metabolic risk caused by overall obesity, abdominal obesity and impaired glycaemia in type 2 diabetic patients.

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

    Science.gov (United States)

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

    2016-02-01

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

  18. The Effect of PCSK9 Loss-of-Function Variants on the Postprandial Lipid and ApoB-Lipoprotein Response.

    Science.gov (United States)

    Ooi, Teik Chye; Krysa, Jacqueline A; Chaker, Seham; Abujrad, Hussein; Mayne, Janice; Henry, Kathy; Cousins, Marion; Raymond, Angela; Favreau, Colette; Taljaard, Monica; Chrétien, Michel; Mbikay, Majambu; Proctor, Spencer D; Vine, Donna F

    2017-09-01

    Proprotein convertase subtilisin kexin 9 (PCSK9) mediates degradation of the low-density lipoprotein receptor (LDLR), thereby increasing plasma low-density lipoprotein cholesterol (LDL-C). Variations in the PCSK9 gene associated with loss of function (LOF) of PCSK9 result in greater expression of hepatic LDLR, lower concentrations of LDL-C, and protection from cardiovascular disease (CVD). Apolipoprotein-B (apoB) remnants also contribute to CVD risk and are similarly cleared by the LDLR. We hypothesized that PCSK9-LOF carriers would have lower fasting and postprandial remnant lipoproteins on top of lower LDL-C. To compare fasting and postprandial concentrations of triglycerides (TGs), total apoB, and apoB48 as indicators of remnant lipoprotein metabolism in PCSK9-LOF carriers with those with no PCSK9 variants. Case-control, metabolic study. Clinical Research Center of The Ottawa Hospital. Persons with one or more copies of the L10ins/A53V and/or I474V and/or R46L PCSK9 variant and persons with no PCSK9 variants. Oral fat tolerance test. Fasting and postprandial plasma TG, apoB48, total apoB, total cholesterol, and PCSK9 were measured at 0, 2, 4, and 6 hours after an oral fat load. Participants with PCSK9-LOF variants (n = 22) had reduced fasting LDL-C (-14%) as well as lower fasting TG (-21%) compared with noncarrier controls (n = 23). LOF variants also had reduced postprandial total apoB (-17%), apoB48 (-23%), and TG (-18%). Postprandial PCSK9 declined in both groups (-24% vs -16%, respectively). Participants carrying PCSK9-LOF variants had attenuated levels of fasting and postprandial TG, apoB48, and total apoB. This may confer protection from CVD and further validate the use of PCSK9 inhibitors to lower CVD risk. Copyright © 2017 Endocrine Society

  19. Regulation of HepG2 cell apolipoprotein B metabolism by the citrus flavanones hesperetin and naringenin.

    Science.gov (United States)

    Borradaile, N M; Carroll, K K; Kurowska, E M

    1999-06-01

    Our previous studies showed that replacing the drinking water of rabbits fed a casein-containing diet with either orange juice or grapefruit juice reduced serum low density lipoprotein cholesterol and hepatic cholesteryl ester concentrations. To determine whether the changes observed in rabbits were due to flavonoids present in the juices acting directly on the liver, the effects of hesperetin and naringenin on net apolipoprotein B (apoB) secretion by HepG2 cells were investigated. These flavanones dose-dependently reduced net apoB secretion by up to 81% after a 24 h incubation, while doses of 60 micrograms/mL reduced net apoB secretion by 50% after 4 h. Coincubation with the proteasome inhibitor, MG-132, did not alter the ability of the flavonoids to reduce net apoB secretion over 4 h, suggesting that the flavonoid-induced changes in apoB metabolism were not due to a direct increase in proteasomal activity. However, the flavonoids were unable to reduce net apoB secretion after 4 h in the presence of oleate, suggesting that these compounds may interfere with the availability of neutral lipids for lipoprotein assembly. Furthermore, our 14C-acetate-labeling studies showed a 50% reduction in cholesteryl ester synthesis in the presence of either flavonoid, which could account for the reduction in net apoB secretion caused by incubation with these compounds. These in vitro studies suggest that hesperetin and naringenin may, in part, reduce net apoB secretion by HepG2 cells by inhibiting cholesteryl ester synthesis and that these compounds are good candidates for further in vivo studies to determine whether they are responsible for the cholesterol-lowering properties of dietary citrus juices.

  20. 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.

  1. High-resolution melting analysis for detection of familial ligand-defective apolipoprotein B-100 mutations

    NARCIS (Netherlands)

    Liyanage, Khemanganee E.; Hooper, Amanda J.; Defesche, Joep C.; Burnett, John R.; van Bockxmeer, Frank M.

    2008-01-01

    Familial ligand-defective apolipoprotein B-100 (FDB) is characterized by elevated plasma concentrations of LDL-cholesterol and apolipoprotein (apo) B, normal triglyceride and HDL-cholesterol levels, the presence of tendon xanthomas, and premature coronary artery disease. FDB cannot be clinically

  2. Serum apolipoprotein e level is not increased in Alzheimer's disease : The Rotterdam study

    NARCIS (Netherlands)

    Slooter, A.J.C.; Knijff, P. de; Hofman, A.; Cruts, M.; Breteler, M.M.B.; Broeckhoven, C. van; Havekes, L.M.; Duijn, C.M. van

    1998-01-01

    The APOE*4 allele of the apolipoprotein E gene (APOE) is an important risk factor for Alzheimer's disease. It has been suggested that levels of apolipoprotein E (apoE) in plasma are increased in Alzheimer's disease. In this population-based study, we found that serum apoE levels were lower in

  3. Plasma metabolism of apolipoprotein A-IV in humans

    International Nuclear Information System (INIS)

    Ghiselli, G.; Krishnan, S.; Beigel, Y.; Gotto, A.M. Jr.

    1986-01-01

    As assessed by molecular sieve chromatography and quantitation by a specific radioimmunoassay, apoA-IV is associated in plasma with the triglyceride-rich lipoproteins, to a high density lipoprotein (HDL) subfraction of smaller size than HDL3, and to the plasma lipoprotein-free fraction (LFF). In this study, the turnover of apoA-IV associated to the triglyceride-rich lipoproteins, HDL and LFF was investigated in vivo in normal volunteers. Human apoA-IV isolated from the thoracic duct lymph chylomicrons was radioiodinated and incubated with plasma withdrawn from normal volunteers after a fatty meal. Radioiodinated apoA-IV-labeled triglyceride-rich lipoproteins, HDL, and LFF were then isolated by chromatography on an AcA 34 column. Shortly after the injection of the radioiodinated apoA-IV-labeled triglyceride-rich lipoproteins, most of the radioactivity could be recovered in the HDL and LFF column fractions. On the other hand, when radioiodinated apoA-IV-labeled HDL or LFF were injected, the radioactivity remained with the originally injected fractions at all times. The residence time in plasma of 125 I-labeled apoA-IV, when injected in association with HDL or LFF, was 1.61 and 0.55 days, respectively. When 125 I-labeled apoA-IV was injected as a free protein, the radioactivity distributed rapidly among the three plasma pools in proportion to their mass. The overall fractional catabolic rate of apoA-IV in plasma was measured in the three normal subjects and averaged 1.56 pools per day. The mean degradation rate of apoA-IV was 8.69 mg/kg X day

  4. Nutritional assessment, health markers and lipoprotein profile in postmenopausal women belonging to a closed community.

    Science.gov (United States)

    Sánchez-Muniz, F J; Carbajal, A; Ródenas, S; Méndez, M T; Bastida, S; Raposo, R; Ruiz, T

    2003-09-01

    To assess the dietary characteristics of a closed community and their relationship with several health markers and lipid and lipoprotein values in postmenopausal women. Energy and nutrient intake, serum lipids, lipoproteins, antioxidants, peroxides and low-density lipoprotein (LDL) peroxides in addition to several health markers were measured in a closed, postmenopausal female community consuming a diet without meat, meat products and alcoholic beverages. Departamento de Nutrición and Sección Departamental de Química Analítica and Escuela de Especialización de Análisis Clínicos, Universidad Complutense de Madrid, Spain and Lerma, Burgos, Spain. Cereals, vegetables, legumes and fruit, together with milk and eggs, constituted the most important ingredients of the diet consumed. Dietary carbohydrates contributed 42%en and lipids 46.4%en. The SFA/MUFA/PUFA ratio was 1/2/1 and the n-3/n-6 ratio 0.05 (SFA=saturated fatty acids, MUFA=monounsaturated fatty acids, PUFA=polyunsaturated fatty acids). The study community diet was monotonous and made for possible deficiencies of iron, magnesium, zinc, vitamin B(6) and vitamin D, in variable proportions. Routine biochemical and haematological normality markers indicate that only one woman presented hyperglycaemia and hyperuricaemia. Two women had haemoglobin levels 6.21 mmol/l) was 42.8%, while that of high LDL-cholesterol levels (>3.88 mmol/l) was 35.7%, but none of the women displayed levels of high-density lipoprotein (HDL)-cholesterol 1.2 mmol/l or an LDL-cholesterol/HDL-cholesterol ratio>3. Only one woman had apolipoprotein (Apo) B levels >1.5 g/l, while most of the women presented Apo B values <1.2 g/l and an ApoA-1/ApoB ratio &<1.1. Plasma and LDL-peroxide levels, together with the tocopherol and carotene intakes, suggest a good antioxidant status in this population. The diet of the study group seems compatible with a healthy life-profile and permits a more-than-acceptable degree of cardiovascular disease

  5. Lipid and lipoprotein profiles among middle aged male smokers: a study from southern India

    Directory of Open Access Journals (Sweden)

    Rajendiran Chinnasamy

    2010-10-01

    Full Text Available Abstract Objectives The objectives were to investigate into the relationship between lipid profile including Apolipoprotein-A1 (Apo-A1 and Apolipoprotein-B (Apo-B and smokers and to relate them with smoking pack years. Materials and Methods A total of 274 active male smokers without any other illnesses and age matched male healthy control subjects (78 with similar socio-cultural background were assessed for clinical details, dietary habits, physical activities, smoking and alcohol consumption. Standard methods were adopted to check the lipid levels. The data were analyzed statistically. Results Their ages ranged from 40 to 59 years, systolic BP from 110 to 130 mmHg, and diastolic BP from 76 to 88 mmHg. All of them had similar pattern of diet (vegetarianism with occasional meat. None was on any medication influences lipid level. Their physical activity was moderate. Number of pack years varied from 10 to 14 (mild, 15 to 19 (moderate and 20 and above (heavy among 69, 90 and 115 cases, whose mean ages were 43, 44 and 49 respectively. The mean (+SD values in mg/dl of total cholesterol (TC, Triglyceride (TGL, Apo-B, low density lipoprotein (LDL cholesterol, high density lipoprotein (HDL cholesterol and Apo-A1 in mg/dl among mild/ moderate/ heavy smokers and control subjects were 198 (30.6/ 224 (27.2/ 240 (24.3 and 160 (20.4; 164(42.6/ 199 (39.5/ 223(41.7 and 124 (31.6; 119 (24.9/ 121 (27/ 127 (28.3 and 116 (21.4; 94 (19.7/ 104 (21.8/ 120 (20.5 and 82 (17.6; 42 (5.9/ 39 (3.1/ 35(4.4 and 48 (5.3; and 120 (17/ 119 (21/ 115 (25 and 126 (19, respectively. In smokers, there was a rise in TC, TGL, LDL, Apo-B and fall in HDL and Apo-A; these changes were significant (P Conclusion Number of pack years was directly proportional to abnormal lipid profile. It is also concluded that changes in Apo-A1 and Apo-B were more significant when compared to HDL and LDL cholesterol among smokers. In the view of double risk for smokers (smoking and altered lipid profile

  6. A Short Synthetic Peptide Mimetic of Apolipoprotein A1 Mediates Cholesterol and Globotriaosylceramide Efflux from Fabry Fibroblasts.

    Science.gov (United States)

    Schueler, Ulrike; Kaneski, Christine; Remaley, Alan; Demosky, Stephen; Dwyer, Nancy; Blanchette-Mackie, Joan; Hanover, John; Brady, Roscoe

    2016-01-01

    Fabry disease is an X-linked sphingolipid storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (AGA, EC 3.2.1.22) resulting in the intracellular accumulation of globotriaosylceramide (Gb3). We found that Gb3 storage also correlates with accumulation of endosomal-lysosomal cholesterol in Fabry fibroblasts. This cholesterol accumulation may contribute to the phenotypic pathology of Fabry disease by slowing endosomal-lysosomal trafficking. We found that LDL receptor expression is not downregulated in Fabry fibroblasts resulting in accumulation of both cholesterol and Gb3. 5A-Palmitoyl oleoyl-phosphatidylcholine (5AP) is a phospholipid complex containing a short synthetic peptide that mimics apolipoprotein A1, the main protein component of high-density lipoprotein (HDL) that mediates the efflux of cholesterol from cells via the ATP-binding cassette transporter. We used 5AP and HDL to remove cholesterol from Fabry fibroblasts to examine the fate of accumulated cellular Gb3. Using immunostaining techniques, we found that 5AP is highly effective for depleting cholesterol and Gb3 in these cells. 5AP restores the ApoA-1-mediated cholesterol efflux leading to mobilization of cholesterol and reduction of Gb3 in Fabry fibroblasts.

  7. Effects of dietary casein and soy protein on metabolism of radiolabelled low density apolipoprotein B in rabbits

    International Nuclear Information System (INIS)

    Samman, S.; Khosla, P.; Carroll, K.K.

    1989-01-01

    Rabbits fed semipurified diets containing casein have elevated plasma cholesterol levels compared to those fed soy protein. As part of continuing studies on the mechanism of casein-induced hypercholesterolemia, two groups of six rabbits were fed these diets for 14 to 16 weeks. Animals fed the casein diet were found to have significantly higher plasma concentrations of protein, cholesterol, triacylglycerol, phospholipid and apolipoprotein B (apo B) associated with low density lipoprotein (LDL) than those fed the soy protein diet. Kinetic studies showed that the fractional catabolic rate of LDL-apo B was significantly lower in animals fed casein than in those fed soy protein regardless of whether the tracer LDL was obtained from donors fed casein or soy protein. The production rate of LDL-apo B was higher in casein-fed animals but this was not statistically significant. These results show that the efficiency of removal of LDL is significantly reduced in animals fed casein compared to those fed soy protein, and that the source of LDL did not affect the efficiency of its subsequent removal. The accumulation of LDL in casein-fed animals is consistent with down-regulation of the LDL receptor

  8. Effect of Mediterranean diet with and without weight loss on apolipoprotein B100 metabolism in men with metabolic syndrome.

    Science.gov (United States)

    Richard, Caroline; Couture, Patrick; Ooi, Esther M M; Tremblay, André J; Desroches, Sophie; Charest, Amélie; Lichtenstein, Alice H; Lamarche, Benoît

    2014-02-01

    To assess the effect of a Mediterranean diet (MedDiet) with and without weight loss (WL) on apolipoprotein B100 (apoB100) metabolism in men with metabolic syndrome. The diet of 19 men with metabolic syndrome (age, 24-62 years) was first standardized to a North American isoenergetic control diet for 5 weeks, followed by an isoenergetic MedDiet for an additional 5 weeks under full-feeding conditions (MedDiet-WL). Participants next underwent a 20-week supervised WL program under free-living conditions (-10.2 ± 2.9% body weight; Pthe MedDiet (5 weeks) under weight-stabilizing feeding conditions (MedDiet+WL). In vivo kinetic of apoB100 was assessed in the fasted state at the end of the 3 controlled diets using a bolus of D3-leucine. Compared with the control diet, MedDiet-WL reduced low-density lipoprotein (LDL)-apoB100 pool size (-14.2%, Pthe control diet primarily through an increase in VLDL-apoB100 fractional catabolic rate (+30.7%; Pthe catabolism of LDL even in the absence of WL in men with metabolic syndrome. MedDiet seems to have a trivial effect on VLDL concentrations and kinetics unless accompanied by significant WL. http://www.clinicaltrials.gov. Unique identifier: NCT00988650.

  9. 21 CFR 862.1475 - Lipoprotein test system.

    Science.gov (United States)

    2010-04-01

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

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

    African Journals Online (AJOL)

    Jane

    2011-08-29

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

  11. Lipoprotein receptors in cultured bovine endothelial cells

    International Nuclear Information System (INIS)

    Struempfer, A.E.M.

    1983-07-01

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

  12. Lipophorin Receptor: The Insect Lipoprotein Receptor

    Indian Academy of Sciences (India)

    IAS Admin

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

  13. Lipophorin Receptor: The Insect Lipoprotein Receptor

    Indian Academy of Sciences (India)

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

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

    Science.gov (United States)

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

    2009-02-01

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

  15. The apolipoprotein m-sphingosine-1-phosphate axis

    DEFF Research Database (Denmark)

    Arkensteijn, Bas W C; Berbée, Jimmy F P; Rensen, Patrick C N

    2013-01-01

    -receptor-1, affecting the function of endothelial cells, and apoM-deficient mice display impaired endothelial permeability in the lung. This review will focus on the putative biological roles of the new apoM-S1P axis in relation to lipoprotein metabolism, lipid disorders and atherosclerosis....

  16. Potential implications of the choice among three alternative treatment targets for apolipoprotein B100 in the management of patients with type 2 diabetes and chronic kidney disease.

    Science.gov (United States)

    Boronat, Mauro; García-Cantón, César; López-Ríos, Laura; Quevedo, Virginia; Lorenzo, Dionisio L; Batista, Fátima; Riaño, Marta; Nóvoa, Francisco J

    2014-01-01

    This study analyses discordance rates between attainment of therapeutic goals for apolipoprotein B100 (apoB) and both low-density lipoprotein-cholesterol (LDL-C) and non-high-density lipoprotein-cholesterol (non-HDL-C) in a sample of 152 patients with type 2 diabetes and chronic kidney disease from Gran Canaria (Spain), using treatment targets recommended by the American Diabetes Association/American College of Cardiology (ADA/ACC), the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) and by a Spanish population-based study. Among subjects with LDL-C levels at therapeutic goal, apoB was above target in 16.3% (ADA/ACC), 6.5% (ESC/EAS) and 39.1% (population-based criteria), and among subjects with non-HDL-C levels at therapeutic goal, apoB was above target in 10.5% (ADA/ACC), 1.2% (ESC/EAS) and 29.6% (population-based criteria). These findings show that clinical management would be very differently altered depending on the criteria used to set treatment targets for apoB. Cut-off points derived from population data identify a greater number of subjects suitable for a more intensive lipid-lowering therapy.

