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Sample records for lipoprotein explain increased

  1. Excess coronary artery disease risk in South Asian immigrants: Can dysfunctional high-density lipoprotein explain increased risk?

    PubMed Central

    Dodani, Sunita

    2008-01-01

    Background: Coronary artery disease (CAD) is the leading cause of mortality and morbidity in the United States (US), and South Asian immigrants (SAIs) have a higher risk of CAD compared to Caucasians. Traditional risk factors may not completely explain high risk, and some of the unknown risk factors need to be explored. This short review is mainly focused on the possible role of dysfunctional high-density lipoprotein (HDL) in causing CAD and presents an overview of available literature on dysfunctional HDL. Discussion: The conventional risk factors, insulin resistance parameters, and metabolic syndrome, although important in predicting CAD risk, may not sufficiently predict risk in SAIs. HDL has antioxidant, antiinflammatory, and antithrombotic properties that contribute to its function as an antiatherogenic agent. Recent Caucasian studies have shown HDL is not only ineffective as an antioxidant but, paradoxically, appears to be prooxidant, and has been found to be associated with CAD. Several causes have been hypothesized for HDL to become dysfunctional, including Apo lipoprotein A-I (Apo A-I) polymorphisms. New risk factors and markers like dysfunctional HDL and genetic polymorphisms may be associated with CAD. Conclusions: More research is required in SAIs to explore associations with CAD and to enhance early detection and prevention of CAD in this high risk group. PMID:19183743

  2. Increased Non-High-Density Lipoprotein Cholesterol in Children and Young Adults with Turner Syndrome Is Not Explained By BMI Alone.

    PubMed

    Kelley, Jennifer C; Gutmark-Little, Iris; Backeljauw, Philippe; Bamba, Vaneeta

    2017-08-02

    Turner syndrome (TS) is associated with an increased risk of cardiovascular disease. Non-high-density lipoprotein cholesterol (non-HDL-C) is a convenient measure of atherogenicity (normal concentration <120 mg/dL) but has not been investigated in TS. We aim to evaluate non-HDL-C patterns in a cohort of pediatric and young adult females with TS. A retrospective chart review was used to obtain demographics, body composition, genetic reports, and lipid profiles in females with TS. Lipid profiles were assessed in 158 females (mean age 13.6 years). Mean non-HDL-C was 118.9 mg/dL (±32.0); the prevalence of high non-HDL-C (≥144 mg/dL) was 17.7% (n = 28). In TS females aged 8-17 years (n = 46), the prevalence of high non-HDL-C was 23.9% (95% CI 11.1-36.7; n = 11) between 2011 and 2012, compared to 9.2% (95% CI 5.6-14.1) in females of the same age in the general population reported in the National Health and Nutrition Examination Survey (NHANES) dataset (p < 0.005). Body mass index (BMI) accounted for only 6% of variance in non-HDL-C values (β coefficient = 1.31, p < 0.05). Children and adolescents aged 8-17 years with TS appear to have a greater prevalence of adverse non-HDL-C levels compared to the general adolescent population. The prevalence of high non-HDL-C was not fully explained by BMI. © 2017 S. Karger AG, Basel.

  3. Increased plasma peroxides and serum oxidized low density lipoprotein antibodies in major depression: markers that further explain the higher incidence of neurodegeneration and coronary artery disease.

    PubMed

    Maes, Michael; Mihaylova, Ivanka; Kubera, Marta; Uytterhoeven, Marc; Vrydags, Nicolas; Bosmans, Eugene

    2010-09-01

    Major depression is characterized by a decreased antioxidant status, an induction of the inflammatory and oxidative and nitrosative (IO&NS) pathways and inflammatory-neurodegenerative (I&ND) pathways. This study examines two markers of oxidative stress in depression, i.e. plasma peroxides and serum oxidized LDL (oxLDL) antibodies. Blood was sampled in 54 patients with major depression (mean+/-SD age=43.5+/-11.6 years) and 37 normal volunteers (43.6+/-11.1 years). The severity of illness was measured by means of the Hamilton Depression Rating Scale. The Fibromyalgia and Chronic Fatigue Syndrome Rating Scale was used to measure severity of "psychosomatic" symptoms in depression. We found significantly higher plasma peroxides (p=0.002) and serum oxLDL antibodies (p=0.0002) in depressed patients as compared to normal controls. There was no significant correlation between both markers and both independently from each other predicted major depression. There were significant correlations between the oxLDL antibodies and the scores on two items of the FF scale, i.e. gastro-intestinal symptoms and headache. The results show that major depression is accompanied by increased oxidative stress and lipid peroxidation. These results further extend the IO&NS pathophysiology of major depression. Since increased peroxides and oxLDL antibodies are predictors of coronary artery disease (CAD) and neurodegeneration, our findings suggest that IO&NS pathways are involved in the increased incidence of both CAD and neurodegeneration in depression. 2010 Elsevier B.V. All rights reserved.

  4. Emerging strategies for increasing high-density lipoprotein.

    PubMed

    Forrester, James S; Shah, Prediman K

    2006-12-01

    High-density lipoprotein cholesterol is a potent and independent epidemiologic risk factor and is a proved antiatherosclerotic agent in animal models of atherosclerosis, acting through the principal mechanisms of accelerating cholesterol efflux and inhibiting oxidation and inflammation. Lifestyle modification increases serum levels by 5% to 15%, whereas niacin, the drug most widely used to increase high-density lipoprotein cholesterol, increases it by 25% to 35% at the highest doses. This review examines the potent methods of increasing high-density lipoprotein and/or enhancing reverse cholesterol transport, including cholesterol ester transfer protein inhibitors, apolipoprotein A-I Milano, D4F, the dual peroxisome proliferator-activated receptor agonists, and rimonabant, that are now in clinical trials. In conclusion, these new agents, used alone or in combination with existing therapies, carry the potential to markedly reduce the incidence of new coronary disease and cardiac events in this decade.

  5. Moderate Exercise Increases Affinity of Large Very Low-Density Lipoproteins for Hydrolysis by Lipoprotein Lipase.

    PubMed

    Ghafouri, Khloud; Cooney, Josephine; Bedford, Dorothy K; Wilson, John; Caslake, Muriel J; Gill, Jason M R

    2015-06-01

    Postprandial triglyceride (TG) concentration is independently associated with cardiovascular disease risk. Exercise reduces postprandial TG concentrations, but the mechanisms responsible are unclear. The objective was to determine the effects of exercise on affinity of chylomicrons, large very low-density lipoproteins (VLDL1), and smaller VLDL (VLDL2) for lipoprotein lipase (LPL)-mediated TG hydrolysis. This was designed as a within-participant crossover study. The setting was a university metabolic investigation unit. Participants were 10 overweight/obese men. Participants undertook two oral fat tolerance tests, separated by 7-14 days, in which they had blood taken while fasting and for 4 hours after a high-fat mixed meal. On the afternoon before one test, they performed a 90-minute treadmill walk at 50% maximal oxygen uptake (exercise trial [EX]); no exercise was performed before the control trial (CON). We measured circulating TG-rich lipoprotein concentrations and affinity of chylomicrons, VLDL1, and VLDL2 for LPL-mediated TG hydrolysis. Exercise significantly reduced fasting VLDL1-TG concentration (CON, 0.49 [0.33-0.72] mmol.L(-1); EX, 0.36 [0.22-0.59] mmol.L(-1); geometric means [95% confidence interval]; P = .04). Time-averaged postprandial chylomicron-TG (CON, 0.55 ± 0.10 mmol.L(-1); EX, 0.39 ± 0.08 mmol.L(-1); mean ± SEM; P = .03) and VLDL1-TG (CON, 0.85 ± 0.13 mmol.L(-1); EX, 0.66 ± 0.10 mmol.L(-1); P = .01) concentrations were both lower in EX than CON. Affinity of VLDL1 for LPL-mediated TG hydrolysis increased by 2.2 (1.3-3.7)-fold [geometric mean (95% confidence interval)] (P = .02) in the fasted state and 2.6 (1.8-2.6)-fold (P = .001) postprandially. Affinity of chylomicrons and VLDL2 was not significantly different between trials. Exercise increases affinity of VLDL1 for LPL-mediated TG hydrolysis both fasting and postprandially. This mechanism is likely to contribute to the TG-lowering effect of exercise.

  6. Fine Mapping of Five Loci Associated with Low-Density Lipoprotein Cholesterol Detects Variants That Double the Explained Heritability

    PubMed Central

    Sidore, Carlo; Kang, Hyun M.; Jackson, Anne U.; Piras, Maria Grazia; Usala, Gianluca; Maninchedda, Giuseppe; Sassu, Alessandro; Serra, Fabrizio; Palmas, Maria Antonietta; Wood, William H.; Njølstad, Inger; Laakso, Markku; Hveem, Kristian; Tuomilehto, Jaakko; Lakka, Timo A.; Rauramaa, Rainer; Boehnke, Michael; Cucca, Francesco; Uda, Manuela; Schlessinger, David; Nagaraja, Ramaiah; Abecasis, Gonçalo R.

    2011-01-01

    Complex trait genome-wide association studies (GWAS) provide an efficient strategy for evaluating large numbers of common variants in large numbers of individuals and for identifying trait-associated variants. Nevertheless, GWAS often leave much of the trait heritability unexplained. We hypothesized that some of this unexplained heritability might be due to common and rare variants that reside in GWAS identified loci but lack appropriate proxies in modern genotyping arrays. To assess this hypothesis, we re-examined 7 genes (APOE, APOC1, APOC2, SORT1, LDLR, APOB, and PCSK9) in 5 loci associated with low-density lipoprotein cholesterol (LDL-C) in multiple GWAS. For each gene, we first catalogued genetic variation by re-sequencing 256 Sardinian individuals with extreme LDL-C values. Next, we genotyped variants identified by us and by the 1000 Genomes Project (totaling 3,277 SNPs) in 5,524 volunteers. We found that in one locus (PCSK9) the GWAS signal could be explained by a previously described low-frequency variant and that in three loci (PCSK9, APOE, and LDLR) there were additional variants independently associated with LDL-C, including a novel and rare LDLR variant that seems specific to Sardinians. Overall, this more detailed assessment of SNP variation in these loci increased estimates of the heritability of LDL-C accounted for by these genes from 3.1% to 6.5%. All association signals and the heritability estimates were successfully confirmed in a sample of ∼10,000 Finnish and Norwegian individuals. Our results thus suggest that focusing on variants accessible via GWAS can lead to clear underestimates of the trait heritability explained by a set of loci. Further, our results suggest that, as prelude to large-scale sequencing efforts, targeted re-sequencing efforts paired with large-scale genotyping will increase estimates of complex trait heritability explained by known loci. PMID:21829380

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

    PubMed

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

    2003-02-01

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

  8. Carbamylated low-density lipoprotein induces proliferation and increases adhesion molecule expression of human coronary artery smooth muscle cells.

    PubMed

    Asci, Gulay; Basci, Ali; Shah, Sudhir V; Basnakian, Alexei; Toz, Huseyin; Ozkahya, Mehmet; Duman, Soner; Ok, Ercan

    2008-12-01

    Presence of accelerated atherosclerosis in dialysis patients cannot be entirely explained by conventional risk factors. Exposure to urea, which is elevated in patients with kidney disease, leads to the carbamylation of proteins. We investigated the effects of carbamylated low-density lipoprotein (cLDL) on human coronary artery vascular smooth muscle cells (VSMC). Native LDL (nLDL) was carbamylated with potassium cyanate. Cells were incubated with different concentrations of cLDL carbamylated at different time points. Cytotoxicity, apoptosis, proliferation (bromodeoxyuridine incorporation), expression of adhesion molecules and extracellular matrix protein synthesis were studied. Carbamylated low-density lipoprotein exposure leads to morphological alterations and presence of cellular debris. Neither nLDL nor cLDL caused apoptosis. Lactate dehydrogenase (LDH) release was not different between groups. Carbamylated low-density lipoprotein led to a striking proliferation in VSMC compared to nLDL. Carbamylated low-density lipoprotein significantly increased intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression compared to the control. The effects of cLDL on proliferation and adhesion molecule expression were dose-dependent and correlated with the degree of low-density lipoprotein carbamylation. cLDL had no effect on extracellular matrix protein synthesis. The results support the hypothesis that cLDL may contribute to the pathogenesis of atherosclerosis in uraemic patients.

  9. Triglyceride content in remnant lipoproteins is significantly increased after food intake and is associated with plasma lipoprotein lipase.

    PubMed

    Nakajima, Katsuyuki; Tokita, Yoshiharu; Sakamaki, Koji; Shimomura, Younosuke; Kobayashi, Junji; Kamachi, Keiko; Tanaka, Akira; Stanhope, Kimber L; Havel, Peter J; Wang, Tao; Machida, Tetsuo; Murakami, Masami

    2017-02-01

    Previous large population studies reported that non-fasting plasma triglyceride (TG) reflect a higher risk for cardiovascular disease than TG in the fasting plasma. This is suggestive of the presence of higher concentration of remnant lipoproteins (RLP) in postprandial plasma. TG and RLP-TG together with other lipids, lipoproteins and lipoprotein lipase (LPL) in both fasting and postprandial plasma were determined in generally healthy volunteers and in patients with coronary artery disease (CAD) after consuming a fat load or a more typical moderate meal. RLP-TG/TG ratio (concentration) and RLP-TG/RLP-C ratio (particle size) were significantly increased in the postprandial plasma of both healthy controls and CAD patients compared with those in fasting plasma. LPL/RLP-TG ratio demonstrated the interaction correlation between RLP concentration and LPL activity The increased RLP-TG after fat consumption contributed to approximately 90% of the increased plasma TG, while approximately 60% after a typical meal. Plasma LPL in postprandial plasma was not significantly altered after either type of meal. Concentrations of RLP-TG found in the TG along with its particle size are significantly increased in postprandial plasma compared with fasting plasma. Therefore, non-fasting TG determination better reflects the presence of higher RLP concentrations in plasma. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

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

    PubMed

    Gabás-Rivera, Clara; Barranquero, Cristina; Martínez-Beamonte, Roberto; Navarro, María A; Surra, Joaquín C; Osada, Jesús

    2014-01-01

    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. 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. 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. 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.

  11. Increased Very Low Density Lipoprotein Secretion, Hepatic Steatosis, and Insulin Resistance

    PubMed Central

    Choi, Sung Hee; Ginsberg, Henry N

    2011-01-01

    Insulin resistance (IR) not only affects regulation of carbohydrate metabolism, but all aspects of lipid and lipoprotein metabolism. IR is associated with increased secretion of very low density lipoproteins (VLDL) and increased plasma triglycerides, as well as hepatic steatosis, despite the increased VLDL secretion. Here, we link IR with increased VLDL secretion and hepatic steatosis at both the physiologic and molecular levels. Increased VLDL secretion, together with the downstream effects on high density lipoprotein cholesterol and low density lipoprotein size is pro-atherogenic. Hepatic steatosis is a risk for steatohepatitis and cirrhosis. Understanding the complex inter-relationship between IR and these abnormalities of liver lipid homeostasis may provide insights relevant to new therapies for these increasing clinical problems. PMID:21616678

  12. Short-term cooling increases serum triglycerides and small high-density lipoprotein levels in humans.

    PubMed

    Hoeke, Geerte; Nahon, Kimberly J; Bakker, Leontine E H; Norkauer, Sabine S C; Dinnes, Donna L M; Kockx, Maaike; Lichtenstein, Laeticia; Drettwan, Diana; Reifel-Miller, Anne; Coskun, Tamer; Pagel, Philipp; Romijn, Fred P H T M; Cobbaert, Christa M; Jazet, Ingrid M; Martinez, Laurent O; Kritharides, Leonard; Berbée, Jimmy F P; Boon, Mariëtte R; Rensen, Patrick C N

    Cold exposure and β3-adrenergic receptor agonism, which both activate brown adipose tissue, markedly influence lipoprotein metabolism by enhancing lipoprotein lipase-mediated catabolism of triglyceride-rich lipoproteins and increasing plasma high-density lipoprotein (HDL) levels and functionality in mice. However, the effect of short-term cooling on human lipid and lipoprotein metabolism remained largely elusive. The objective was to assess the effect of short-term cooling on the serum lipoprotein profile and HDL functionality in men. Body mass index-matched young, lean men were exposed to a personalized cooling protocol for 2 hours. Before and after cooling, serum samples were collected for analysis of lipids and lipoprotein composition by (1)H-nuclear magnetic resonance. Adenosine triphosphate-binding cassette A1 (ABCA1)-mediated cholesterol efflux capacity of HDL was measured using [(3)H]cholesterol-loaded ABCA1-transfected Chinese hamster ovary cells. Short-term cooling increased serum levels of free fatty acids, triglycerides, and cholesterol. Cooling increased the concentration of large very low-density lipoprotein (VLDL) particles accompanied by increased mean size of VLDL particles. In addition, cooling enhanced the concentration of small LDL and small HDL particles as well as the cholesterol levels within these particles. The increase in small HDL was accompanied by increased ABCA1-dependent cholesterol efflux in vitro. Our data show that short-term cooling increases the concentration of large VLDL particles and increases the generation of small LDL and HDL particles. We interpret that cooling increases VLDL production and turnover, which results in formation of surface remnants that form small HDL particles that attract cellular cholesterol. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  13. Plasma high density lipoprotein is increased in man when low density lipoprotein (LDL) is lowered by LDL-pheresis.

    PubMed Central

    Parker, T S; Gordon, B R; Saal, S D; Rubin, A L; Ahrens, E H

    1986-01-01

    Plasma high density lipoprotein (HDL) concentrations were increased in five hypercholesterolemic normoglyceridemic patients after removal of plasma low density lipoprotein (LDL) by LDL-pheresis. In each patient up to 80% of circulating LDL was removed by passing plasma through immunoadsorption columns containing antibody to apolipoprotein B immobilized to Sepharose. Rebound of LDL was slow after the procedure: 5-7 days in four non-familial hypercholesterolemic patients and greater than 14 days in one patient with homozygous familial hypercholesterolemia. Plasma HDL rose above the pretreatment baseline during the interval between treatments in four of the five patients. When treatments were repeated weekly, time-averaged plasma LDL was lowered by 40-70%, while plasma HDL cholesterol and apolipoprotein AI were increased up to 2-fold, depending on the degree of LDL lowering. Plasma HDL concentrations fell back to their baseline values when LDL-pheresis was stopped and rose again when treatment was restarted. Thus, LDL-pheresis may augment the therapeutic effectiveness of LDL lowering by raising plasma HDL levels and the concentration of HDL relative to LDL. PMID:3511474

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

    PubMed

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

    2014-12-01

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

  15. Dietary Squalene Increases High Density Lipoprotein-Cholesterol and Paraoxonase 1 and Decreases Oxidative Stress in Mice

    PubMed Central

    Gabás-Rivera, Clara; Barranquero, Cristina; Martínez-Beamonte, Roberto; Navarro, María A.; Surra, Joaquín C.; Osada, Jesús

    2014-01-01

    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. PMID:25117703

  16. A rapid increase in lipoprotein (a) levels after ethanol withdrawal in alcoholic men

    SciTech Connect

    Kervinen, K.; Savolainen, J.J.; Kesaeniemi, Y.A. )

    1991-01-01

    Plasma concentrations of lipoprotein (a) (Lp(a)) were studied in 11 male alcoholics at the end of a drinking period and monitored during subsequent abstinence. Lp(a) levels showed a daily increase for four consecutive days after the beginning of abstinence, the values for the third and the fourth day being significantly higher than those of the first day. The changes in Lp(a) showed no association with the changes in low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels. In one alcoholic subject with a heterozygous form of familial hypercholesterolemia who was monitored for 11 days, the Lp(a) levels rose up to the fourth day and remained at a high level thereafter. These results suggest that ethanol ingestion may be associated with a lower of Lp(a) levels, which may contribute to the delayed progression of atherosclerosis observed in alcohol drinkers.

  17. Increases in plasma pool size of lipoprotein components in copper-deficient hamsters

    SciTech Connect

    Al-Othman, A.A.; Rosenstein, F.; Lei, K.Y. )

    1991-03-15

    Twenty-four male Golden Syrian hamsters, were randomly assigned to 2 dietary copper (Cu) treatments; deficient and adequate. Reductions in weight gain, hematocrit and liver Cu as well as increases in heart weight and plasma volume were observed in CD hamsters after 7 weeks of treatment. Plasma very low (VLDL), low (LDL) and high (HDL) density lipoproteins were isolated by ultracentrifugation and Sepharose column chromatography. The percentage of total plasma cholesterol carried by LDL was increased from 20 to 24% but was reduced from 71 to 68% for HDL as a result of Cu deficiency. In LDL the % composition of triglycerides (TG) and phospholipids (PL) was increased by 25% but that of cholesterol was reduced by 13%. The % composition of protein was reduced 24% but that of TG was increased 18% in VLDL by Cu deficiency. Since plasma volume was increased 50% in CD hamsters, the data were expressed as the amount present in the plasma pool corrected for body weight. With the exceptions of smaller increased in VLDL protein and PL as well as the more than threefold increases in LDL TG and PL plasma pool size, the pool size for the rest of the lipoprotein components were increased about twofold in CD hamsters. The lipoprotein data further indicate that Cu deficiency increased the particle number of VLDL, LDL and HDL but enlarged the size of only VLDL and LDL.

  18. Chitosan oligosaccharide decreases very-low-density lipoprotein triglyceride and increases high-density lipoprotein cholesterol in high-fat-diet-fed rats.

    PubMed

    Wang, Daxin; Han, Jiju; Yu, Yang; Li, Xueping; Wang, Yun; Tian, Hua; Guo, Shoudong; Jin, Shiguang; Luo, Tian; Qin, Shucun

    2011-09-01

    It is well known that chitosan has beneficial lipid-regulating effects, but it remains unknown whether chitosan oligosaccharide (COS), the chitosan degradation product, has the same lipid benefits. High-fat-diet-fed Wistar rats were administrated with COS by gastric gavage for three weeks. The effects of COS on lipids, lipoprotein components and lipid metabolism related protein activities were investigated. Plasma lipids level assays by an enzyme method showed that COS decreased triglyceride (TG) by 29-31%, and increased high-density lipoprotein (HDL) cholesterol by 8-11%, but did not affect low-density lipoprotein (LDL) cholesterol. Lipid distribution analysis through fast protein liquid chromatography indicated that COS significantly decreased TG content distributed in very-low-density lipoprotein (VLDL)/LDL fractions but increased cholesterol content in HDL fractions. Apolipoprotein analysis through plasma ultracentrifugation and sodium dodecyl sulfate polyacrylamide gel electrophoresis displayed that COS decreased apolipoprotein B-100 of LDL and increased apolipoprotein E of LDL and apolipoprotein B-100 of VLDL, but did not change apoA-I content of HDL particles. Lipoprotein formation associated protein determination showed that COS also increased plasma activity of lecithin cholesterol acyl transferase but not phospholipid transfer protein. The present study suggests that COS may play a beneficial role in plasma lipid regulation of rats with dyslipidemia induced by high-fat diet. The COS-decreased VLDL/LDL TG and -enhanced HDL cholesterol may be related to the upregulated activity of lecithin cholesterol acyl transferase.

  19. Increased production of apolipoprotein B and its lipoproteins by oleic acid in Caco-2 cells.

    PubMed

    Dashti, N; Smith, E A; Alaupovic, P

    1990-01-01

    The production of lipids, apolipoproteins (apo), and lipoproteins induced by oleic acid has been examined in Caco-2 cells. The rates of accumulation in the control medium of 15-day-old Caco-2 cells of triglycerides, unesterified cholesterol, and cholesteryl esters were 102 +/- 8, 73 +/- 5, and 11 +/- 1 ng/mg cell protein/h, respectively; the accumulation rates for apolipoproteins A-I, B, C-III, and E were 111 +/- 9, 53 +/- 4, 13 +/- 1, and 63 +/- 4 ng/mg cell protein/h, respectively. Whereas apolipoproteins A-IV and C-II were detected by immunoblotting, apoA-II was absent in most culture media. In contrast to an early production of apolipoproteins A-I and E occurring 2 days after plating, the apoB expression appeared to be differentiation-dependent and was not measurable in the medium until the sixth day post-confluency. In the control medium, very low density lipoproteins (VLDL), low density lipoproteins (LDL), high density lipoproteins (HDL), and lipid-poor very high density lipoproteins (VHDL) accounted for 12%, 46%, 18%, and 24% of the total lipid and apolipoprotein contents, respectively. The triglyceride-rich VLDL contained mainly apoE (75%) and apoB (23%), while the protein moiety of LDL was composed of apoB (59%), apoE (20%), apoA-I (15%), and apoC-III (6%). The cholesterol-rich HDL contained mainly apoA-I (69%) and apoE (27%). In the control medium, major portions of apolipoproteins B and C-III (93-97%) were present in LDL, whereas the main parts of apoA-I (92%) and apoE (76%) were associated with HDL and VHDL. Oleate increased the production of triglycerides 10-fold, cholesteryl esters 7-fold, and apoB 2- to 4-fold. There was also a moderate increase (39%) in the production of apoC-III but no significant changes in those of apolipoproteins A-I and E. These increases were reflected mainly in a 55-fold elevation in the concentration of VLDL, and a 2-fold increase in the level of LDL; there were no significant changes in HDL and VHDL. VLDL contained the

  20. [Increased lipoprotein(a) in a paediatric patient associated with nephrotic syndrome].