  17. Influences of a-tocopherol on cholesterol metabolism and fatty streak development in apolipoprotein E-deficient mice fed an atherogenic diet

    Directory of Open Access Journals (Sweden)

    Peluzio M.C.G.

    2001-01-01

    Full Text Available Although the role of oxidized lipoproteins is well known in atherogenesis, the role of vitamin E supplementation is still controversial. There is also little information about cholesterol metabolism (hepatic concentration and fecal excretion in the new models of atherosclerosis. In the present study, we evaluated the effect of moderate vitamin E supplementation on cholesterol metabolism and atherogenesis in apolipoprotein E (apo E-deficient mice. Apo E-deficient mice were fed an atherogenic diet containing 40 or 400 mg/kg of alpha-tocopherol acetate for 6 weeks. Total cholesterol in serum and liver and 3-OH-alpha-sterols in feces, and fecal excretion of bile acids were determined and histological analyses of aortic lesion were performed. A vitamin E-rich diet did not affect body weight, food intake or serum cholesterol. Serum and hepatic concentrations of cholesterol as well as sterol concentration in feces were similar in both groups. However, when compared to controls, the alpha-tocopherol-treated mice showed a reduction of about 60% in the atherosclerotic lesions when both the sum of lesion areas and the average of the largest lesion area were considered. These results demonstrate that supplementation of moderate doses of alpha-tocopherol was able to slow atherogenesis in apo E-deficient mice and to reduce atherogenic lipoproteins without modifying the hepatic pool or fecal excretion of cholesterol and bile acids.

  18. Amphotericin B induced interdigitation of apolipoprotein stabilized nanodisk bilayers

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, T; Weers, P M; Sulchek, T; Hoeprich, P D; Ryan, R O

    2006-12-07

    Amphotericin B nanodisks (AMB-ND) are ternary complexes of AMB, phospholipid (PL) and apolipoprotein organized as discrete nanometer scale disk-shaped bilayers. In gel filtration chromatography experiments, empty ND lacking AMB elute as a single population of particles with a molecular weight in the range of 200 kDa. AMB-ND formulated at a 4:1 PL:AMB weight ratio, separated into two peaks. Peak 1 eluted at the position of control ND lacking AMB while the second peak, containing all of the AMB present in the original sample, eluted in the void volume. When ND prepared with increased AMB (1:1 phospholipid:AMB molar ratio) were subjected to gel filtration chromatography, an increased proportion of phospholipid and apolipoprotein were recovered in the void volume with the AMB. Prior to gel filtration the AMB-ND sample could be passed through a 0.22 {micro}m filter without loss of AMB while the voided material was lost. Native gel electrophoresis studies corroborated the gel permeation chromatography data. Far UV circular dichroism analyses revealed that apoA-I associated with AMB-ND denatures at a lower guanidine HCl concentration than apoA-I associated with ND lacking AMB. Atomic force microscopy revealed that AMB induces compression of the ND bilayer thickness consistent with bilayer interdigitation, a phenomenon that is likely related to the ability of AMB to induce pore formation in susceptible membranes.

  19. Clinical application of human serum apolipoprotein B ria

    International Nuclear Information System (INIS)

    He Rongxia

    1988-01-01

    The serum apolipoprotein B (Apo B) was measured in 89 normal subjects with radioimmunoassay method established by the authors, among them 50 patients with coronary heart disease (CHD), 19 patients with cerebrae-vascular accident (CVA) and 46 patients with hyperlipemia. Meanwhile the serum cholesterol and triglyceride were also measured. Although cholesterol, triglyceride, and Apo B levels in disease groups were all significantly higher than control group, there are more overlap between the control and disease group for cholesterol and triglyceride. The Apo B level was 723.9 +- 195.9 mg/L in control group, 1097 +- 236.0 mg/L in CHD group and in CVA group, and this difference was highly significant (P < 0.001). Besides, less overlap of the Apo B value between disease and countrol group was observed in both disease groups. When the Apo B was used as single parameter for the diagnosis CHD, the accuracy rate reached 82%. The results of this study indicated that measurement of Apo B can offer important prediction for coronary artery disease, especially in those having normal levels of plasma cholesterol. In conclusion, the study of apolipoprotein is more significant than lipid component in discriminating between atherosclerotic patients and normal persons

  20. Hemostasis and Lipoprotein Indices Signify Exacerbated Lung Injury in TB With Diabetes Comorbidity.

    Science.gov (United States)

    Dong, Zhengwei; Shi, Jingyun; Dorhoi, Anca; Zhang, Jie; Soodeen-Lalloo, Adiilah K; Tan, WenLing; Yin, Hongyun; Sha, Wei; Li, Weitong; Zheng, Ruijuan; Liu, Zhonghua; Yang, Hua; Qin, Lianhua; Wang, Jie; Huang, Xiaochen; Wu, Chunyan; Kaufmann, Stefan H E; Feng, Yonghong

    2017-12-07

    Exacerbated immunopathology is a frequent consequence of TB that is complicated by diabetes mellitus (DM); however, the underlying mechanisms are still poorly defined. In the two groups of age- and sex-matched patients with TB and DM (DM-TB) and with TB and without DM, we microscopically evaluated the areas of caseous necrosis and graded the extent of perinecrotic fibrosis in lung biopsies from the sputum smear-negative (SN) patients. We scored acid-fast bacilli in sputum smear-positive (SP) patients and compiled CT scan data from both the SN and SP patients. We compared inflammatory biomarkers and routine hematologic and biochemical parameters. Binary logistic regression analyses were applied to define the indices associated with the extent of lung injury. Enlarged caseous necrotic areas with exacerbated fibrotic encapsulations were found in SN patients with DM-TB, consistent with the higher ratio of thick-walled cavities and more bacilli in the sputum from SP patients with DM-TB. Larger necrotic foci were detected in men compared with women within the SN TB groups. Significantly higher fibrinogen and lower high-density lipoprotein cholesterol (HDL-C) were observed in SN patients with DM-TB. Regression analyses revealed that diabetes, activation of the coagulation pathway (shown by increased platelet distribution width, decreased mean platelet volume, and shortened prothrombin time), and dyslipidemia (shown by decreased low-density lipoprotein cholesterol, HDL-C, and apolipoprotein A) are risk factors for severe lung lesions in both SN and SP patients with TB. Hemostasis and dyslipidemia are associated with granuloma necrosis and fibroplasia leading to exacerbated lung damage in TB, especially in patients with DM-TB. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  1. Trypanosome lytic factor, an antimicrobial high-density lipoprotein, ameliorates Leishmania infection.

    Directory of Open Access Journals (Sweden)

    Marie Samanovic

    2009-01-01

    Full Text Available Innate immunity is the first line of defense against invading microorganisms. Trypanosome Lytic Factor (TLF is a minor sub-fraction of human high-density lipoprotein that provides innate immunity by completely protecting humans from infection by most species of African trypanosomes, which belong to the Kinetoplastida order. Herein, we demonstrate the broader protective effects of human TLF, which inhibits intracellular infection by Leishmania, a kinetoplastid that replicates in phagolysosomes of macrophages. We show that TLF accumulates within the parasitophorous vacuole of macrophages in vitro and reduces the number of Leishmania metacyclic promastigotes, but not amastigotes. We do not detect any activation of the macrophages by TLF in the presence or absence of Leishmania, and therefore propose that TLF directly damages the parasite in the acidic parasitophorous vacuole. To investigate the physiological relevance of this observation, we have reconstituted lytic activity in vivo by generating mice that express the two main protein components of TLFs: human apolipoprotein L-I and haptoglobin-related protein. Both proteins are expressed in mice at levels equivalent to those found in humans and circulate within high-density lipoproteins. We find that TLF mice can ameliorate an infection with Leishmania by significantly reducing the pathogen burden. In contrast, TLF mice were not protected against infection by the kinetoplastid Trypanosoma cruzi, which infects many cell types and transiently passes through a phagolysosome. We conclude that TLF not only determines species specificity for African trypanosomes, but can also ameliorate an infection with Leishmania, while having no effect on T. cruzi. We propose that TLFs are a component of the innate immune system that can limit infections by their ability to selectively damage pathogens in phagolysosomes within the reticuloendothelial system.

  2. Metabolism of triglyceride-rich nascent rat hepatic high density lipoproteins

    International Nuclear Information System (INIS)

    Winkler, K.E.; Marsh, J.B.

    1989-01-01

    Nascent high density lipoprotein (HDL) and nascent very low density lipoprotein (VLDL) were isolated from rat livers that had been perfused with [3H]glycerol to label the triglyceride. When injected into intact rats, the labeled HDL-triglyceride disappeared as rapidly as the VLDL-triglyceride, with only 10% of the injected label remaining in the plasma after 30 min. The protein moiety of nascent HDL was labeled with [35S]methionine in a similar fashion and the labeled nascent HDL was separated into nonretained (NR) and retained (R) fractions by heparin-Sepharose affinity chromatography. When injected into rats, 55% of the injected label in nascent fraction NR and 72% of that in nascent fraction R was recovered from plasma at 30 min, compared to only 10% of the triglyceride label from unfractionated nascent HDL, indicating dissociation of triglyceride and apolipoprotein clearance. The plasma decay curves for both triglyceride and protein were biexponential. By 5 min, 15% of the 35S label remaining in plasma represented apoE and apoC that had been transferred from nascent HDL fractions NR and R to the d less than 1.063 g/ml fraction of plasma. Plasma HDL was labeled in vivo with [35S]methionine, separated into fractions NR and R, and the clearance of the two plasma HDL fractions was compared with that of the corresponding nascent HDL fractions. Except for a faster rate of removal of the nascent HDL fractions during the first 5 min, the serum decay curves were very similar

  3. 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...

  4. Dietary Flaxseed Oil Prevents Western-Type Diet-Induced Nonalcoholic Fatty Liver Disease in Apolipoprotein-E Knockout Mice

    Directory of Open Access Journals (Sweden)

    Hao Han

    2017-01-01

    Full Text Available The prevalence of nonalcoholic fatty liver disease (NAFLD has dramatically increased globally during recent decades. Intake of n-3 polyunsaturated fatty acids (PUFAs, mainly eicosapentaenoic acid (EPA, C20:5n-3 and docosahexaenoic acid (DHA, C22:6n-3, is believed to be beneficial to the development of NAFLD. However, little information is available with regard to the effect of flaxseed oil rich in α-linolenic acid (ALA, C18:3n-3, a plant-derived n-3 PUFA, in improving NAFLD. This study was to gain the effect of flaxseed oil on NAFLD and further investigate the underlying mechanisms. Apolipoprotein-E knockout (apoE-KO mice were given a normal chow diet, a western-type high-fat and high-cholesterol diet (WTD, or a WTD diet containing 10% flaxseed oil (WTD + FO for 12 weeks. Our data showed that consumption of flaxseed oil significantly improved WTD-induced NAFLD, as well as ameliorated impaired lipid homeostasis, attenuated oxidative stress, and inhibited inflammation. These data were associated with the modification effects on expression levels of genes involved in de novo fat synthesis (SREBP-1c, ACC, triacylglycerol catabolism (PPARα, CPT1A, and ACOX1, inflammation (NF-κB, IL-6, TNF-α, and MCP-1, and oxidative stress (ROS, MDA, GSH, and SOD.

  5. 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.

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

    Science.gov (United States)

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

    2014-08-01

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

  7. Preferential interactions between ApoE-containing lipoproteins and Aβ revealed by a detection method that combines size exclusion chromatography with non-reducing gel-shift.

    Science.gov (United States)

    LaDu, Mary Jo; Munson, Gregory W; Jungbauer, Lisa; Getz, Godfrey S; Reardon, Catherine A; Tai, Leon M; Yu, Chunjiang

    2012-02-01

    The association between apolipoprotein E (apoE) and amyloid-β peptide (Aβ) may significantly impact the function of both proteins, thus affecting the etiology of Alzheimer's disease (AD). However, apoE/Aβ interactions remain fundamentally defined by the stringency of the detection method. Here we use size exclusion chromatography (SEC) as a non-stringent approach to the detection of apoE/Aβ interactions in solution, specifically apoE and both endogenous and exogenous Aβ from plasma, CSF and astrocyte conditioned media. By SEC analysis, Aβ association with plasma and CNS lipoproteins is apoE-dependent. While endogenous Aβ elutes to specific human plasma lipoproteins distinct from those containing apoE, it is the apoE-containing lipoproteins that absorb excess amounts of exogenous Aβ40. In human CSF, apoE, endogenous Aβ and phospholipid elute in an almost identical profile, as do apoE, exogenous Aβ and phospholipid from astrocyte conditioned media. Combining SEC fractionation with subsequent analysis for SDS-stable apoE/Aβ complex reveals that apoE-containing astrocyte lipoproteins exhibit the most robust interactions with Aβ. Thus, standardization of the methods for detecting apoE/Aβ complex is necessary to determine its functional significance in the neuropathology characteristic of AD. Importantly, a systematic understanding of the role of apoE-containing plasma and CNS lipoproteins in Aβ homeostasis could potentially contribute to identifying a plasma biomarker currently over-looked because it has multiple components. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Effect of Roux-en-Y Bariatric Surgery on Lipoproteins, Insulin Resistance, and Systemic and Vascular Inflammation in Obesity and Diabetes.

    Science.gov (United States)

    Yadav, Rahul; Hama, Salam; Liu, Yifen; Siahmansur, Tarza; Schofield, Jonathan; Syed, Akheel A; France, Michael; Pemberton, Philip; Adam, Safwaan; Ho, Jan Hoong; Aghamohammadzadeh, Reza; Dhage, Shaishav; Donn, Rachelle; Malik, Rayaz A; New, John P; Jeziorska, Maria; Durrington, Paul; Ammori, Basil A; Soran, Handrean

    2017-01-01

    Obesity is a major modifiable risk factor for cardiovascular disease. Bariatric surgery is considered to be the most effective treatment option for weight reduction in obese patients with and without type 2 diabetes (T2DM). To evaluate changes in lipoproteins, insulin resistance, mediators of systemic and vascular inflammation, and endothelial dysfunction following Roux-en-Y bariatric surgery in obese patients with and without diabetes. Lipoproteins, insulin resistance, mediators of systemic and vascular inflammation, and endothelial dysfunction were measured in 37 obese patients with ( n  = 17) and without ( n  = 20) T2DM, before and 6 and 12 months after Roux-en-Y bariatric surgery. Two way between subject ANOVA was carried out to study the interaction between independent variables ( time since surgery and presence of diabetes ) and all dependent variables. There was a significant effect of time since surgery on (large effect size) weight, body mass index (BMI), waist circumference, triglycerides (TG), small-dense LDL apolipoprotein B (sdLDL ApoB), HOMA-IR, CRP, MCP-1, ICAM-1, E-selectin, P-selectin, leptin, and adiponectin. BMI and waist circumference had the largest impact of time since surgery . The effect of time since surgery was noticed mostly in the first 6 months. Absence of diabetes led to a significantly greater reduction in total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol although the effect size was small to medium. There was a greater reduction in TG and HOMA-IR in patients with diabetes with a small effect size. No patients were lost to follow up. Lipoproteins, insulin resistance, mediators of systemic and vascular inflammation, and endothelial dysfunction improve mostly 6 months after bariatric surgery in obese patients with and without diabetes. www.ClinicalTrials.gov, identifier: NCT02169518. https://clinicaltrials.gov/ct2/show/NCT02169518?term=paraoxonase&cntry1=EU%3AGB&rank=1.

  9. Serum apolipoprotein B-100 concentration predicts the virological response to pegylated interferon plus ribavirin combination therapy in patients infected with chronic hepatitis C virus genotype 1b.

    Science.gov (United States)

    Yoshizawa, Kai; Abe, Hiroshi; Aida, Yuta; Ishiguro, Haruya; Ika, Makiko; Shimada, Noritomo; Tsubota, Akihito; Aizawa, Yoshio

    2013-07-01

    Host lipoprotein metabolism is associated closely with the life cycle of hepatitis C virus (HCV), and serum lipid profiles have been linked to the response to pegylated interferon (Peg-IFN) plus ribavirin (RBV) therapy. Polymorphisms in the human IL28B gene and amino acid substitutions in the core and interferon sensitivity-determining region (ISDR) in NS5A of HCV genotype 1b (G1b) were also shown to strongly affect the outcome of Peg-IFN plus RBV therapy. In this study, an observational cohort study was performed in 247 HCV G1b-infected patients to investigate whether the response to Peg-IFN and RBV combination therapy in these patients is independently associated with the level of lipid factors, especially apolipoprotein B-100 (apoB-100), an obligatory structural component of very low density lipoprotein and low density lipoprotein. The multivariate logistic analysis subsequently identified apoB-100 (odds ratio (OR), 1.602; 95% confidence interval (CI), 1.046-2.456), alpha-fetoprotein (OR, 0.764; 95% CI, 0.610-0.958), non-wild-type ISDR (OR, 5.617; 95% CI, 1.274-24.754), and the rs8099917 major genotype (OR, 34.188; 95% CI, 10.225-114.308) as independent factors affecting rapid initial virological response (decline in HCV RNA levels by ≥3-log10 at week 4). While lipid factors were not independent predictors of complete early or sustained virological response, the serum apoB-100 level was an independent factor for sustained virological response in patients carrying the rs8099917 hetero/minor genotype. Together, we conclude that serum apoB-100 concentrations could predict virological response to Peg-IFN plus RBV combination therapy in patients infected with HCV G1b, especially in those with the rs8099917 hetero/minor genotype. Copyright © 2013 Wiley Periodicals, Inc.

  10. Increased transvascular lipoprotein transport in diabetes

    DEFF Research Database (Denmark)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  12. 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.)

  13. Chitosan-modified carbon nanotubes-based platform for low-density lipoprotein detection.

    Science.gov (United States)

    Ali, Md Azahar; Singh, Nawab; Srivastava, Saurabh; Agrawal, Ved V; John, Renu; Onoda, M; Malhotra, Bansi D

    2014-10-01

    We have fabricated an immunosensor based on carbon nanotubes and chitosan (CNT-CH) composite for detection of low density lipoprotein (LDL) molecules via electrochemical impedance technique. The CNT-CH composite deposited on indium tin oxide (ITO)-coated glass electrode has been used to covalently interact with anti-apolipoprotein B (antibody: AAB) via a co-entrapment method. The biofunctionalization of AAB on carboxylated CNT-CH surface has been confirmed by Fourier transform infrared spectroscopic and electron microscopic studies. The covalent functionalization of antibody on transducer surface reveals higher stability and reproducibility of the fabricated immunosensor. Electrochemical properties of the AAB/CNT-CH/ITO electrode have been investigated using cyclic voltammetric and impedimetric techniques. The impedimetric response of the AAB/CNT-CH/ITO immunoelectrode shows a high sensitivity of 0.953 Ω/(mg/dL)/cm(2) in a detection range of 0-120 mg/dL and low detection limit of 12.5 mg/dL with a regression coefficient of 0.996. The observed low value of association constant (0.34 M(-1)s(-1)) indicates high affinity of AAB/CNT-CH/ITO immunoelectrode towards LDL molecules. This fabricated immunosensor allows quantitative estimation of LDL concentration with distinguishable variation in the impedance signal.

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

    Science.gov (United States)

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

    2003-01-01

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

  15. A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

    Science.gov (United States)

    Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2014-01-01

    Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

  16. Lipoprotein(a Is the Best Single Marker in Assessing Unstable Angina Pectoris

    Directory of Open Access Journals (Sweden)

    Vidosava B. Djordjević

    2011-01-01

    Full Text Available This study evaluated whether statin therapy changed a diagnostic validity of lipid and inflammatory markers in ischemic heart disease (IHD patients. Levels of lipids, lipoproteins, apolipoproteins, inflammatory markers, and atherogenic indexes were determined in 49 apparently healthy men and women, 82 patients having stable angina pectoris (SAP, 80 patients with unstable angina (USAP, and 106 patients with acute ST-elevation myocardial infarction (STEMI treated or not treated with statins. Diagnostic accuracy of markers was determined by ROC curve analysis. Significantly lower apoA-I in all statin-treated groups and significantly higher apoB in statin-treated STEMI group compared to non-statin-treated groups were observed. CRP showed the best ROC characteristics in the assessment of STEMI patients. Lp(a is better in the evaluation of SAP and USAP patients, considering that Lp(a showed the highest area under the curve (AUC. Regarding atherogenic indexes, the highest AUC in SAP group was obtained for TG/apoB and in USAP and STEMI patients for TG/HDL-c. Statins lowered total cholesterol, LDL-c, and TG but fail to normalize apoA-I in patients with IHD.

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

    Science.gov (United States)

    Cho, Kyung-Hyun

    2009-07-31

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

  18. Analyzing the molecular mechanism of lipoprotein localization in Brucella

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  20. 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.

  1. Apolipoprotein E gene polymorphisms are associated with primary hyperuricemia in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Jie Wu

    Full Text Available OBJECTIVE: Primary hyperuricemia, an excess of uric acid in the blood, is a major public health problem. In addition to the morbidity that is attributable to gout, hyperuricemia is also associated with metabolic syndrome, hypertension, and cardiovascular disease. This study aims to assess the genetic associations between Apolipoprotein E (APOE polymorphisms and hyperuricemia in a Chinese population. METHODS: A total of 770 subjects (356 hyperuricemic cases and 414 normouricemic controls were recruited from the Ningxia Hui Autonomous Region, China. A physical examination was performed and fasting blood was collected for biochemical tests, including determination of the levels of serum lipid, creatinine, and uric acid. Multi-ARMS PCR was applied to determine the APOE genotypes, followed by an investigation of the distribution of APOE genotypes and alleles frequencies in the controls and cases. RESULTS: The frequencies of the APOE-ε2ε3 genotype (17.70% vs. 10.39%, P = 0.003 and the APOE-ε2 allele (10.53% vs. 5.80%, P = 0.001 were significantly higher in the hyperuricemic group than in the normouricemic group. Furthermore, male cases were more likely to have the APOE-ε2ε3 genotype and APOE-ε2 allele, compared with male controls. In both Han and Hui subjects, cases were more likely to have the APOE-ε2ε3 genotype and the APOE-ε2 allele compared with controls. Furthermore, multivariate logistic regression showed that carriers of the APOE-ε2ε3 genotype (P = 0.001, OR = 2.194 and the ε2 allele (P = 0.001, OR = 2.099 were significantly more likely to experience hyperuricemia than carriers of the ε3/ε3 genotype and the ε3 allele after adjustment for sex, body mass index (BMI, diastolic blood pressure (DBP, triglyceride (TG, low density lipoprotein cholesterol (LDL-C, creatinine (Cr and fasting blood glucose (FBG. CONCLUSIONS: The APOE-ε2ε3 genotype and the APOE-ε2 allele are associated with serum uric acid levels

  2. Apolipoprotein E as a novel therapeutic neuroprotection target after traumatic spinal cord injury.

    Science.gov (United States)

    Cheng, Xiaoxin; Zheng, Yiyan; Bu, Ping; Qi, Xiangbei; Fan, Chunling; Li, Fengqiao; Kim, Dong H; Cao, Qilin

    2018-01-01

    Apolipoprotein E (apoE), a plasma lipoprotein well known for its important role in lipid and cholesterol metabolism, has also been implicated in many neurological diseases. In this study, we examined the effect of apoE on the pathophysiology of traumatic spinal cord injury (SCI). ApoE-deficient mutant (apoE -/- ) and wild-type mice received a T9 moderate contusion SCI and were evaluated using histological and behavioral analyses after injury. At 3days after injury, the permeability of spinal cord-blood-barrier, measured by extravasation of Evans blue dye, was significantly increased in apoE -/- mice compared to wild type. The inflammation and spared white matter was also significantly increased and decreased, respectively, in apoE -/- mice compared to the wild type ones. The apoptosis of both neurons and oligodendrocytes was also significantly increased in apoE -/- mice. At 42days after injury, the inflammation was still robust in the injured spinal cord in apoE -/- but not wild type mice. CD45+ leukocytes from peripheral blood persisted in the injured spinal cord of apoE -/- mice. The spared white matter was significantly decreased in apoE -/- mice compared to wild type ones. Locomotor function was significantly decreased in apoE -/- mice compared to wild type ones from week 1 to week 8 after contusion. Treatment of exogenous apoE mimetic peptides partially restored the permeability of spinal cord-blood-barrier in apoE -/- mice after SCI. Importantly, the exogenous apoE peptides decreased inflammation, increased spared white matter and promoted locomotor recovery in apoE -/- mice after SCI. Our results indicate that endogenous apoE plays important roles in maintaining the spinal cord-blood-barrier and decreasing inflammation and spinal cord tissue loss after SCI, suggesting its important neuroprotective function after SCI. Our results further suggest that exogenous apoE mimetic peptides could be a novel and promising neuroprotective reagent for SCI. Copyright

  3. Function and Comorbidities of Apolipoprotein E in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Valérie Leduc

    2011-01-01

    Full Text Available Alzheimer's disease (AD—the most common type of dementia among the elderly—represents one of the most challenging and urgent medical mysteries affecting our aging population. Although dominant inherited mutation in genes involved in the amyloid metabolism can elicit familial AD, the overwhelming majority of AD cases, dubbed sporadic AD, do not display this Mendelian inheritance pattern. Apolipoprotein E (APOE, the main lipid carrier protein in the central nervous system, is the only gene that has been robustly and consistently associated with AD risk. The purpose of the current paper is thus to highlight the pleiotropic roles and the structure-function relationship of APOE to stimulate both the functional characterization and the identification of novel lipid homeostasis-related molecular targets involved in AD.

  4. Cardiovascular effects of uremia in apolipoprotein E-deficient mice

    DEFF Research Database (Denmark)

    Bro, Susanne

    2009-01-01

    The purpose of this thesis work was to establish an experimental mouse model for studying the pathogenesis and therapy of accelerated atherosclerosis in uremia. Uremia was induced by surgical 5/6 nephrectomy in apolipoprotein E-deficient (apoE-/-) mice and led to development of severe aortic...... atherosclerosis independently of BP and plasma homocysteine levels. Also, the accelerated atherosclerosis could not be fully explained by changes in total plasma cholesterol. Morphologic and biochemical analyses of aortas suggested that accelerated initiation and expansion rather than a specific uremic lesion...... composition characterize atherosclerosis in the uremic mice. Increased expression of inflammatory genes in aortas of uremic mice suggests that an augmented inflammatory response in the arterial wall might be an important impetus for accelerated atherosclerosis in uremia. A marked downregulation of expression...

  5. Antiatherogenic effects of oleanolic acid in apolipoprotein E knockout mice

    DEFF Research Database (Denmark)

    Buus, Niels Henrik; Hansson, Nicolaj Christopher; Rodriguez-Rodriguez, Rosalia

    2011-01-01

    Oleanolic acid (OA) is a plant triterpenoid steroid with potentially antiatherogenic properties. We investigated whether OA affected atherosclerosis development and vascular function in apolipoprotein E knockout (ApoE(-/-)) mice. ApoE(-/-) mice were fed a high cholesterol Western-type diet...... in combination with OA (100 mg/kg/day), fluvastatin (5 mg/kg/day) or vehicle, with wild type (WT) mice serving as controls. After 8 weeks of treatment atherosclerotic plaque areas in the aortic arch and plasma lipid concentrations were determined. Vasoconstriction and relaxation of the proximal part of aorta...... were investigated in vitro. Inducible nitric oxide synthase (iNOS) was visualized using immunoblotting. As opposed to WT and fluvastatin- and vehicle-treated mice, OA-fed ApoE(-/-) mice gained no weight during the treatment period. Plasma concentrations of total-cholesterol and triglyceride were...

  6. Silent coronary artery disease in type 2 diabetes mellitus: the role of Lipoprotein(a, homocysteine and apo(a polymorphism

    Directory of Open Access Journals (Sweden)

    Falcone Colomba

    2002-11-01

    Full Text Available Abstract Background There is little data on the relationship between novel cardiovascular risk factors and silent coronary artery disease (CAD in diabetic patients. We investigated whether Lipoprotein(a, homocysteine and apolipoprotein(a polymorphism are associated with angiographically assessed asymptomatic coronary artery disease (CAD in diabetic patients. Methods 1,971 type 2 diabetic patients without clinical signs of cardiovascular diseases and with a negative history of CAD were consecutively evaluated. Among them, 179 patients showed electrocardiographic abnormalities suggestive of ischemia or previous asymptomatic myocardial infarction. These 179 patients were subjected to a non-invasive test for CAD (ECG stress testing and/or scintigraphy. Among patients with a highly positive stress testing (n = 19 or a positive scintigraphy (n = 74, 75 showed an angiographically documented CAD (CAD group. Seventy-five patients without CAD (NO CAD group were matched by age, sex and duration of diabetes to CAD patients. In NO CAD patients an exercise ECG test, a 48-hour ambulatory ECG and a stress echocardiogram were negative for CAD. Results Lipoprotein(a levels (22.0 ± 18.9 versus 16.0 ± 19.4 mg/dl; p Conclusions The present investigation shows an independent association of Lipoprotein(a, homocysteine and apo(a polymorphism with silent CAD. Other studies are needed to establish whether these parameters are suitable for CAD screening in diabetic patients.

  7. [Frequency of apolipoprotein E in a Nahua population].

    Science.gov (United States)

    Suástegui Román, Roberto Alfonso; Yescas Gómez, Petra; Guerrero Camacho, Jorge Luis; Ochoa Morales, Adriana; Granados, Julio; Jara Prado, Aurelio; López-Caro, Oscar Alejandro; Alonso Vilatela, Ma Elisa

    2002-01-01

    The presence of different ethnic groups in Mexico may give rise to genetic diversity between the native Indian population and the Mestizos. It is therefore of medical and anthropological interest to analyze the genotypes of disease-associated loci, such as polymorphism in the apolipoprotein E gene, whose 4/4 allele increases the risk of Alzheimer's disease and coronary heart disease in other populations. We studied a Nahua Indian-population in the State of Morelos (Santo Domingo Ocotitlan). The ABO blood type of all individuals was determined and compared with the findings of other Nahua group from the State of Puebla. Without statistical significant differences in O, A and AB groups between both populations (p > 0.05). The allelic and genotypic frequency of apolipoprotein E was similar to that observed in other Mexican indian (Mazatecans, Mayans) and Mestizo populations, however there was a statistically significant difference when the results were compared to the allelic frequencies of other Amerinds: The Cayapa (Ecuador) for the epsilon 3 and epsilon 4 alleles (p < 0.002); the Nuuk (Greenland) for epsilon 3 and epsilon 4 alleles (p < 0.0001 and p < 0.002 respectively); and the Ammssalik (Greenland) for both alleles with p < 0.0001 and p = 0.04 respectively. In the case of the genotypes, there was statistically significant difference for the 4/3 genotypes, but a non significant difference for the 4/4 genotype. This is a descriptive study which contributes to the knowledge of the genetic structure of Mexican population.

  8. Apolipoprotein and lipid abnormalities in chronic liver failure

    Directory of Open Access Journals (Sweden)

    A.C. Spósito

    1997-11-01

    Full Text Available Total serum lipids, as well as apolipoproteins A-I (apo A-I and B (apo B, were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36%, 24% and 46%, respectively (P<0.001. Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P<0.001. However, the reduction of HDL cholesterol (HDLc was more pronounced than that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P<0.05. We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver

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

    Science.gov (United States)

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

    2006-11-01

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

  10. Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins

    DEFF Research Database (Denmark)

    Varkey, Jobin; Isas, Jose Mario; Mizuno, Naoko

    2010-01-01

    Synucleins and apolipoproteins have been implicated in a number of membrane and lipid trafficking events. Lipid interaction for both types of proteins is mediated by 11 amino acid repeats that form amphipathic helices. This similarity suggests that synucleins and apolipoproteins might have compar...... density of tubulating proteins may be important. How cellular safeguarding mechanisms prevent such potentially toxic events and whether they go awry in disease remains to be determined....

  11. Predictive value of serum apolipoprotein B/apolipoprotein A-I ratio in metabolic syndrome risk: a Chinese cohort study.

    Science.gov (United States)

    Chou, Yu-Ching; Kuan, Jen-Chun; Bai, Chyi-Huey; Yang, Tsan; Chou, Wan-Yun; Hsieh, Po-Chien; You, San-Lin; Hwang, Lee-Ching; Chen, Chien-Hua; Wei, Cheng-Yu; Sun, Chien-An

    2015-06-01

    The purpose of this study was to evaluate whether the apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio is a promising risk predictor of metabolic syndrome (MetS) and to determine the optimal cut-off value of this ratio in detecting subjects with MetS in a Chinese population. A prospective study was conducted using a representative sample of non-institutionized people in Taiwan. A total of 3,343 participants with mean age (±SD) of 39.86 (±15.61) years old were followed up from 2002 to 2007. The primary outcome was the incidence of MetS. The MetS was defined according to a unified criterion established by several major organizations. There were 462 cases of incident MetS during a mean follow-up period of 5.26 years. A significantly stepwise increase in the incidence of MetS across quartiles of the apoB/apoA-I ratio was noted in both sexes after adjustment for potential confounders (p for trend risk of MetS in both men [adjusted hazard ratio (HR) = 6.29, 95 % confidence interval (CI) = 2.79-9.13] and women (adjusted HR = 3.82, 95 % CI = 1.06-6.63). Comparisons of receiver operating characteristics curves indicated that the predictive ability of apoB/apoA-I ratio to detect MetS was better than conventional lipid ratio measurements. Furthermore, the optimal cut-off value of apoB/apoA-I ratio for MetS diagnosis was 0.71 in men and 0.56 in women. These results suggest that an elevated apoB/apoA-I ratio might constitute a potentially crucial measure linked to the risk of developing MetS.

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

    Science.gov (United States)

    Smith, Caroline C; McMahon, Lori L

    2006-08-16

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

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

    Science.gov (United States)

    Kumar, Gaurav; Patnaik, Ranjana

    2016-07-01

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

  14. High Density Lipoprotein and it's Dysfunction.

    Science.gov (United States)

    Eren, Esin; Yilmaz, Necat; Aydin, Ozgur

    2012-01-01

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

  15. Serum Lipoprotein Changes in Dogs with Renal Disease

    OpenAIRE

    Behling?Kelly, E.

    2014-01-01

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

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

    Science.gov (United States)

    Konovalova, Anna; Silhavy, Thomas J

    2015-10-05

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

  17. Identification of Apolipoprotein N-Acyltransferase (Lnt) in Mycobacteria*

    Science.gov (United States)

    Tschumi, Andreas; Nai, Corrado; Auchli, Yolanda; Hunziker, Peter; Gehrig, Peter; Keller, Peter; Grau, Thomas; Sander, Peter

    2009-01-01

    Lipoproteins of Gram-negative and Gram-positive bacteria carry a thioether-bound diacylglycerol but differ by a fatty acid amide bound to the α-amino group of the universally conserved cysteine. In Escherichia coli the N-terminal acylation is catalyzed by the N-acyltransferase Lnt. Using E. coli Lnt as a query in a BLASTp search, we identified putative lnt genes also in Gram-positive mycobacteria. The Mycobacterium tuberculosis lipoprotein LppX, heterologously expressed in Mycobacterium smegmatis, was N-acylated at the N-terminal cysteine, whereas LppX expressed in a M. smegmatis lnt::aph knock-out mutant was accessible for N-terminal sequencing. Western blot analyses of a truncated and tagged form of LppX indicated a smaller size of about 0.3 kDa in the lnt::aph mutant compared with the parental strain. Matrix-assisted laser desorption ionization time-of-flight/time-of-flight analyses of a trypsin digest of LppX proved the presence of the diacylglycerol modification in both strains, the parental strain and lnt::aph mutant. N-Acylation was found exclusively in the M. smegmatis parental strain. Complementation of the lnt::aph mutant with M. tuberculosis ppm1 restored N-acylation. The substrate for N-acylation is a C16 fatty acid, whereas the two fatty acids of the diacylglycerol residue were identified as C16 and C19:0 fatty acid, the latter most likely tuberculostearic acid. We demonstrate that mycobacterial lipoproteins are triacylated. For the first time to our knowledge, we identify Lnt activity in Gram-positive bacteria and assigned the responsible genes. In M. smegmatis and M. tuberculosis the open reading frames are annotated as MSMEG_3860 and M. tuberculosis ppm1, respectively. PMID:19661058

  18. Identification of apolipoprotein N-acyltransferase (Lnt) in mycobacteria.

    Science.gov (United States)

    Tschumi, Andreas; Nai, Corrado; Auchli, Yolanda; Hunziker, Peter; Gehrig, Peter; Keller, Peter; Grau, Thomas; Sander, Peter

    2009-10-02

    Lipoproteins of Gram-negative and Gram-positive bacteria carry a thioether-bound diacylglycerol but differ by a fatty acid amide bound to the alpha-amino group of the universally conserved cysteine. In Escherichia coli the N-terminal acylation is catalyzed by the N-acyltransferase Lnt. Using E. coli Lnt as a query in a BLASTp search, we identified putative lnt genes also in Gram-positive mycobacteria. The Mycobacterium tuberculosis lipoprotein LppX, heterologously expressed in Mycobacterium smegmatis, was N-acylated at the N-terminal cysteine, whereas LppX expressed in a M. smegmatis lnt::aph knock-out mutant was accessible for N-terminal sequencing. Western blot analyses of a truncated and tagged form of LppX indicated a smaller size of about 0.3 kDa in the lnt::aph mutant compared with the parental strain. Matrix-assisted laser desorption ionization time-of-flight/time-of-flight analyses of a trypsin digest of LppX proved the presence of the diacylglycerol modification in both strains, the parental strain and lnt::aph mutant. N-Acylation was found exclusively in the M. smegmatis parental strain. Complementation of the lnt::aph mutant with M. tuberculosis ppm1 restored N-acylation. The substrate for N-acylation is a C16 fatty acid, whereas the two fatty acids of the diacylglycerol residue were identified as C16 and C19:0 fatty acid, the latter most likely tuberculostearic acid. We demonstrate that mycobacterial lipoproteins are triacylated. For the first time to our knowledge, we identify Lnt activity in Gram-positive bacteria and assigned the responsible genes. In M. smegmatis and M. tuberculosis the open reading frames are annotated as MSMEG_3860 and M. tuberculosis ppm1, respectively.