    PubMed

    Menéndez Valladares, Paloma; Arrobas Velilla, Teresa; Bermúdez de la Vega, José Antonio; Romero Pérez, María Del Mar; Fabiani Romero, Fernando; González Rodríguez, Concepción

    A common complication in paediatric patients with nephrotic syndrome (NS) is hyperlipidaemia. About 20% of children do not respond to treatment with corticosteroids, presenting with a cortico-resistant NS (CRNS), which can progress to kidney failure. It has been observed that paediatric patients with CRNS have an elevated low density lipoprotein cholesterol (LDL-c), very low density lipoprotein cholesterol (VLDL-c), and triglycerides levels, as well as elevated Lipoprotein-a [Lp (a)] levels. The case is presented of a 5 year old boy, diagnosed with CRNS, presenting with dyslipidaemia with increased LDL-c, Apo-B100, and Lp(a) levels. After the poor prognosis of the renal function, immunosuppressant treatment was started with tacrolimus and atorvastatin to control dyslipidaemia. Although tacrolimus causes an elevation of total cholesterol and LDL-c, the significant alterations of the children lipid profile suggest the existence of a high cardiovascular risk. In these cases, it would be interesting to have reference values in children in our health area. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Inhibitors of cholesterol biosynthesis increase hepatic low-density lipoprotein receptor protein degradation.

    PubMed

    Ness, G C; Zhao, Z; Lopez, D

    1996-01-15

    Inhibitors of cholesterol biosynthesis are believed to lower serum cholesterol levels by enhancing the removal of serum low-density lipoprotein (LDL) by increasing hepatic LDL receptor function. Thus, the effects of several different inhibitors of cholesterol biosynthesis were examined for their effects on the expression of the hepatic LDL receptor in rats. We found that administration of inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase such as lovastatin, pravastatin, fluvastatin, and rivastatin resulted in increased hepatic LDL receptor mRNA levels. Surprisingly, these agents failed to increase levels of immunoreactive LDL receptor protein in rat liver even when the dose and length of treatment were increased. Treatment of rats with zaragozic acid A, an inhibitor of squalene synthase, caused even greater increases in hepatic LDL receptor mRNA levels, but did not increase levels of immunoreactive protein. Further investigation revealed that the rate of degradation of the hepatic LDL receptor was increased in rats given inhibitors of cholesterol biosynthesis. The greatest increase in the rate of degradation was seen in animals treated with zaragozic acid A which caused the largest increase in hepatic LDL receptor mRNA levels. In contrast, hepatic LDL receptor protein was stabilized in cholesterol-fed rats. It appears that increased potential for LDL receptor protein synthesis, reflected in increased mRNA levels, is offset by a corresponding increase in the rate of receptor protein degradation resulting in constant steady-state levels of hepatic LDL receptor protein. These findings are suggestive of increased cycling of the hepatic LDL receptor. This postulated mechanism can provide for enhanced hepatic uptake of lipoproteins without increasing steady-state levels of LDL receptor protein.

  2. Streptococcal Serum Opacity Factor Increases Hepatocyte Uptake of Human Plasma High Density Lipoprotein-Cholesterol1

    PubMed Central

    Gillard, Baiba K.; Rosales, Corina; Pillai, Biju K.; Lin, Hu Yu; Courtney, Harry S.; Pownall, Henry J.

    2010-01-01

    Serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes, converts plasma high density lipoproteins (HDL) to three distinct species: lipid-free apolipoprotein (apo) A-I, neo HDL, a small discoidal HDL-like particle, and a large cholesteryl ester-rich microemulsion (CERM), that contains the cholesterol esters (CE) of up to ~400,000 HDL particles and apo E as its major protein. Similar SOF reaction products are obtained with HDL, total plasma lipoproteins and whole plasma. We hypothesized that hepatic uptake of CERM-CE via multiple apo E dependent receptors would be faster than that of HDL-CE. We tested our hypothesis using human hepatoma cells and lipoprotein receptor-specific Chinese hamster ovary (CHO) cells. [3H]CE uptake by HepG2 and Huh7 cells from HDL after SOF treatment, which transfers >90% of HDL-CE to CERM, was respectively 2.4 and 4.5 times faster than from control HDL. CERM-[3H]CE uptake was inhibited by LDL and HDL, suggestive of uptake by both the LDL receptor (LDL-R) and scavenger receptor class B type I (SR-BI). Studies in CHO cells specifically expressing LDL-R and SR-BI confirmed CERM-[3H]CE uptake by both receptors. RAP and heparin inhibit CERM-[3H]CE but not HDL-[3H]CE uptake thereby implicating LRP-1 and cell surface proteoglycans in this process. These data demonstrate that SOF treatment of HDL increases CE uptake via multiple hepatic apo E receptors. In so doing, SOF might increase hepatic disposal of plasma cholesterol in a way that is therapeutically useful. PMID:20879789

  3. The effect of increased lipoproteins levels on the disposition of vincristine in rat.

    PubMed

    Khalil, Hadeel A; Belal, Tarek S; El-Yazbi, Ahmed F; Hamdy, Dalia A

    2016-09-09

    Vincristine (VCR), an antineoplastic agent, is a key component in the treatment of acute lymphoblastic leukemia, lymphomas, rhabdomyosarcoma, neuroblastoma, and Wilms' tumor diseases. Recently, high incidence of hyperlipidemia was reported to be associated with allogenic hematopoietic stem cell transplantation and VCR/L-asparaginase therapy. The aim of this study is to test the effects of incremental increase in lipoproteins levels on vincristine disposition in rat. To study VCR pharmacokinetics and protein binding, rats (n = 25) were assigned to three groups, normal lipidemic (NL), intermediate (IHL) and extreme hyperlipidemic (HL). Hyperlipidemia was induced by ip injection of (1 g/Kg) poloxamer 407 in rats. Serial blood samples were collected using the pre-inserted jugular vein cannula for 72 h post VCR (0.15 mg/Kg) i.v. dose. VCR unbound fractions in NL, IHL and HL plasma were determined using ultrafiltration kits. VCR demonstrated a rapid distribution phase (6-8 h) followed by a slower elimination phase with a mean elimination t½ of ~ 14 h. VCR exhibited moderate binding to plasma proteins ~ 83 %. It showed a relatively small Vc (~0.17 L/Kg) and a larger Vβ (1.53 L/Kg) indicating good tissue distribution. As the lipoproteins levels were increased, no significant changes were noted in VCR unbound fraction, plasma concentration, or volume of distribution indicating low affinity to lipoprotein binding. Induced HL also did not affect VCR elimination where similar VCR AUC0-∞, Cl and elimination phase t½ were reported along the different lipemic groups. Incremental increase in lipoprotein levels resulted in no significant effect on VCR disposition as such ALL malignant lymphoma and allogenic hematopoietic stem cell transplantation patients need not to worry about HL-VCR interaction. Whether, HL can potentiate another drug-drug or drug-disease interaction involving VCR warrants further studying and monitoring to ensure therapeutic safety and

  4. Increased expression of apolipoprotein E in transgenic rabbits results in reduced levels of very low density lipoproteins and an accumulation of low density lipoproteins in plasma.

    PubMed Central

    Fan, J; Ji, Z S; Huang, Y; de Silva, H; Sanan, D; Mahley, R W; Innerarity, T L; Taylor, J M

    1998-01-01

    Transgenic rabbits expressing human apo E3 were generated to investigate mechanisms by which apo E modulates plasma lipoprotein metabolism. Compared with nontransgenic littermates expressing approximately 3 mg/dl of endogenous rabbit apo E, male transgenic rabbits expressing approximately 13 mg/dl of human apo E had a 35% decrease in total plasma triglycerides that was due to a reduction in VLDL levels and an absence of large VLDL. With its greater content of apo E, transgenic VLDL had an increased binding affinity for the LDL receptor in vitro, and injected chylomicrons were cleared more rapidly by the liver in transgenic rabbits. In contrast to triglyceride changes, transgenic rabbits had a 70% increase in plasma cholesterol levels due to an accumulation of LDL and apo E-rich HDL. Transgenic and control LDL had the same binding affinity for the LDL receptor. Both transgenic and control rabbits had similar LDL receptor levels, but intravenously injected human LDL were cleared more slowly in transgenic rabbits than in controls. Changes in lipoprotein lipolysis did not contribute to the accumulation of LDL or the reduction in VLDL levels. These observations suggest that the increased content of apo E3 on triglyceride-rich remnant lipoproteins in transgenic rabbits confers a greater affinity for cell surface receptors, thereby increasing remnant clearance from plasma. The apo E-rich large remnants appear to compete more effectively than LDL for receptor-mediated binding and clearance, resulting in delayed clearance and the accumulation of LDL in plasma. PMID:9593771

  5. Down-regulation of lipoprotein lipase increases glucose uptake in L6 muscle cells

    SciTech Connect

    Lopez, Veronica; Saraff, Kumuda; Medh, Jheem D.

    2009-11-06

    Thiazolidinediones (TZDs) are synthetic hypoglycemic agents used to treat type 2 diabetes. TZDs target the peroxisome proliferator activated receptor-gamma (PPAR-{gamma}) and improve systemic insulin sensitivity. The contributions of specific tissues to TZD action, or the downstream effects of PPAR-{gamma} activation, are not very clear. We have used a rat skeletal muscle cell line (L6 cells) to demonstrate that TZDs directly target PPAR-{gamma} in muscle cells. TZD treatment resulted in a significant repression of lipoprotein lipase (LPL) expression in L6 cells. This repression correlated with an increase in glucose uptake. Down-regulation of LPL message and protein levels using siRNA resulted in a similar increase in insulin-dependent glucose uptake. Thus, LPL down-regulation improved insulin sensitivity independent of TZDs. This finding provides a novel method for the management of insulin resistance.

  6. S-adenosylmethionine increases circulating very-low density lipoprotein clearance in nonalcoholic fatty liver disease

    PubMed Central

    Martinez-Una, Maite; Varela-Rey, Marta; Mestre, Daniela; Fernandez-Ares, Larraitz; Fresnedo, Olatz; Fernandez-Ramos, David; Juan, Virginia Gutierrez-de; Martin-Guerrero, Idoia; Garcia-Orad, Africa; Luka, Zigmund; Wagner, Conrad; Lu, Shelly C; Garcia-Monzon, Carmelo; Finnell, Richard H; Aurrekoetxea, Igor; Buque, Xabier; Martinez-Chantar, M. Luz; Mato, Jose M.; Aspichueta, Patricia

    2014-01-01

    Background Very-low density-lipoproteins (VLDL) export lipids from liver to peripheral tissues and are the precursors of low-density-lipoproteins. Low levels of hepatic S-adenosylmethionine (SAMe) decrease triglyceride (TG) secretion in VLDL contributing to hepatosteatosis in methionine adenosyltransferase 1A knockout mice but nothing is known about the effect of SAMe over circulating VLDL metabolism. Objective We wanted to investigate whether excess SAMe could disrupt VLDL plasma metabolism and unravel the mechanisms involved. Methods Glycine N-methyltransferase (GNMT) knockout (KO), GNMT-PLIN2-KO and their respective wild types (WT) were used. A high fat diet (HFD) or a methionine deficient diet (MDD) was administrated to exacerbate or recover VLDL metabolism, respectively. Finally, 33 patients with nonalcoholic fatty-liver disease (NAFLD); 11 with hypertriglyceridemia and 22 with normal lipidemia were used in this study. Results We found that excess SAMe increases turnover of hepatic TG stores for secretion in VLDL in GNMT-KO mice, a model of NAFLD with high SAMe levels. The disrupted VLDL assembly resulted in the secretion of enlarged, phosphatidylethanolamine-poor, TG-and apoE-enriched VLDL-particles; special features that lead to increased VLDL clearance and decreased serum TG levels. Re-establishing normal SAMe levels restore VLDL secretion, features and metabolism. In NAFLD patients, serum TG levels are lower when hepatic GNMT-protein expression is decreased. Conclusion Excess hepatic SAMe levels disrupt VLDL assembly and features and increase circulating VLDL clearance which will cause increased VLDL-lipid supply to tissues and might contribute to the extrahepatic complications of NAFLD. Electronic word count: 235 PMID:25457203

  7. Inactive lipoprotein lipase (LPL) alone increases selective cholesterol ester uptake in vivo, whereas in the presence of active LPL it also increases triglyceride hydrolysis and whole particle lipoprotein uptake.

    PubMed

    Merkel, Martin; Heeren, Jörg; Dudeck, Wiebke; Rinninger, Franz; Radner, Herbert; Breslow, Jan L; Goldberg, Ira J; Zechner, Rudolf; Greten, Heiner

    2002-03-01

    We have previously shown that transgenic expression of catalytically inactive lipoprotein lipase (LPL) in muscle (Mck-N-LPL) enhances triglyceride hydrolysis as well as whole particle lipoprotein and selective cholesterol ester uptake. In the current study, we have examined whether these functions can be performed by inactive LPL alone or require the presence of active LPL expressed in the same tissue. To study inactive LPL in the presence of active LPL in the same tissue, the Mck-N-LPL transgene was bred onto the heterozygous LPL-deficient (LPL1) background. At 18 h of age, Mck-N-LPL reduced triglycerides by 35% and markedly increased muscle lipid droplets. In adult mice, it reduced triglycerides by 40% and increased lipoprotein particle uptake into muscle by 60% and cholesterol ester uptake by 110%. To study inactive LPL alone, the Mck-N-LPL transgene was bred onto the LPL-deficient (LPL0) background. These mice die at approximately 24 h of age. At 18 h of age, in the absence of active LPL, inactive LPL expression did not diminish triglycerides nor did it result in the accumulation of muscle lipid droplets. To study inactive LPL in the absence of active LPL in the same tissue in adult animals, the Mck-N-LPL transgene was bred onto mice that only expressed active LPL in the heart (LPL0/He-LPL). In this case, Mck-N-LPL did not reduce triglycerides or increase the uptake of lipoprotein particles but did increase muscle uptake of chylomicron and very low density lipoprotein cholesterol ester by 40%. Thus, in the presence of active LPL in the same tissue, inactive LPL augments triglyceride hydrolysis and increases whole particle triglyceride-rich lipoprotein and selective cholesterol ester uptake. In the absence of active LPL in the same tissue, inactive LPL only mediates selective cholesterol ester uptake.

  8. Lecithin:cholesterol acyltransferase deficiency increases atherosclerosis in the low density lipoprotein receptor and apolipoprotein E knockout mice.

    PubMed

    Furbee, James W; Sawyer, Janet K; Parks, John S

    2002-02-01

    The purpose of the present study was to test the hypothesis that lecithin:cholesterol acyltransferase (LCAT) deficiency would accelerate atherosclerosis development in low density lipoprotein (LDL) receptor (LDLr-/-) and apoE (apoE-/-) knockout mice. After 16 weeks of atherogenic diet (0.1% cholesterol, 10% calories from palm oil) consumption, LDLr-/- LCAT-/- double knockout mice, compared with LDLr-/- mice, had similar plasma concentrations of free (FC), esterified (EC), and apoB lipoprotein cholesterol, increased plasma concentrations of phospholipid and triglyceride, decreased HDL cholesterol, and 2-fold more aortic FC (142 +/- 28 versus 61 +/- 20 mg/g protein) and EC (102 +/- 27 versus 61+/- 27 mg/g). ApoE-/- LCAT-/- mice fed the atherogenic diet, compared with apoE-/- mice, had higher concentrations of plasma FC, EC, apoB lipoprotein cholesterol, and phospholipid, and significantly more aortic FC (149 +/- 62 versus 109 +/- 33 mg/g) and EC (101 +/- 23 versus 69 +/- 20 mg/g) than did the apoE-/- mice. LCAT deficiency resulted in a 12-fold increase in the ratio of saturated + monounsaturated to polyunsaturated cholesteryl esters in apoB lipoproteins in LDLr-/- mice and a 3-fold increase in the apoE-/- mice compared with their counterparts with active LCAT. We conclude that LCAT deficiency in LDLr-/- and apoE-/- mice fed an atherogenic diet resulted in increased aortic cholesterol deposition, likely due to a reduction in plasma HDL, an increased saturation of cholesteryl esters in apoB lipoproteins and, in the apoE-/- background, an increased plasma concentration of apoB lipoproteins.

  9. Oxidized low density lipoprotein increases acetylcholinesterase activity correlating with reactive oxygen species production.

    PubMed

    Yamchuen, Panit; Aimjongjun, Sathid; Limpeanchob, Nanteetip

    2014-12-01

    Hyperlipidemia, low density lipoproteins (LDL) and their oxidized forms, and oxidative stress are suspected to be a key combination in the onset of AD and acetylcholinesterase (AChE) plays a part in this pathology. The present study aimed to link these parameters using differentiated SH-SY5Y human neuroblastoma cells in culture. Both mildly and fully oxidized human LDL (mox- and fox-LDL), but not native (non-oxidized) LDL were cytotoxic in dose- and time-dependent patterns and this was accompanied by an increased production of intracellular reactive oxygen species (ROS). Oxidized LDL (10-200 μg/mL) augmented AChE activity after 4 and 24h treatments, respectively while the native LDL was without effect. The increased AChE with oxidized LDLs was accompanied by a proportionate increase in intracellular ROS formation (R=0.904). These findings support the notion that oxidized LDLs are cytotoxic and that their action on AChE may reduce central cholinergic transmission in AD and affirm AChE as a continued rational for anticholinesterase therapy but in conjunction with antioxidant/antihyperlipidemic cotreatments.

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

    PubMed

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

    2015-09-01

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

  11. Increasing adipocyte lipoprotein lipase improves glucose metabolism in high fat diet-induced obesity.

    PubMed

    Walton, R Grace; Zhu, Beibei; Unal, Resat; Spencer, Michael; Sunkara, Manjula; Morris, Andrew J; Charnigo, Richard; Katz, Wendy S; Daugherty, Alan; Howatt, Deborah A; Kern, Philip A; Finlin, Brian S

    2015-05-01

    Lipid accumulation in liver and skeletal muscle contributes to co-morbidities associated with diabetes and obesity. We made a transgenic mouse in which the adiponectin (Adipoq) promoter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissue lipid storage. These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well as increased energy expenditure when challenged with a high fat diet (HFD). To identify the mechanism(s) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to reduce peripheral lipotoxicity, but we found no evidence for this. Instead, characterization of the adipose tissue of the male mice after HFD challenge revealed that the mRNA levels of peroxisome proliferator-activated receptor-γ (PPARγ) and a number of PPARγ-regulated genes were higher in the epididymal fat pads of Adipoq-LPL mice than control mice. This included adiponectin, whose mRNA levels were increased, leading to increased adiponectin serum levels in the Adipoq-LPL mice. In many respects, the adipose phenotype of these animals resembles thiazolidinedione treatment except for one important difference, the Adipoq-LPL mice did not gain more fat mass on HFD than control mice and did not have increased expression of genes in adipose such as glycerol kinase, which are induced by high affinity PPAR agonists. Rather, there was selective induction of PPARγ-regulated genes such as adiponectin in the adipose of the Adipoq-LPL mice, suggesting that increasing adipose tissue LPL improves glucose metabolism in diet-induced obesity by improving the adipose tissue phenotype. Adipoq-LPL mice also have increased energy expenditure.

  12. Goat milk fat naturally enriched with conjugated linoleic acid increased lipoproteins and reduced triacylglycerol in rats.

    PubMed

    Rodrigues, Raphaela; Soares, Juliana; Garcia, Hugo; Nascimento, Claudenice; Medeiros, Maria; Bomfim, Marco; Medeiros, Maria Carmo; Queiroga, Rita

    2014-03-24

    Goat milk is source of different lipids, including conjugated linoleic acid (CLA). CLA reduces body fat and protect against cardiovascular diseases. In the present study fat from goat milk naturally enriched with CLA was used. Male Wistar rats were divided into three groups that received during a 10 week diet with different lipid sources: soybean oil (CON), coconut oil (CO) and goat milk fat naturally enriched with CLA (GM-CLA). We evaluated the effects of a GM-CLA on biochemistry parameters--high density lipoprotein (HDL), triacylglycerol (TAG), TAG/HDL ratio, total cholesterol and glucose, body weight and histopathological aspects of the intestine and liver. GM-CLA increased body weight from the second to the fifth week of the experiment compared to CON. Feed intake differed between the CON group and GM-CLA early in the first to third week of the experiments and later between the ninth and tenth week. The CLA-diet group showed increased levels of HDL, reduced levels of TAG and TAG/HDL ratio and no effect on LDL, but enhanced total cholesterol. Serum glucose of the GM-CLA group showed no difference from the control group. Thus, a GM-CLA diet promoted growth in young rats and acted as protector of cardiovascular function, but further studies are still needed to clarify these effects.

  13. Cholecystectomy increases hepatic triglyceride content and very-low-density lipoproteins production in mice.

    PubMed

    Amigo, Ludwig; Husche, Constanze; Zanlungo, Silvana; Lütjohann, Dieter; Arrese, Marco; Miquel, Juan Francisco; Rigotti, Attilio; Nervi, Flavio

    2011-01-01

    Bile acid (BA) pool size remains unchanged after cholecystectomy (XGB) but it circulates faster, exposing the enterohepatic system to an increased flux of BA. Triglyceride (TG) and BA metabolisms are functionally inter-related. We investigated whether ablation of the gallbladder (GB) modifies hepatic TG metabolism. Male mice were subjected to XGB and fed a normal diet. In some experiments, mice received a 1% nicotinic acid diet to block lipolysis. Parameters of BA and TG metabolism, and microsomal triglyceride transfer protein (MTTP) activity were measured 1-2 months after XGB. Serum parameters, hepatic lipids and mRNA expression of genes of lipid metabolism were determined. BA pool size and synthesis were normal, but biliary BA secretion doubled during the diurnal light phase in XGB mice. Serum and hepatic TG concentrations increased 25% (P<0.02), and hepatic very-low-density lipoproteins (VLDL)-TG and apoB-48 productions increased 15% (P<0.03) and 50% (P<0.01), respectively, after XGB. Feeding a 1% nicotinic acid did normalize VLDL production. MTTP activity increased 15% (P<0.005) after XGB. Hepatic free fatty acid (FFA) synthesis and content, and mRNA levels of lipid metabolism-related genes remained normal in XGD mice. XGB increased serum and hepatic TG levels, and VLDL production, which were restored to normal by nicotinic acid. The results suggest that FFA flux from adipose tissue to the liver is increased in XGB mice. They support the hypothesis that the GB has a role in the regulation of hepatic TG metabolism and that XGB may favour the accumulation of fat in the liver. © 2010 John Wiley & Sons A/S.