  19. Discordance Between Apolipoprotein B and LDL-Cholesterol in Young Adults Predicts Coronary Artery Calcification: The CARDIA Study.

    Science.gov (United States)

    Wilkins, John T; Li, Ron C; Sniderman, Allan; Chan, Cheeling; Lloyd-Jones, Donald M

    2016-01-19

    High levels of apolipoprotein B (apoB) have been shown to predict atherosclerotic cardiovascular disease (CVD) in adults even in the context of low levels of low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C). This study aimed to quantify the associations between apoB and the discordance between apoB and LDL-C or non-HDL-C in young adults and measured coronary artery calcium (CAC) in midlife. Data were derived from a multicenter cohort study of young adults recruited at ages 18 to 30 years. All participants with complete baseline CVD risk factor data, including apoB and year 25 (Y25) CAC score, were entered into this study. Presence of CAC was defined as having a positive, nonzero Agatston score as determined by computed tomography. Baseline apoB values were divided into tertiles of 4 mutually exclusive concordant/discordant groups, based on median apoB and LDL-C or non-HDL-C. Analysis included 2,794 participants (mean age: 25 ± 3.6 years; body mass index: 24.5 ± 5 kg/m(2); and 44.4% male). Mean lipid values were as follows: total cholesterol: 177.3 ± 33.1 mg/dl; LDL-C: 109.9 ± 31.1 mg/dl; non-HDL-C: 124.0 ± 33.5 mg/dl; HDL-C: 53 ± 12.8 mg/dl; and apoB: 90.7 ± 24 mg/dl; median triglycerides were 61 mg/dl. Compared with the lowest apoB tertile, higher odds of developing Y25 CAC were seen in the middle (odds ratio [OR]: 1.53) and high (OR: 2.28) tertiles based on traditional risk factor-adjusted models. High apoB and low LDL-C or non-HDL-C discordance was also associated with Y25 CAC in adjusted models (OR: 1.55 and OR: 1.45, respectively). These data suggest a dose-response association between apoB in young adults and the presence of midlife CAC independent of baseline traditional CVD risk factors. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  20. Vascular endothelial growth factor downregulates apolipoprotein M expression by inhibiting Foxa2 in a Nur77-dependent manner.

    Science.gov (United States)

    Hu, Yan-Wei; Zheng, Lei; Wang, Qian; Zhong, Tian-Yu; Yu, Xia; Bao, Jie; Cao, Nan-Nan; Li, Bo; Si-Tu, Bo

    2012-08-01

    We aimed to investigate whether vascular endothelial growth factor (VEGF) influences apolipoprotein M (ApoM) expression and pre-β-high-density lipoprotin (HDL) formation, and whether forkhead box A2 (Foxa2) and Nur77 are involved in this process. We analyzed the serum VEGF concentrations of 264 adults who underwent a medical checkup and found that VEGF concentration was positively correlated with serum triglyceride, total cholesterol, LDL cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), and ApoB concentrations, but was negatively correlated with serum high-density lipoprotein cholesterol (HDL-C) and ApoM concentrations. We further investigated the effects of VEGF on ApoM expression and pre-β-HDL formation, and the mechanisms responsible, in HepG2 cells and mouse primary hepatocytes. VEGF markedly downregulated ApoM expression and pre-β-HDL formation. At the same time, expression of Foxa2 was also inhibited, whereas expression of Nur77 was increased by treatment with VEGF. Furthermore, small interfering (si) RNA knockdown of Foxa2 made the downregulation of VEGF on ApoM expression and pre-β-HDL formation even more obvious. In addition, siRNA knockdown of Nur77 significantly compensated for the inhibitory effect of VEGF on Foxa2 expression, whereas the Nur77 agonist cytosporone B led to the downregulation of Foxa2 expression more significantly than VEGF. Moreover, overexpression of a Nur77 transgene in C57BL/6 mice resulted in decreased serum ApoM and pre-β-HDL levels, whereas si-Nur77-treated mice displayed upregulated serum ApoM and pre-β-HDL levels. These results provide evidence that VEGF may first downregulate expression of Foxa2 by enhancing Nur77 activity and then decrease expression of ApoM and pre-β-HDL formation. Therefore, our study may be useful in understanding the critical effect of VEGF in the pathogenesis of atherosclerosis.

  1. SERUM LEVEL OF LIPIDS, APOLIPOPROTEINS AND VITAMIN D IN CHILDREN AT HIGH RISK OF CORONARY ARTERY DISEASE

    Directory of Open Access Journals (Sweden)

    M BASHTAM

    2002-06-01

    Full Text Available Introduction. Coronary artery disease (CAD is one of the most prevalent disease in human population that has high prevalence and mortality in lsfahan (Iran. As positive family history and changes in serum lipids and lipoproteins are risk factors of these diseases, and also studies have showed the relationship between serum vitamin D and CAD, we studied serum level of lipids, lipoproteins and vitamin D in high risk children compared with control group, and the relation between serum vitamin D and other factors. Methods. This case-control study was done on 44 subjects (25 boys, 19 girls aged 2-18 years old with positive CAD family history as case group and also 44 persons with negative CAD family history as control group with the same age groups. The subjects were selected by convenience sampling method. Children who consumed antiepilepthic drugs as phenytoin or phenobarbital and those who had positive family histroy for renal stone were excluded for variable vitamin D levels due to drug interaction and genetic susceptibility, respectively. All subjects were invited to Isfahan Cardiovascular Research Center. Using a questionnaire, information on personal characteristics, CVD family history and ... were obtained. A fasting (12-14 hr blood sample was drawn from each one. Serum APOA1, APO B100 and vitamin Dwere measured by radioimmunoassay and serum lipids by ELAN 2000 autoanalyzer. Statistical analysis was done by SPSS. The level of serum APOA1, APO B100 and vitamin D were compared between two groups by independent t test and the relation of the mentioned apolipoproteins with vitamin D was studied using multiple linear regression. Results. Serum vitamin D was significantly lower in case group (P < 0.045. Among studied factors, only triglyceride was significantly higher in control group (P < 0.0001 and also no significant relaitonship was observed between serum APO A1, APO B100 and vitamin D. Sex comparision in case group showed those mean levels

  2. Regulation of high-density lipoprotein metabolism.

    Science.gov (United States)

    Rye, Kerry-Anne; Barter, Philip J

    2014-01-03

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

  3. The Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Protects against Dyslipidemia-Related Kidney Injury in Apolipoprotein E Knockout Mice

    Directory of Open Access Journals (Sweden)

    Jingjing Li

    2014-06-01

    Full Text Available The goal of this study was to investigate the possible protective effects of sitagliptin against dyslipidemia-related kidney injury in apolipoprotein E knockout (apoE−/− mice. Eight-week-old male apoE−/− mice were randomized to receive either a high fat diet (HFD, apoE−/− group or HFD mixed with sitagliptin (sita + apoE−/− group for 16 weeks. A control group of age- and gender-matched C57BL/6J mice were fed a HFD. The apoE−/− group exhibited increases in body weight and serum lipid levels in addition to high-density lipoprotein, and increases in 24-h urinary 8-hydroxy-2-deoxyguanosine and albuminuria excretion. Decreased insulin sensitivity was also observed in the apoE−/− group. These mice additionally contained enlargements of the glomerular mesangial matrix area, lipid deposition area, and renal interstitium collagen area. The apoE−/− group also demonstrated down-regulation of phosphorylated AMP-activated protein kinase (AMPK, increases in renal mRNA expression of transforming growth factor-beta 1 (TGF-β1 and fibronectin (FN, and increased protein expression of Akt, TGF-β1, FN and p38/ERK mitogen-activated protein kinase (MAPK. Sitagliptin treatment successfully ameliorated all the deleterious effects of dyslipidemia tested. To our knowledge, this is the first time that sitagliptin has been shown to reverse the renal dysfunction and structural damage induced by dyslipidemia in apoE−/− mice. Our results suggest that the renoprotective mechanism of sitagliptin may be due to a reduction in Akt levels, a restoration of AMPK activity, and inhibition of TGF-β1, FN, and p38/ERK MAPK signaling pathways.

  4. MicroRNA-122 associates with serum apolipoprotein B but not liver fibrosis markers in CHC genotype 1 infection.

    Science.gov (United States)

    Lee, Tzu-Hao; Matta, Bassem; King, Bernard D; Hodges, Michael R; Tillmann, Hans L; Patel, Keyur

    2015-10-01

    miR-122 is the predominant liver miRNA that regulates hepatic lipid metabolism and inflammation. Hepatitis C virus (HCV) modulates host intracellular lipid metabolism. HCV stability and propagation also depend on an interaction between virus and miR-122. Our aims were to examine the associations between miR-122, apolipoproteins, and serum makers of fibrosis in chronic hepatitis C (CHC) patients. We evaluated baseline sera from 36 CHC genotype 1 patients who completed the Phase IIa study of miravirsen (LNA oligonucleotide targeting miR-122). Samples were assessed for liver transaminases, IL 28B genotype, IP-10, and lipid profiles. The noninvasive markers of liver fibrosis, APRI, and FIB-4, were calculated using standard formulae. miR-122 levels were measured using RT-PCR and expressed as fold-change compared to normal healthy controls. CHC patients were mostly male (61%) with mean age 47.5 ± 11.6 years. Patients with higher ApoB (ApoB/ULN ≥ 0.5) has significantly lower miR-122 levels in compared to patients with lower ApoB (ApoB/ULN HCV RNA and lipoproteins. There were no differences in miR-122 levels between patients with different stages of fibrosis determined by APRI or FIB-4. Patients with lower ApoB had higher serum miR-122 levels. However, we cannot identify significant association between miR-122, ApoA-1, or fibrosis markers in this small cohort of CHC genotype 1 patients. The mechanism of HCV dyslipidemia is complex and could partly relate to the effect of miR-122 on lipid metabolism which requires further evaluation in a larger study. © 2015 Wiley Periodicals, Inc.

  5. Defective Lipid Delivery Modulates Glucose Tolerance and Metabolic Response to Diet in Apolipoprotein E–Deficient Mice

    Science.gov (United States)

    Hofmann, Susanna M.; Perez-Tilve, Diego; Greer, Todd M.; Coburn, Beth A.; Grant, Erin; Basford, Joshua E.; Tschöp, Matthias H.; Hui, David Y.

    2010-01-01

    OBJECTIVE Apolipoprotein E (ApoE) regulates plasma lipid levels via modulation of lipolysis and serving as ligand for receptor-mediated clearance of triglyceride (TG)-rich lipoproteins. This study tested the impact of modulating lipid delivery to tissues on insulin responsiveness and diet-induced obesity. RESEARCH DESIGN AND METHODS ApoE+/+ and apoE−/− mice were placed on high-fat–high-sucrose diabetogenic diet or control diet for 24 weeks. Plasma TG clearance, glucose tolerance, and tissue uptake of dietary fat and glucose were assessed. RESULTS Plasma TG clearance and lipid uptake by adipose tissue were impaired, whereas glucose tolerance was improved in control diet–fed apoE−/− mice compared with apoE+/+ mice after an oral lipid load. Fat mass was reduced in apoE−/− mice compared with apoE+/+ mice under both dietary conditions. The apoE−/− mice exhibited lower body weight and insulin levels than apoE+/+ mice when fed the diabetogenic diet. Glucose tolerance and uptake by muscle and brown adipose tissue (BAT) was also improved in mice lacking apoE when fed the diabetogenic diet. Indirect calorimetry studies detected no difference in energy expenditure and respiratory quotient between apoE+/+ and apoE−/− mice on control diet. Energy expenditure and uncoupling protein-1 expression in BAT were slightly but not significantly increased in apoE−/− mice on diabetogenic diet. CONCLUSIONS These results demonstrated that decreased lipid delivery to insulin-sensitive tissues improves insulin sensitivity and ameliorates diet-induced obesity. PMID:17914034

  6. Role of cysteine-protease CGHC motifs of ER-60, a protein disulfide isomerase, in hepatic apolipoprotein B100 degradation.

    Science.gov (United States)

    Rutledge, Angela C; Qiu, Wei; Zhang, Rianna; Urade, Reiko; Adeli, Khosrow

    2013-09-01

    Apolipoprotein B100 (apoB), the structural component of very low density lipoproteins (VLDL), is susceptible to misfolding and subsequent degradation by several intracellular pathways. ER-60, which has been implicated in apoB degradation, is a protein disulfide isomerase (PDI) that forms or rearranges disulfide bonds in substrate proteins and also possesses cysteine protease activity. To determine which ER-60 function is important for apoB degradation, adenoviruses encoding wild-type human ER-60 or a mutant form of human ER-60 (C60A, C409A) that lacked cysteine protease activity were overexpressed in HepG2 cells. Overexpression of wild-type ER-60 in HepG2 cells promoted apoB degradation and impaired apoB secretion, but mutant ER-60 overexpression did not. In McArdle RH-7777 cells, VLDL secretion was markedly inhibited following overexpression of wild-type but not mutant ER-60, an effect that could be blocked by oleate treatment. Mutant ER-60 was not trapped on apoB as it was with the control substrate tapasin, suggesting that ER-60's role in apoB degradation is likely unrelated to its protein disulfide isomerase activity. Thus, ER-60 may participate in apoB degradation by acting as a cysteine protease. We postulate that apoB cleavage by ER-60 within the ER lumen could facilitate proteasomal degradation of the C-terminus of translocationally-arrested apoB. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Ischemic stroke in a young adult with extremely elevated lipoprotein(a): A case report and review of literature.

    Science.gov (United States)

    Lakshminarayan, Dharshan; Elajami, Tarec K; Devabhaktuni, Suresh; Welty, Francine K

    2016-01-01

    Lipoprotein(a) [Lp(a)] is an apolipoprotein(a) molecule bound to 1 apolipoprotein B-100. Elevated levels of Lp(a) are thought to be an independent risk factor for atherosclerosis and to promote thrombosis through incompletely understood mechanisms. We report a 34-year-old man with an ischemic stroke in the setting of an extremely high Lp(a) level-212 mg/dL. He developed severe carotid artery stenosis over a 6-year period and had thrombus formation post-carotid endarterectomy. To our knowledge, this case is unique because the Lp(a) is the highest reported level in a patient without renal disease. Moreover, this is the first reported case of the youngest individual with a stroke presumably related to development of carotid plaque over a 6-year period. The thrombotic complication after endarterectomy may have been related to the prothrombotic properties of Lp(a). Of note, the Lp(a) level did not respond to atorvastatin but did decrease 15% after aspirin 325 mg was added although his Lp(a) levels were variable, and it is not clear that this was cause and effect. This case highlights the need to better understand the relation between Lp(a) and vascular disease and the need to screen family members for elevated Lp(a). We also review treatment options to lower Lp(a) and ongoing clinical trials of newer lipid-lowering drugs that can also lower Lp(a). Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  8. The effect of the addition of resistance training to a dietary education intervention on apolipoproteins and diet quality in overweight and obese older adults

    Directory of Open Access Journals (Sweden)

    Valente EA

    2011-09-01

    -density lipoprotein (all P < 0.05.Conclusion: The addition of RT effectively reduced CHD risk factors, body composition, and diet quality in overweight and obese older adults; DERT was more effective than DE alone in improving DASH Diet Index scores and lowering apoB concentrations but was not more effective in increasing apoA-I concentrations. Future research is needed to determine if apolipoproteins are superior to lipoprotein cholesterol concentrations in predicting CHD risk.Keywords: physical activity, health education, lipids, DASH Diet Index

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

    Science.gov (United States)

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

    2016-01-01

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

  10. Liraglutide suppresses postprandial triglyceride and apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, cross-over trial.

    Science.gov (United States)

    Hermansen, K; Bækdal, T A; Düring, M; Pietraszek, A; Mortensen, L S; Jørgensen, H; Flint, A

    2013-11-01

    Postprandial triglyceridaemia is a risk factor for cardiovascular disease (CVD). This study investigated the effects of steady-state liraglutide 1.8 mg versus placebo on postprandial plasma lipid concentrations after 3 weeks of treatment in patients with type 2 diabetes mellitus (T2DM). In a cross-over trial, patients with T2DM (n = 20, 18-75 years, BMI 18.5-40 kg/m²) were randomized to once-daily subcutaneous liraglutide (weekly dose escalation from 0.6 to 1.8 mg) and placebo. After each 3-week period, a standardized fat-rich meal was provided, and the effects of liraglutide on triglyceride (primary endpoint AUC(0-8h)), apolipoprotein B48, non-esterified fatty acids, glycaemic responses and gastric emptying were assessed. ClinicalTrials.gov ID: NCT00993304. Novo Nordisk A/S. After 3 weeks, mean postprandial triglyceride (AUC(0-8h) liraglutide/placebo treatment-ratio 0.72, 95% CI [0.62-0.83], p = 0.0004) and apolipoprotein B48 (AUC(0-8h) ratio 0.65 [0.58-0.73], p postprandial glucose and glucagon AUC(0-8h) and C(max) were significantly reduced with liraglutide versus placebo. Postprandial gastric emptying rate [assessed by paracetamol absorption (liquid phase) and the ¹³C-octanoate breath test (solid phase)] displayed no treatment differences. Mean low-density lipoprotein and total cholesterol decreased significantly with liraglutide versus placebo. Liraglutide treatment in patients with T2DM significantly reduced postprandial excursions of triglyceride and apolipoprotein B48 after a fat-rich meal, independently of gastric emptying. Results indicate liraglutide's potential to reduce CVD risk via improvement of postprandial lipaemia. © 2013 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  11. Soy milk powder supplemented with phytosterol esters reduced serum cholesterol level in hypercholesterolemia independently of lipoprotein E genotype: a random clinical placebo-controlled trial.

    Science.gov (United States)

    Dong, Shan; Zhang, Ran; Ji, Ya-Cheng; Hao, Jia-Yin; Ma, Wei-Wei; Chen, Xu-Dong; Xiao, Rong; Yu, Huan-Ling

    2016-08-01

    Phytosterols (PSs) are reported to lower the serum total cholesterol and low-density lipoprotein cholesterol concentrations enriched in some fatty foods, such as margarine. However, these high-fat foods are not very suitable for older people. Soy milk is the favorite food for elderly people in China; therefore, we hypothesized that the consumption of soy milk powder supplemented with PSs would decrease the serum cholesterol levels in older Chinese people independent of the genotypes of apolipoprotein E (ApoE). Mild to moderate hyperlipidemic patients (n = 170) were recruited from different communities and treated with placebo soy milk powder or 3.4 g PS esters-enriched soy milk powder (2.0 g/d free PS in 30 g soy milk powder). The fasting serum lipid profiles at the baseline and after 3 and 6 months of intervention were measured. The ApoE genotype was also determined. After 3 months of PS intervention, the serum lipid profile was not changed significantly in either group. The serum total cholesterol, low-density lipoprotein cholesterol, and non- high-density lipoprotein cholesterol levels decreased by 9.3%, 11.4%, and 12.6%, respectively, in the PS group at the end of the intervention (6 months) compared with the control group, whereas the serum high-density lipoprotein cholesterol and triglyceride levels were not affected significantly. In the PS group, both the ApoE3 and ApoE4 carriers had a similar response to PS consumption. These findings suggested that PS-fortified soy milk powder was effective in lowering the serum cholesterol levels in older Chinese volunteers with mild to moderate hypercholesterolemia in both the ApoE3 and ApoE4 carriers. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

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

  13. Chlordecone, a mixed pregnane X receptor (PXR) and estrogen receptor alpha (ERα) agonist, alters cholesterol homeostasis and lipoprotein metabolism in C57BL/6 mice

    International Nuclear Information System (INIS)

    Lee, Junga; Scheri, Richard C.; Zhang Yuan; Curtis, Lawrence R.

    2008-01-01

    Chlordecone (CD) is one of many banned organochlorine (OC) insecticides that are widespread persistent organic pollutants. OC insecticides alter lipid homeostasis in rodents at doses that are not neurotoxic or carcinogenic. Pretreatment of mice or rats with CD altered tissue distribution of a subsequent dose of [ 14 C]CD or [ 14 C]cholesterol (CH). Nuclear receptors regulate expression of genes important in the homeostasis of CH and other lipids. In this study, we report that CD suppresses in vitro reporter systems for human liver X receptors (LXRs) and activates those for human farnesoid X receptor (FXR), pregnane X receptor (PXR) and estrogen receptor α (ERα) in a concentration-dependent manner (0-50 μM). Consistent with human PXR activation in vitro, three days after a single dose of CD (15 mg/kg) hepatic microsomal CYP3A11 protein increases in C57BL/6 mice. CD decreases hepatic CH ester content without altering total CH concentration. Apolipoprotein A-I (apoA-I) contents of hepatic lipoprotein-rich and microsomal fractions of CD-treated mice are higher than controls. There is a significant reduction in non-high density lipoprotein CH but not apolipoprotein B-48/100 (apoB-48/100) in plasma from CD-treated mice after a 4 h fast. At 14 days after 15 mg CD/kg apoA-I and apoB-100 proteins but not CYP3A11 protein in hepatic microsomes are similar to controls. This work indicates that altered CH homeostasis is a mode of OC insecticide action of relevance after a single dose. This at least partially explains altered CH tissue distribution in CD-pretreated mice

  14. Homozygous Familial Hypercholesterolemia Patients With Identical Mutations Variably Express the LDLR (Low-Density Lipoprotein Receptor): Implications for the Efficacy of Evolocumab.

    Science.gov (United States)

    Thedrez, Aurélie; Blom, Dirk J; Ramin-Mangata, Stéphane; Blanchard, Valentin; Croyal, Mikaël; Chemello, Kévin; Nativel, Brice; Pichelin, Matthieu; Cariou, Bertrand; Bourane, Steeve; Tang, Lihua; Farnier, Michel; Raal, Frederick J; Lambert, Gilles

    2018-03-01

    Evolocumab, a PCSK9 (proprotein convertase subtilisin kexin type 9)-neutralizing antibody, lowers low-density lipoprotein cholesterol (LDL-C) in homozygous familial hypercholesterolemic (HoFH) patients with reduced LDLR (low-density lipoprotein receptor) function. However, their individual responses are highly variable, even among carriers of identical LDLR genetic defects. We aimed to elucidate why HoFH patients variably respond to PCSK9 inhibition. Lymphocytes were isolated from 22 HoFH patients enrolled in the TAUSSIG trial (Trial Assessing Long Term Use of PCSK9 Inhibition in Subjects With Genetic LDL Disorders). Ten patients were true homozygotes (FH1/FH1) and 5 identical compound heterozygotes (FH1/FH2). Lymphocytes were plated with or without mevastatin, recombinant PCSK9 (rPCSK9), or a PCSK9-neutralizing antibody. Cell surface LDLR expression was analyzed by flow cytometry. All HoFH lymphocytes had reduced cell surface LDLR expression compared with non-FH lymphocytes, for each treatment modality. Lymphocytes from FH1/FH2 patients (LDLR defective/negative) displayed the lowest LDLR expression levels followed by lymphocytes from FH1/FH1 patients (defective/defective). Mevastatin increased, whereas rPCSK9 reduced LDLR expression. The PCSK9-neutralizing antibody restored LDLR expression. Lymphocytes displaying higher LDLR expression levels were those isolated from patients presenting with lowest levels of LDL-C and apolipoprotein B, before and after 24 weeks of evolocumab treatment. These negative correlations remained significant in FH1/FH1 patients and appeared more pronounced when patients with apolipoprotein E3/E3 genotypes were analyzed separately. Significant positive correlations were found between the levels of LDLR expression and the percentage reduction in LDL-C on evolocumab treatment. Residual LDLR expression in HoFH is a major determinant of LDL-C levels and seems to drive their individual response to evolocumab. © 2017 American Heart Association

  15. Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Bo Li

    Full Text Available Although there is evidence that visfatin is associated with atherogenesis, the effect of visfatin on plaque stability has not yet been explored.In vivo, vulnerable plaques were established by carotid collar placement in apolipoprotein E-deficient (ApoE-/- mice, and lentivirus expressing visfatin (lenti-visfatin was locally infused in the carotid artery. The lipid, macrophage, smooth muscle cell (SMC and collagen levels were evaluated, and the vulnerability index was calculated. In vitro, RAW264.7 cells were stimulated with visfatin, and the MMPs expressions were assessed by western blot and immunofluorescence. And the mechanism that involved in visfatin-induced MMP-8 production was investigated.Transfection with lenti-visfatin significantly promoted the expression of visfatin which mainly expressed in macrophages in the plaque. Lenti-visfatin transfection significantly promoted the accumulation of lipids and macrophages, modulated the phenotypes of smooth muscle cells and decreased the collagen levels in the plaques, which significantly decreased the plaque stability. Simultaneously, transfection with lenti-visfatin significantly up-regulated the expression of MMP-8 in vivo, as well as MMP-1, MMP-2 and MMP-9. Recombinant visfatin dose- and time-dependently up-regulated the in vitro expression of MMP-8 in macrophages. Visfatin promoted the translocation of NF-κB, and inhibition of NF-κB significantly reduced visfatin-induced MMP-8 production.Visfatin increased MMP-8 expression, promoted collagen degradation and increased the plaques vulnerability index.

  16. Apolipoprotein M mediates sphingosine-1-phosphate efflux from erythrocytes

    DEFF Research Database (Denmark)

    Christensen, Pernille M.; Bosteen, Markus H.; Hajny, Stefan

    2017-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive lipid implicated in e.g. angiogenesis, lymphocyte trafficking, and endothelial barrier function. Erythrocytes are a main source of plasma S1P together with platelets and endothelial cells. Apolipoprotein M (apoM) in HDL carries 70% of plasma S1P, whereas...... 30% is carried by albumin. The current aim was to investigate the role of apoM in export of S1P from human erythrocytes. Erythrocytes exported S1P more efficiently to HDL than to albumin, particularly when apoM was present in HDL. In contrast, export of sphingosine to HDL was unaffected...... by the presence of apoM. The specific ability of apoM to promote export of S1P was independent of apoM being bound in HDL particles. Treatment with MK-571, an inhibitor of the ABCC1 transporter, effectively reduced export of S1P from human erythrocytes to apoM, whereas the export was unaffected by inhibitors...

  17. Apolipoprotein L1 Gene Effects on Kidney Transplantation.

    Science.gov (United States)

    Freedman, Barry I; Locke, Jayme E; Reeves-Daniel, Amber M; Julian, Bruce A

    2017-11-01

    The pathogenesis of many common etiologies of nephropathy has been informed by recent molecular genetic breakthroughs. It now is apparent that the ethnic disparity in the risk for nondiabetic chronic kidney disease between African Americans and European Americans is explained largely by variation in the apolipoprotein L1 gene (APOL1). The presence of two APOL1 renal risk variants markedly increases an individual's risk for kidney disease. In transplantation, kidneys from deceased African Americans with two APOL1 renal risk variants have shorter survival intervals after engraftment, regardless of the ethnicity of the recipient. Precision medicine will transform the clinical practice of nephrology and kidney transplantation, and play an important role in the allocation of kidneys from deceased and living kidney donors with recent African ancestry. This article reviews existing data on APOL1 in deceased-donor and living-donor kidney transplantation. It considers the impact of including APOL1 genotyping in decisions on the allocation and discard of deceased-donor kidneys, as well as the selection of living donors. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Apolipoprotein E: Essential Catalyst of the Alzheimer Amyloid Cascade

    Directory of Open Access Journals (Sweden)

    Huntington Potter

    2012-01-01

    Full Text Available The amyloid cascade hypothesis remains a robust model of AD neurodegeneration. However, amyloid deposits contain proteins besides Aβ, such as apolipoprotein E (apoE. Inheritance of the apoE4 allele is the strongest genetic risk factor for late-onset AD. However, there is no consensus on how different apoE isotypes contribute to AD pathogenesis. It has been hypothesized that apoE and apoE4 in particular is an amyloid catalyst or “pathological chaperone”. Alternatively it has been posited that apoE regulates Aβ clearance, with apoE4 been worse at this function compared to apoE3. These views seem fundamentally opposed. The former would indicate that removing apoE will reduce AD pathology, while the latter suggests increasing brain ApoE levels may be beneficial. Here we consider the scientific basis of these different models of apoE function and suggest that these seemingly opposing views can be reconciled. The optimal therapeutic target may be to inhibit the interaction of apoE with Aβ rather than altering apoE levels. Such an approach will not have detrimental effects on the many beneficial roles apoE plays in neurobiology. Furthermore, other Aβ binding proteins, including ACT and apo J can inhibit or promote Aβ oligomerization/polymerization depending on conditions and might be manipulated to effect AD treatment.

  19. Apolipoprotein D Internalization Is a Basigin-dependent Mechanism*

    Science.gov (United States)

    Najyb, Ouafa; Brissette, Louise; Rassart, Eric

    2015-01-01

    Apolipoprotein D (apoD), a member of the lipocalin family, is a 29-kDa secreted glycoprotein that binds and transports small lipophilic molecules. Expressed in several tissues, apoD is up-regulated under different stress stimuli and in a variety of pathologies. Numerous studies have revealed that overexpression of apoD led to neuroprotection in various mouse models of acute stress and neurodegeneration. This multifunctional protein is internalized in several cells types, but the specific internalization mechanism remains unknown. In this study, we demonstrate that the internalization of apoD involves a specific cell surface receptor in 293T cells, identified as the transmembrane glycoprotein basigin (BSG, CD147); more particularly, its low glycosylated form. Our results show that internalized apoD colocalizes with BSG into vesicular compartments. Down-regulation of BSG disrupted the internalization of apoD in cells. In contrast, overexpression of basigin in SH-5YSY cells, which poorly express BSG, restored the uptake of apoD. Cyclophilin A, a known ligand of BSG, competitively reduced apoD internalization, confirming that BSG is a key player in the apoD internalization process. In summary, our results demonstrate that basigin is very likely the apoD receptor and provide additional clues on the mechanisms involved in apoD-mediated functions, including neuroprotection. PMID:25918162

  20. Apolipoprotein D Internalization Is a Basigin-dependent Mechanism.

    Science.gov (United States)

    Najyb, Ouafa; Brissette, Louise; Rassart, Eric

    2015-06-26

    Apolipoprotein D (apoD), a member of the lipocalin family, is a 29-kDa secreted glycoprotein that binds and transports small lipophilic molecules. Expressed in several tissues, apoD is up-regulated under different stress stimuli and in a variety of pathologies. Numerous studies have revealed that overexpression of apoD led to neuroprotection in various mouse models of acute stress and neurodegeneration. This multifunctional protein is internalized in several cells types, but the specific internalization mechanism remains unknown. In this study, we demonstrate that the internalization of apoD involves a specific cell surface receptor in 293T cells, identified as the transmembrane glycoprotein basigin (BSG, CD147); more particularly, its low glycosylated form. Our results show that internalized apoD colocalizes with BSG into vesicular compartments. Down-regulation of BSG disrupted the internalization of apoD in cells. In contrast, overexpression of basigin in SH-5YSY cells, which poorly express BSG, restored the uptake of apoD. Cyclophilin A, a known ligand of BSG, competitively reduced apoD internalization, confirming that BSG is a key player in the apoD internalization process. In summary, our results demonstrate that basigin is very likely the apoD receptor and provide additional clues on the mechanisms involved in apoD-mediated functions, including neuroprotection. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Apolipoprotein M in lipid metabolism and cardiometabolic diseases

    DEFF Research Database (Denmark)

    Borup, Anna; Christensen, Pernille Meyer; Nielsen, Lars B.

    2015-01-01

    PURPOSE: This review will address recent findings on apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) in lipid metabolism and inflammatory diseases. RECENT FINDINGS: ApoM's likely role(s) in health and disease has become more diverse after the discovery that apoM functions...... as a chaperone for S1P. Hence, apoM has recently been implicated in lipid metabolism, diabetes and rheumatoid arthritis through in-vivo, in-vitro and genetic association studies. It remains to be established to which degree such associations with apoM can be attributed to its ability to bind S1P. SUMMARY......: The apoM/S1P axis and its implications in atherosclerosis and lipid metabolism have been thoroughly studied. Owing to the discovery of the apoM/S1P axis, the scope of apoM research has broadened. ApoM and S1P have been implicated in lipid metabolism, that is by modulating HDL particles. Also...

  2. Glucose Regulates the Expression of the Apolipoprotein A5 Gene

    Energy Technology Data Exchange (ETDEWEB)

    Fruchart, Jamila; Nowak, Maxime; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Moitrot, Emmanuelle; Rommens, Corinne; Pennacchio, Len A.; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2008-04-07

    The apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. D-glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using D-glucose analogs and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter. We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that D-glucose regulates APOA5 gene via a dephosphorylation mechanism, thereby resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that APOA5 gene is up regulated by D-glucose and USF through phosphatase activation. These findings may provide a new cross talk between glucose and lipid metabolism.

  3. Impact of corpulence parameters and haemoglobin A1c on metabolic control in type 2 diabetic patients: comparison of apolipoprotein B/A-I ratio with fasting and postprandial conventional lipid ratios

    Directory of Open Access Journals (Sweden)

    Mustapha Diaf

    2015-05-01

    Full Text Available Background and objective: The incidence of diabetes co-morbidities could probably be better assessed by studying its associations with major corpulence parameters and glycaemic control indicators. We assessed the utility of body mass index (BMI, waist circumference (WC, and glycosylated haemoglobin (HbA1c levels in metabolic control for type 2 diabetic patients. Methods: Fasting and postprandial blood samples were collected from 238 type 2 diabetic patients aged 57.4±11.9 years. The sera were analysed for glucose, HbA1c, total cholesterol (TC, triglycerides (TG, high-density lipoprotein cholesterol (HDL-c, low-density lipoprotein cholesterol (LDL-c, and apolipoproteins (apoA-I and apoB. Ratios of lipids and apolipoproteins were calculated and their associations with BMI, WC, and HbA1c levels were analysed. Results: Our investigation showed increases in most fasting and postprandial lipid parameters according to BMI and WC. In men, postprandial HDL-c and TG levels were significantly higher (p<0.05 in overweight and obese patients, respectively, as well as in patients with abdominal obesity. Contrariwise, postprandial TC levels were significantly higher (p<0.01 in overweight and abdominal obese women. However, elevations of apoA-I and apoB levels were according to BMI and WC in both genders. There was a strong influence of BMI, WC, and HbA1c levels on the apoB/apoA-I ratio compared to traditional fasting and postprandial lipid ratios in both men and women. The apoB/apoA-I ratio was more correlated with postprandial TC/HDL and LDL-c/HDL-c ratios in men and with postprandial TG/HDL-c in women. Conclusion: The apoB/apoA-I ratio is helpful in assessing metabolic risk caused by overall obesity, abdominal obesity and impaired glycaemia in type 2 diabetic patients.