  14. Electronegative Low-density Lipoprotein Increases Coronary Artery Disease Risk in Uremia Patients on Maintenance Hemodialysis

    PubMed Central

    Chang, Chiz-Tzung; Wang, Guei-Jane; Kuo, Chin-Chi; Hsieh, Ju-Yi; Lee, An-Sean; Chang, Chia-Ming; Wang, Chun-Cheng; Shen, Ming-Yi; Huang, Chiu-Ching; Sawamura, Tatsuya; Yang, Chao-Yuh; Stancel, Nicole; Chen, Chu-Huang

    2016-01-01

    Abstract Electronegative low-density lipoprotein (LDL) is a recognized factor in the pathogenesis of coronary artery disease (CAD) in the general population, but its role in the development of CAD in uremia patients is unknown. L5 is the most electronegative subfraction of LDL isolated from human plasma. In this study, we examined the distribution of L5 (L5%) and its association with CAD risk in uremia patients. The LDL of 39 uremia patients on maintenance hemodialysis and 21 healthy controls was separated into 5 subfractions, L1–L5, with increasing electronegativity. We compared the distribution and composition of plasma L5 between uremia patients and controls, examined the association between plasma L5% and CAD risk in uremia patients, and studied the effects of L5 from uremia patients on endothelial function. Compared to controls, uremia patients had significantly increased L5% (P < 0.001) and L5 that was rich in apolipoprotein C3 and triglycerides. L5% was significantly higher in uremia patients with CAD (n = 10) than in those without CAD (n = 29) (P < 0.05). Independent of other major CAD risk factors, the adjusted odds ratio for CAD was 1.88 per percent increase in plasma L5% (95% CI, 1.01–3.53), with a near-linear dose–response relationship. Compared with controls, uremia patients had decreased flow-mediated vascular dilatation. In ex vivo studies with preconstricted rat thoracic aortic rings, L5 from uremia patients inhibited acetylcholine-induced relaxation. In cultured human endothelial cells, L5 inhibited endothelial nitric oxide synthase activation and induced endothelial dysfunction. Our findings suggest that elevated plasma L5% may induce endothelial dysfunction and play an important role in the increased risk of CAD in uremia patients. PMID:26765403

  15. Lipoprotein Lipase and PPAR Alpha Gene Polymorphisms, Increased Very-Low-Density Lipoprotein Levels, and Decreased High-Density Lipoprotein Levels as Risk Markers for the Development of Visceral Leishmaniasis by Leishmania infantum

    PubMed Central

    Carvalho, Márcia Dias Teixeira; Alonso, Diego Peres; Vendrame, Célia Maria Vieira; Costa, Dorcas Lamounier; Costa, Carlos Henrique Nery; Werneck, Guilherme Loureiro; Ribolla, Paulo Eduardo Martins

    2014-01-01

    In visceral leishmaniasis (VL) endemic areas, a minority of infected individuals progress to disease since most of them develop protective immunity. Therefore, we investigated the risk markers of VL within nonimmune sector. Analyzing infected symptomatic and, asymptomatic, and noninfected individuals, VL patients presented with reduced high-density lipoprotein cholesterol (HDL-C), elevated triacylglycerol (TAG), and elevated very-low-density lipoprotein cholesterol (VLDL-C) levels. A polymorphism analysis of the lipoprotein lipase (LPL) gene using HindIII restriction digestion (N = 156 samples) (H+ = the presence and H− = the absence of mutation) revealed an increased adjusted odds ratio (OR) of VL versus noninfected individuals when the H+/H+ was compared with the H−/H− genotype (OR = 21.3; 95% CI = 2.32–3335.3; P = 0.003). The H+/H+ genotype and the H+ allele were associated with elevated VLDL-C and TAG levels (P < 0.05) and reduced HDL-C levels (P < 0.05). An analysis of the L162V polymorphism in the peroxisome proliferator-activated receptor alpha (PPARα) gene (n = 248) revealed an increased adjusted OR when the Leu/Val was compared with the Leu/Leu genotype (OR = 8.77; 95% CI = 1.41–78.70; P = 0.014). High TAG (P = 0.021) and VLDL-C (P = 0.023) levels were associated with susceptibility to VL, whereas low HDL (P = 0.006) levels with resistance to infection. The mutated LPL and the PPARα Leu/Val genotypes may be considered risk markers for the development of VL. PMID:25242866

  16. [Atherogenic lipoprotein remnants in humans].

    PubMed

    Wikinski, Regina; Schreier, Laura E; Berg, Gabriela A; Brites, Fernando D; López, Graciela; González, Ana I; Zago, Valeria

    2010-01-01

    Remnant lipoproteins (RLPs) are the lipolytic product of triglycerides transported by very low density lipoproteins (VLDL) of hepatic and intestinal origin and intestinal chylomicrons. Lipoprotein lipase activity hydrolyse triglycerides in several steps, producing heterogeneous particles. Fasting plasma concentration in normolipidemic subjects is low, but it increases in post-prandial states. Genetic alterations in Apo-E subtypes increases RLPs plasma concentration and produce dyslipoproteinemia phenotype. RLPs atherogenicity depends on their role as endothelial injuring factors, their impaired recognition by lipoprotein receptors, and their susceptibility to oxidative stress. They also promote the circulation of molecular adhesion molecules, the internalization in subendothelial macrophages via scavenger receptors and the accumulation in foam cells, all of them early mechanisms of atheromatosis. RLPs metabolism has been a subject of controversial studies. Their origin from different lipoproteins may explain their structural heterogeneity, therefore increasing the methodological difficulties to include RLPs in the atherogenic lipoprotein profile in the epidemiological studies of the field. Last advances on metabolism of RLPs and their emergent clinical role justifies an up dated revision of RLPs.

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

    PubMed

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

    2017-05-04

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

  18. Minimal oxidation and storage of low density lipoproteins result in an increased susceptibility to phospholipid hydrolysis by phospholipase A2.

    PubMed

    Eckey, R; Menschikowski, M; Lattke, P; Jaross, W

    1997-07-25

    In vitro-studies have shown that phospholipid hydrolysis of low density lipoproteins (LDL) by bee venom or porcine pancreatic phospholipase A2 (PLA2) leads to an increased uptake of these lipoproteins by macrophages transforming them into foam cells. Recently, a secretory phospholipase A2, group II, was detected in human atherosclerotic plaques. In order to investigate the role of this enzyme in the pathogenesis of atherosclerosis, a structurally identical human secretory PLA2 was purified from the medium of HepG2 cells stimulated with interleukin-6 and tumor necrosis factor-alpha. The activity of the purified enzyme towards the phospholipids of native and modified low density lipoproteins was compared with the activity towards Escherichia coli-membranes and other phospholipid substrates. Compared to E. coli-membranes, native LDL proved to be a poor substrate for group II PLA2. After mild oxidation induced by copper ions or by 2,2-azobis(2-amidinopropane) (AAPH), the susceptibility of LDL to phospholipid hydrolysis was found to be increased by 25 and 23%, respectively, whereas extensive copper-mediated oxidation caused a decreased hydrolysis. Aging of LDL at 6 degrees C for weeks or at 37 degrees C for hours resulted in an increase in PLA2-catalyzed phospholipid hydrolysis of up to 26-fold. LDL protected from oxidation by probucol during aging showed a lesser increase in susceptibility to phospholipid hydrolysis. Our results suggest that PLA2, group II, can increase the atherogenicity of LDL by its ability to hydrolyze the phospholipids of these lipoproteins, especially after modifications that are likely to occur in vivo.

  19. Low HDL cholesterol is associated with increased atherogenic lipoproteins and insulin resistance in women classified with metabolic syndrome.

    PubMed

    Fernandez, Maria Luz; Jones, Jennifer J; Ackerman, Daniela; Barona, Jacqueline; Calle, Mariana; Comperatore, Michael V; Kim, Jung-Eun; Andersen, Catherine; Leite, Jose O; Volek, Jeff S; McIntosh, Mark; Kalynych, Colleen; Najm, Wadie; Lerman, Robert H

    2010-12-01

    Both metabolic syndrome (MetS) and elevated LDL cholesterol (LDL-C) increase the risk for cardiovascular disease (CVD). We hypothesized that low HDL cholesterol (HDL-C) would further increase CVD risk in women having both conditions. To assess this, we recruited 89 women with MetS (25-72 y) and LDL-C ≥ 2.6 mmol/L. To determine whether plasma HDL-C concentrations were associated with dietary components, circulating atherogenic particles, and other risk factors for CVD, we divided the subjects into two groups: high HDL-C (H-HDL) (≥ 1.3 mmol/L, n = 32) and low HDL-C (L-HDL) (< 1.3 mmol/L, n = 57). Plasma lipids, insulin, adiponectin, apolipoproteins, oxidized LDL, Lipoprotein(a), and lipoprotein size and subfractions were measured, and 3-d dietary records were used to assess macronutrient intake. Women with L-HDL had higher sugar intake and glycemic load (P < 0.05), higher plasma insulin (P < 0.01), lower adiponectin (P < 0.05), and higher numbers of atherogenic lipoproteins such as large VLDL (P < 0.01) and small LDL (P < 0.001) than the H-HDL group. Women with L-HDL also had larger VLDL and both smaller LDL and HDL particle diameters (P < 0.001). HDL-C was positively correlated with LDL size (r = 0.691, P < 0.0001) and HDL size (r = 0.606, P < 0.001), and inversely correlated with VLDL size (r = -0.327, P < 0.01). We concluded that L-HDL could be used as a marker for increased numbers of circulating atherogenic lipoproteins as well as increased insulin resistance in women who are already at risk for CVD.

  20. Low HDL cholesterol is associated with increased atherogenic lipoproteins and insulin resistance in women classified with metabolic syndrome

    PubMed Central

    Jones, Jennifer J; Ackerman, Daniela; Barona, Jacqueline; Calle, Mariana; Comperatore, Michael V; Kim, Jung-Eun; Andersen, Catherine; Leite, Jose O; Volek, Jeff S; McIntosh, Mark; Kalynych, Colleen; Najm, Wadie; Lerman, Robert H

    2010-01-01

    Both metabolic syndrome (MetS) and elevated LDL cholesterol (LDL-C) increase the risk for cardiovascular disease (CVD). We hypothesized that low HDL cholesterol (HDL-C) would further increase CVD risk in women having both conditions. To assess this, we recruited 89 women with MetS (25-72 y) and LDL-C ≥ 2.6 mmol/L. To determine whether plasma HDL-C concentrations were associated with dietary components, circulating atherogenic particles, and other risk factors for CVD, we divided the subjects into two groups: high HDL-C (H-HDL) (≥ 1.3 mmol/L, n = 32) and low HDL-C (L-HDL) (< 1.3 mmol/L, n = 57). Plasma lipids, insulin, adiponectin, apolipoproteins, oxidized LDL, Lipoprotein(a), and lipoprotein size and subfractions were measured, and 3-d dietary records were used to assess macronutrient intake. Women with L-HDL had higher sugar intake and glycemic load (P < 0.05), higher plasma insulin (P < 0.01), lower adiponectin (P < 0.05), and higher numbers of atherogenic lipoproteins such as large VLDL (P < 0.01) and small LDL (P < 0.001) than the H-HDL group. Women with L-HDL also had larger VLDL and both smaller LDL and HDL particle diameters (P < 0.001). HDL-C was positively correlated with LDL size (r = 0.691, P < 0.0001) and HDL size (r = 0.606, P < 0.001), and inversely correlated with VLDL size (r = -0.327, P < 0.01). We concluded that L-HDL could be used as a marker for increased numbers of circulating atherogenic lipoproteins as well as increased insulin resistance in women who are already at risk for CVD. PMID:21286407

  1. Increased expression of low-density lipoprotein receptors in a Smith-Lemli-Opitz infant with elevated bilirubin levels.

    PubMed

    Ness, G C; Lopez, D; Borrego, O; Gilbert-Barness, E

    1997-01-31

    We report on an infant girl with severe RSH or Smith-Lemli-Opitz syndrome with hyperbilirubinemia. The infant died at age 2 months. Sterol analysis of liver and brain tissues showed marked elevations of 7-dehydrocholesterol with decreased levels of cholesterol. Immunocytochemical analysis demonstrated remarkable increases in low-density lipoprotein (LDL) receptors in these tissues, indicative of a deficiency in available cholesterol for tissue needs.

  2. Interactions between Defining, Explaining and Classifying: The Case of Increasing and Decreasing Sequences

    ERIC Educational Resources Information Center

    Alcock, Lara; Simpson, Adrian

    2017-01-01

    This paper describes a study in which we investigated relationships between defining mathematical concepts--increasing and decreasing infinite sequences--explaining their meanings and classifying consistently with formal definitions. We explored the effect of defining, explaining or studying a definition on subsequent classification, and the…

  3. Interactions between Defining, Explaining and Classifying: The Case of Increasing and Decreasing Sequences

    ERIC Educational Resources Information Center

    Alcock, Lara; Simpson, Adrian

    2017-01-01

    This paper describes a study in which we investigated relationships between defining mathematical concepts--increasing and decreasing infinite sequences--explaining their meanings and classifying consistently with formal definitions. We explored the effect of defining, explaining or studying a definition on subsequent classification, and the…

  4. Protection from Cardiovascular Disease Due to Increased High-Density Lipoprotein Cholesterol in African Black Populations: Myth or Reality?

    PubMed

    Woudberg, Nicholas J; Goedecke, Julia H; Lecour, Sandrine

    2016-10-20

    The burden of cardiovascular disease (CVD) in sub-Saharan Africa has increased over the last decade. Despite this, African Black populations present with relatively low incidences of coronary heart disease and ischemic heart disease, which may be attributed to their lower total cholesterol, triglycerides and low-density lipoprotein cholesterol concentrations, compared with White populations. Commensurate with these lower lipid levels, it was believed that high-density lipoprotein cholesterol (HDL-C) concentrations would be higher in Black populations compared with their White counterparts. This is based on data from previous studies of African and African American populations; however, recent studies conducted in Africa found similar or lower HDL-C concentrations in Black compared with White individuals. Current research, therefore, suggests that HDL-C may not be a good indicator of cardiovascular risk and future research should focus on HDL quality (vs quantity), by measuring HDL functionality and subclass.

  5. Fenofibrate Increases Very Low Density Lipoprotein Triglyceride Production Despite Reducing Plasma Triglyceride Levels in APOE*3-Leiden.CETP Mice*

    PubMed Central

    Bijland, Silvia; Pieterman, Elsbet J.; Maas, Annemarie C. E.; van der Hoorn, José W. A.; van Erk, Marjan J.; van Klinken, Jan B.; Havekes, Louis M.; van Dijk, Ko Willems; Princen, Hans M. G.; Rensen, Patrick C. N.

    2010-01-01

    The peroxisome proliferator-activated receptor alpha (PPARα) activator fenofibrate efficiently decreases plasma triglycerides (TG), which is generally attributed to enhanced very low density lipoprotein (VLDL)-TG clearance and decreased VLDL-TG production. However, because data on the effect of fenofibrate on VLDL production are controversial, we aimed to investigate in (more) detail the mechanism underlying the TG-lowering effect by studying VLDL-TG production and clearance using APOE*3-Leiden.CETP mice, a unique mouse model for human-like lipoprotein metabolism. Male mice were fed a Western-type diet for 4 weeks, followed by the same diet without or with fenofibrate (30 mg/kg bodyweight/day) for 4 weeks. Fenofibrate strongly lowered plasma cholesterol (−38%) and TG (−60%) caused by reduction of VLDL. Fenofibrate markedly accelerated VLDL-TG clearance, as judged from a reduced plasma half-life of glycerol tri[3H]oleate-labeled VLDL-like emulsion particles (−68%). This was associated with an increased post-heparin lipoprotein lipase (LPL) activity (+110%) and an increased uptake of VLDL-derived fatty acids by skeletal muscle, white adipose tissue, and liver. Concomitantly, fenofibrate markedly increased the VLDL-TG production rate (+73%) but not the VLDL-apolipoprotein B (apoB) production rate. Kinetic studies using [3H]palmitic acid showed that fenofibrate increased VLDL-TG production by equally increasing incorporation of re-esterified plasma fatty acids and liver TG into VLDL, which was supported by hepatic gene expression profiling data. We conclude that fenofibrate decreases plasma TG by enhancing LPL-mediated VLDL-TG clearance, which results in a compensatory increase in VLDL-TG production by the liver. PMID:20501652

  6. Fenofibrate increases very low density lipoprotein triglyceride production despite reducing plasma triglyceride levels in APOE*3-Leiden.CETP mice.

    PubMed

    Bijland, Silvia; Pieterman, Elsbet J; Maas, Annemarie C E; van der Hoorn, José W A; van Erk, Marjan J; van Klinken, Jan B; Havekes, Louis M; van Dijk, Ko Willems; Princen, Hans M G; Rensen, Patrick C N

    2010-08-13

    The peroxisome proliferator-activated receptor alpha (PPARalpha) activator fenofibrate efficiently decreases plasma triglycerides (TG), which is generally attributed to enhanced very low density lipoprotein (VLDL)-TG clearance and decreased VLDL-TG production. However, because data on the effect of fenofibrate on VLDL production are controversial, we aimed to investigate in (more) detail the mechanism underlying the TG-lowering effect by studying VLDL-TG production and clearance using APOE*3-Leiden.CETP mice, a unique mouse model for human-like lipoprotein metabolism. Male mice were fed a Western-type diet for 4 weeks, followed by the same diet without or with fenofibrate (30 mg/kg bodyweight/day) for 4 weeks. Fenofibrate strongly lowered plasma cholesterol (-38%) and TG (-60%) caused by reduction of VLDL. Fenofibrate markedly accelerated VLDL-TG clearance, as judged from a reduced plasma half-life of glycerol tri[(3)H]oleate-labeled VLDL-like emulsion particles (-68%). This was associated with an increased post-heparin lipoprotein lipase (LPL) activity (+110%) and an increased uptake of VLDL-derived fatty acids by skeletal muscle, white adipose tissue, and liver. Concomitantly, fenofibrate markedly increased the VLDL-TG production rate (+73%) but not the VLDL-apolipoprotein B (apoB) production rate. Kinetic studies using [(3)H]palmitic acid showed that fenofibrate increased VLDL-TG production by equally increasing incorporation of re-esterified plasma fatty acids and liver TG into VLDL, which was supported by hepatic gene expression profiling data. We conclude that fenofibrate decreases plasma TG by enhancing LPL-mediated VLDL-TG clearance, which results in a compensatory increase in VLDL-TG production by the liver.

  7. Lipoprotein(a) Mass Levels Increase Significantly According to APOE Genotype: An Analysis of 431 239 Patients.

    PubMed

    Moriarty, Patrick M; Varvel, Stephen A; Gordts, Philip L S M; McConnell, Joseph P; Tsimikas, Sotirios

    2017-03-01

    Lipoprotein(a) [Lp(a)] levels are genetically determined by hepatocyte apolipoprotein(a) synthesis, but catabolic pathways also influence circulating levels. APOE genotypes have different affinities for the low-density lipoprotein (LDL) receptor and LDL-related protein-1, with ε2 having the weakest binding to LDL receptor at <2% relative to ε3 and ε4. APPROACH AND RESULTS: APOE genotypes (ε2/ε2, ε2/ε3, ε2/ε4, ε3/ε3, ε3/ε4, and ε4/ε4), Lp(a) mass, directly measured Lp(a)-cholesterol levels, and a variety of apoB-related lipoproteins were measured in 431 239 patients. The prevalence of APOE traits were ε2: 7.35%, ε3: 77.56%, and ε4: 15.09%. Mean (SD) Lp(a) levels were 65% higher in ε4/ε4 compared with ε2/ε2 genotypes and increased significantly according to APOE genotype: ε2/ε2: 23.4 (29.2), ε2/ε3: 31.3 (38.0), ε2/ε4: 32.8 (38.5), ε3/ε3: 33.2 (39.1), ε3/ε4: 35.5 (41.6), and ε4/ε4: 38.5 (44.1) mg/dL (P<0.0001). LDL-cholesterol, apoB, Lp(a)-cholesterol, LDL-cholesterol corrected for Lp(a)-cholesterol content, LDL-particle number, and small, dense LDL also had similar patterns. Patients with LDL-cholesterol ≥250 mg/dL, who are more likely to have LDL receptor mutations and reduced affinity for apoB, had higher Lp(a) levels across all apoE isoforms, but particularly in patients with ε2 alleles, compared with LDL <250 mg/dL. The lowest Lp(a) mass levels were present in patients with ε2 isoforms and lowest LDL-cholesterol. APOE genotypes strongly influence Lp(a) and apoB-related lipoprotein levels. This suggests that differences in affinity of apoE proteins for lipoprotein clearance receptors may affect Lp(a) catabolism, suggesting a competition between Lp(a) and apoE protein for similar receptors. © 2017 American Heart Association, Inc.

  8. Increased Free Cholesterol in Plasma Low and Very Low Density Lipoproteins in Non-Insulin-Dependent Diabetes Mellitus: Its Role in the Inhibition of Cholesteryl Ester Transfer

    NASA Astrophysics Data System (ADS)

    Fielding, Christopher J.; Reaven, Gerald M.; Liu, George; Fielding, Phoebe E.

    1984-04-01

    Recombination of low and very low density lipoproteins (VLDL and LDL) from normal subjects with plasma from patients with non-insulin-dependent diabetes mellitus significantly increased the reduced rate of transfer of cholesteryl ester to these lipoproteins, which is characteristic of diabetic plasma, whereas diabetic VLDL and LDL reduced cholesteryl ester transfer rates in normal plasma. VLDL and LDL from diabetic plasma had an increased ratio of free cholesterol to phospholipid compared to normal, and unlike normal VLDL and LDL spontaneously lost free cholesterol to high density lipoprotein. These data suggest that the block to cholesteryl ester transfer to these lipoproteins in non-insulin-dependent diabetes is mediated by their increased free cholesterol content and may be related to the increased risk of these patients for developing atherosclerosis.

  9. The role of conventional and novel mechanisms in explaining increased risk of cardiovascular events in offspring with positive parental history.

    PubMed

    Hamer, Mark; Chida, Yoichi; Stamatakis, Emmanuel

    2009-10-01

    Parental history is a widely accepted risk factor for offspring cardiovascular events, although the mechanisms remain unclear. We examined the contribution of conventional and novel risk factors in explaining the excess risk of cardiovascular events in offspring with positive parental history (PH+). We collected conventional (blood pressure, cholesterol, adiposity), lifestyle, and novel (C-reactive protein, CRP) risk factors at baseline in participants from the Scottish Health Surveys (n = 5946, 44.5% men, aged 53.6 +/- 12.4 years), who were followed up over an average of 7.1 years for cardiovascular disease (CVD) events (a composite of fatal and nonfatal events incorporating acute myocardial infarction, coronary artery bypass surgery, percutaneous coronary angioplasty, stroke, heart failure). Younger PH+ participants (<65 years) were at higher risk of incident CVD events [age-adjusted and sex-adjusted hazard ratio = 1.91, 95% confidence interval (CI) 1.21-3.00] compared with PH-. Despite an association of PH+ with blood pressure, total and high-density lipoprotein cholesterol, CRP, and physical activity, less than 15% of the excess risk was explained through conventional and novel risk factors. However, the greatest risk of CVD was observed in PH+ participants with elevated CRP (> or =3 mg/l) (hazard ratio = 2.99, 95% CI 2.15-4.16) or hypertension (hazard ratio = 2.87, 95% CI 2.07-3.99). Only a small amount of the excess CVD risk associated with PH+ is accounted for by conventional and novel mechanisms. However, the combination of elevated CRP or hypertension with PH+ substantially increases the risk of CVD.

  10. Nerve growth factor induces rapid increases in functional cell surface low density lipoprotein receptor-related protein.

    PubMed

    Bu, G; Sun, Y; Schwartz, A L; Holtzman, D M

    1998-05-22

    The low density lipoprotein receptor-related protein (LRP) is a large endocytic receptor that binds multiple ligands and is highly expressed in neurons. Several LRP ligands, including apolipoprotein E/lipoproteins and amyloid precursor protein, have been shown to participate either in Alzheimer's disease pathogenesis or pathology. However, factors that regulate LRP expression in neurons are unknown. In the current study, we analyzed the effects of nerve growth factor (NGF) treatment on LRP expression, distribution, and function within neurons in two neuronal cell lines. Our results show that NGF induces a rapid increase of cell surface LRP expression in a central nervous system-derived neuronal cell line, GT1-1 Trk, which was seen within 10 min and reached a maximum at about 1 h of NGF treatment. This increase of cell surface LRP expression is concomitant with an increase in the endocytic activity of LRP as measured via ligand uptake and degradation assays. We also found that the cytoplasmic tail of LRP is phosphorylated and that NGF rapidly increases the amount of phosphorylation. Furthermore, we detected a significant increase of LRP expression at the messenger RNA level following 24 h of NGF treatment. Both rapid and long term induction of LRP expression were also detected in peripheral nervous system-derived PC12 cells following NGF treatment. Taken together, our results demonstrate that NGF regulates LRP expression in neuronal cells.

  11. Streptococcal serum opacity factor increases the rate of hepatocyte uptake of human plasma high-density lipoprotein cholesterol.