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

    African Journals Online (AJOL)

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

  5. Redefining the essential trafficking pathway for outer membrane lipoproteins

    Science.gov (United States)

    Grabowicz, Marcin; Silhavy, Thomas J.

    2017-01-01

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

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

    Science.gov (United States)

    Grabowicz, Marcin; Silhavy, Thomas J

    2017-05-02

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

  10. 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

  11. 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...

  12. Cholestasis and hypercholesterolemia in SCD1-deficient mice fed a low-fat, high-carbohydrate diet

    NARCIS (Netherlands)

    Flowers, Matthew T.; Groen, Albert K.; Oler, Angie Tebon; Keller, Mark P.; Choi, YounJeong; Schueler, Kathryn L.; Richards, Oliver C.; Lan, Hong; Miyazaki, Makoto; Kuipers, Folkert; Kendziorski, Christina M.; Ntambi, James M.; Attie, Alan D.

    2006-01-01

    Stearoyl-coenzyme A desaturase 1-deficient (SCD1(-/-)) mice have impaired MUFA synthesis. When maintained on a very low-fat (VLF) diet, SCD1(-/-) mice developed severe hypercholesterolemia, characterized by an increase in apolipoprotein B (apoB)-containing lipoproteins and the appearance of

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

    Lifescience Database Archive (English)

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

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  15. Nanotechnology for Synthetic High Density Lipoproteins

    Science.gov (United States)

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

    2014-01-01

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

  16. Effects of hydrogen peroxide and apolipoprotein E isoforms on apolipoprotein E trafficking in HepG2 cells.

    Science.gov (United States)

    Sabaretnam, Tharani; Harris, Matthew J; Kockx, Maaike; Witting, Paul K; Le Couteur, David G; Kritharides, Leonard

    2009-12-01

    1. The major source of apolipoprotein E (apoE) is the liver. In the present study, the effects of oxidative stress and apoE isoforms on apoE distribution and trafficking were established using the HepG2 liver tumour cell line. 2. Hydrogen peroxide (0, 25, 250 and 1000 micromol/L) was associated with rapid and concentration-dependent redistribution of apoE into the early endosomal compartment. This redistribution was achieved with a much lower concentration (25 micromol/L) than that needed to induce changes in intracellular apoE mRNA expression, apoE protein levels and markers of oxidative stress (250-1000 micromol/L). 3. Live cell imaging of apoE3-green fluorescent protein revealed a significant decrease in traffic velocity in response to oxidative stress. 4. The E4 isoform was associated with reduced trafficking velocity compared with the E3 isoform under basal conditions. 5. The results indicate that oxidative stress and apoE isoforms influence apoE trafficking and distribution within HepG2 cells. Altered apoE hepatocyte trafficking may provide a mechanistic link between oxidative stress, ageing and some diseases in older people.

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    OpenAIRE

    Hasija, Kiran; Bagga, Hardeep K.

    2005-01-01

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

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

    NARCIS (Netherlands)

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

    1991-01-01

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

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

    NARCIS (Netherlands)

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

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

  2. Impact of psychological stress on the associations between apolipoprotein E variants and metabolic traits: findings in an American sample of caregivers and controls.

    Science.gov (United States)

    Kring, Sofia I Iqbal; Brummett, Beverly H; Barefoot, John; Garrett, Melanie E; Ashley-Koch, Allison E; Boyle, Stephen H; Siegler, Ilene C; Sørensen, Thorkild I A; Williams, Redford B

    2010-06-01

    To examine the association between apolipoprotein E (APOE) gene variants and waist circumference, fasting plasma glucose, serum insulin, serum high-density lipoprotein cholesterol, and serum triglycerides, all metabolic traits known as cardiovascular disease (CVD) endophenotypes, in a population of stressed individuals and controls. Abdominal obesity, insulin resistance, elevated serum lipid concentration, and APOE polymorphisms have been associated with CVD risk. Current evidence supports the hypothesis that gene-environment interactions modulate serum lipid concentrations. The association between rs769450, rs405509, rs439401, and metabolic traits were analyzed in a U.S. sample of 126 white caregivers of a relative with Alzheimer';s disease or other major dementia and 122 white controls. The associations were analyzed, using multivariate analysis of variance adjusted for age, sex, and medications. Significant multivariate interactions were found, using both additive (p = .009) and dominant (p = .047) models between rs439401 (C/T) and caregiver stress in relation to a profile of metabolic variables. Univariate analyses found the TT genotype to be associated with more adverse levels of waist circumference (interaction, p = .026), triglycerides (interaction, p = .001) and high-density lipoprotein cholesterol (interaction, p = .001) among caregivers but with a more favorable profile of these endophenotypes among controls. There were no significant associations or interactions involving the other two single nucleotide polymorphisms. The APOE rs439401 TT genotype is associated with an adverse metabolic profile among chronically stressed individuals compared with individuals not similarly stressed in whom a more favorable profile is expressed. Confirmation of these results in further research would indicate that the TT genotype can be used to identify persons at high risk for CVD when subjected to chronic stress.

  3. Apolipoprotein M regulates the orphan nuclear receptor LRH-1 gene expression through binding to its promoter region in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Pan Y

    2015-04-01

    Full Text Available Yi Pan,1,2,* Hou-gang Zhou,1,* Hui Zhou,3 Min Hu,1 Li-jun Tang2 1Clinical Laboratory, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Molecular Biology Research Center, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China; 3Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China *These authors contributed equally to this work Abstract: Apolipoprotein M (ApoM is predominantly located in the high-density lipoprotein in human plasma. It has been demonstrated that ApoM expression could be regulated by several crucial nuclear receptors that are involved in the bile acid metabolism. In the present study, by combining gene-silencing experiments, overexpression studies, and chromatin immunoprecipitation assays, we showed that ApoM positively regulated liver receptor homolog-1 (LRH-1 gene expression via direct binding to an LRH-1 promoter region (nucleotides -406/-197. In addition, we investigated the effects of farnesoid X receptor agonist GW4064 on hepatic ApoM expression in vitro. In HepG2 cell cultures, both mRNA and protein levels of ApoM and LRH-1 were decreased in a time-dependent manner in the presence of 1 µM GW4064, and the inhibition effect was gradually attenuated after 24 hours. In conclusion, our findings present supportive evidence that ApoM is a regulator of human LRH-1 transcription, and further reveal the importance of ApoM as a critical regulator of bile acids metabolism. Keywords: bile acids, chromatin immunoprecipitation assay, farnesoid X receptor, GW4064, high-density lipoprotein 

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

    Directory of Open Access Journals (Sweden)

    E.C.R. Quintão

    2010-12-01

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

  5. Effects of MAT9001 containing eicosapentaenoic acid and docosapentaenoic acid, compared to eicosapentaenoic acid ethyl esters, on triglycerides, lipoprotein cholesterol, and related variables.

    Science.gov (United States)

    Maki, Kevin C; Bobotas, George; Dicklin, Mary R; Huebner, Margie; Keane, William F

    Long-chain omega-3 fatty acid concentrate pharmaceuticals are used in the United States for treatment of severe hypertriglyceridemia (≥500 mg/dL) and are under investigation as adjuncts to statins for lowering cardiovascular risk in patients with high triglycerides (TGs; 200-499 mg/dL). To evaluate MAT9001, an investigational prescription-only omega-3 fatty acid agent containing predominantly eicosapentaenoic acid (EPA) and docosapentaenoic acid, in 42 men and women with fasting TG 200 to 400 mg/dL. In this open-label, crossover trial, subjects received MAT9001 and EPA ethyl esters (EPA-EE) in random order. They were housed in a clinical research unit for 2 14-day treatment periods, separated by a ≥35-day washout. Lipoprotein lipids, apolipoproteins (Apos) and proprotein convertase subtilisin kexin type 9 levels were measured before and at the end of each treatment period. MAT9001, compared with EPA-EE, resulted in significantly (P < .05) larger reductions from pretreatment levels for TG (-33.2% vs -10.5%), total cholesterol (-9.0% vs -6.2%), non-high-density lipoprotein cholesterol (-8.8% vs -4.6%), very low-density lipoprotein cholesterol (-32.5% vs -8.1%), Apo C3 (-25.5% vs -5.0%), and proprotein convertase subtilisin kexin type 9 (-12.3% vs +8.8%). MAT9001 also produced a significantly (P = .003) larger reduction in Apo A1 (-15.3% vs -10.2%), but responses for high-density lipoprotein cholesterol (-11.3% vs -11.1%), low-density lipoprotein cholesterol (-2.4% vs -4.3%), and Apo B (-3.8% vs -0.7%), respectively, were not significantly different relative to EPA-EE. MAT9001 produced significantly larger reductions than EPA-EE in several lipoprotein-related variables that would be expected to favorably alter cardiovascular disease risk in men and women with hypertriglyceridemia. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  6. Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism

    DEFF Research Database (Denmark)

    Helgadottir, Anna; Gretarsdottir, Solveig; Thorleifsson, Gudmar

    2012-01-01

    The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components.......The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components....

  7. Apolipoprotein E polymorphism in Brazilian dyslipidemic individuals: Ouro Preto study.

    Science.gov (United States)

    Mendes-Lana, A; Pena, G G; Freitas, S N; Lima, A A; Nicolato, R L C; Nascimento-Neto, R M; Machado-Coelho, G L L; Freitas, R N

    2007-01-01

    The influence of apolipoprotein E alleles and genotypes on plasma lipid levels was determined in 185 individuals of mixed ethnicity living in Ouro Preto, Brazil. DNA was obtained from blood samples and the genotypes were determined by an RFLP-PCR procedure. The *3 allele was the most frequent (72%), followed by *4 (20%) and *2 (8%); *4 frequency was higher and *2 frequency was lower in the dyslipidemic group than in the normal control group. The *2 carriers presented lower LDL and total cholesterol levels compared to the *3 and *4 carriers. All six expected genotypes were observed in the individuals genotyped: E2/2 (2.1%), E4/4 (2.7%), E2/4 (3.7%), E2/3 (8.0%), E3/3 (53.3%), E3/4 (29.9%); no difference in genotype frequencies was found between the normal and dyslipidemic groups. Compared with *2, the presence of *3 increases more than two times the risk for dyslipidemia (OR = 2.31; P = 0.025; 95% CI = 1.06-5.06) and the presence of *4 increases it three times (OR = 3.31; P = 0.006; 95% CI = 1.36-8.04). The only significant effect of genotype was an increased risk for dyslipidemia in the *4 genotype carriers (E3/4 + E4/4) compared with the *2 genotype carriers (E2/2 + E2/3) with OR = 3.69 (95% CI = 1.25-10.88). The present study indicates that in the Ouro Preto admixed population the presence of APOE *2 can confer a protective effect, whereas the presence of APOE *4 implies an enhanced risk for dyslipidemia.

  8. The plant Apolipoprotein D ortholog protects Arabidopsis against oxidative stress

    Directory of Open Access Journals (Sweden)

    Houde Mario

    2008-07-01

    Full Text Available Abstract Background Lipocalins are a large and diverse family of small, mostly extracellular proteins implicated in many important functions. This family has been studied in bacteria, invertebrate and vertebrate animals but little is known about these proteins in plants. We recently reported the identification and molecular characterization of the first true lipocalins from plants, including the Apolipoprotein D ortholog AtTIL identified in the plant model Arabidopsis thaliana. This study aimed to determine its physiological role in planta. Results Our results demonstrate that the AtTIL lipocalin is involved in modulating tolerance to oxidative stress. AtTIL knock-out plants are very sensitive to sudden drops in temperature and paraquat treatment, and dark-grown plants die shortly after transfer to light. These plants accumulate a high level of hydrogen peroxide and other ROS, which causes an oxidative stress that is associated with a reduction in hypocotyl growth and sensitivity to light. Complementation of the knock-out plants with the AtTIL cDNA restores the normal phenotype. On the other hand, overexpression enhances tolerance to stress caused by freezing, paraquat and light. Moreover, this overexpression delays flowering and maintains leaf greenness. Microarray analyses identified several differentially-regulated genes encoding components of oxidative stress and energy balance. Conclusion This study provides the first functional evidence that a plant lipocalin is involved in modulating tolerance to oxidative stress. These findings are in agreement with recently published data showing that overexpression of ApoD enhances tolerance to oxidative stress and increases life span in mice and Drosophila. Together, the three papers strongly support a similar function of lipocalins in these evolutionary-distant species.

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

    Science.gov (United States)

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

    2011-06-01

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

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

    Science.gov (United States)

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

    2017-06-20

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

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

    Science.gov (United States)

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

    2010-02-12

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

  13. Does high-density lipoprotein protect vascular function in healthy pregnancy?

    Science.gov (United States)

    Sulaiman, Wan N Wan; Caslake, Muriel J; Delles, Christian; Karlsson, Helen; Mulder, Monique T; Graham, Delyth; Freeman, Dilys J

    2016-04-01

    The maternal adaptation to pregnancy includes hyperlipidaemia, oxidative stress and chronic inflammation. In non-pregnant individuals, these processes are usually associated with poor vascular function. However, maternal vascular function is enhanced in pregnancy. It is not understood how this is achieved in the face of the adverse metabolic and inflammatory environment. Research into cardiovascular disease demonstrates that plasma HDL (high-density lipoprotein), by merit of its functionality rather than its plasma concentration, exerts protective effects on the vascular endothelium. HDL has vasodilatory, antioxidant, anti-thrombotic and anti-inflammatory effects, and can protect against endothelial cell damage. In pregnancy, the plasma HDL concentration starts to rise at 10 weeks of gestation, peaking at 20 weeks. The initial rise in plasma HDL occurs around the time of the establishment of the feto-placental circulation, a time when the trophoblast plugs in the maternal spiral arteries are released, generating oxidative stress. Thus there is the intriguing possibility that new HDL of improved function is synthesized around the time of the establishment of the feto-placental circulation. In obese pregnancy and, to a greater extent, in pre-eclampsia, plasma HDL levels are significantly decreased and maternal vascular function is reduced. Wire myography studies have shown an association between the plasma content of apolipoprotein AI, the major protein constituent of HDL, and blood vessel relaxation. These observations lead us to hypothesize that HDL concentration, and function, increases in pregnancy in order to protect the maternal vascular endothelium and that in pre-eclampsia this fails to occur. © 2016 Authors; published by Portland Press Limited.

  14. High-density lipoprotein maintains skeletal muscle function by modulating cellular respiration in mice.

    Science.gov (United States)

    Lehti, Maarit; Donelan, Elizabeth; Abplanalp, William; Al-Massadi, Omar; Habegger, Kirk M; Weber, Jon; Ress, Chandler; Mansfeld, Johannes; Somvanshi, Sonal; Trivedi, Chitrang; Keuper, Michaela; Ograjsek, Teja; Striese, Cynthia; Cucuruz, Sebastian; Pfluger, Paul T; Krishna, Radhakrishna; Gordon, Scott M; Silva, R A Gangani D; Luquet, Serge; Castel, Julien; Martinez, Sarah; D'Alessio, David; Davidson, W Sean; Hofmann, Susanna M

    2013-11-26

    Abnormal glucose metabolism is a central feature of disorders with increased rates of cardiovascular disease. Low levels of high-density lipoprotein (HDL) are a key predictor for cardiovascular disease. We used genetic mouse models with increased HDL levels (apolipoprotein A-I transgenic [apoA-I tg]) and reduced HDL levels (apoA-I-deficient [apoA-I ko]) to investigate whether HDL modulates mitochondrial bioenergetics in skeletal muscle. ApoA-I ko mice exhibited fasting hyperglycemia and impaired glucose tolerance test compared with wild-type mice. Mitochondria isolated from gastrocnemius muscle of apoA-I ko mice displayed markedly blunted ATP synthesis. Endurance capacity during exercise exhaustion test was impaired in apoA-I ko mice. HDL directly enhanced glucose oxidation by increasing glycolysis and mitochondrial respiration rate in C2C12 muscle cells. ApoA-I tg mice exhibited lower fasting glucose levels, improved glucose tolerance test, increased lactate levels, reduced fat mass, associated with protection against age-induced decline of endurance capacity compared with wild-type mice. Circulating levels of fibroblast growth factor 21, a novel biomarker for mitochondrial respiratory chain deficiencies and inhibitor of white adipose lipolysis, were significantly reduced in apoA-I tg mice. Consistent with an increase in glucose utilization of skeletal muscle, genetically increased HDL and apoA-I levels in mice prevented high-fat diet-induced impairment of glucose homeostasis. In view of impaired mitochondrial function and decreased HDL levels in type 2 diabetes mellitus, our findings indicate that HDL-raising therapies may preserve muscle mitochondrial function and address key aspects of type 2 diabetes mellitus beyond cardiovascular disease.

  15. Behavioral versus genetic correlates of lipoproteins and adiposity in identical twins discordant for exercise.

    Science.gov (United States)

    Williams, Paul T; Blanche, Patricia J; Krauss, Ronald M

    2005-07-19

    Lipoprotein and weight differences between vigorously active and sedentary monozygotic (MZ) twins were used to (1) estimate the effects of training while controlling for genotype and (2) estimate genetic concordance (ie, similarity) in the presence of divergent lifestyles. Thirty-five pairs of MZ twins (25 male, 10 female) were recruited nationally who were discordant for vigorous exercise (running distances differed by > or =40 km in male and > or =32 km in female twins). The active twins ran an average (mean+/-SD) of 63.0+/-20.4 km/wk, whereas the mostly sedentary twins averaged 7.0+/-13.5 km/wk. The active twins had significantly lower body mass index (difference+/-SE, -2.12+/-0.57 kg/m2, P=0.0007) and significantly higher HDL cholesterol (0.14+/-0.04 mmol/L, P=0.004), HDL2 (2.71+/-1.04 U, P=0.01), and apolipoprotein (apo) A-I (0.10+/-0.03 g/L, P=0.004). Despite the difference in lifestyle, when adjusted for sex, the correlations between the discordant MZ twin pairs were significant (PHDL cholesterol (r=0.69), apoA-I (r=0.58), and HDL2 (r=0.67). There was no significant MZ twin correlation for body mass index (r=0.17). None of the active twins having an overweight twin were themselves overweight. Behavior (vigorous exercise) may reduce genetic influences on body mass index. In contrast, genetics (or shared environment) substantially influences HDL cholesterol and HDL subclasses, even in the presence of extreme behavioral differences. There may be greater individual control over moderate degrees of obesity, whereas low HDL cholesterol may be largely predetermined and less effectively treated by vigorous exercise.

  16. Lipoprotein(a) levels are associated with aortic valve calcification in asymptomatic patients with familial hypercholesterolaemia.

    Science.gov (United States)

    Vongpromek, R; Bos, S; Ten Kate, G-J R; Yahya, R; Verhoeven, A J M; de Feyter, P J; Kronenberg, F; Roeters van Lennep, J E; Sijbrands, E J G; Mulder, M T

    2015-08-01

    Lipoprotein(a) [Lp(a)] is an independent risk factor for aortic valve stenosis and aortic valve calcification (AVC) in the general population. In this study, we determined the association between AVC and both plasma Lp(a) levels and apolipoprotein(a) [apo(a)] kringle IV repeat polymorphisms in asymptomatic statin-treated patients with heterozygous familial hypercholesterolaemia (FH). A total of 129 asymptomatic heterozygous FH patients (age 40-69 years) were included in this study. AVC was detected using computed tomography scanning. Lp(a) concentration and apo(a) kringle IV repeat number were measured using immunoturbidimetry and immunoblotting, respectively. Univariate and multivariate logistic regression were used to assess the association between Lp(a) concentration and the presence of AVC. Aortic valve calcification was present in 38.2% of patients, including three with extensive AVC (>400 Agatston units). Lp(a) concentration was significantly correlated with gender, number of apo(a) kringle IV repeats and the presence and severity of AVC, but not with coronary artery calcification (CAC). AVC was significantly associated with plasma Lp(a) level, age, body mass index, blood pressure, duration of statin use, cholesterol-year score and CAC score. After adjustment for all significant covariables, plasma Lp(a) concentration remained a significant predictor of AVC, with an odds ratio per 10-mg dL(-1) increase in Lp(a) concentration of 1.11 (95% confidence interval 1.01-1.20, P = 0.03). In asymptomatic statin-treated FH patients, plasma Lp(a) concentration is an independent risk indicator for AVC. © 2014 The Association for the Publication of the Journal of Internal Medicine.

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

  18. Lipoprotein-specific transport of circulating lipid peroxides.

    Science.gov (United States)

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

    2010-10-01

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

  19. Triglyceride-rich lipoprotein metabolism in women: roles of apoC-II and apoC-III.

    Science.gov (United States)

    Ooi, Esther M; Chan, Dick C; Hodson, Leanne; Adiels, Martin; Boren, Jan; Karpe, Fredrik; Fielding, Barbara A; Watts, Gerald F; Barrett, P Hugh R

    2016-08-01

    Experimental data suggest that apolipoprotein (apo) C-II and C-III regulate triglyceride-rich lipoprotein (TRL) metabolism, but there are limited studies in humans. We investigated the metabolic associations of TRLs with apoC-II and apoC-III concentrations and kinetics in women. The kinetics of plasma apoC-II, apoC-III and very low-density lipoprotein (VLDL) apoB-100 and triglycerides were measured in the postabsorptive state using stable isotopic techniques and compartmental modelling in 60 women with wide-ranging body mass index (19·5-32·9 kg/m(2) ). Plasma apoC-II and apoC-III concentrations were positively associated with the concentrations of plasma triglycerides, VLDL1 - and VLDL2 -apoB-100 and triglyceride (all P triglyceride concentration and VLDL1 triglyceride PR, while apoC-II fractional catabolic rate (FCR) was positively associated with VLDL1 triglyceride FCR (all P triglyceride kinetics. ApoC-III PR, but not FCR, was positively associated with VLDL1 triglyceride, and VLDL2 -apoB-100 and triglyceride concentrations (all P triglyceride kinetics. In multivariable analysis, including homoeostasis model assessment score, menopausal status and obesity, apoC-II concentration was significantly associated with plasma triglyceride, VLDL1 -apoB-100 and VLDL1 triglyceride concentrations and PR. Using the same multivariable analysis, apoC-III was significantly associated with plasma triglyceride and VLDL1 - and VLDL2 -apoB-100 and triglyceride concentrations and FCR. In women, plasma apoC-II and apoC-III concentrations are regulated by their respective PR and are significant, independent determinants of the kinetics and plasma concentrations of TRLs. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

  20. Apolipoprotein A-1 mimetic peptide 4F promotes endothelial repairing and compromises reendothelialization impaired by oxidized HDL through SR-B1

    Directory of Open Access Journals (Sweden)

    Dan He

    2018-05-01

    Full Text Available Disruption of endothelial monolayer integrity is the primary instigating factor for many cardiovascular diseases. High density lipoprotein (HDL oxidized by heme enzyme myeloperoxidase (MPO is dysfunctional in promoting endothelial repair. Apolipoprotein A-1 mimetic 4F with its pleiotropic benefits has been proven effective in many in vivo models. In this study we investigated whether 4F promotes endothelial repair and restores the impaired function of oxidized HDL (Cl/NO2-HDL in promoting re-endothelialization. We demonstrate that 4F and Cl/NO2-HDL act on scavenger receptor type I (SR-B1 using human aorta endothelial cells (HAEC and SR-B1 (-/- mouse aortic endothelial cells. Wound healing, transwell migration, lamellipodia formation and single cell migration assay experiments show that 4F treatment is associated with a recovery of endothelial cell migration and associated with significantly increased endothelial nitric oxide synthase (eNOS activity, Akt phosphorylation and SR-B1 expression. 4F increases NO generation and diminishes oxidative stress. In vivo, 4F can stimulate cell proliferation and re-endothelialization in the carotid artery after treatment with Cl/NO2-HDL in a carotid artery electric injury model but fails to do so in SR-B1(-/- mice. These findings demonstrate that 4F promotes endothelial cell migration and has a potential therapeutic benefit against early endothelial injury in cardiovascular diseases.

  1. Dietary fat manipulation has a greater impact on postprandial lipid metabolism than the apolipoprotein E (epsilon) genotype-insights from the SATgenε study.

    Science.gov (United States)

    Jackson, Kim G; Lockyer, Stacey; Carvalho-Wells, Andrew L; Williams, Christine M; Minihane, Anne M; Lovegrove, Julie A

    2012-12-01

    Our aim was to determine the effects of chronic dietary fat manipulation on postprandial lipaemia according to apolipoprotein (APO)E genotype. Men (mean age 53 (SD 9) years), prospectively recruited for the APOE genotype (n = 12 E3/E3, n = 11 E3/E4), were assigned to a low fat (LF), high fat, high-saturated fat (HSF), and HSF diet with 3.45 g/day docosahexaenoic acid (HSF-DHA), each for an 8-week period in the same order. At the end of each dietary period, a postprandial assessment was performed using a test meal with a macronutrient profile representative of that dietary intervention. A variable postprandial plasma triacylglycerol (TAG) response according to APOE genotype was evident, with a greater sensitivity to the TAG-lowering effects of DHA in APOE4 carriers (p ≤ 0.005). There was a lack of an independent genotype effect on any of the lipid measures. In the groups combined, dietary fat manipulation had a significant impact on lipids in plasma and Svedberg flotation rate (S(f) ) 60-400 TAG-rich lipoprotein fraction, with lower responses following the HSF-DHA than HSF intervention (p postprandial lipid response in normolipidaemic men. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Folate and S-adenosylmethionine modulate synaptic activity in cultured cortical neurons: acute differential impact on normal and apolipoprotein-deficient mice

    International Nuclear Information System (INIS)

    Serra, Michael; Chan, Amy; Dubey, Maya; Shea, Thomas B; Gilman, Vladimir

    2008-01-01

    Folate deficiency is accompanied by a decline in the cognitive neurotransmitter acetylcholine and a decline in cognitive performance in mice lacking apolipoprotein E (ApoE−/− mice), a low-density lipoprotein that regulates aspects of lipid metabolism. One direct consequence of folate deficiency is a decline in S-adenosylmethionine (SAM). Since dietary SAM supplementation maintains acetylcholine levels and cognitive performance in the absence of folate, we examined herein the impact of folate and SAM on neuronal synaptic activity. Embryonic cortical neurons from mice expressing or lacking ApoE (ApoE+/+ or −/−, respectively) were cultured for 1 month on multi-electrode arrays, and signaling was recorded. ApoE+/+ cultures displayed significantly more frequent spontaneous signals than ApoE−/− cultures. Supplementation with 166 µm SAM (not normally present in culture medium) increased signal frequency and decreased signal amplitude in ApoE+/+ cultures. SAM also increased the frequency of tightly clustered signal bursts. Folate deprivation reversibly reduced signal frequency in ApoE+/+ cultures; SAM supplementation maintained signal frequency despite folate deprivation. These findings support the importance of dietary supplementation with folate and SAM on neuronal health. Supplementation with 166 µm SAM did not alter signaling in ApoE−/− cultures, which may be a reflection of the reduced SAM levels in ApoE−/− mice. The differential impact of SAM on ApoE+/+ and −/− neurons underscores the combined impact of nutritional and genetic deficiencies on neuronal homeostasis. (communication)

  3. IMB2026791, a Xanthone, Stimulates Cholesterol Efflux by Increasing the Binding of Apolipoprotein A-I to ATP-Binding Cassette Transporter A1

    Directory of Open Access Journals (Sweden)

    Zijian Xie

    2012-03-01

    Full Text Available It is known that the ATP-binding cassette transporter A1 (ABCA1 plays a major role in cholesterol homeostasis and high density lipoprotein (HDL metabolism. Several laboratories have demonstrated that ABCA1 binding to lipid-poor apolipoprotein A-I (apoA-I will mediate the assembly of nascent HDL and cellular cholesterol efflux, which suggests a possible receptor-ligand interaction between ABCA1 and apoA-I. In this study, a cell-based-ELISA-like high-throughput screening (HTS method was developed to identify the synthetic and natural compounds that can regulate binding activity of ABCA1 to apoA-I. The cell-based-ELISA-like high-throughput screen was conducted in a 96-well format using Chinese hamster ovary (CHO cells stably transfected with ABCA1 pIRE2-EGFP (Enhanced Green Fluorecence Protein expression vector and the known ABCA1 inhibitor glibenclamide as the antagonist control. From 2,600 compounds, a xanthone compound (IMB 2026791 was selected using this HTS assay, and it was proved as an apoA-I binding agonist to ABCA1 by a flow cytometry assay and western blot analysis. The [3H] cholesterol efflux assay of IMB2026791 treated ABCA1-CHO cells and PMA induced THP-1 macrophages (human acute monocytic leukemia cell further confirmed the compound as an accelerator of cholesterol efflux in a dose-dependent manner with an EC50 of 25.23 μM.

  4. Apolipoprotein D is elevated in oligodendrocytes in the peri-infarct region after experimental stroke

    DEFF Research Database (Denmark)

    Rickhag, Karl Mattias; Deierborg, Tomas; Patel, Shutish

    2008-01-01

    trafficking of macromolecular components including cholesterol and phospholipids, a transport carried out by apolipoproteins including apolipoprotein D (apoD). We investigated the changes in the levels of apoD mRNA and protein, and its cellular localization during a recovery period up to 30 days after...... experimental stroke in the rat brain. In the core of the brain infarct, apoD immunoreactivity but not mRNA increased in dying pyramidal neurons, indicative of cellular redistribution of lipids. During 2 to 7 days of recovery after stroke, the apoD levels increased in the peri-infarct and white matter areas...

  5. Redefining the essential trafficking pathway for outer membrane lipoproteins

    OpenAIRE

    Grabowicz, Marcin; Silhavy, Thomas J.

    2017-01-01

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

  6. 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.

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

    Science.gov (United States)

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

    2018-02-02

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

  8. Low-Density Lipoproteins Oxidation and Endometriosis

    Directory of Open Access Journals (Sweden)

    Grzegorz Polak

    2013-01-01

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

  9. 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.

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

    Science.gov (United States)

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

    1992-06-01

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

  11. Osbpl8 deficiency in mouse causes an elevation of high-density lipoproteins and gender-specific alterations of lipid metabolism.

    Directory of Open Access Journals (Sweden)

    Olivier Béaslas

    Full Text Available OSBP-related protein 8 (ORP8 encoded by Osbpl8 is an endoplasmic reticulum sterol sensor implicated in cellular lipid metabolism. We generated an Osbpl8(-/- (KO C57Bl/6 mouse strain. Wild-type and Osbpl8KO animals at the age of 13-weeks were fed for 5 weeks either chow or high-fat diet, and their plasma lipids/lipoproteins and hepatic lipids were analyzed. The chow-fed Osbpl8KO male mice showed a marked elevation of high-density lipoprotein (HDL cholesterol (+79% and phospholipids (+35%, while only minor increase of apolipoprotein A-I (apoA-I was detected. In chow-fed female KO mice a less prominent increase of HDL cholesterol (+27% was observed, while on western diet the HDL increment was prominent in both genders. The HDL increase was accompanied by an elevated level of HDL-associated apolipoprotein E in male, but not female KO animals. No differences between genotypes were observed in lecithin:cholesterol acyltransferase (LCAT or hepatic lipase (HL activity, or in the fractional catabolic rate of fluorescently labeled mouse HDL injected in chow-diet fed animals. The Osbpl8KO mice of both genders displayed reduced phospholipid transfer protein (PLTP activity, but only on chow diet. These findings are consistent with a model in which Osbpl8 deficiency results in altered biosynthesis of HDL. Consistent with this hypothesis, ORP8 depleted mouse hepatocytes secreted an increased amount of nascent HDL into the culture medium. In addition to the HDL phenotype, distinct gender-specific alterations in lipid metabolism were detected: Female KO animals on chow diet showed reduced lipoprotein lipase (LPL activity and increased plasma triglycerides, while the male KO mice displayed elevated plasma cholesterol biosynthetic markers cholestenol, desmosterol, and lathosterol. Moreover, modest gender-specific alterations in the hepatic expression of lipid homeostatic genes were observed. In conclusion, we report the first viable OsbplKO mouse model

  12. Sildenafil restores endothelial function in the apolipoprotein E knockout mouse

    Directory of Open Access Journals (Sweden)

    Balarini Camille M

    2013-01-01

    Full Text Available Abstract Background Atherosclerosis is an inflammatory process of the arterial walls and is initiated by endothelial dysfunction accompanied by an imbalance in the production of reactive oxygen species (ROS and nitric oxide (NO. Sildenafil, a selective phosphodiesterase-5 (PDE5 inhibitor used for erectile dysfunction, exerts its cardiovascular effects by enhancing the effects of NO. The aim of this study was to investigate the influence of sildenafil on endothelial function and atherosclerosis progression in apolipoprotein E knockout (apoE−/− mice. Methods ApoE−/− mice treated with sildenafil (Viagra®, 40 mg/kg/day, for 3 weeks, by oral gavage were compared to the untreated apoE−/− and the wild-type (WT mice. Aortic rings were used to evaluate the relaxation responses to acetylcholine (ACh in all of the groups. In a separate set of experiments, the roles of NO and ROS in the relaxation response to ACh were evaluated by incubating the aortic rings with L-NAME (NO synthase inhibitor or apocynin (NADPH oxidase inhibitor. In addition, the atherosclerotic lesions were quantified and superoxide production was assessed. Results Sildenafil restored the vasodilator response to acetylcholine (ACh in the aortic rings of the apoE−/− mice. Treatment with L-NAME abolished the vasodilator responses to ACh in all three groups of mice and revealed an augmented participation of NO in the endothelium-dependent vasodilation in the sildenafil-treated animals. The normalized endothelial function in sildenafil-treated apoE−/− mice was unaffected by apocynin highlighting the low levels of ROS production in these animals. Moreover, morphological analysis showed that sildenafil treatment caused approximately a 40% decrease in plaque deposition in the aorta. Conclusion This is the first study demonstrating the beneficial effects of chronic treatment with sildenafil on endothelial dysfunction and atherosclerosis in a model of spontaneous

  13. Thyroid hormones upregulate apolipoprotein E gene expression in astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Roman, Corina; Fuior, Elena V.; Trusca, Violeta G. [Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest (Romania); Kardassis, Dimitris [University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology of Hellas, Heraklion, Crete (Greece); Simionescu, Maya [Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest (Romania); Gafencu, Anca V., E-mail: anca.gafencu@icbp.ro [Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest (Romania)

    2015-12-04

    Apolipoprotein E (apoE), a protein mainly involved in lipid metabolism, is associated with several neurodegenerative disorders including Alzheimer's disease. Despite numerous attempts to elucidate apoE gene regulation in the brain, the exact mechanism is still uncovered. The mechanism of apoE gene regulation in the brain involves the proximal promoter and multienhancers ME.1 and ME.2, which evolved by gene duplication. Herein we questioned whether thyroid hormones and their nuclear receptors have a role in apoE gene regulation in astrocytes. Our data showed that thyroid hormones increase apoE gene expression in HTB14 astrocytes in a dose-dependent manner. This effect can be intermediated by the thyroid receptor β (TRβ) which is expressed in these cells. In the presence of triiodothyronine (T3) and 9-cis retinoic acid, in astrocytes transfected to overexpress TRβ and retinoid X receptor α (RXRα), apoE promoter was indirectly activated through the interaction with ME.2. To determine the location of TRβ/RXRα binding site on ME.2, we performed DNA pull down assays and found that TRβ/RXRα complex bound to the region 341–488 of ME.2. This result was confirmed by transient transfection experiments in which a series of 5′- and 3′-deletion mutants of ME.2 were used. These data support the existence of a biologically active TRβ binding site starting at 409 in ME.2. In conclusion, our data revealed that ligand-activated TRβ/RXRα heterodimers bind with high efficiency on tissue-specific distal regulatory element ME.2 and thus modulate apoE gene expression in the brain. - Highlights: • T3 induce a dose-dependent increase of apoE expression in astrocytes. • Thyroid hormones activate apoE promoter in a cell specific manner. • Ligand activated TRβ/RXRα bind on the distal regulatory element ME.2 to modulate apoE. • The binding site of TRβ/RXRα heterodimer is located at 409 bp on ME.2.

  14. Thyroid hormones upregulate apolipoprotein E gene expression in astrocytes

    International Nuclear Information System (INIS)

    Roman, Corina; Fuior, Elena V.; Trusca, Violeta G.; Kardassis, Dimitris; Simionescu, Maya; Gafencu, Anca V.