    PubMed

    Gillard, Baiba K; Rosales, Corina; Pillai, Biju K; Lin, Hu Yu; Courtney, Harry S; Pownall, Henry J

    2010-11-16

    Serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes, converts plasma high-density lipoproteins (HDL) to three distinct species: lipid-free apolipoprotein (apo) A-I, neo HDL, a small discoidal HDL-like particle, and a large cholesteryl ester-rich microemulsion (CERM) that contains the cholesterol esters (CE) of up to ∼400000 HDL particles and apo E as its major protein. Similar SOF reaction products are obtained with HDL, total plasma lipoproteins, and whole plasma. We hypothesized that hepatic uptake of CERM-CE via multiple apo E-dependent receptors would be faster than that of HDL-CE. We tested our hypothesis using human hepatoma cells and lipoprotein receptor-specific Chinese hamster ovary (CHO) cells. The uptake of [(3)H]CE by HepG2 and Huh7 cells from HDL after SOF treatment, which transfers >90% of HDL-CE to CERM, was 2.4 and 4.5 times faster, respectively, than from control HDL. CERM-[(3)H]CE uptake was inhibited by LDL and HDL, suggestive of uptake by both the LDL receptor (LDL-R) and scavenger receptor class B type I (SR-BI). Studies in CHO cells specifically expressing LDL-R and SR-BI confirmed CERM-[(3)H]CE uptake by both receptors. RAP and heparin inhibit CERM-[(3)H]CE but not HDL-[(3)H]CE uptake, thereby implicating LRP-1 and cell surface proteoglycans in this process. These data demonstrate that SOF treatment of HDL increases the rate of CE uptake via multiple hepatic apo E receptors. In so doing, SOF might increase the level of hepatic disposal of plasma cholesterol in a way that is therapeutically useful.

  12. Uptake and Trafficking of Mildly Oxidized LDL and Acetylated LDL in THP-1 Cells Does Not Explain the Differences in Lysosomal Metabolism of These Two Lipoproteins

    NASA Astrophysics Data System (ADS)

    Yancey, Patricia G.; Miles, Stacia; Schwegel, Jennifer; Gray Jerome, W.

    2002-04-01

    Foam cells in the atherosclerotic lesion have substantial cholesterol stores within large, swollen lysosomes. This feature is mimicked by incubating THP-1 macrophages with mildly oxidized low density lipoprotein (LDL). Incubation of THP-1 cells with acetylated LDL produces cytoplasmic cholesteryl ester accumulation rather than lysosomal storage. The differences could be due to differences in uptake and delivery of lipoprotein to lysosomes or to lysosomal and post-lysosomal processing events. We compared uptake and lysosomal trafficking of acetylated and oxidized LDL using colloidal gold-labeled lipoproteins. Labeling did not alter cellular cholesterol accumulation. We found that uptake and delivery to lysosomes are not different for acetylated and oxidized LDL. In fact, both oxidized and acetylated LDL can be delivered to the same lysosomes. Sequential incubation with oxidized LDL followed by acetylated LDL showed that the lipid-engorged lysosomes are long-lived structures, continuously accepting newly ingested lipoprotein. Comparison of acetylated and oxidized LDL in mouse peritoneal macrophages, a cell which does not accumulate substantial lysosomal lipid, also revealed no differences in uptake. This indicates that in THP-1 cells, the differences in metabolism of oxidized and acetylated LDL are due to cell-specific lysosomal or post-lysosomal events not present in B6C3F1 mouse macrophages.

  13. Explaining the Increase in Publication Productivity among Academic Staff: A Generational Perspective

    ERIC Educational Resources Information Center

    Kyvik, Svein; Aksnes, Dag W.

    2015-01-01

    In Norwegian research universities, a large individual increase has taken place in scientific and scholarly publishing over the last 30 years. The purpose of this article is to explain the reasons for this growth in a generational perspective. We put forward six hypotheses that can be illuminated by cross-sectional data drawn from five surveys to…

  14. Antagonism of Secreted PCSK9 Increases Low Density Lipoprotein Receptor Expression in HepG2 Cells

    SciTech Connect

    McNutt, Markey C.; Kwon, Hyock Joo; Chen, Chiyuan; Chen, Justin R.; Horton, Jay D.; Lagace, Thomas A.

    2009-07-10

    PCSK9 is a secreted protein that degrades low density lipoprotein receptors (LDLRs) in liver by binding to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR. It is not known whether PCSK9 causes degradation of LDLRs within the secretory pathway or following secretion and reuptake via endocytosis. Here we show that a mutation in the LDLR EGF-A domain associated with familial hypercholesterolemia, H306Y, results in increased sensitivity to exogenous PCSK9-mediated cellular degradation because of enhanced PCSK9 binding affinity. The crystal structure of the PCSK9-EGF-A(H306Y) complex shows that Tyr-306 forms a hydrogen bond with Asp-374 in PCSK9 at neutral pH, which strengthens the interaction with PCSK9. To block secreted PCSK9 activity, LDLR (H306Y) subfragments were added to the medium of HepG2 cells stably overexpressing wild-type PCSK9 or gain-of-function PCSK9 mutants associated with hypercholesterolemia (D374Y or S127R). These subfragments blocked secreted PCSK9 binding to cell surface LDLRs and resulted in the recovery of LDLR levels to those of control cells. We conclude that PCSK9 acts primarily as a secreted factor to cause LDLR degradation. These studies support the concept that pharmacological inhibition of the PCSK9-LDLR interaction extracellularly will increase hepatic LDLR expression and lower plasma low density lipoprotein levels.

  15. Antagonism of secreted PCSK9 increases low density lipoprotein receptor expression in HepG2 cells.

    PubMed

    McNutt, Markey C; Kwon, Hyock Joo; Chen, Chiyuan; Chen, Justin R; Horton, Jay D; Lagace, Thomas A

    2009-04-17

    PCSK9 is a secreted protein that degrades low density lipoprotein receptors (LDLRs) in liver by binding to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR. It is not known whether PCSK9 causes degradation of LDLRs within the secretory pathway or following secretion and reuptake via endocytosis. Here we show that a mutation in the LDLR EGF-A domain associated with familial hypercholesterolemia, H306Y, results in increased sensitivity to exogenous PCSK9-mediated cellular degradation because of enhanced PCSK9 binding affinity. The crystal structure of the PCSK9-EGF-A(H306Y) complex shows that Tyr-306 forms a hydrogen bond with Asp-374 in PCSK9 at neutral pH, which strengthens the interaction with PCSK9. To block secreted PCSK9 activity, LDLR (H306Y) subfragments were added to the medium of HepG2 cells stably overexpressing wild-type PCSK9 or gain-of-function PCSK9 mutants associated with hypercholesterolemia (D374Y or S127R). These subfragments blocked secreted PCSK9 binding to cell surface LDLRs and resulted in the recovery of LDLR levels to those of control cells. We conclude that PCSK9 acts primarily as a secreted factor to cause LDLR degradation. These studies support the concept that pharmacological inhibition of the PCSK9-LDLR interaction extracellularly will increase hepatic LDLR expression and lower plasma low density lipoprotein levels.

  16. Impact of increases in high-density lipoprotein cholesterol on cardiovascular outcomes during the armed forces regression study.

    PubMed

    Devendra, Ganesh P; Whitney, Edwin J; Krasuski, Richard A

    2010-12-01

    high-density lipoprotein (HDL) cholesterol is a well-established inverse risk factor for cardiovascular disease. The extent to which cardiovascular risk can be modified through changes in HDL, however, is less clear. We further examined the role of aggressive HDL raising therapy on cardiovascular outcomes in the 143 patients enrolled in the Armed Forces Regression Study (AFREGS). reanalysis of the AFREGS population. Patients with stable coronary disease were randomized to receive gemfibrozil, niacin, and cholestyramine in combination or matching placebos, on top of aggressive dietary and exercise modification for a 30-month period. Blood work was performed at baseline and repeated after 1 year of therapy. patients were divided into 3 groups based on their therapeutic response: no HDL increase, mild HDL increase, and large HDL increase (% change in HDL ≤ 0, ≤ the lower 2 tertiles of HDL increase, and > the upper tertile of HDL increase, respectively). A progressive decrease in cardiovascular events was noted across these groups (30.4%, 19.4%, and 3.2%, respectively, P = .01). Kaplan-Meier analysis according to percentage change in HDL demonstrated a similar improvement in event-free survival (P = .01). Proportional hazards modeling also demonstrated that increasing HDL predicted a lower hazard of cardiovascular events, even after adjusting for changes in low-density lipoprotein ([LDL] P < .01). For every 1% increase in HDL achieved, a 2% decrease in events was recognized. these data suggest that in a population of patients with stable atherosclerosis, the greater the percentage increase in HDL achieved, the greater the cardioprotective benefit. This further supports HDL raising as a beneficial therapeutic strategy.

  17. Increased Antioxidant Quality Versus Lower Quantity of High Density Lipoprotein in Benign Prostatic Hyperplasia

    PubMed Central

    Aydin, Ozgur; Ellidag, Hamit Yasar; Eren, Esin; Ay, Nurullah; Yalçınkaya, Soner; Yilmaz, Necat

    2015-01-01

    Summary Background Oxidative stress may be involved in the pathogenesis of every human disease. To understand its possible role in benign prostatic hyperplasia (BPH), we measured the overall oxidative status of patients with BPH and the serum activity of the high density lipoprotein (HDL)-related antioxidant enzymes paraoxonase 1 (PON1) and arylesterase (ARE). Methods Fifty-six urology outpatient clinic patients with BPH (mean age 64±8.6 years) were prospectively included in the study. Forty volunteer healthy controls from the laboratory staff (mean age 62±10 years) were enrolled for comparison. Serum total antioxidant status (TAS), total oxidant status (TOS), PON1, ARE, and HDL levels were measured by commercially available, ready-to-use kits. Results Serum TAS and HDL levels were significantly lower in the BPH group than in the control group (P=0.004 and P=0.02, respectively). No significant between-group differences were observed for TOS levels or PON1 and ARE enzyme activities (P=0.30, P=0.89, and P=0.74, respectively). In the BPH group, the calculated parameters PON1/HDL and ARE/HDL were significantly higher (P=0.02 and P=0.04, respectively). Conclusions Our findings agree with the previous reports of impaired oxidant/antioxidant balance in BPH patients. The activities of HDL-related enzymes between groups with significantly different HDL levels may be deceptive; adjusted values may help to reach more accurate conclusions.

  18. Income Inequality Explains Why Economic Growth Does Not Always Translate to an Increase in Happiness.

    PubMed

    Oishi, Shigehiro; Kesebir, Selin

    2015-10-01

    One of the most puzzling social science findings in the past half century is the Easterlin paradox: Economic growth within a country does not always translate into an increase in happiness. We provide evidence that this paradox can be partly explained by income inequality. In two different data sets covering 34 countries, economic growth was not associated with increases in happiness when it was accompanied by growing income inequality. Earlier instances of the Easterlin paradox (i.e., economic growth not being associated with increasing happiness) can thus be explained by the frequent concurrence of economic growth and growing income inequality. These findings suggest that a more even distribution of growth in national wealth may be a precondition for raising nationwide happiness.

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

    PubMed

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

    2016-01-01

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

  20. Relevance of intermediate-density lipoprotein cholesterol to Framingham risk score of coronary heart disease in middle-aged men with increased non-HDL cholesterol.

    PubMed

    Ito, Kumie; Yoshida, Hiroshi; Yanai, Hidekatsu; Kurosawa, Hideo; Sato, Ryo; Manita, Daisuke; Hirowatari, Yuji; Tada, Norio

    2013-10-09

    Cholesterol levels of non-high-density lipoprotein (non-HDL), which contains low-density lipoprotein (LDL), intermediate-density lipoprotein (IDL), very low-density lipoprotein (VLDL) and chylomicron (CM) remnant, have been proven to perform a significant predictor of coronary heart disease (CHD) better than LDL-cholesterol regardless of triglyceride (TG) levels. The present study investigated the relevance of TG-rich lipoproteins (IDL, VLDL, CM) to Framingham risk score (FRS) predictive of 10-year CHD risk. Lipoprotein profiles (cholesterol levels of HDL, LDL, IDL, VLDL, CM) in Japanese men (n = 487) who underwent medical check-up were determined by using our developed anion-exchange high performance liquid chromatography (AEX-HPLC). Total-cholesterol (TC), TG, fasting blood sugar (FBS) and hemoglobin (Hb) A1c were measured by routine methods. The lipoprotein profiles, non-HDL-cholesterol, TC, and TG were examined on these associations with FRS. The lipid levels except for CM-cholesterol were significantly different between two groups (low FRS, < 10%; high FRS, ≥10%) (P < 0.0001), and body mass index (BMI), TC, TG, IDL-, and VLDL-cholesterol were significantly and positively correlated with FRS. Among them, the significant association of non-HDL-cholesterol to FRS was noted (r = 0.411, P < 0.0001). Multiple stepwise regression analysis shows that, in addition to non-HDL-cholesterol, IDL-cholesterol in TG-rich lipoproteins was significantly correlated with FRS in independently of BMI. These correlation results were similarly found even when the part of the study subjects (n = 348) without the drug therapy for hyperlipidemia, diabetes, and hypertension was investigated. These results suggest that IDL-cholesterol may serve as a useful marker for CHD risk in Japanese men with increased non-HDL-cholesterol. © 2013.

  1. Low level of low-density lipoprotein cholesterol increases hemorrhagic transformation in large artery atherothrombosis but not in cardioembolism.

    PubMed

    Kim, Beom Joon; Lee, Seung-Hoon; Ryu, Wi-Sun; Kang, Bong Su; Kim, Chi Kyung; Yoon, Byung-Woo

    2009-05-01

    Low cholesterol level is known to be associated with increased cerebral hemorrhage. However, the associations of hemorrhagic transformation (HTf) after acute ischemic stroke and the low levels of total cholesterol (TC) or low-density lipoprotein cholesterol (LDLC) are largely undiscovered. Of the 1034 patients with acute ischemic stroke who were consecutively admitted to our hospital, 377 patients with stroke attributable to large artery atherothrombosis (LAA; n=210) or cardioembolism (n=167) were selected for this study. Demographic and clinical information was collected and HTf was evaluated through follow-up T2*-weighted gradient-echo MRI performed usually within 1 week after stroke. Measurement of lipid parameters included TC, LDLC, high-density lipoprotein cholesterol, and triglyceride. Of the 377 patients, HTf was noted in 74 patients (19.6%). When patients were divided into 4 groups according to their TC and LDLC levels, the incidence of HTf was significantly elevated in the lowest quartile of each TC (P<0.01) and LDLC (P<0.01) level in LAA subgroup, but not in cardioembolism. After adjusting covariates, a low level of LDLC (OR, 0.46 per 1 mmol/L-increase; 95% CI, 0.22-0.98) was independently associated with HTf in LAA, but not in cardioembolism. There was no significant association between low levels of TC (OR, 0.63 per 1 mmol/L-increase; 95% CI, 0.35-1.15) and HTf in LAA. Low levels of LDLC, and possibly TC, are associated with greater risk of hemorrhagic transformation after acute ischemic stroke attributable to LAA.

  2. The ACAT inhibitor avasimibe increases the fractional clearance rate of postprandial triglyceride-rich lipoproteins in miniature pigs.

    PubMed

    Burnett, John R; Telford, Dawn E; Barrett, P Hugh R; Huff, Murray W

    2005-12-30

    Previously, we have shown, in vivo, that the acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitor avasimibe decreases hepatic apolipoprotein (apo) B secretion into plasma. To test the hypothesis that avasimibe modulates postprandial triglyceride-rich lipoprotein (TRL) metabolism in vivo, an oral fat load (2 g fat/kg) containing retinol was given to 9 control miniature pigs and to 9 animals after 28 days treatment with avasimibe (10 mg/kg/day, n=5; 25 mg/kg/day, n=4). The kinetic parameters for plasma retinyl palmitate (RP) metabolism were determined by multi-compartmental modeling using SAAM II. Avasimibe decreased the 2-h TRL (d<1.006 g/mL; S(f)>20) triglyceride concentrations by 34%. The TRL triglyceride 0-12 h area under the curve (AUC) was decreased by 21%. In contrast, avasimibe had no effect on peak TRL RP concentrations, time to peak, or its rate of appearance into plasma, however, the TRL RP 0-12 h AUC was decreased by 17%. Analysis of the RP kinetic parameters revealed that the TRL fractional clearance rate (FCR) was increased 1.4-fold with avasimibe. The TRL RP FCR was negatively correlated with very low density lipoprotein (VLDL) apoB production rate measured in the fasting state (r=-0.504). No significant changes in total intestinal lipid concentrations were observed. Thus, although avasimibe had no effect on intestinal TRL secretion, plasma TRL clearance was significantly increased; an effect that may relate to a decreased competition with hepatic VLDL for removal processes.

  3. Arterial retention of remnant lipoproteins ex vivo is increased in insulin resistance because of increased arterial biglycan and production of cholesterol-rich atherogenic particles that can be improved by ezetimibe in the JCR:LA-cp rat.

    PubMed

    Mangat, Rabban; Warnakula, Samantha; Borthwick, Faye; Hassanali, Zahra; Uwiera, Richard R E; Russell, James C; Cheeseman, Christopher I; Vine, Donna F; Proctor, Spencer D

    2012-10-01

    Literature supports the "response-to-retention" hypothesis-that during insulin resistance, impaired metabolism of remnant lipoproteins can contribute to accelerated cardiovascular disease progression. We used the JCR:LA-cp rat model of metabolic syndrome (MetS) to determine the extent of arterial accumulation of intestinal-derived remnants ex vivo and potential mechanisms that contribute to exacerbated cholesterol deposition in insulin resistance. Arteries from control and MetS (insulin-resistant) JCR:LA-cp rats were perfused ex vivo with Cy5-labeled remnant lipoproteins, and their arterial retention was quantified by confocal microscopy. Arterial proteoglycans were isolated from control and MetS rats at 6, 12, and 32 weeks of age. There was a significant increase in the arterial retention of remnants and in associated cholesterol accumulation in MetS rats as compared to control rats. Mechanistic studies reveal that increased cholesterol deposition is a result of greater arterial biglycan content; longer glycosaminoglycans and increased production of cholesterol-rich intestinal-derived remnants, as compared to controls. Additionally, perfusion of vessels treated with ezetimibe, alone or in combination with simvastatin, with remnants isolated from the respective treatment group reduced ex vivo arterial retention of remnant-derived cholesterol ex vivo as compared to untreated controls. Increased progression of atherosclerotic cardiovascular disease in MetS and type 2 diabetes mellitus might be explained in part by an increase in the arterial retention of cholesterol-rich remnants. Furthermore, ezetimibe alone or in combination treatment with simvastatin could be beneficial in ameliorating atherosclerotic cardiovascular disease in insulin resistance and MetS.

  4. Arterial Retention of Remnant Lipoproteins Ex Vivo Is Increased in Insulin Resistance Because of Increased Arterial Biglycan and Production of Cholesterol-Rich Atherogenic Particles That Can Be Improved by Ezetimibe in the JCR:LA-cp Rat

    PubMed Central

    Mangat, Rabban; Warnakula, Samantha; Borthwick, Faye; Hassanali, Zahra; Uwiera, Richard R.E.; Russell, James C.; Cheeseman, Christopher I.; Vine, Donna F.; Proctor, Spencer D

    2012-01-01

    Background Literature supports the “response-to-retention” hypothesis—that during insulin resistance, impaired metabolism of remnant lipoproteins can contribute to accelerated cardiovascular disease progression. We used the JCR:LA-cp rat model of metabolic syndrome (MetS) to determine the extent of arterial accumulation of intestinal-derived remnants ex vivo and potential mechanisms that contribute to exacerbated cholesterol deposition in insulin resistance. Methods and Results Arteries from control and MetS (insulin-resistant) JCR:LA-cp rats were perfused ex vivo with Cy5-labeled remnant lipoproteins, and their arterial retention was quantified by confocal microscopy. Arterial proteoglycans were isolated from control and MetS rats at 6, 12, and 32 weeks of age. There was a significant increase in the arterial retention of remnants and in associated cholesterol accumulation in MetS rats as compared to control rats. Mechanistic studies reveal that increased cholesterol deposition is a result of greater arterial biglycan content; longer glycosaminoglycans and increased production of cholesterol-rich intestinal-derived remnants, as compared to controls. Additionally, perfusion of vessels treated with ezetimibe, alone or in combination with simvastatin, with remnants isolated from the respective treatment group reduced ex vivo arterial retention of remnant-derived cholesterol ex vivo as compared to untreated controls. Conclusions Increased progression of atherosclerotic cardiovascular disease in MetS and type 2 diabetes mellitus might be explained in part by an increase in the arterial retention of cholesterol-rich remnants. Furthermore, ezetimibe alone or in combination treatment with simvastatin could be beneficial in ameliorating atherosclerotic cardiovascular disease in insulin resistance and MetS. PMID:23316299

  5. Lipoprotein metabolism indicators improve cardiovascular risk prediction

    USDA-ARS?s Scientific Manuscript database

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

  6. Elevated Mutagenesis Does Not Explain the Increased Frequency of Antibiotic Resistant Mutants in Starved Aging Colonies

    PubMed Central

    Katz, Sophia; Hershberg, Ruth

    2013-01-01

    The frequency of mutants resistant to the antibiotic rifampicin has been shown to increase in aging (starved), compared to young colonies of Eschierchia coli. These increases in resistance frequency occur in the absence of any antibiotic exposure, and similar increases have also been observed in response to additional growth limiting conditions. Understanding the causes of such increases in the frequency of resistance is important for understanding the dynamics of antibiotic resistance emergence and spread. Increased frequency of rifampicin resistant mutants in aging colonies is cited widely as evidence of stress-induced mutagenesis (SIM), a mechanism thought to allow bacteria to increase mutation rates upon exposure to growth-limiting stresses. At the same time it has been demonstrated that some rifampicin resistant mutants are relatively fitter in aging compared to young colonies, indicating that natural selection may also contribute to increased frequency of rifampicin resistance in aging colonies. Here, we demonstrate that the frequency of mutants resistant to both rifampicin and an additional antibiotic (nalidixic-acid) significantly increases in aging compared to young colonies of a lab strain of Escherichia coli. We then use whole genome sequencing to demonstrate conclusively that SIM cannot explain the observed magnitude of increased frequency of resistance to these two antibiotics. We further demonstrate that, as was previously shown for rifampicin resistance mutations, mutations conferring nalidixic acid resistance can also increase fitness in aging compared to young colonies. Our results show that increases in the frequency of antibiotic resistant mutants in aging colonies cannot be seen as evidence of SIM. Furthermore, they demonstrate that natural selection likely contributes to increases in the frequency of certain antibiotic resistance mutations, even when no selection is exerted due to the presence of antibiotics. PMID:24244205

  7. Can we explain increases in young people's psychological distress over time?

    PubMed

    Sweeting, Helen; West, Patrick; Young, Robert; Der, Geoff

    2010-11-01

    This paper aims to explain previously described increases in self-reported psychological distress between 1987 and 2006 among samples identical in respect of age (15 years), school year and geographical location (West of Scotland). Such increases might be explained by changes in exposure (changes in levels of risk or protective factors) and/or by changes in vulnerability (changes in the relationship between risk/protective factors and psychological distress). Key areas of social change over this time period allow identification of potential explanatory factors, categorised as economic, family, educational, values and lifestyle and represented by variables common to each study. Psychological distress was measured via the 12-item General Health Questionnaire, Likert scored. Analyses were conducted on those with complete data on all variables (N = 3276 of 3929), and separately for males and females. Between 1987 and 2006, levels of almost every potential explanatory factor changed in line with general societal trends. Associations between explanatory factors and GHQ tended to be stronger among females, and at the later date. The strongest associations were with worries, arguments with parents, and, at the later date, school disengagement. The factors which best accounted for the increase in mean GHQ between 1987 and 2006 were arguments with parents, school disengagement, worry about school and, for females, worry about family relationships, reflecting both increasing exposure and vulnerability to these risk factors. A number of limitations to our analysis can be identified. However, our results reinforce the conclusions of others in highlighting the role of family and educational factors as plausible explanations for increases in young people's psychological distress.