    2015-01-01

    Apolipoprotein E (apoE), a protein mainly involved in lipid metabolism, is associated with several neurodegenerative disorders including Alzheimer's disease. Despite numerous attempts to elucidate apoE gene regulation in the brain, the exact mechanism is still uncovered. The mechanism of apoE gene regulation in the brain involves the proximal promoter and multienhancers ME.1 and ME.2, which evolved by gene duplication. Herein we questioned whether thyroid hormones and their nuclear receptors have a role in apoE gene regulation in astrocytes. Our data showed that thyroid hormones increase apoE gene expression in HTB14 astrocytes in a dose-dependent manner. This effect can be intermediated by the thyroid receptor β (TRβ) which is expressed in these cells. In the presence of triiodothyronine (T3) and 9-cis retinoic acid, in astrocytes transfected to overexpress TRβ and retinoid X receptor α (RXRα), apoE promoter was indirectly activated through the interaction with ME.2. To determine the location of TRβ/RXRα binding site on ME.2, we performed DNA pull down assays and found that TRβ/RXRα complex bound to the region 341–488 of ME.2. This result was confirmed by transient transfection experiments in which a series of 5′- and 3′-deletion mutants of ME.2 were used. These data support the existence of a biologically active TRβ binding site starting at 409 in ME.2. In conclusion, our data revealed that ligand-activated TRβ/RXRα heterodimers bind with high efficiency on tissue-specific distal regulatory element ME.2 and thus modulate apoE gene expression in the brain. - Highlights: • T3 induce a dose-dependent increase of apoE expression in astrocytes. • Thyroid hormones activate apoE promoter in a cell specific manner. • Ligand activated TRβ/RXRα bind on the distal regulatory element ME.2 to modulate apoE. • The binding site of TRβ/RXRα heterodimer is located at 409 bp on ME.2.

  15. The low resolution structure of ApoA1 in spherical high density lipoprotein revealed by small angle neutron scattering.

    Science.gov (United States)

    Wu, Zhiping; Gogonea, Valentin; Lee, Xavier; May, Roland P; Pipich, Vitaliy; Wagner, Matthew A; Undurti, Arundhati; Tallant, Thomas C; Baleanu-Gogonea, Camelia; Charlton, Francesca; Ioffe, Alexander; DiDonato, Joseph A; Rye, Kerry-Anne; Hazen, Stanley L

    2011-04-08

    Spherical high density lipoprotein (sHDL), a key player in reverse cholesterol transport and the most abundant form of HDL, is associated with cardiovascular diseases. Small angle neutron scattering with contrast variation was used to determine the solution structure of protein and lipid components of reconstituted sHDL. Apolipoprotein A1, the major protein of sHDL, forms a hollow structure that cradles a central compact lipid core. Three apoA1 chains are arranged within the low resolution structure of the protein component as one of three possible global architectures: (i) a helical dimer with a hairpin (HdHp), (ii) three hairpins (3Hp), or (iii) an integrated trimer (iT) in which the three apoA1 monomers mutually associate over a portion of the sHDL surface. Cross-linking and mass spectrometry analyses help to discriminate among the three molecular models and are most consistent with the HdHp overall architecture of apoA1 within sHDL.

  16. Lipoprotein-biomimetic nanostructure enables efficient targeting delivery of siRNA to Ras-activated glioblastoma cells via macropinocytosis

    Science.gov (United States)

    Huang, Jia-Lin; Jiang, Gan; Song, Qing-Xiang; Gu, Xiao; Hu, Meng; Wang, Xiao-Lin; Song, Hua-Hua; Chen, Le-Pei; Lin, Ying-Ying; Jiang, Di; Chen, Jun; Feng, Jun-Feng; Qiu, Yong-Ming; Jiang, Ji-Yao; Jiang, Xin-Guo; Chen, Hong-Zhuan; Gao, Xiao-Ling

    2017-05-01

    Hyperactivated Ras regulates many oncogenic pathways in several malignant human cancers including glioblastoma and it is an attractive target for cancer therapies. Ras activation in cancer cells drives protein internalization via macropinocytosis as a key nutrient-gaining process. By utilizing this unique endocytosis pathway, here we create a biologically inspired nanostructure that can induce cancer cells to `drink drugs' for targeting activating transcription factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in glioblastoma. Apolipoprotein E3-reconstituted high-density lipoprotein is used to encapsulate the siRNA-loaded calcium phosphate core and facilitate it to penetrate the blood-brain barrier, thus targeting the glioblastoma cells in a macropinocytosis-dependent manner. The nanostructure carrying ATF5 siRNA exerts remarkable RNA-interfering efficiency, increases glioblastoma cell apoptosis and inhibits tumour cell growth both in vitro and in xenograft tumour models. This strategy of targeting the macropinocytosis caused by Ras activation provides a nanoparticle-based approach for precision therapy in glioblastoma and other Ras-activated cancers.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    1987-12-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  1. The apolipoprotein E polymorphism in Greenland Inuit in its global perspective

    DEFF Research Database (Denmark)

    Gerdes, Lars Ulrik; Gerdes, C; Hansen, Peter Sten

    1996-01-01

    was relatively high, about 23%. As in most other populations, mean plasma lipoprotein-related variables, except high-density lipoprotein (HDL) cholesterol, were higher in both Inuit men and women with epsilon 4 than in epsilon 3 epsilon 3 genotypes (P HDL cholesterol...

  2. Importance of apolipoprotein A-I in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Lidia A Gardner

    2015-11-01

    Full Text Available Jean-Martin Charcot has first described multiple sclerosis (MS as a disease of the central nervous system (CNS over a century ago. MS remains incurable today, and treatment options are limited to disease modifying drugs. Over the years, significant advances in understanding disease pathology have been made in autoimmune and neurodegenerative components. Despite the fact that brain is the most lipid rich organ in human body, the importance of lipid metabolism has not been extensively studied in this disorder. In MS, the CNS is under attack by a person’s own immune system. Autoantigens and autoantibodies are known to cause devastation of myelin through up regulation of T-cells and cytokines, which penetrate through the blood brain barrier to cause inflammation and myelin destruction.The anti-inflammatory role of high-density lipoproteins (HDLs has been implicated in a plethora of biological processes: vasodilation, immunity to infection, oxidation, inflammation, and apoptosis. However it is not known what role HDL plays in neurological function and myelin repair in MS. Understanding of lipid metabolism in the CNS and in the periphery might unveil new therapeutic targets and explain the partial success of some existing MS therapies.

  3. Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor ROR alpha

    International Nuclear Information System (INIS)

    Genoux, Annelise; Dehondt, Helene; Helleboid-Chapman, Audrey; Duhem, Christian; Hum, Dean W.; Martin, Genevieve; Pennacchio, Len; Staels, Bart; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-01-01

    Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoa5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis

  4. Apolipoprotein H, a new mediator in the inflammatory changes ensuring in jeopardised human myocardium

    NARCIS (Netherlands)

    Niessen, H. W.; Lagrand, W. K.; Rensink, H. J.; Meijer, C. J.; Aarden, L.; Hack, C. E.; Visser, C.

    2000-01-01

    AIM: To investigate the presence of membrane "flip flop" in ischaemic human myocardium, we assessed depositions of apolipoprotein H (apoH; beta 2-glycoprotein 1) in ischaemic myocardium. Serum protein apoH can bind to negatively charged phospholipids and can also inhibit blood coagulation in vitro.

  5. Apolipoprotein D is associated with long-term outcome in patients with schizophrenia

    DEFF Research Database (Denmark)

    Hansen, Thomas Folkmann; Hemmingsen, R P; Wang, A G

    2006-01-01

    Accumulating evidence implicates deficiencies in apolipoprotein D (ApoD) function and arachidonic acid signaling in schizophrenic disorders. We addressed two hypotheses in relation to ApoD: first, polymorphisms in the ApoD gene confer susceptibility to or are markers of disease, and, second...

  6. Human apolipoprotein E genotypes differentially modify house dust mite-induced airway disease in mice

    DEFF Research Database (Denmark)

    Yao, Xianglan; Dai, Cuilian; Fredriksson, Karin

    2012-01-01

    Apolipoprotein E (apoE) is an endogenous negative regulator of airway hyperreactivity (AHR) and mucous cell metaplasia in experimental models of house dust mite (HDM)-induced airway disease. The gene encoding human apoE is polymorphic, with three common alleles (e2, e3, and e4) reflecting single...

  7. Apolipoproteins A-I, B, and C-III and Obesity in Young Adult Cherokee

    Directory of Open Access Journals (Sweden)

    Wenyu Wang

    2017-01-01

    Full Text Available Since young adult Cherokee are at increased risk for both diabetes and cardiovascular disease, we assessed association of apolipoproteins (A-I, B, and C-III in non-HDL and HDL with obesity and related risk factors. Obese participants (BMI ≥ 30 aged 20–40 years (n=476 were studied. Metabolically healthy obese (MHO individuals were defined as not having any of four components of the ATP-III metabolic syndrome after exclusion of waist circumference, and obese participants not being MHO were defined as metabolically abnormal obese (MAO. Associations were evaluated by correlation and regression modeling. Obesity measures, blood pressure, insulin resistance, lipids, and apolipoproteins were significantly different between groups except for total cholesterol, LDL-C, and HDL-apoC-III. Apolipoproteins were not correlated with obesity measures with the exception of apoA-I with waist and the waist : height ratio. In a logistic regression model apoA-I and the apoB : apoA-I ratio were significantly selected for identifying those being MHO, and the result (C-statistic = 0.902 indicated that apoA-I and the apoB : apoA-I ratio can be used to identify a subgroup of obese individuals with a significantly less atherogenic lipid and apolipoprotein profile, particularly in obese Cherokee men in whom MHO is more likely.

  8. Improving prediction of ischemic cardiovascular disease in the general population using apolipoprotein B

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Gorm Boje

    2007-01-01

    Apolipoprotein B (apoB) levels predict fatal myocardial infarction. Whether apoB also predicts nonfatal ischemic cardiovascular events is unclear. We tested the following hypotheses: apoB predicts ischemic cardiovascular events, and apoB is a better predictor of ischemic cardiovascular events than...

  9. Hyperlipidemia and cutaneous abnormalities in transgenic mice overexpressing human apolipoprotein C1

    NARCIS (Netherlands)

    Jong, M.C.; Gijbels, M.J.J.; Dahlmans, V.E.H.; Gorp, P.J.J. van; Koopman, S.-J.; Ponec, M.; Hofker, M.H.; Havekes, L.M.

    1998-01-01

    Transgenic mice were generated with different levels of human apolipoprotein C1 (APOC1) expression in liver and skin. At 2 mo of age, serum levels of cholesterol, triglycerides (TG), and FFA were strongly elevated in APOC1 transgenic mice compared with wild-type mice. These elevated levels of serum

  10. Development of atopic dermatitis in mice transgenic for human apolipoprotein C1

    NARCIS (Netherlands)

    Nagelkerken, Lex; Verzaal, Perry; Lagerweij, Tonny; Persoon-Deen, Carla; Berbee, Jimmy F. P.; Prens, Errol P.; Havekes, Louis M.; Oranje, Arnold P.

    Mice with transgenic expression of human apolipoprotein C1 (APOC1) in liver and skin have strongly increased serum levels of cholesterol, triglycerides, and free fatty acids, indicative of a disturbed lipid metabolism. Importantly, these mice display a disturbed skin barrier function, evident from

  11. Capillary electrophoresis with laser-induced fluorescence detection for fast and reliable apolipoprotein E genotyping

    NARCIS (Netherlands)

    Somsen, GW; Welten, HTME; Mulder, FP; Swart, CW; Kema, IP; de Jong, GJ

    2002-01-01

    The use of capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection for the rapid determination of apolipoprotein E (apoE) genotypes was studied. High resolution and sensitive detection of the concerned DNA restriction fragments was achieved using CE buffers with

  12. Conformational switching and fibrillogenesis in the amyloidogenic fragment of apolipoprotein a-I.

    Science.gov (United States)

    Andreola, Alessia; Bellotti, Vittorio; Giorgetti, Sofia; Mangione, Palma; Obici, Laura; Stoppini, Monica; Torres, Jaume; Monzani, Enrico; Merlini, Giampaolo; Sunde, Margaret

    2003-01-24

    The N-terminal portion of apolipoprotein A-I corresponding to the first 93 residues has been identified as the main component of apolipoprotein A-I fibrils in a form of systemic amyloidosis. We have been able to characterize the process of conformational switching and fibrillogenesis in this fragment of apolipoprotein A-I purified directly from ex vivo amyloid material. The peptide exists in an unstructured form in aqueous solution at neutral pH. The acidification of the solution provokes a collapse into a more compact, intermediate state and the transient appearance of a helical conformation that rapidly converts to a stable, mainly beta-structure in the fibrils. The transition from helical to sheet structure occurs concomitantly with peptide self-aggregation, and fibrils are detected after 72 h. The alpha-helical conformation is induced by the addition of trifluoroethanol and phospholipids. Interaction of the amyloidogenic polypeptide with phospholipids prevents the switching from helical to beta-sheet form and inhibits fibril formation. The secondary structure propensity of the apolipoprotein A-I fragment appears poised between helix and the beta-sheet. These findings reinforce the idea of a delicate balance between natively stabilizing interactions and fatally stabilizing interactions and stress the importance of cellular localization and environment in the maintenance of protein conformation.

  13. Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice

    Czech Academy of Sciences Publication Activity Database

    Dolejší, Eva; Liraz, O.; Rudajev, Vladimír; Zimčík, Pavel; Doležal, Vladimír; Michaelson, D. M.

    2016-01-01

    Roč. 136, č. 3 (2016), s. 503-509 ISSN 0022-3042 R&D Projects: GA MŠk(CZ) LH13269 Institutional support: RVO:67985823 Keywords : acetylcholine release * Alzheimer's disease (AD) * apolipoprotein E4 (apoE4) * hippocampus Subject RIV: FH - Neurology Impact factor: 4.083, year: 2016

  14. Nutrient Intake, Apolipoprotein A5 -1131T>C Polymorphism and Its Relationship with Obesity

    Science.gov (United States)

    Sari, M. I.; Sari, D. I.

    2017-03-01

    Obesity is associated with the development of some of the most prevalent diseases of modern society. The World Health Organization estimates that at least 2.8 million adult die each year as result of being obesity. Nutrient intake is a key environmental factor that may interact with genotype to affect risk of obesity. The aim of study was assess the relation between nutrient intake and apolipoprotein A5 -1131T>C polimorphism with obesity. A cross sectional study has been carried out on 139 subjects. Nutrient intake data was collected by using a 24 hour dietary recall and analyzed by nutrisurvey software. Anthropometric variables were measured and body mass index (BMI). Apolipoprotein A5 -1131T>C polymorphism was visualized with 5% agarose gel after restriction length fragment polymorphism (RFLP) digested with MseI. Results : Subjects in this study were 55 male and 84 female, with average age 19.20 ± 1.08, 75 had obese and 64 non obese. Based on the chi square test is found a relationship between total energy intake and protein intake in obese group compared to the non-obese group (p = 0.029, p = 0.006) and no relationship was found in Apolipoprotein A5 -1131T> C polymorphism with obesity. These findings indicate that nutrient intake no depending with apolipoprotein A5 gene variant to modulate obesity

  15. Apolipoprotein A-1 (apoA-1) deposition in, and release from, the enterocyte brush border

    DEFF Research Database (Denmark)

    Danielsen, E Michael; Hansen, Gert H; Rasmussen, Karina

    2012-01-01

    resistant membranes (DRMs), indicative of localization in lipid raft microdomains. The apolipoprotein was not readily released from microvillar vesicles by high salt or by incubation with phosphatidylcholine-specific phospholipase C or trypsin, indicating a relatively firm attachment to the membrane bilayer...

  16. Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor ROR alpha

    Energy Technology Data Exchange (ETDEWEB)

    Genoux, Annelise; Dehondt, Helene; Helleboid-Chapman, Audrey; Duhem, Christian; Hum, Dean W.; Martin, Genevieve; Pennacchio, Len; Staels, Bart; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-10-01

    Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoa5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis

  17. The use of transgenic animals to study lipoprotein metabolism

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-12-01

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

  18. Recent advances in lipoprotein and atherosclerosis: nutrigenomic approach

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  20. Replacement of partially hydrogenated soybean oil by palm oil in margarine without unfavorable effects on serum lipoproteins.

    Science.gov (United States)

    Müller, H; Jordal, O; Kierulf, P; Kirkhus, B; Pedersen, J I

    1998-09-01

    We have compared the effects of three different margarines, one based on palm oil (PALM-margarine), one based on partially hydrogenated soybean oil (TRANS-margarine) and one with a high content of polyunsaturated fatty acids (PUFA-margarine), on serum lipids in 27 young women. The main purpose of the study was to test if replacement of trans fatty acids in margarine by palmitic acid results in unfavorable effects on serum lipids. The sum of saturated fatty acids (12:0, 14:0, 16:0) was 36.3% of total fatty acids in the PALM-diet, the same as the sum of saturated (12:0, 14:0, 16:0) (12.5%) and trans (23.1%) fatty acids in the TRANS-diet. This sum was 20.7% in the PUFA-diet. The content of oleic acid was 37.9, 35.2, and 38.6%, respectively, in the three diets, whereas linoleic acid amounted to 16, 13.5, and 27.3%, respectively. Total fat provided 30-31% and the test margarines 26% of total energy in all three diets. The subjects consumed each of the diets for 17 d in a Latin-square crossover design. There were no significant differences in total cholesterol, low density lipoprotein (LDL)-cholesterol and apolipoprotein B (apoB) between the TRANS- and the PALM-diets. High density lipoprotein (HDL)-cholesterol and apoA-1 were significantly higher on the PALM-diet compared to the TRANS-diet whereas the ratio of LDL-cholesterol to HDL-cholesterol was lower, although not significantly (P = 0.077) on the PALM-diet. Total cholesterol, LDL-cholesterol, and apoB were significantly lower on the PUFA-diet compared to the two other diets. HDL-cholesterol was not different on the PALM- and the PUFA-diets but it was significantly lower on the TRANS-diet compared to the PUFA diet. Compared to the PUFA-diet the ratio of LDL- to HDL-cholesterol was higher on both the PALM- and the TRANS-diets whereas apoA-1 was not different. Triglycerides and lipoprotein (a) were not significantly different among the three diets. We concluded that nutritionally, palmitic acid from palm oil may be a