  8. Can we explain increases in young people’s psychological distress over time?

    PubMed Central

    Sweeting, Helen; West, Patrick; Young, Robert; Der, Geoff

    2010-01-01

    This paper aims to explain previously described increases in self-reported psychological distress between 1987 and 2006 among samples identical in respect of age (15 years), school year and geographical location (West of Scotland). Such increases might be explained by changes in exposure (changes in levels of risk or protective factors) and/or by changes in vulnerability (changes in the relationship between risk/protective factors and psychological distress). Key areas of social change over this time period allow identification of potential explanatory factors, categorised as economic, family, educational, values and lifestyle and represented by variables common to each study. Psychological distress was measured via the 12-item General Health Questionnaire, Likert scored. Analyses were conducted on those with complete data on all variables (N = 3276 of 3929), and separately for males and females. Between 1987 and 2006, levels of almost every potential explanatory factor changed in line with general societal trends. Associations between explanatory factors and GHQ tended to be stronger among females, and at the later date. The strongest associations were with worries, arguments with parents, and, at the later date, school disengagement. The factors which best accounted for the increase in mean GHQ between 1987 and 2006 were arguments with parents, school disengagement, worry about school and, for females, worry about family relationships, reflecting both increasing exposure and vulnerability to these risk factors. A number of limitations to our analysis can be identified. However, our results reinforce the conclusions of others in highlighting the role of family and educational factors as plausible explanations for increases in young people’s psychological distress. PMID:20870334

  9. Evidence for genetic factors explaining the association between birth weight and low-density lipoprotein cholesterol and possible intrauterine factors influencing the association between birth weight and high-density lipoprotein cholesterol: analysis in twins.

    PubMed

    IJzerman, R G; Stehouwer, C D; Van Weissenbruch, M M; De Geus, E J; Boomsma, D I

    2001-11-01

    Recent studies have demonstrated an association between low weight at birth and an atherogenic lipid profile in later life. To examine the influences of intrauterine and genetic factors, we investigated 53 dizygotic and 61 monozygotic adolescent twin pairs. Regression analysis demonstrated that low birth weight was associated with high levels of total cholesterol, low-density lipoprotein (LDL) cholesterol and apolipoprotein B (-0.17 mmol/liter per kg, P = 0.07; -0.18 mmol/liter per kg, P = 0.04; and -0.07 g/liter per kg, P = 0.02, respectively) and with low levels of high-density lipoprotein (HDL) cholesterol (+0.04 mmol/liter per kg, P = 0.1), after adjustment for age, sex, and body mass index. Intrapair differences in birth weight were significantly associated with differences in total cholesterol, LDL cholesterol, and apolipoprotein B in dizygotic twins after adjustment for differences in current body mass index (-0.49 mmol/liter per kg, P = 0.02; -0.51 mmol/liter per kg, P = 0.01; and -0.10 g/liter per kg, P = 0.04, respectively), demonstrating that the larger the difference in birth weight, the higher these risk factors in the twin with the lower birth weight, compared with the cotwin with the higher birth weight. In monozygotic twins, however, the associations between intrapair differences in birth weight and differences in total cholesterol, LDL cholesterol, and apolipoprotein B were in the opposite direction (+0.32 mmol/liter per kg, P = 0.03; +0.23 mmol/liter per kg, P = 0.08; and +0.06 g/liter per kg, P = 0.04, respectively). The association between intrapair differences in birth weight and differences in HDL cholesterol was not significant in dizygotic twins (+0.04 mmol/liter per kg, P = 0.6) and of borderline significance in monozygotic twins (+0.11 mmol/liter per kg, P = 0.05). These data suggest that genetic factors account for the association of low birth weight with high levels of total cholesterol, LDL cholesterol, and apolipoprotein B, whereas

  10. Evolutionary conservatism explains increasing relatedness of plant communities along a flooding gradient.

    PubMed

    Tanentzap, Andrew J; Lee, William G

    2017-01-01

    Abiotic filters have been found either to increase or reduce evolutionary relatedness in plant communities, making it difficult to generalize responses of this major feature of biodiversity to future environmental change. Here, we hypothesized that the responses of phylogenetic structure to environmental change ultimately depend on how species have evolved traits for tolerating the resulting abiotic changes. Working within ephemeral wetlands, we tested whether species were increasingly related as flooding duration intensified. We also identified the mechanisms underlying increased relatedness by measuring root aerenchyma volume (RAV), a trait which promotes waterlogging tolerance. We found that species-specific responses to flooding explained most of the variation in occurrence for 63 vascular plant species across 5170 plots. For a subset of 22 species, we attributed these responses to variation in RAV. Large RAV specifically increased occurrence when flooding lasted for longer time periods, because large RAV reduced above-ground biomass loss. As large RAV was evolutionarily conserved within obligate wetland species, communities were more phylogenetically related as flooding increased. Our study shows how reconstructing the evolutionary history of traits that influence the responses of species to environmental change can help to predict future patterns in phylogenetic structure.

  11. Does low birth weight help to explain the increased prevalence of asthma among African-Americans?

    PubMed

    Joseph, Christine L M; Ownby, Dennis R; Peterson, Edward L; Johnson, Christine C

    2002-05-01

    Racial disparities in asthma prevalence are not fully explained. Previous studies have reported an association between low birth weight (LBW) and asthma. African-Americans are at a heightened risk for both conditions. The objective of this analysis was to study a sample of suburban schoolchildren to determine if increased asthma prevalence in African-Americans could be explained by report of LBW. Logistic regression was used to analyze telephone survey and clinical data for a sample of 126 children, aged 6 to 8 years. African-Americans reported asthma (12.5% vs 5.3%) and LBW (16.6% vs 3.9%) more frequently than non-African-Americans. After adjusting for LBW, the odds ratio for the association of African-American race to asthma was reduced from 2.6 to 1.8, whereas LBW remained independently associated with asthma, adjusted odds ratio = 5.1 (95% CI:1.4 to 18.9). The adjusted population risk for asthma due to LBW was 0.31. High rates of LBW for African-Americans may contribute to racial disparities in asthma prevalence.

  12. Oxidized low density lipoprotein increases RANKL level in human vascular cells. Involvement of oxidative stress

    SciTech Connect

    Mazière, Cécile; Salle, Valéry; Gomila, Cathy; Mazière, Jean-Claude

    2013-10-18

    Highlights: •Oxidized LDL enhances RANKL level in human smooth muscle cells. •The effect of OxLDL is mediated by the transcription factor NFAT. •UVA, H{sub 2}O{sub 2} and buthionine sulfoximine also increase RANKL level. •All these effects are observed in human fibroblasts and endothelial cells. -- Abstract: Receptor Activator of NFκB Ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) have been shown to play a role not only in bone remodeling but also in inflammation, arterial calcification and atherosclerotic plaque rupture. In human smooth muscle cells, Cu{sup 2+}-oxidized LDL (CuLDL) 10–50 μg/ml increased reactive oxygen species (ROS) and RANKL level in a dose-dependent manner, whereas OPG level was not affected. The lipid extract of CuLDL reproduced the effects of the whole particle. Vivit, an inhibitor of the transcription factor NFAT, reduced the CuLDL-induced increase in RANKL, whereas PKA and NFκB inhibitors were ineffective. LDL oxidized by myeloperoxidase (MPO-LDL), or other pro-oxidant conditions such as ultraviolet A (UVA) irradiation, incubation with H{sub 2}O{sub 2} or with buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis{sub ,} also induced an oxidative stress and enhanced RANKL level. The increase in RANKL in pro-oxidant conditions was also observed in fibroblasts and endothelial cells. Since RANKL is involved in myocardial inflammation, vascular calcification and plaque rupture, this study highlights a new mechanism whereby OxLDL might, by generation of an oxidative stress, exert a deleterious effect on different cell types of the arterial wall.

  13. Can Drug Effects Explain the Recent Temporal Increase in Atonic Postpartum Haemorrhage?

    PubMed Central

    Joseph, K. S.; Sheehy, Odile; Mehrabadi, Azar; Urquia, Marcelo L.; Hutcheon, Jennifer A.; Kramer, Michael

    2015-01-01

    Abstract Background Rates of postpartum haemorrhage and atonic postpartum haemorrhage have increased in several high‐income countries. We carried out a study to examine if drug use in pregnancy, or drug and other interactions, explained this increase in postpartum haemorrhage. Methods The linked administrative and hospital databases of the Québec Pregnancy Cohort were used to define a cohort of pregnant women in Québec, Canada, from 1998 to 2009 (n = 138 704). Case–control studies on any postpartum haemorrhage and atonic postpartum haemorrhage were carried out within this population, with up to five controls randomly selected for each case after matching on index date and hospital of delivery (incidence density sampling). Conditional logistic regression was used to estimate the effects of drug use on postpartum haemorrhage and atonic postpartum haemorrhage. Results There was an unexpected non‐linear, declining temporal pattern in postpartum haemorrhage and atonic postpartum haemorrhage between 1998 and 2009. Use of antidepressants (mainly selective serotonin reuptake inhibitors) was associated with higher rates of postpartum haemorrhage [adjusted rate ratio (aRR) 1.48, 95% confidence interval (CI) 1.23, 1.77] and atonic postpartum haemorrhage [aRR 1.40, 95% CI 1.13, 1.74]. Thrombocytopenia was also associated with higher rates of postpartum haemorrhage [aRR 1.52, 95% CI 1.16, 2.00]. There were no statistically significant drug interactions. Adjustment for maternal factors and drug use had little effect on temporal trends in postpartum haemorrhage and atonic postpartum haemorrhage. Conclusions Although antidepressant use and thrombocytopenia were associated with higher rates of atonic postpartum haemorrhage, antidepressant and other drug use did not explain temporal trends in postpartum haemorrhage. PMID:25847112

  14. Increased concentration of clusterin/apolipoprotein J (apoJ) in hyperlipemic serum is paradoxically associated with decreased apoJ content in lipoproteins.

    PubMed

    Rull, Anna; Martínez-Bujidos, Maria; Pérez-Cuellar, Montserrat; Pérez, Antonio; Ordóñez-Llanos, Jordi; Sánchez-Quesada, José Luis

    2015-08-01

    Clusterin/apolipoprotein J (apoJ) circulates in blood in part associated to lipoproteins or in unbound form. When bound to HDL, apoJ is antiatherogenic by inhibiting endothelial cell apoptosis; thus, any factor modifying apoJ association to HDL would decrease its antiatherogenic function. However, the exact distribution of apoJ in each lipoprotein fraction, or in lipoprotein-non bound form has not been specifically investigated either in normolipemia or in dyslipemia. Basic lipid profile and apoJ concentration were determined in sera from 70 subjects, including a wide range of cholesterol and triglyceride concentrations. Lipoproteins were isolated by ultracentrifugation and their lipid and apolipoprotein composition was assessed. In the overall population, serum apoJ positively associated with cholesterol, triglyceride and VLDL-C concentrations, and HDL-C and triglyceride were independent predictors of increased apoJ concentration. Approximately, 20.5% of circulating apoJ was associated with lipoproteins (18.5% HDL, 0.9% LDL and 1.1% VLDL) and 79.5% was not bound to lipoproteins. Serum apoJ concentration was higher in hypercholesterolemic (HC), hypertriglyceridemic (HTG) and combined hyperlipidemic (CHL) sera compared to normolipemic (NL) sera (HC, 98.15 ± 33.6 mg/L; HTG, 103.3 ± 36.8 mg/L; CHL, 131.7 ± 26.8 mg/L; NL, 66.7 ± 33.8 mg/L; P < 0.001). ApoJ distribution was also altered in hyperlipidemia; approximately 30% of circulating apoJ was associated to lipoproteins in the NL group whereas this proportion rounded 15% in hyperlipidemic subjects. Our findings indicate that hyperlipidemia increases the concentration of apoJ in serum but, in turn, the content of lipoprotein-associated apoJ decreases. The redistribution of apoJ in hyperlipidemia could compromise the antiatherogenic properties of HDL. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Increased susceptibility to amyloid-β-induced neurotoxicity in mice lacking the low-density lipoprotein receptor.

    PubMed

    de Oliveira, Jade; Moreira, Eduardo Luiz Gasnhar; dos Santos, Danúbia Bonfanti; Piermartiri, Tetsadê Camboim; Dutra, Rafael Cypriano; Pinton, Simone; Tasca, Carla Inês; Farina, Marcelo; Prediger, Rui Daniel Schröder; de Bem, Andreza Fabro

    2014-01-01

    Familial hypercholesterolemia is caused by inherited genetic abnormalities that directly or indirectly affect the function of the low-density lipoprotein (LDL) receptor. This condition is characterized by defective catabolism of LDL which results in increased plasma cholesterol concentrations and premature coronary artery disease. Nevertheless, there is increasing preclinical and clinical evidence indicating that familial hypercholesterolemia subjects show a particularly high incidence of mild cognitive impairment. Moreover, the LDL receptor (LDLr) has been implicated as the main central nervous system apolipoprotein E receptor that regulates amyloid deposition in distinct mouse models of β-amyloidosis. In this regard, herein we hypothesized that the lack of LDLr would enhance the susceptibility to amyloid-β-(Aβ)-induced neurotoxicity in mice. Using the acute intracerebroventricular injection of aggregated Aβ(1-40) peptide (400 pmol/mouse), a useful approach for the investigation of molecular mechanisms involved in Aβ toxicity, we observed oxidative stress, neuroinflammation, and neuronal membrane damage within the hippocampus of C57BL/6 wild-type mice, which were associated with spatial reference memory and working memory impairments. In addition, our data show that LDLr knockout (LDLr(-/-)) mice, regardless of Aβ treatment, displayed memory deficits and increased blood-brain barrier permeability. Nonetheless, LDLr(-/-) mice treated with Aβ(1-40) peptide presented increased acetylcholinesterase activity, astrogliosis, oxidative imbalance, and cell permeability within the hippocampus in comparison with Aβ(1-40)-treated C57BL/6 wild-type mice. Overall, the present study shows that the lack of LDLr increases the susceptibility to Aβ-induced neurotoxicity in mice providing new evidence about the crosslink between familial hypercholesterolemia and cognitive impairment.

  16. Adenovirus-mediated transfer of a gene encoding cholesterol 7 alpha-hydroxylase into hamsters increases hepatic enzyme activity and reduces plasma total and low density lipoprotein cholesterol.

    PubMed Central

    Spady, D K; Cuthbert, J A; Willard, M N; Meidell, R S

    1995-01-01

    Clinical interventions that accelerate conversion of cholesterol to bile acids reduce circulating low density lipoprotein (LDL) cholesterol concentrations. The initial and rate-limiting step in the bile acid biosynthetic pathway is catalyzed by hepatic cholesterol 7 alpha-hydroxylase. To examine the effects of transient primary overexpression of this enzyme on sterol metabolism and lipoprotein transport, we constructed a recombinant adenovirus in which a cDNA encoding rat 7 alpha-hydroxylase is expressed from the human cytomegalovirus immediate-early promoter (AdCMV7 alpha). Syrian hamsters administered AdCMV7 alpha intravenously accumulated transgene-specific mRNA in the liver and demonstrated a dose-dependent increase in hepatic microsomal 7 alpha-hydroxylase activity. The increased conversion of cholesterol to bile acids resulted in a compensatory increase in hepatic cholesterol synthesis. In addition, overexpression of 7 alpha-hydroxylase reduced the rate of LDL cholesterol entry into the plasma space and, in animals maintained on a Western-type diet, restored hepatic LDL receptor expression. As a consequence, plasma LDL concentrations fell by approximately 60% in animals maintained on control diet and by approximately 75% in animals consuming a Western-type diet. Plasma high density lipoprotein cholesterol levels were reduced to a lesser degree. These results demonstrate that transient upregulation of bile acid synthesis by direct transfer of a 7 alpha-hydroxylase gene favorably alters circulating lipoprotein profiles and suggest one potential molecular target for genetic strategies aimed at reducing cardiovascular risk. Images PMID:7635963

  17. A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase

    PubMed Central

    Fu, Zhiyao; Abou-Samra, Abdul B.; Zhang, Ren

    2015-01-01

    Lipasin/Angptl8 is a feeding-induced hepatokine that regulates triglyceride (TAG) metabolism; its therapeutical potential, mechanism of action, and relation to the lipoprotein lipase (LPL), however, remain elusive. We generated five monoclonal lipasin antibodies, among which one lowered the serum TAG level when injected into mice, and the epitope was determined to be EIQVEE. Lipasin-deficient mice exhibited elevated postprandial activity of LPL in the heart and skeletal muscle, but not in white adipose tissue (WAT), suggesting that lipasin suppresses the activity of LPL specifically in cardiac and skeletal muscles. Consistently, mice injected with the effective antibody or with lipasin deficiency had increased postprandial cardiac LPL activity and lower TAG levels only in the fed state. These results suggest that lipasin acts, at least in part, in an endocrine manner. We propose the following model: feeding induces lipasin, activating the lipasin-Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles to direct circulating TAG to WAT for storage; conversely, fasting induces Angptl4, which inhibits LPL in WAT to direct circulating TAG to cardiac and skeletal muscles for oxidation. This model suggests a general mechanism by which TAG trafficking is coordinated by lipasin, Angptl3 and Angptl4 at different nutritional statuses. PMID:26687026

  18. A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase.

    PubMed

    Fu, Zhiyao; Abou-Samra, Abdul B; Zhang, Ren

    2015-12-21

    Lipasin/Angptl8 is a feeding-induced hepatokine that regulates triglyceride (TAG) metabolism; its therapeutical potential, mechanism of action, and relation to the lipoprotein lipase (LPL), however, remain elusive. We generated five monoclonal lipasin antibodies, among which one lowered the serum TAG level when injected into mice, and the epitope was determined to be EIQVEE. Lipasin-deficient mice exhibited elevated postprandial activity of LPL in the heart and skeletal muscle, but not in white adipose tissue (WAT), suggesting that lipasin suppresses the activity of LPL specifically in cardiac and skeletal muscles. Consistently, mice injected with the effective antibody or with lipasin deficiency had increased postprandial cardiac LPL activity and lower TAG levels only in the fed state. These results suggest that lipasin acts, at least in part, in an endocrine manner. We propose the following model: feeding induces lipasin, activating the lipasin-Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles to direct circulating TAG to WAT for storage; conversely, fasting induces Angptl4, which inhibits LPL in WAT to direct circulating TAG to cardiac and skeletal muscles for oxidation. This model suggests a general mechanism by which TAG trafficking is coordinated by lipasin, Angptl3 and Angptl4 at different nutritional statuses.

  19. Maternal undernutrition leads to elevated hepatic triglycerides in male rat offspring due to increased expression of lipoprotein lipase.

    PubMed

    Zhu, Wei-Fen; Zhu, Jian-Fang; Liang, Li; Shen, Zheng; Wang, Ying-Min

    2016-05-01

    Small for gestational age (SGA) at birth increases the risk of developing metabolic syndrome, which encompasses various symptoms including hypertriglyceridemia. The aim of the present study was to determine whether maternal undernutrition during pregnancy may lead to alterations in hepatic triglyceride content and the gene expression levels of hepatic lipoprotein lipase (LPL) in SGA male offspring. The present study focused on the male offspring in order to prevent confounding factors, such as estrus cycle and hormone profile. Female Sprague Dawley rats were arbitrarily assigned to receive an ad libitum chow diet or 50% food restricted diet from pregnancy day 1 until parturition. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to measure the gene expression levels of hepatic LPL at day 1 and upon completion of the third week of age. Chromatin immunoprecipitation quantified the binding activity of liver X receptor‑α (LXR‑α) gene to the LXR response elements (LXRE) on LPL promoter and LPL epigenetic characteristics. At 3 weeks of age, SGA male offspring exhibited significantly elevated levels of hepatic triglycerides, which was concomitant with increased expression levels of LPL. Since LPL is regulated by LXR‑α, the expression levels of LXR‑α were detected in appropriate for gestational age and SGA male offspring. Maternal undernutrition during pregnancy led to an increase in the hepatic expression levels of LXR‑α, and enriched binding to the putative LXR response elements in the LPL promoter regions in 3‑week‑old male offspring. In addition, enhanced acetylation of histone H3 [H3 lysine (K)9 and H3K14] was detected surrounding the LPL promoter. The results of the present study indicated that maternal undernutrition during pregnancy may lead to an increase in hepatic triglycerides, via alterations in the transcriptional and epigenetic regulation of the LPL gene.

  20. Plasma levels of lipoprotein-associated phospholipase A2 are increased in patients with β-thalassemia

    PubMed Central

    Tselepis, Alexandros D.; Hahalis, George; Tellis, Constantinos C.; Papavasiliou, Eleni C.; Mylona, Panagiota T.; Kourakli, Alexandra; Alexopoulos, Dimitrios C.

    2010-01-01

    Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent cardiovascular risk factor. We investigated the plasma levels of Lp-PLA2 activity and mass as a function of plasma lipid levels, LDL subclass profile, and oxidative stress in patients with β-thalassemia. Thirty-five patients with β-thalassemia major (β-TM) and 25 patients with β-thalassemia intermedia (β-TI) participated in the study. Lp-PLA2 activity and mass were measured in total plasma, in apolipoprotein (apo)B-depleted plasma (HDL-Lp-PLA2), and in LDL subclasses. Lp-PLA2 activity produced and secreted from peripheral blood monocytes in culture was also determined. Patients with β-thalassemia are characterized by a predominance of small-dense LDL particles, increased oxidative stress, and very high plasma levels of Lp-PLA2 mass and activity, despite low LDL-cholesterol levels. A significant positive correlation between plasma Lp-PLA2 activity or mass and 8-isoprostane (8-epiPGF2a) and ferritin levels as well as intima-media thickness (IMT) values was observed. An increase in secreted and cell-associated Lp-PLA2 activity from monocytes in culture was observed in both patient groups. The HDL-Lp-PLA2 activity and mass as well as the ratio of HDL-Lp-PLA2/plasma Lp-PLA2 were significantly higher in both patient groups compared with the control group. In conclusion, patients with β-thalassemia exhibit high plasma Lp-PLA2 levels, attributed to increased enzyme secretion from monocytes/macrophages and to the predominance of sdLDL particles in plasma. Plasma Lp-PLA2 is correlated with carotid IMT, suggesting that this enzyme may be implicated in premature carotid atherosclerosis observed in β-thalassemia. PMID:20625038

  1. Rapid Increase in Serum Low-Density Lipoprotein Cholesterol Concentration during Hepatitis C Interferon-Free Treatment

    PubMed Central

    Abiru, Seigo; Komori, Atsumasa; Nagaoka, Shinya; Saeki, Akira; Uchida, Shinjiro; Bekki, Shigemune; Kugiyama, Yuki; Nagata, Kazuyoshi; Nakamura, Minoru; Migita, Kiyoshi; Nakao, Kazuhiko

    2016-01-01

    Background & Aim We performed lipid analyses at the early period of therapy in patients with chronic hepatitis C who underwent interferon (IFN)-free direct-acting antiviral (DAA) treatment, and we attempted to identify the factors that contributed to a rapid increase in the patients’ serum low-density lipoprotein cholesterol (LDL-C) concentration. Methods We retrospectively analyzed the cases of 100 consecutive patients with HCV infection treated at the National Hospital Organization Nagasaki Medical Center: 24 patients underwent daclatasvir (DCV) and asunaprevir (ASV) combination therapy (DCV/ASV) for 24 weeks, and the other 76 patients underwent ledipasvir and sofosbuvir combination therapy (LDV/SOF) for 12 weeks. ΔLDL-C was defined as the changed in LDL-C level at 28 days from the start of therapy. To determine whether ΔLDL-C was associated with several kinds of factors including viral kinetics, we performed a stepwise multiple linear regression analysis. Results The LDL-C levels in patients treated with LDV/SOF were markedly and significantly elevated (87.45 to 122.5 mg/dl; p<10−10) compared to those in the DCV/ASV-treated patients (80.15 to 87.8 mg/dl; p = 0.0056). The median levels of ΔLDL-C in the LDV/SOF and DCV/ASV groups were 33.2 and 13.1, respectively. LDV/SOF combination therapy as an IFN-free regimen (p<0.001) and ΔHCV core antigen (0–1 day drop) (p<0.044) were identified as independent factors that were closely related to the ΔLDL-C. Conclusions A rapid increase in the serum LDL-C concentration during the IFN-free treatment of hepatitis C was associated with the type of HCV therapy and a decline of HCV core protein. PMID:27680885

  2. Trans-Ethnic Fine-Mapping of Lipid Loci Identifies Population-Specific Signals and Allelic Heterogeneity That Increases the Trait Variance Explained

    PubMed Central

    Wu, Ying; Waite, Lindsay L.; Jackson, Anne U.; Sheu, Wayne H-H.; Buyske, Steven; Absher, Devin; Arnett, Donna K.; Boerwinkle, Eric; Bonnycastle, Lori L.; Carty, Cara L.; Cheng, Iona; Cochran, Barbara; Croteau-Chonka, Damien C.; Dumitrescu, Logan; Eaton, Charles B.; Franceschini, Nora; Guo, Xiuqing; Henderson, Brian E.; Hindorff, Lucia A.; Kim, Eric; Kinnunen, Leena; Komulainen, Pirjo; Lee, Wen-Jane; Le Marchand, Loic; Lin, Yi; Lindström, Jaana; Lingaas-Holmen, Oddgeir; Mitchell, Sabrina L.; Narisu, Narisu; Robinson, Jennifer G.; Schumacher, Fred; Stančáková, Alena; Sundvall, Jouko; Sung, Yun-Ju; Swift, Amy J.; Wang, Wen-Chang; Wilkens, Lynne; Wilsgaard, Tom; Young, Alicia M.; Adair, Linda S.; Ballantyne, Christie M.; Bůžková, Petra; Chakravarti, Aravinda; Collins, Francis S.; Duggan, David; Feranil, Alan B.; Ho, Low-Tone; Hung, Yi-Jen; Hunt, Steven C.; Hveem, Kristian; Juang, Jyh-Ming J.; Kesäniemi, Antero Y.; Kuusisto, Johanna; Laakso, Markku; Lakka, Timo A.; Lee, I-Te; Leppert, Mark F.; Matise, Tara C.; Moilanen, Leena; Njølstad, Inger; Peters, Ulrike; Quertermous, Thomas; Rauramaa, Rainer; Rotter, Jerome I.; Saramies, Jouko; Tuomilehto, Jaakko; Uusitupa, Matti; Wang, Tzung-Dau; Mohlke, Karen L.

    2013-01-01

    Genome-wide association studies (GWAS) have identified ∼100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1×10−4 in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies. PMID:23555291

  3. Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained.

    PubMed

    Wu, Ying; Waite, Lindsay L; Jackson, Anne U; Sheu, Wayne H-H; Buyske, Steven; Absher, Devin; Arnett, Donna K; Boerwinkle, Eric; Bonnycastle, Lori L; Carty, Cara L; Cheng, Iona; Cochran, Barbara; Croteau-Chonka, Damien C; Dumitrescu, Logan; Eaton, Charles B; Franceschini, Nora; Guo, Xiuqing; Henderson, Brian E; Hindorff, Lucia A; Kim, Eric; Kinnunen, Leena; Komulainen, Pirjo; Lee, Wen-Jane; Le Marchand, Loic; Lin, Yi; Lindström, Jaana; Lingaas-Holmen, Oddgeir; Mitchell, Sabrina L; Narisu, Narisu; Robinson, Jennifer G; Schumacher, Fred; Stančáková, Alena; Sundvall, Jouko; Sung, Yun-Ju; Swift, Amy J; Wang, Wen-Chang; Wilkens, Lynne; Wilsgaard, Tom; Young, Alicia M; Adair, Linda S; Ballantyne, Christie M; Bůžková, Petra; Chakravarti, Aravinda; Collins, Francis S; Duggan, David; Feranil, Alan B; Ho, Low-Tone; Hung, Yi-Jen; Hunt, Steven C; Hveem, Kristian; Juang, Jyh-Ming J; Kesäniemi, Antero Y; Kuusisto, Johanna; Laakso, Markku; Lakka, Timo A; Lee, I-Te; Leppert, Mark F; Matise, Tara C; Moilanen, Leena; Njølstad, Inger; Peters, Ulrike; Quertermous, Thomas; Rauramaa, Rainer; Rotter, Jerome I; Saramies, Jouko; Tuomilehto, Jaakko; Uusitupa, Matti; Wang, Tzung-Dau; Boehnke, Michael; Haiman, Christopher A; Chen, Yii-Der I; Kooperberg, Charles; Assimes, Themistocles L; Crawford, Dana C; Hsiung, Chao A; North, Kari E; Mohlke, Karen L

    2013-03-01

    Genome-wide association studies (GWAS) have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1 × 10(-4) in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies.

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

    PubMed Central

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

    2012-01-01

    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 < 0.05) by approximately sevenfold in response to 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 < 0.04), 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 < 0.001). We conclude that testosterone is a potent skeletal muscle protein anabolic agent, but not an important regulator of plasma lipid homeostasis in obese women. PMID:22252942

  5. Dietary cholesterol affects plasma lipid levels, the intravascular processing of lipoproteins and reverse cholesterol transport without increasing the risk for heart disease.

    PubMed

    Barona, Jacqueline; Fernandez, Maria Luz

    2012-08-01

    The associations between dietary cholesterol and heart disease are highly controversial. While epidemiological studies and clinical interventions have shown the lack of correlation between cholesterol intake and cardiovascular disease (CVD) risk, there is still concern among health practitioners and the general population regarding dietary cholesterol. In this review, several clinical studies utilizing cholesterol challenges are analyzed in terms of changes that occur in lipoprotein metabolism resulting from excess consumption of cholesterol. Dietary cholesterol has been shown to increase both LDL and HDL in those individuals who respond to a cholesterol challenge without altering the LDL cholesterol/HDL cholesterol ratio, a key marker of CVD risk. Further, dietary cholesterol has been shown to increase only HDL with no changes in LDL with average cholesterol consumption and during weight loss interventions. Ingestion of cholesterol has also been shown to increase the size of both LDL and HDL particles with the associated implications of a less atherogenic LDL particle as well as more functional HDL in reverse cholesterol transport. Other changes observed in lipoprotein metabolism are a greater number of large LDL and decreases in small LDL subfractions. All this information put together points to specific roles of dietary cholesterol in substantially altering intravascular processing of lipoproteins as well as reverse cholesterol transport.

  6. Dietary Cholesterol Affects Plasma Lipid Levels, the Intravascular Processing of Lipoproteins and Reverse Cholesterol Transport without Increasing the Risk for Heart Disease

    PubMed Central

    Barona, Jacqueline; Fernandez, Maria Luz

    2012-01-01

    The associations between dietary cholesterol and heart disease are highly controversial. While epidemiological studies and clinical interventions have shown the lack of correlation between cholesterol intake and cardiovascular disease (CVD) risk, there is still concern among health practitioners and the general population regarding dietary cholesterol. In this review, several clinical studies utilizing cholesterol challenges are analyzed in terms of changes that occur in lipoprotein metabolism resulting from excess consumption of cholesterol. Dietary cholesterol has been shown to increase both LDL and HDL in those individuals who respond to a cholesterol challenge without altering the LDL cholesterol/HDL cholesterol ratio, a key marker of CVD risk. Further, dietary cholesterol has been shown to increase only HDL with no changes in LDL with average cholesterol consumption and during weight loss interventions. Ingestion of cholesterol has also been shown to increase the size of both LDL and HDL particles with the associated implications of a less atherogenic LDL particle as well as more functional HDL in reverse cholesterol transport. Other changes observed in lipoprotein metabolism are a greater number of large LDL and decreases in small LDL subfractions. All this information put together points to specific roles of dietary cholesterol in substantially altering intravascular processing of lipoproteins as well as reverse cholesterol transport. PMID:23016129

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

    PubMed

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

    2013-12-01

    We hypothesized that dietary monounsaturated fatty acids (MUFA) and exercise increase high-density lipoprotein cholesterol (HDL-C) by independent mechanisms, so there would be additive effects between a single, intensive session of exercise and high-MUFA ground beef on HDL-C and blood risk factors for cardiovascular disease. Seventeen postmenopausal women completed a 2-way crossover design in which they consumed five 114-g ground beef patties per week for two 6-week periods separated by a 4-week washout (habitual diet) period. The ground beef patties contained 21% total fat with either 9.97 (low-MUFA) or 12.72 (high-MUFA) g total MUFA. Blood was taken at entry, at the end of each 6-week diet period, after the 4-week washout period, and 24 hours after aerobic exercise sessions (75% VO₂peak, 2.07 MJ). After the ground beef intervention, the high-MUFA ground beef increased plasma palmitoleic acid and oleic acid, low-density lipoprotein (LDL) particle density, HDL-C, and HDL2b-C (all P < .05), whereas the low-MUFA ground beef increased LDL density. After the washout (habitual diet) period, the single exercise session increased serum LDL cholesterol, HDL-C, and HDL2a and decreased TAG and oleic acid. After the low-MUFA ground beef diet, exercise increased LDL size and HDL density and decreased LDL density and very low-density lipoprotein cholesterol, but had no effect on HDL-C fractions. After the high-MUFA ground beef intervention, exercise decreased palmitioleic acid, oleic acid, HDL-C, and HDL2a-C, but not HDL2b-C. Contrary to our hypothesis, the effects of exercise and a high-MUFA diet were not additive; instead, exercise attenuated the effects of the high-MUFA ground beef on HDL-C and plasma MUFAs. The differential effects of high-MUFA ground beef and exercise on HDL2a-C and HDL2b-C indicate that diet and exercise affect HDL-C by different mechanisms.

  8. Electronegative Low-Density Lipoprotein Increases C-Reactive Protein Expression in Vascular Endothelial Cells through the LOX-1 Receptor

    PubMed Central

    Chu, Chih-Sheng; Wang, Yu-Chen; Lu, Long-Sheng; Walton, Brian; Yilmaz, H. Ramazan; Huang, Roger Y.; Sawamura, Tatsuya; Dixon, Richard A. F.; Lai, Wen-Ter; Chen, Chu-Huang; Lu, Jonathan

    2013-01-01

    Objectives Increased plasma C-reactive protein (CRP) levels are associated with the occurrence and severity of acute coronary syndrome. We investigated whether CRP can be generated in vascular endothelial cells (ECs) after exposure to the most electronegative subfraction of low-density lipoprotein (LDL), L5, which is atherogenic to ECs. Because L5 and CRP are both ligands for the lectin-like oxidized LDL receptor-1 (LOX-1), we also examined the role of LOX-1. Methods and Results Plasma LDL samples isolated from asymptomatic hypercholesterolemic (LDL cholesterol [LDL-C] levels, 154.6±20 mg/dL; n = 7) patients and normocholesterolemic (LDL-C levels, 86.1±21 mg/dL; P<0.001; n = 7) control individuals were chromatographically resolved into 5 subfractions, L1-L5. The L5 percentage (L5%) and the plasma L5 concentration ([L5]  =  L5% × LDL-C) in the patient and control groups were 8.1±2% vs. 2.3±1% (P<0.001) and 12.6±4 mg/dL vs. 1.9±1 mg/dL (P<0.001), respectively. In hypercholesterolemic patients treated with atorvastatin for 6 months (10 mg/day), [L5] decreased from 12.6±4 mg/dL to 4.5±1.1 mg/dL (P = 0.011; n = 5), whereas both [L5] and L5% returned to baseline levels in 2 noncompliant patients 3 months after discontinuation. In cultured human aortic ECs (HAECs), L5 upregulated CRP expression in a dose- and time-dependent manner up to 2.5-fold (P<0.01), whereas the least electronegative subfraction, L1, had no effect. DiI-labeled L1, internalized through the LDL receptor, became visible inside HAECs within 30 seconds. In contrast, DiI-labeled L5, internalized through LOX-1, became apparent after 5 minutes. L5-induced CRP expression manifested at 30 minutes and was attenuated by neutralizing LOX-1. After 30 minutes, L5 but not L1 induced reactive oxygen species (ROS) production. Both L5-induced ROS and CRP production were attenuated by ROS inhibitor N-acetyl cysteine. Conclusions Our results suggest that CRP, L5, and LOX-1 form a cyclic

  9. Lipoprotein-specific transport of circulating lipid peroxides.

    PubMed

    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.

  10. Warming-related increases in soil CO2 efflux are explained by increased below-ground carbon flux

    Treesearch

    Christian P. Giardina; Creighton M. Litton; Susan E. Crow; Gregory P Asner

    2014-01-01

    The universally observed exponential increase in soil-surface CO2 effux (‘soil respiration’; FS) with increasing temperature has led to speculation that global warming will accelerate soil organic carbon (SOC) decomposition, reduce SOC storage, and drive a positive feedback to future warming. However, interpreting temperature–FS relationships,...

  11. Lipoprotein metabolism and CKD: overview.

    PubMed

    Barter, Philip

    2014-04-01

    Patients with chronic kidney disease (CKD) frequently display abnormalities of plasma lipids and lipoproteins. These abnormalities include hypertriglyceridemia associated with elevated levels of very low-density lipoproteins (VLDLs) and chylomicrons. There is often also an increase in the concentration of the atherogenic, cholesterol-enriched remnants of VLDLs and chylomicrons. The concentration of low-density lipoprotein cholesterol is usually normal, but there is frequently a decrease in concentration of the cardio-protective high-density lipoproteins. There is also often an increase in the concentration of the atherogenic lipoprotein (a) particles. This article provides an overview of plasma lipoprotein transport and identifies mechanisms responsible for the abnormalities observed in patients with CKD.

  12. Increases in oxidized low-density lipoprotein and other inflammatory and adhesion molecules with a concomitant decrease in high-density lipoprotein in the individuals exposed to arsenic in Bangladesh.

    PubMed

    Karim, Md Rezaul; Rahman, Mashiur; Islam, Khairul; Mamun, Abdullah Al; Hossain, Shakhawoat; Hossain, Ekhtear; Aziz, Abdul; Yeasmin, Fouzia; Agarwal, Smita; Hossain, Md Imam; Saud, Zahangir Alam; Nikkon, Farjana; Hossain, Mostaque; Mandal, Abul; Jenkins, Richard O; Haris, Parvez I; Miyataka, Hideki; Himeno, Seiichiro; Hossain, Khaled

    2013-09-01

    Elevated exposure to arsenic has been suggested to be associated with atherosclerosis leading to cardiovascular disease (CVD). However, biochemical events underlying the arsenic-induced atherosclerosis have not yet been fully documented. The aim of this study was to investigate the associations of circulating molecules involved in atherosclerosis with arsenic exposure in the individuals exposed to arsenic in Bangladesh. A total of 324 study subjects, 218 from arsenic-endemic areas and 106 from nonendemic areas in Bangladesh, were recruited. Drinking water, hair, nail, and blood samples were collected from the study subjects for analysis. Total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels were lower in arsenic-endemic subjects than those of nonendemic subjects. Oxidized LDL (Ox-LDL), C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) levels were significantly higher in arsenic-endemic subjects than those in nonendemic subjects. All these circulating molecules showed significant correlations with arsenic exposure (water, hair, and nail arsenic concentrations), and all these relations were significant before and after adjusting for relevant covariates. Among the circulating molecules tested in this study, HDL, Ox-LDL, and CRP showed dose-response relationships with arsenic exposure. Ox-LDL/HDL ratios were increased with the increasing concentrations of arsenic in the water, hair, and nails. Furthermore, non-HDL cholesterol and TC/HDL ratios were significantly correlated with arsenic exposure before and after adjusting for relevant covariates. Thus, all the observed associations may be the major features of arsenic exposure-related atherosclerosis leading to CVD.

  13. Small high-density lipoprotein (HDL) subclasses are increased with decreased activity of HDL-associated phospholipase A₂ in subjects with prediabetes.

    PubMed

    Filippatos, Theodosios D; Rizos, Evangelos C; Tsimihodimos, Vasilios; Gazi, Irene F; Tselepis, Alexandros D; Elisaf, Moses S

    2013-06-01

    Alterations in high-density lipoprotein (HDL) subclass distribution, as well as in the activities of HDL-associated enzymes, have been associated with increased cardiovascular disease (CVD) risk. HDL subclass distribution and the activities of HDL-associated enzymes remain unknown in prediabetic patients, a condition also associated with increased CVD risk. The aim of the present study was to assess any differences in HDL subclass distribution (using polyacrylamide gel electrophoresis) and in activities of HDL-associated enzymes between prediabetic (impaired fasting glucose, IFG, n = 80) and non-prediabetic subjects (n = 105). Subjects with prediabetes had significantly increased waist circumference, blood pressure and triacylglycerol (TAG) levels compared with subjects with fasting glucose levels <100 mg/dL (all p < 0.05). The proportion of small HDL3 over HDL cholesterol (HDL-C) was significantly increased in prediabetic subjects compared with their controls (p < 0.05). The activity of the anti-atherogenic HDL-associated lipoprotein-associated phospholipase A₂ (HDL-LpPLA₂) was significantly lower in subjects with prediabetes (p < 0.05), whereas the activity of paraoxonase 1 (using both paraoxon and phenyl acetate as substrates) did not significantly differ between subjects with or without prediabetes. In a stepwise linear regression analysis, the proportion of small HDL3 over HDL-C concentration was independently associated with the presence of prediabetes and with total cholesterol and TAG concentration (positively), as well as with HDL-C levels (negatively). We also observed a trend of increased small dense low-density lipoprotein cholesterol levels in prediabetic subjects compared with their controls. Subjects with IFG exhibit increased proportion of small HDL3 particles combined with decreased activity of the anti-atherogenic HDL-LpPLA₂.

  14. Brazil nut ingestion increased plasma selenium but had minimal effects on lipids, apolipoproteins, and high-density lipoprotein function in human subjects.

    PubMed

    Strunz, Célia C; Oliveira, Tatiane V; Vinagre, Juliana C M; Lima, Adriana; Cozzolino, Silvia; Maranhão, Raul C

    2008-03-01

    The Brazil nut (Bertholletia excelsa) of the Amazon region is consumed worldwide. It is rich in both monounsaturated fatty acids and polyunsaturated fatty acids and is known for its high selenium content. This study tested the hypothesis whether the consumption of this nut could affect the plasma lipids and apolipoproteins and some functional properties of the antiatherogenic high-density lipoprotein (HDL). Fifteen normolipidemic subjects aged 27.3 +/- 3.9 years and with body mass index of 23.8 +/- 2.8 kg/m(2) consumed 45 g of Brazil nuts per day during a 15-day period. On days 0 and 15, blood was collected for biochemical analysis, determination of HDL particle size, paraoxonase 1 activity, and lipid transfer from a lipoprotein-like nanoparticle to the HDL fraction. Brazil nut ingestion did not alter HDL, low-density lipoprotein cholesterol, triacylglycerols, apolipoprotein A-I, or apolipoprotein B concentrations. HDL particle diameter and the activity of antioxidative paraoxonase 1, mostly found in the HDL fraction, were also unaffected. Supplementation increased the reception of cholesteryl esters (P < .05) by the HDL yet did not alter the reception of phospholipids, free cholesterol, or triacylglycerols. As expected, plasma selenium was significantly increased. However, the consumption of Brazil nuts for short duration by normolipidemic subjects in comparable amounts to those tested for other nuts did not alter serum lipid profile. The only alteration in HDL function was the increase in cholesteryl ester transfer. This latter finding may be beneficial because it would improve the nonatherogenic reverse cholesterol transport pathway.

  15. [Deprivation versus importation: a model explaining the increase of suicide rates in custody].

    PubMed

    Frottier, P; Frühwald, S; Ritter, K; König, F

    2001-02-01

    High suicide rates in jail, lock-up or prison settings have given rise to a debate about whether suicides result chiefly from the type of people confined, or from the types of places they are confined in, the types of confinement. This is summarily framed by the terms of an associated debate in criminology, between importation and deprivation theory. This paper describes the importation versus deprivation theory, concerning the circumstances in Austrian prisons and jails. The article reports on all completed suicides over the period from 1947 to 1999 (n = 410). The increase of suicide rates in Austrian jails and prisons is significant over the last fifty years. While the rate was stable between 1947 and 1975, we have a significantly increasing rate since 1975. In 1975 there was an important legislational reform of the criminal law in Austria. The implications of this reform are discussed in the light of the importation/deprivation theory.

  16. Symptoms of notalgia paresthetica may be explained by increased dermal innervation.

    PubMed

    Springall, D R; Karanth, S S; Kirkham, N; Darley, C R; Polak, J M

    1991-09-01

    Notalgia paresthetica is a sensory neuropathy characterized by infrascapular pruritus, burning pain, hyperalgesia, or tenderness. To assess whether the symptoms may be caused by alterations in the cutaneous innervation, skin from the affected area of patients (n = 5) was compared with controls (n = 10) comprising the contralateral unaffected area from the same patients and site-matched biopsies of normals, using immunohistochemistry. Frozen sections were immunostained with antisera to the neuropeptides substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, and neuropeptide with tyrosine, and to the general neural marker PGP 9.5 and the glial marker S-100 to show the overall innervation and glial cells, respectively. No discernible change in the distribution of neuropeptide-immunoreactive axons was found, but all of the specimens from the affected areas had a significant increase in the number of intradermal PGP 9.5-immunoreactive nerve fibers compared with unaffected areas from the same patients and normal controls. Epidermal dendritic cells immunoreactive for S-100, possibly Langerhans cells, were substantially increased. It is concluded that there is an increase in the sensory epidermal innervation in the affected skin areas in notalgia paresthetica, which could contribute to the symptoms, and that neural immunohistochemistry of skin biopsies could be helpful in the diagnosis of the disease.

  17. Do historical changes in parent-child relationships explain increases in youth conduct problems?

    PubMed

    Collishaw, Stephan; Gardner, Frances; Maughan, Barbara; Scott, Jacqueline; Pickles, Andrew

    2012-01-01

    The coincidence of historical trends in youth antisocial behavior and change in family demographics has led to speculation of a causal link, possibly mediated by declining quality of parenting and parent-child relationships. No study to date has directly assessed whether and how parenting and parent-child relationships have changed. Two national samples of English adolescents aged 16-17 years in 1986 (N = 4,524 adolescents, 7,120 parents) and 2006 (N = 716 adolescents, 734 parents) were compared using identical questionnaire assessments. Youth-reported parental monitoring, expectations, and parent-child quality time increased between 1986 and 2006. Ratings of parental interest did not change. Parenting differences between affluent and disadvantaged families narrowed over time. There was thus little evidence of a decline in quality of parenting for the population as a whole or for disadvantaged subgroups. Parent-reported youth conduct problems showed a modest increase between 1986 and 2006. Findings suggested that the increase in youth conduct problems was largely unrelated to observed change in parent-child relationships.

  18. A Minimalistic Resource Allocation Model to Explain Ubiquitous Increase in Protein Expression with Growth Rate

    PubMed Central

    Keren, Leeat; Segal, Eran; Milo, Ron

    2016-01-01

    Most proteins show changes in level across growth conditions. Many of these changes seem to be coordinated with the specific growth rate rather than the growth environment or the protein function. Although cellular growth rates, gene expression levels and gene regulation have been at the center of biological research for decades, there are only a few models giving a base line prediction of the dependence of the proteome fraction occupied by a gene with the specific growth rate. We present a simple model that predicts a widely coordinated increase in the fraction of many proteins out of the proteome, proportionally with the growth rate. The model reveals how passive redistribution of resources, due to active regulation of only a few proteins, can have proteome wide effects that are quantitatively predictable. Our model provides a potential explanation for why and how such a coordinated response of a large fraction of the proteome to the specific growth rate arises under different environmental conditions. The simplicity of our model can also be useful by serving as a baseline null hypothesis in the search for active regulation. We exemplify the usage of the model by analyzing the relationship between growth rate and proteome composition for the model microorganism E.coli as reflected in recent proteomics data sets spanning various growth conditions. We find that the fraction out of the proteome of a large number of proteins, and from different cellular processes, increases proportionally with the growth rate. Notably, ribosomal proteins, which have been previously reported to increase in fraction with growth rate, are only a small part of this group of proteins. We suggest that, although the fractions of many proteins change with the growth rate, such changes may be partially driven by a global effect, not necessarily requiring specific cellular control mechanisms. PMID:27073913

  19. Liquid films on shake flask walls explain increasing maximum oxygen transfer capacities with elevating viscosity.

    PubMed

    Giese, Heiner; Azizan, Amizon; Kümmel, Anne; Liao, Anping; Peter, Cyril P; Fonseca, João A; Hermann, Robert; Duarte, Tiago M; Büchs, Jochen

    2014-02-01

    In biotechnological screening and production, oxygen supply is a crucial parameter. Even though oxygen transfer is well documented for viscous cultivations in stirred tanks, little is known about the gas/liquid oxygen transfer in shake flask cultures that become increasingly viscous during cultivation. Especially the oxygen transfer into the liquid film, adhering on the shake flask wall, has not yet been described for such cultivations. In this study, the oxygen transfer of chemical and microbial model experiments was measured and the suitability of the widely applied film theory of Higbie was studied. With numerical simulations of Fick's law of diffusion, it was demonstrated that Higbie's film theory does not apply for cultivations which occur at viscosities up to 10 mPa s. For the first time, it was experimentally shown that the maximum oxygen transfer capacity OTRmax increases in shake flasks when viscosity is increased from 1 to 10 mPa s, leading to an improved oxygen supply for microorganisms. Additionally, the OTRmax does not significantly undermatch the OTRmax at waterlike viscosities, even at elevated viscosities of up to 80 mPa s. In this range, a shake flask is a somehow self-regulating system with respect to oxygen supply. This is in contrary to stirred tanks, where the oxygen supply is steadily reduced to only 5% at 80 mPa s. Since, the liquid film formation at shake flask walls inherently promotes the oxygen supply at moderate and at elevated viscosities, these results have significant implications for scale-up. © 2013 Wiley Periodicals, Inc.

  20. A Minimalistic Resource Allocation Model to Explain Ubiquitous Increase in Protein Expression with Growth Rate.

    PubMed

    Barenholz, Uri; Keren, Leeat; Segal, Eran; Milo, Ron

    2016-01-01

    Most proteins show changes in level across growth conditions. Many of these changes seem to be coordinated with the specific growth rate rather than the growth environment or the protein function. Although cellular growth rates, gene expression levels and gene regulation have been at the center of biological research for decades, there are only a few models giving a base line prediction of the dependence of the proteome fraction occupied by a gene with the specific growth rate. We present a simple model that predicts a widely coordinated increase in the fraction of many proteins out of the proteome, proportionally with the growth rate. The model reveals how passive redistribution of resources, due to active regulation of only a few proteins, can have proteome wide effects that are quantitatively predictable. Our model provides a potential explanation for why and how such a coordinated response of a large fraction of the proteome to the specific growth rate arises under different environmental conditions. The simplicity of our model can also be useful by serving as a baseline null hypothesis in the search for active regulation. We exemplify the usage of the model by analyzing the relationship between growth rate and proteome composition for the model microorganism E.coli as reflected in recent proteomics data sets spanning various growth conditions. We find that the fraction out of the proteome of a large number of proteins, and from different cellular processes, increases proportionally with the growth rate. Notably, ribosomal proteins, which have been previously reported to increase in fraction with growth rate, are only a small part of this group of proteins. We suggest that, although the fractions of many proteins change with the growth rate, such changes may be partially driven by a global effect, not necessarily requiring specific cellular control mechanisms.

  1. Increased tissue oxygenation explains the attenuation of hyperaemia upon repetitive pneumatic compression of the lower leg.

    PubMed

    Messere, Alessandro; Ceravolo, Gianluca; Franco, Walter; Maffiodo, Daniela; Ferraresi, Carlo; Roatta, Silvestro

    2017-08-17

    Aim The rapid hyperaemia evoked by muscle compression is short-lived and was recently shown to undergo a rapid decrease even in spite of continuing mechanical stimulation. The present study aims at investigating the mechanisms underlying this attenuation which include local metabolic mechanisms, desensitization of mechano-sensitive pathways, and reduced efficacy of the muscle pump. Methods In 10 healthy subjects short sequences of mechanical compressions (n=3-6; 150 mmHg) of the lower leg were delivered at different inter-stimulus intervals (ranging from 20 to 160 s) through a customized pneumatic device. Hemodynamic monitoring included near infrared spectroscopy, detecting tissue oxygenation and blood volume in calf muscles, as well as simultaneous echo-Doppler measurement of arterial (superficial femoral artery) and venous (femoral vein) blood flow. Results The results indicate that: i) a long lasting (>100 s) increase in local tissue oxygenation follows the compression-induced hyperaemia ; ii) the compression-induced hyperaemia exhibits different patterns of attenuation depending on the inter-stimulus interval; iii) the amplitude of the hyperaemia is not correlated with the amount of blood volume displaced by the compression; iv) the extent of attenuation negatively correlates with tissue oxygenation (r=-0,78, P<0.05). Conclusion Increased tissue oxygenation appears to be the key factor for the attenuation of hyperaemia upon repetitive compressive stimulation. Tissue oxygenation monitoring is suggested as a useful integration in medical treatments aimed at improving local circulation by repetitive tissue compression. Copyright © 2017, Journal of Applied Physiology.

  2. Behavioral correlations provide a mechanism for explaining high invader densities and increased impacts on native prey.

    PubMed

    Pintor, Lauren M; Sih, Andrew; Kerby, Jacob L

    2009-03-01

    The fact that superabundant invasive pests are also sometimes highly aggressive represents an interesting paradox. Strong intraspecific aggression should result in high intraspecific competition and limit the densities reached by exotic species. One mechanism that can allow invaders to attain high densities despite high intraspecific aggression, involves positive correlations between aggression and other behaviors such as foraging activity. We conducted a mesocosm experiment to quantify the ecological implications of correlations between aggressiveness and foraging activity among groups of exotic signal crayfish (Pacifastacus leniusculus) at low and high densities. Our results showed that high invader densities increased intraspecific aggression and per capita interactions between crayfish, but also increased foraging activity and impacts on preferred prey. As a result, exotic crayfish did not show density-dependent reductions in per capita feeding or growth rates. We suggest that the positive correlation between aggression and activity is part of an aggression syndrome whereby some individuals are generally more aggressive/active than others across situations. An aggression syndrome can couple aggressive behaviors important to population establishment of invasive species with foraging activity that enhances the ability of invaders to attain high densities and have large impacts on invaded communities.

  3. Expectations of increased and decreased pain explain the effect of conditioned pain modulation in females

    PubMed Central

    Bjørkedal, Espen; Flaten, Magne Arve

    2012-01-01

    Objective Chronic pain is believed to be related to a dysfunction of descending pain modulatory mechanisms. Functioning of descending pain modulation can be assessed by various methods, including conditioned pain modulation (CPM). CPM refers to the inhibition of one source of pain by a second noxious stimulus, termed the conditioning stimulus. This procedure can activate an endogenous pain inhibitory mechanism that inhibits early nociceptive processing. Chronic pain and anxiety disorders are more prevalent among females and it has been hypothesized that females react with more negative emotions towards unpleasant stimuli and this might be part of the explanation of greater pain sensitivity in females. The present study investigated whether expectations modulate the effect of conditioning stimulation on pain, subjective stress, and heart rate. In addition, we investigated whether the modulation of CPM by expectations differed between males and females. Methods Seventy-two subjects (including 36 women) received six noxious heat stimuli to the forearm. During three of these stimuli, a conditioning stimulus (cold-water bath) was applied to the contralateral arm in order to activate CPM. One third of the subjects were told that this would reduce pain (analgesia group), one-third that it would increase pain (hyperalgesia group), and one third received no information about its effect (no info group). Results Information that conditioning stimulation decreased or enhanced pain had the corresponding effect in females, but not in males. Conditioning stimulation increased stress, but not heart rate in females in the hyperalgesia group. A higher expectation of analgesia and lower stress during conditioning stimulation was associated with larger inhibitory CPM. Conclusion These results suggest that reduced inhibitory CPM can be due to contextually induced cognitive and emotional factors and not necessarily a dysfunction of descending inhibitory pathways. PMID:23049277

  4. Pulmonary abnormalities after cardiac surgery are better explained by atelectasis than by increased permeability oedema.

    PubMed

    Verheij, J; van Lingen, A; Raijmakers, P G H M; Spijkstra, J-J; Girbes, A R J; Jansen, E K; van den Berg, F G; Groeneveld, A B J

    2005-10-01

    Cardiac surgery can be complicated by pulmonary abnormalities, but it is unclear how various manifestations interrelate. A prospective study in the intensive care unit was performed on 26 mechanically ventilated patients without cardiac failure within 3 h after elective cardiac surgery involving cardiopulmonary bypass. Oedema (extravascular lung water, EVLW) was measured by the thermal-dye technique and permeability by a dual radionuclide technique, yielding a pulmonary leak index (PLI). Radiographic, mechanical and gas exchange features were used to calculate the lung injury score (LIS), ranging between 0 and 4. Evidence for left lower lobe atelectasis was obtained from plain radiographs. The plasma colloid osmotic pressure (COP) was measured by an oncometer. The EVLW (normal, <7 ml/kg) was elevated in 36% of patients and the PLI (normal, <14.1 x 10(-3)/min) in 44%, but the variables did not interrelate directly. Patients with a supranormal EVLW had a lower COP than patients with normal EVLW. The duration of mechanical ventilation was prolonged in patients (20%) with EVLW > 10 ml/kg. There was no difference in EVLW and PLI in patients with LIS < 1 and LIS > 1 (31% of patients). In patients with radiographic evidence for atelectasis (46%), the positive end-expiratory pressure and inspiratory O2 fraction to maintain oxygenation were higher than in those without. After cardiac surgery, mild pulmonary oedema is relatively common, even in the absence of high filling pressures, and is mainly attributable to a low COP, irrespective of increased permeability in about one-half of patients. It may prolong mechanical ventilation at EVLW > 10 ml/kg. However, pulmonary radiographic and ventilatory abnormalities may result, at least in part, from atelectasis rather than increased permeability oedema.

  5. Increased inflammation in sanctuary sites may explain viral blips in HIV infection

    DOE PAGES

    Piovoso, Michael J.; Cardozo, E. Fabian; Zurakowski, Ryan

    2016-08-01

    Here, combined antiretroviral therapy (cART) suppress HIV-1 viral replication, such that viral load in plasma remains below the limit of detection in standard assays. However, intermittent episodes of transient viremia (blips) occur in a set of HIV-patients. Given that follicular hyperplasia occurs during lymphoid inflammation as a normal response to infection, it is hypothesised that when the diameter of the lymph node follicle (LNF) increases and crosses a critical size, a viral blip occurs due to cryptic viremia. To study this hypothesis, a theoretical analysis of a mathematical model is performed to find the conditions for virus suppression in allmore » compartments and different scenarios of LNF size changes are simulated. According to the analysis, blips with duration of around 30 days arise when the diameter rise rate is between 0.02 and 0.03 days–1. Moreover, the final diameter of the site is directly related to the steady states of the virus load after the occurrence of a blip. When the value of R0 is around 2.1, to have a steady-state below the limit of detection after the viral blip, the maximum final diameters should be greater than 0.7 mm so that there is a relative loss of connection between compartments.« less

  6. Increased inflammation in sanctuary sites may explain viral blips in HIV infection

    SciTech Connect

    Piovoso, Michael J.; Cardozo, E. Fabian; Zurakowski, Ryan

    2016-08-01

    Here, combined antiretroviral therapy (cART) suppress HIV-1 viral replication, such that viral load in plasma remains below the limit of detection in standard assays. However, intermittent episodes of transient viremia (blips) occur in a set of HIV-patients. Given that follicular hyperplasia occurs during lymphoid inflammation as a normal response to infection, it is hypothesised that when the diameter of the lymph node follicle (LNF) increases and crosses a critical size, a viral blip occurs due to cryptic viremia. To study this hypothesis, a theoretical analysis of a mathematical model is performed to find the conditions for virus suppression in all compartments and different scenarios of LNF size changes are simulated. According to the analysis, blips with duration of around 30 days arise when the diameter rise rate is between 0.02 and 0.03 days–1. Moreover, the final diameter of the site is directly related to the steady states of the virus load after the occurrence of a blip. When the value of R0 is around 2.1, to have a steady-state below the limit of detection after the viral blip, the maximum final diameters should be greater than 0.7 mm so that there is a relative loss of connection between compartments.

  7. Increased inflammation in sanctuary sites may explain viral blips in HIV infection

    SciTech Connect

    Piovoso, Michael J.; Cardozo, E. Fabian; Zurakowski, Ryan

    2016-08-01

    Here, combined antiretroviral therapy (cART) suppress HIV-1 viral replication, such that viral load in plasma remains below the limit of detection in standard assays. However, intermittent episodes of transient viremia (blips) occur in a set of HIV-patients. Given that follicular hyperplasia occurs during lymphoid inflammation as a normal response to infection, it is hypothesised that when the diameter of the lymph node follicle (LNF) increases and crosses a critical size, a viral blip occurs due to cryptic viremia. To study this hypothesis, a theoretical analysis of a mathematical model is performed to find the conditions for virus suppression in all compartments and different scenarios of LNF size changes are simulated. According to the analysis, blips with duration of around 30 days arise when the diameter rise rate is between 0.02 and 0.03 days–1. Moreover, the final diameter of the site is directly related to the steady states of the virus load after the occurrence of a blip. When the value of R0 is around 2.1, to have a steady-state below the limit of detection after the viral blip, the maximum final diameters should be greater than 0.7 mm so that there is a relative loss of connection between compartments.

  8. Increased inflammation in sanctuary sites may explain viral blips in HIV infection.

    PubMed

    Cardozo, E Fabian; Piovoso, Michael J; Zurakowski, Ryan

    2016-08-01

    Combined antiretroviral therapy (cART) suppress HIV-1 viral replication, such that viral load in plasma remains below the limit of detection in standard assays. However, intermittent episodes of transient viremia (blips) occur in a set of HIV-patients. Given that follicular hyperplasia occurs during lymphoid inflammation as a normal response to infection, it is hypothesised that when the diameter of the lymph node follicle (LNF) increases and crosses a critical size, a viral blip occurs due to cryptic viremia. To study this hypothesis, a theoretical analysis of a mathematical model is performed to find the conditions for virus suppression in all compartments and different scenarios of LNF size changes are simulated. According to the analysis, blips with duration of around 30 days arise when the diameter rise rate is between 0.02 and 0.03 days(-1). Moreover, the final diameter of the site is directly related to the steady states of the virus load after the occurrence of a blip. When the value of R0 is around 2.1, to have a steady-state below the limit of detection after the viral blip, the maximum final diameters should be greater than 0.7 mm so that there is a relative loss of connection between compartments.

  9. Increased total sodium concentration in gray matter better explains cognition than atrophy in MS.

    PubMed

    Maarouf, Adil; Audoin, Bertrand; Pariollaud, Fanelly; Gherib, Soraya; Rico, Audrey; Soulier, Elisabeth; Confort-Gouny, Sylviane; Guye, Maxime; Schad, Lothar; Pelletier, Jean; Ranjeva, Jean-Philippe; Zaaraoui, Wafaa

    2017-01-17

    To investigate whether brain total sodium accumulation assessed by (23)Na MRI is associated with cognitive deficit in relapsing-remitting multiple sclerosis (RRMS). Eighty-nine participants were enrolled in the study (58 patients with RRMS with a disease duration ≤10 years and 31 matched healthy controls). Patients were classified as cognitively impaired if they failed at least 2 tasks on the Brief Repeatable Battery. MRI was performed at 3T using (23)Na MRI to obtain total sodium concentration (TSC) in the different brain compartments (lesions, normal-appearing white matter [NAWM], gray matter [GM]) and (1)H- magnetization-prepared rapid gradient echo to assess GM atrophy (GM fraction). The mean disease duration was 3.1 years and the median Expanded Disability Status Scale score was 1 (range 0-4.5). Thirty-seven patients were classified as cognitively preserved and 21 as cognitively impaired. TSC was increased in GM and NAWM in cognitively impaired patients compared to cognitively preserved patients and healthy controls. Voxel-wise analysis demonstrated that sodium accumulation was mainly located in the neocortex in cognitively impaired patients. Regression analysis evidenced than the 2 best independent predictors of cognitive impairment were GM TSC and age. Receiver operating characteristic analyses demonstrated that sensitivity and specificity of the GM TSC to classify patients according to their cognitive status were 76% and 71%, respectively. This study provides 2 main findings. (1) In RRMS, total sodium accumulation in the GM is better associated with cognitive impairment than GM atrophy; and (2) total sodium accumulation in patients with cognitive impairment is mainly located in the neocortex. © 2016 American Academy of Neurology.

  10. Increased Binding of Apolipoproteins A-I and E4 to Triglyceride-Rich Lipoproteins is linked to Induction of Hypertriglyceridemia.

    PubMed

    Gorshkova, Irina N; Atkinson, David

    2017-01-01

    Hypertriglyceridemia (HTG) is an independent factor of atherosclerotic cardiovascular disease and a hallmark of many metabolic disorders. However, the molecular etiology of HTG is still largely unknown. In mice, severe HTG may be induced by expression of specific mutants of apolipoprotein (apo) A-I or wild type (WT) apoE4. Expression of a certain apoE4 mutant results in mild HTG, while expression of another apoE4 mutant or WT apoA-I results in normal plasma triglyceride (TG) levels. Biophysical studies of the apoA-I and apoE4 forms associated with HTG help better understand the molecular mechanisms of induction of HTG by these proteins. The studies show that the apoA-I and apoE4 forms that induce HTG have a destabilized and more loosely folded conformation in solution than their counterparts not associated with HTG. Disruption of the protein salt bridge networks by the mutations is likely responsible for the observed structural changes. Each apoA-I and apoE4 form that induced HTG show enhanced binding to model TG-rich particles. HTG appeared to positively correlate with the apolipoprotein ability to bind to TG-rich particles. This implies that in vivo, the conformational changes in the apolipoproteins that induce HTG facilitate their binding to plasma TG-rich lipoproteins. We discuss metabolic pathways leading to the development of HTG that may result from enhanced binding of the apolipoproteins to TG-rich lipoproteins in circulation. While various factors may be involved in the development of HTG in humans, it is possible that structural alterations that increase affinity of apolipoproteins to TG-rich lipoproteins may contribute to some cases of this disorder.

  11. Higher Levels of Lipoprotein Associated Phospholipase A2 is associated with Increased Prevalence of Cognitive Impairment: the APAC Study

    PubMed Central

    Jiang, Ruixuan; Chen, Shengyun; Shen, Yuan; Wu, Jianwei; Chen, Shuohua; Wang, Anxin; Wu, Shouling; Zhao, Xingquan

    2016-01-01

    Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a unique circulating phospholipase with inflammatory and oxidative activities and the limited data regarding the relationship between Lp-PLA2 and cognitive impairment are conflicted. We conducted a cross-sectional study including 1,374 Chinese adults recruited from 2010 to 2011, aiming to evaluate the relationship between Lp-PLA2 levels and the prevalence of cognitive impairment in a Chinese community-based population. Participants underwent standardized evaluation. Serum Lp-PLA2 mass was measured by ELISA. Cognition status was evaluated via the Mini-Mental Status Exam (MMSE) and cognitive impairment was identified as MMSE <24. Multivariable logistic regression models were used to assess the associations of Lp-PLA2 mass with cognitive impairment. Lp-PLA2 mass was significantly associated with the prevalence of cognitive impairment after adjusting for other potential confounding factors (compared with the first quartile, adjusted ORs of the second, third, and fourth quartile were 2.058 (95% CI, 0.876–4.835), 2.834 (95% CI, 1.255–6.398), and 4.882 (95% CI, 2.212–10.777), p < 0.0001). In conclusion, elevated level of Lp-PLA2 mass was independently associated with the prevalence of cognitive impairment in Chinese adults. PMID:27609335

  12. Postprandial lipemia in the elderly involves increased incorporation of ingested fat in plasma free fatty acids and small (Sf 20-400) triglyceride-rich lipoproteins.

    PubMed

    Puga, Guilherme M; Meyer, Christian; Everman, Sarah; Mandarino, Lawrence J; Katsanos, Christos S

    2011-08-01

    In the elderly, the rise in postprandial plasma triglyceride (TG) concentrations is increased, contributing to their increased risk of cardiovascular disease. We sought to determine the incorporation of ingested fat (whipping cream enriched with [1,1,1-(13)C]triolein) into plasma lipids during the postprandial period in six healthy elderly (67 ± 1 yr old) and six healthy young (23 ± 2 yr old) subjects. Blood and expired air samples were taken before and at 2-h intervals during the 8-h postprandial period. As expected, the area under the curve of postprandial plasma TG concentrations was larger in the elderly compared with the young subjects (152 ± 38 vs. 66 ± 27 mg·dl(-1)·h, P < 0.05). The incorporation of [(13)C]oleate in plasma free fatty acids (FFAs) and TG of the small (S(f) = 20-400) triglyceride-rich lipoprotein (TRL) fraction was significantly higher in the elderly compared with the young subjects, resulting in increased postprandial contributions of the ingested lipid to plasma FFAs (41 ± 3 vs. 26 ± 6%, P < 0.05) and the small TRL fraction (36 ± 5 vs. 21 ± 3%, P < 0.05) in elderly. Plasma apoB-100 concentration was higher, whereas the rate of oxidation of the ingested lipid was lower (P < 0.05) in the elderly. We conclude that increased postprandial lipemia in the elderly involves increased contribution of ingested lipid to the plasma small TRLs. This appears to be driven at least in part by increased appearance of the ingested fat as plasma FFA and increased availability of apo B-100 lipoproteins in the elderly.

  13. Postprandial lipemia in the elderly involves increased incorporation of ingested fat in plasma free fatty acids and small (Sf 20–400) triglyceride-rich lipoproteins

    PubMed Central

    Puga, Guilherme M.; Meyer, Christian; Everman, Sarah; Mandarino, Lawrence J.

    2011-01-01

    In the elderly, the rise in postprandial plasma triglyceride (TG) concentrations is increased, contributing to their increased risk of cardiovascular disease. We sought to determine the incorporation of ingested fat (whipping cream enriched with [1,1,1-13C]triolein) into plasma lipids during the postprandial period in six healthy elderly (67 ± 1 yr old) and six healthy young (23 ± 2 yr old) subjects. Blood and expired air samples were taken before and at 2-h intervals during the 8-h postprandial period. As expected, the area under the curve of postprandial plasma TG concentrations was larger in the elderly compared with the young subjects (152 ± 38 vs. 66 ± 27 mg·dl−1·h, P < 0.05). The incorporation of [13C]oleate in plasma free fatty acids (FFAs) and TG of the small (Sf = 20–400) triglyceride-rich lipoprotein (TRL) fraction was significantly higher in the elderly compared with the young subjects, resulting in increased postprandial contributions of the ingested lipid to plasma FFAs (41 ± 3 vs. 26 ± 6%, P < 0.05) and the small TRL fraction (36 ± 5 vs. 21 ± 3%, P < 0.05) in elderly. Plasma apoB-100 concentration was higher, whereas the rate of oxidation of the ingested lipid was lower (P < 0.05) in the elderly. We conclude that increased postprandial lipemia in the elderly involves increased contribution of ingested lipid to the plasma small TRLs. This appears to be driven at least in part by increased appearance of the ingested fat as plasma FFA and increased availability of apo B-100 lipoproteins in the elderly. PMID:21558545

  14. Surface properties of native human plasma lipoproteins and lipoprotein models.

    PubMed Central

    Massey, J B; Pownall, H J

    1998-01-01

    Plasma lipoprotein surface properties are important but poorly understood determinants of lipoprotein catabolism. To elucidate the relation between surface properties and surface reactivity, the physical properties of surface monolayers of native lipoproteins and lipoprotein models were investigated by fluorescent probes of surface lipid fluidity, surface lateral diffusion, and interfacial polarity, and by their reactivity to Naja melanoleuca phospholipase A2 (PLA2). Native lipoproteins were human very low, low-, and subclass 3 high-density lipoproteins (VLDL, LDL, and HDL3); models were 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or its ether analog in single-bilayer vesicles, large and small microemulsions of POPC and triolein, and reassembled HDL (apolipoprotein A-I plus phospholipid). Among lipoproteins, surface lipid fluidity increased in the order HDL3 < LDL < VLDL, varying inversely with their (protein + cholesterol)/phospholipid ratios. Models resembled VLDL in fluidity. Both lateral mobility in the surface monolayer and polarity of the interfacial region were lower in native lipoproteins than in models. Among native lipoproteins and models, increased fluidity in the surface monolayer was associated with increased reactivity to PLA2. Addition of cholesterol (up to 20 mol%) to models had little effect on PLA2 activity, whereas the addition of apolipoprotein C-III stimulated it. Single-bilayer vesicles, phospholipid-triolein microemulsions, and VLDL have surface monolayers that are quantitatively similar, and distinct from those of LDL and HDL3. Surface property and enzymatic reactivity differences between lipoproteins and models were associated with differences in surface monolayer protein and cholesterol contents. Thus differences in the surface properties that regulate lipolytic reactivity are a predictable function of surface composition. PMID:9533698

  15. Echium oil reduces plasma triglycerides by increasing intravascular lipolysis in apoB100-only low density lipoprotein (LDL) receptor knockout mice.

    PubMed

    Forrest, Lolita M; Lough, Christopher M; Chung, Soonkyu; Boudyguina, Elena Y; Gebre, Abraham K; Smith, Thomas L; Colvin, Perry L; Parks, John S

    2013-07-12

    Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.

  16. Echium Oil Reduces Plasma Triglycerides by Increasing Intravascular Lipolysis in apoB100-Only Low Density Lipoprotein (LDL) Receptor Knockout Mice

    PubMed Central

    Forrest, Lolita M.; Lough, Christopher M.; Chung, Soonkyu; Boudyguina, Elena Y.; Gebre, Abraham K.; Smith, Thomas L.; Colvin, Perry L.; Parks, John S.

    2013-01-01

    Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model. PMID:23857172

  17. Niacin Therapy Increases High-Density Lipoprotein Particles and Total Cholesterol Efflux Capacity But Not ABCA1-Specific Cholesterol Efflux in Statin-Treated Subjects.

    PubMed

    Ronsein, Graziella E; Hutchins, Patrick M; Isquith, Daniel; Vaisar, Tomas; Zhao, Xue-Qiao; Heinecke, Jay W

    2016-02-01

    We investigated relationships between statin and niacin/statin combination therapy and the concentration of high-density lipoprotein particles (HDL-P) and cholesterol efflux capacity, 2 HDL metrics that might better assess cardiovascular disease risk than HDL-cholesterol (HDL-C) levels. In the Carotid Plaque Composition Study, 126 subjects with a history of cardiovascular disease were randomized to atorvastatin or combination therapy (atorvastatin/niacin). At baseline and after 1 year of treatment, the concentration of HDL and its 3 subclasses (small, medium, and large) were quantified by calibrated ion mobility analysis (HDL-PIMA). We also measured total cholesterol efflux from macrophages and ATP-binding cassette transporter A1 (ABCA1)-specific cholesterol efflux capacity. Atorvastatin decreased low-density lipoprotein cholesterol by 39% and raised HDL-C by 11% (P=0.0001) but did not increase HDL-PIMA or macrophage cholesterol efflux. Combination therapy raised HDL-C by 39% (P<0.0001) but increased HDL-PIMA by only 14%. Triglyceride levels did not correlate with HDL-PIMA (P=0.39), in contrast to their strongly negative correlation with HDL-C (P<0.0001). Combination therapy increased macrophage cholesterol efflux capacity (16%, P<0.0001) but not ABCA1-specific efflux. ABCA1-specific cholesterol efflux capacity decreased significantly (P=0.013) in statin-treated subjects, with or without niacin therapy. Statin therapy increased HDL-C levels but failed to increase HDL-PIMA. It also reduced ABCA1-specific cholesterol efflux capacity. Adding niacin to statin therapy increased HDL-C and macrophage efflux, but had much less effect on HDL-PIMA. It also failed to improve ABCA1-specific efflux, a key cholesterol exporter in macrophages. Our observations raise the possibility that niacin might not target the relevant atheroprotective population of HDL. © 2015 American Heart Association, Inc.

  18. Lipid composition of human serum lipoproteins

    PubMed Central

    Skipski, V. P.; Barclay, Marion; Barclay, R. K.; Fetzer, Valentina A.; Good, J. J.; Archibald, F. M.

    1967-01-01

    1. The lipid compositions of the low-density lipoproteins, the high-density lipoproteins and the ultracentrifugal residue of human serum are presented, with emphasis on certain lipoprotein classes and lipid components not previously described. 2. Except for the lipoproteins with the lowest and highest densities, there is a trend for stepwise successive increase or, respectively, decrease in the relative amounts of the main constituents of lipoproteins. 3. High-density lipoprotein-2 and high-density lipoprotein-3 have different amounts of certain lipids; high-density lipoprotein-2 has relatively more free cholesterol and sphingomyelin; high-density lipoprotein-3 has more free fatty acids, diglycerides and ceramide monohexosides. 4. All the lipoproteins contain hydrocarbons of the alkane series. The greatest amount, which averages 4·4% of total lipid extracted, is in the ultracentrifugal residue; n-alkanes comprise 18–50% of the hydrocarbons. 5. All the lipoproteins contain ceramide monohexosides. The highest relative contents of these glycolipids are in high-density lipoprotein-3 and in the ultracentrifugal residue. 6. The ultracentrifugal residue contains 55% of the total quantity of free fatty acids present in serum. The remaining free fatty acids are distributed among the other lipoprotein classes. 7. The choline-containing phospholipids (phosphatidylcholine, lysophosphatidylcholine and sphingomyelin) comprise about 90% of the phospholipids in all the lipoprotein classes except the low-density lipoprotein-2, which contains about 80% of these phospholipids. 8. The presence of a large amount of lysophosphatidylcholine in the ultracentrifugal residue and the successive decrease of sphingomyelin from the low-density lipoprotein-1 to the ultracentrifugal residue was confirmed. 9. The low-density lipoprotein-2 and the ultracentrifugal residue are characterized by relatively high contents of the lower glycerides. PMID:6048776

  19. Can the progressive increase of C₄ bundle sheath leakiness at low PFD be explained by incomplete suppression of photorespiration?

    PubMed

    Kromdijk, Johannes; Griffiths, Howard; Schepers, Hans E

    2010-11-01

    The ability to concentrate CO₂ around Rubisco allows C₄ crops to suppress photorespiration. However, as phosphoenolpyruvate regeneration requires ATP, the energetic efficiency of the C₄ pathway at low photosynthetic flux densities (PFD) becomes a balancing act between primary fixation and concentration of CO₂ in mesophyll (M) cells, and CO₂ reduction in bundle sheath (BS) cells. At low PFD, retro-diffusion of CO₂ from BS cells, relative to the rate of bicarbonate fixation in M cells (termed leakiness φ), is known to increase. This paper investigates whether this increase in ϕ could be explained by incomplete inhibition of photorespiration. The PFD response of φ was measured at various O₂ partial pressures in young Zea mays plants grown at 250 (LL) and 750 µmol m⁻² s⁻¹ PFD (HL). φ increased at low PFD and was positively correlated with O₂ partial pressure. Low PFD during growth caused BS conductance and interveinal distance to be lower in the LL plants, compared to the HL plants, which correlated with lower φ. Model analysis showed that incomplete inhibition of photorespiration, especially in the HL plants, and an increase in the relative contribution of mitochondrial respiration at low PFD could explain the observed increases in φ.

  20. A framework for lipoprotein ontology.

    PubMed

    Chen, Meifania; Hadzic, Maja

    2011-01-01

    Clinical and epidemiological studies have established a significant correlation between abnormal plasma lipoprotein levels and cardiovascular disease, which remains the leading cause of mortality in the world today. In addition, lipoprotein dysregulation, known as dyslipidemia, is a central feature in disease states, such as diabetes and hypertension, which increases the risk of cardiovascular disease. While a corpus of literature exists on different areas of lipoprotein research, one of the major challenges that researchers face is the difficulties in accessing and integrating relevant information amidst massive quantities of heterogeneous data. Semantic web technologies, specifically ontologies, target these problems by providing an organizational framework of the concepts involved in a system of related instances to support systematic querying of information. In this paper, we identify issues within the lipoprotein research domain and present a preliminary framework for Lipoprotein Ontology, which consists of five specific areas of lipoprotein research: Classification, Metabolism, Pathophysiology, Etiology, and Treatment. By integrating specific aspects of lipoprotein research, Lipoprotein Ontology will provide the basis for the design of various applications to enable interoperability between research groups or software agents, as well as the development of tools for the diagnosis and treatment of dyslipidemia.

  1. [Control rate of increased low-density lipoprotein cholesterol levels in cardiology outpatients with coronary heart disease in Beijing].

    PubMed

    Ding, Rong-jing; Ma, Chang-sheng; Chen, Hong; Wu, Yan; Yang, Xin-chun; Hua, Qi; Li, Rui-jie; Ren, Wen-lin; Wang, Ming-sheng; Xiang, Xiao-ping; Du, Xin; Pi, Lin; Hu, Da-yi

    2013-03-01

    To investigate the low-density lipoprotein cholesterol (LDL-C) levels in outpatients with coronary heart disease (CHD) visiting cardiology outpatient clinics of 8 hospitals in Beijing. A total of 903 outpatients with CHD were enrolled from 4 three-tier hospitals and 4 two-tier hospitals in Beijing. All patients were asked to finish the questionnaire including demographic data, CHD history, the knowledge on cholesterol, and the use of statins. Blood lipid was examined and the LDL-C control rate and related factors were then analyzed. Questionnaire was obtained from 876 patients [619 male: 70.7%, mean age: (64.9 ± 10.7) years old] and blood lipid data were available in 709 patients. The general LDL-C control rate was 36.9% (262/709) and was 13.5% (27/173) in very high risk CHD patients, and lower in patients treated in two-tier hospitals than patients treated in three-tier hospitals[31.3% (121/386) vs. 43.7% (141/323), P < 0.01], in female patients than in male patients [27.1% (60/261) vs. 41.3% (201/496), P < 0.01] and in diabetic patients than in non-diabetic patients [13.5% (27/200) vs. 44.7% (197/441), P < 0.01]. The LDL-C control rate was lower in patients less than 60 years old and patients over 80 years old than that in 60-70 years old patients and 70 - 80 years old patients (P < 0.05). LDL-C control rate was not affected by the history of hypertension, percutaneous coronary intervention or coronary artery bypass grafting, smoking, lipid examination frequency, knowledge on goal level of LDL-C, diet control and regularly physical exercising (all P > 0.05). There were 18.2% (129/709) patients not taking statins or not aware if they were taking statin or not. The main reason for not taking statin [47.9% (23/48)] was statin was no prescribed by doctors, followed by withdrawal by patients due to various reasons [27.1% (13/48)]. LDL-C control rate was low in patients with CHD visiting cardiology outpatient clinics in Beijing. The CHD patients and cardiologists

  2. Changes in plasma lipids and increased low-density lipoprotein susceptibility to oxidation in pregnancies complicated by gestational diabetes: consequences of obesity.

    PubMed

    Sánchez-Vera, Isabel; Bonet, Bartolome; Viana, Marta; Quintanar, Amalia; Martín, Maria D; Blanco, Pilar; Donnay, Sergio; Albi, Manuel

    2007-11-01

    Dyslipidemia is associated with increased low-density lipoprotein (LDL) susceptibility to oxidation, a phenomenon associated with endothelial dysfunction, atherosclerosis, cell toxicity, and intrauterine growth retardation. The present study was designed to determine if women developing gestational diabetes mellitus (GDM) have both increased plasma lipids and LDL susceptibility to oxidation throughout pregnancy. We also wanted to study the effects of obesity upon these parameters. A nested case-control study was carried out in 45 women with uncomplicated pregnancies and 62 women diagnosed with GDM following the criteria of the American Diabetes Association. In all women, blood was drawn at 15, 24, and 32 weeks of gestation. Low-density lipoprotein oxidation was initiated by the addition of CuCl2, and formation of conjugated dienes was monitored. Glucose, cholesterol, triglycerides, vitamin E, estradiol, and progesterone were determined. In GDM, elevated levels of glucose, cholesterol, and triglycerides were observed when compared with the control group even in the first trimester, before the detection of diabetes. In the control group, the lag phase in the LDL oxidation was 85.3, 84.4, and 95.6 minutes at 15, 24, and 32 weeks of pregnancy, compared with 63.3, 63.4, and 74.5 minutes in the GDM group (P < .001 in the 3 periods). These differences remained when adjusted for the body mass index. In a multiple linear regression analysis, a negative correlation was observed between the lag phase and the body mass index (P < .001) and cholesterol (P < .001), whereas a positive one appeared with vitamin E (P < .05) and time of gestation (P < .001). In pregnancy, GDM increases LDL susceptibility to oxidation. Obesity and hypercholesterolemia further exacerbate this effect.

  3. Additional consumption of one egg per day increases serum lutein plus zeaxanthin concentration and lowers oxidized low-density lipoprotein in moderately hypercholesterolemic males.

    PubMed

    Kishimoto, Yoshimi; Taguchi, Chie; Saita, Emi; Suzuki-Sugihara, Norie; Nishiyama, Hiroshi; Wang, Wei; Masuda, Yasunobu; Kondo, Kazuo

    2017-09-01

    The egg is a nutrient-dense food and contains antioxidative carotenoids, lutein and zeaxanthin, but its impact on serum cholesterol levels has been a matter of concern, especially for individuals who have high serum cholesterol levels. We conducted this study to determine whether and how the daily additional consumption of one egg affects serum lipid profiles and parameters of LDL oxidation in moderately hypercholesterolemic males. Nineteen male Japanese adults (total cholesterol [TC]>5.2mmol/L) participated, consuming one soft boiled egg per day for 4weeks in addition to their habitual diet. Despite the significant increase in their intake of dietary cholesterol during the intervention period, the subjects' serum concentrations of TC and low-density lipoprotein cholesterol (LDL-C) did not increase. Their serum malondialdehyde modified low-density lipoprotein (MDA-LDL) concentrations were significantly decreased and their LDL oxidation lag times, reflecting the resistance of free-radical-induced LDL lipid peroxidation (ex vivo), was prolonged after 2 and 4weeks. At weeks 2 and 4, the subjects' serum lutein+zeaxanthin concentrations were significantly higher than their baseline values and showed both an inverse relation with MDA-LDL and a positive relationship with the LDL oxidation lag time. These data showed that in moderately hypercholesterolemic males, the additional consumption of one egg per day for 4weeks did not have adverse effects on serum TC or LDL-C, and it might reduce the susceptibility of LDL to oxidation through an increase in the serum lutein and zeaxanthin concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Participation of decreased serum cholesteryl ester transfer activity, independent of increased serum lipoprotein(a), in angina pectoris in normolipemic elderly subjects.

    PubMed

    Miyashita, Y; Morimoto, S; Fukuo, K; Imanaka, S; Koh, E; Tamatani, M; Ogihara, T

    1992-01-01

    The cholesteryl ester transfer activity (CETA) is a measurement of the transfer of cholesteryl ester from HDL to VLDL, LDL or peripheral cells. Its role in the development of early coronary heart disease is not clear. In the present study, serum levels of CETA, lipoprotein(a) [Lp(a)] and other lipid-related factors were compared in 10 normal young subjects, 28 healthy elderly subjects and 14 normolipemic elderly patients with angina pectoris. Compared to the young normals and healthy elderly subjects, the elderly patients with angina pectoris showed significantly decreased mean serum CETA levels, and significantly increased mean serum levels of Lp(a) and apoprotein B. These results may indicate that decreased serum values of CETA participate in the development of angina pectoris in normolipemic elderly patients.

  5. Intrauterine growth restriction combined with a maternal high-fat diet increases hepatic cholesterol and low-density lipoprotein receptor activity in rats.

    PubMed

    Zinkhan, Erin K; Zalla, Jennifer M; Carpenter, Jeanette R; Yu, Baifeng; Yu, Xing; Chan, Gary; Joss-Moore, Lisa; Lane, Robert H

    2016-07-01

    Intrauterine growth restriction (IUGR) and maternal consumption of a high-saturated-fat diet (HFD) increase the risk of hypercholesterolemia, a leading cause of morbidity and mortality. Many pregnant women eat a HFD, thus exposing the fetus to a HFD in utero. The cumulative effect of in utero exposure to IUGR and a HFD on offspring cholesterol levels remains unknown. Furthermore, little is known about the mechanism through which IUGR and maternal HFD consumption increase cholesterol. We hypothesize that IUGR combined with a maternal HFD would increase offspring serum and hepatic cholesterol accumulation via alteration in levels of key proteins involved in cholesterol metabolism. To test our hypothesis we used a rat model of surgically induced IUGR and fed the dams a regular diet or a HFD HFD-fed dams consumed the same kilocalories as regular diet-fed dams, with no difference between surgical intervention groups. In the offspring, IUGR combined with a maternal HFD increased hepatic cholesterol levels, low-density lipoprotein (LDL) receptor protein levels, and Ldlr activity in female rat offspring at birth and both sexes at postnatal day 14 relative to non-IUGR offspring both from regular diet- and HFD-fed dams. These findings suggest that IUGR combined with a maternal HFD increases hepatic cholesterol accumulation via increased LDL cholesterol uptake into the liver with resulting persistent increases in hepatic cholesterol accumulation.

  6. Consumption of a liquid high-fat meal increases triglycerides but decreases high-density lipoprotein cholesterol in abdominally obese subjects with high postprandial insulin resistance.

    PubMed

    Wang, Feng; Lu, Huixia; Liu, Fukang; Cai, Huizhen; Xia, Hui; Guo, Fei; Xie, Yulan; Huang, Guiling; Miao, Miao; Shu, Guofang; Sun, Guiju

    2017-07-01

    Abdominal obesity is associated with an increased risk of insulin resistance, which may be a potential contributor to dyslipidemia. However, the relationship between postprandial insulin resistance and lipid metabolism in abdominally obese subjects remains unknown. We hypothesized that postprandial dyslipidemia would be exaggerated in abdominally obese subjects with high postprandial insulin resistance. To test this hypothesis, serum glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B were measured at baseline and postprandial state at 0.5, 1, 2, 4, 6, and 8 hours after a liquid high-fat meal in non-abdominally obese controls (n=44) and abdominally obese subjects with low (AO-LPIR, n=40), middle (n=40), and high postprandial insulin resistance (AO-HPIR, n=40) based on the tertiles ratio of the insulin to glucose areas under the curve (AUC). Their serum adipokines were tested at baseline only. Fasting serum leptin was higher (P<.05) in AO-HPIR than that in AO-LPIR and controls. Postprandial triglycerides AUC was higher (P<.05), whereas high-density lipoprotein cholesterol AUC was lower (P<.05), in AO-HPIR than those in AO-LPIR and controls. Postprandial AUCs for total cholesterol and apolipoprotein B were similar in abdominally obese subjects with different degrees of postprandial insulin resistance and controls. The present study indicated that the higher degree of postprandial insulin resistance, the more adverse lipid profiles in abdominally obese subjects, which provides insight into opportunity for screening in health. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The effects of glibenclamide and insulin on plasma high density lipoprotein in diabetics.

    PubMed

    Tamai, T; Nakai, T; Yamada, S; Kobayashi, T; Hayashi, T; Kutsumi, Y; Oida, K; Takeda, R

    1981-01-01

    The purpose of the present study was to investigate the effects of various types of treatment such as glibenclamide and insulin on plasma lipids and lipoprotein concentration in diabetics. Treatment of diabetes mellitus was reevaluated from the standpoint of high density lipoprotein (HDL) metabolism. Twenty-one diabetic patients (6 men and 15 women) who have been admitted in the hospital and kept on Japanese standard diet for diabetes mellitus, have been studied. Changes of plasma lipoprotein in diabetic patients were followed up before and after treatment with glibenclamide or insulin. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) were decreased and HDL was increased with insulin treatment. However, glibenclamide induced a significant decrease in HDL- cholesterol (Ch). Relationship between triglyceride (TG)-rich lipoproteins and HDL metabolism was studied. A significant negative correlation was found between pretreatment VLDL-TG and changes of VLDL-TG with insulin treatment, indicating an accelerated catabolism of VLDL-TG with possible increase of triglyceride lipases. There was a significant negative correlation between VLDL-TG and HDL-Ch before insulin treatment, but not after treatment. There was no negative correlation between changes of VLDL-TG and changes of HDL-Ch with insulin therapy. These results indicate that an increment of HDL with insulin treatment can not be explained solely by increased HDL formation from TG-rich lipoprotein and that insulin might increase synthesis and secretion of HDL in liver and/or intestine.

  8. Regulation of Plasma Cholesterol by Lipoprotein Receptors

    NASA Astrophysics Data System (ADS)

    Brown, Michael S.; Kovanen, Petri T.; Goldstein, Joseph L.

    1981-05-01

    The lipoprotein transport system holds the key to understanding the mechanisms by which genes, diet, and hormones interact to regulate the plasma cholesterol level in man. Crucial components of this system are lipoprotein receptors in the liver and extrahepatic tissues that mediate the uptake and degradation of cholesterol-carrying lipoproteins. The number of lipoprotein receptors, and hence the efficiency of disposal of plasma cholesterol, can be increased by cholesterol-lowering drugs. Regulation of lipoprotein receptors can be exploited pharmacologically in the therapy of hypercholesterolemia and atherosclerosis in man.

  9. Does plasticity in plant physiological traits explain the rapid increase in water use efficiency? An ecohydrological modeling approach

    NASA Astrophysics Data System (ADS)

    Mastrotheodoros, Theodoros; Fatichi, Simone; Pappas, Christoforos; Molnar, Peter; Burlando, Paolo

    2016-04-01

    The rise of atmospheric CO2 concentration is expected to stimulate plant productivity by enhancing photosynthesis and reducing stomatal conductance and thus increasing plant water use efficiency (WUE) worldwide. An analysis of eddy covariance flux tower data from 21 forested ecosystems across the north hemisphere detected an unexpectedly large increase in WUE (Keenan et al, 2013), which was six times larger than the increase found by most previous studies based on controlled experiments (e.g., FACE), leaf-scale analyses, and numerical modelling. This increase could be solely attributed to the increase in atmospheric CO2 since other confounding factors were ruled out. Here, we investigate the potential contribution of plant plasticity, reflected in the temporal adjustment of major plant physiological traits, on changes in WUE using the ecohydrological model Tethys and Chloris (T&C). We hypothesize that the increase in WUE can be attributed to small variations in plant physiological traits, undetectable through observations, eventually triggered by the atmospheric CO2 increase. Data from the 21 sites in the above mentioned study are used to force the model. Simulation results with and without plasticity in the physiological traits (i.e., model parameters in our numerical experiments) are compared with the observed trends in WUE. We test several plant adaptation strategies in being effective in explaining the observed increase in WUE using a multifactorial numerical experiment in which we perturb in a systematic way selected plant parameters. Keenan, T. F., Hollinger, D. Y., Bohrer, G., Dragoni, D., Munger, J. W., Schmid, H. P., and Richardson, A. D. (2013). Increase in forest water-use efficiency as atmospheric carbon dioxide concentrations rise. Nature, 499(7458), 324-7.

  10. An increase in minimum metabolic rate and not activity explains field metabolic rate changes in a breeding seabird.

    PubMed

    Green, J A; Aitken-Simpson, E J; White, C R; Bunce, A; Butler, P J; Frappell, P B

    2013-05-01

    The field metabolic rate (FMR) of a free-ranging animal can be considered as the sum of its maintenance costs (minimum metabolic rate, MMR) and additional costs associated with thermoregulation, digestion, production and activity. However, the relationships between FMR and BMR and how they relate to behaviour and extrinsic influences is not clear. In seabirds, FMR has been shown to increase during the breeding season. This is presumed to be the result of an increase in foraging activity, stimulated by increased food demands from growing chicks, but few studies have investigated in detail the factors that underlie these increases. We studied free-ranging Australasian gannets (Morus serrator) throughout their 5 month breeding season, and evaluated FMR, MMR and activity-related metabolic costs on a daily basis using the heart rate method. In addition, we simultaneously recorded behaviour (flying and diving) in the same individuals. FMR increased steadily throughout the breeding season, increasing by 11% from the incubation period to the long chick-brooding period. However, this was not accompanied by either an increase in flying or diving behaviour, or an increase in the energetic costs of activity. Instead, the changes in FMR could be explained exclusively by a progressive increase in MMR. Seasonal changes in MMR could be due to a change in body composition or a decrease in body condition associated with changing the allocation of resources between provisioning adults and growing chicks. Our study highlights the importance of measuring physiological parameters continuously in free-ranging animals in order to understand fully the mechanisms underpinning seasonal changes in physiology and behaviour.

  11. Role of lipoprotein lipase activity on lipoprotein metabolism and the fate of circulating triglycerides in pregnancy.

    PubMed

    Herrera, E; Lasunción, M A; Gomez-Coronado, D; Aranda, P; López-Luna, P; Maier, I

    1988-06-01

    The mechanism that induces maternal hypertriglyceridemia in late normal pregnancy, and its physiologic significance are reviewed as a model of the effects of sex steroids on lipoprotein metabolism. In the pregnant rat, maternal carcass fat content progressively increases up to day 19 of gestation, then declines at day 21. The decline may be explained by the augmented lipolytic activity in adipose tissue that is seen in late pregnancy in the rat. This change causes maternal circulating free fatty acids and glycerol levels to rise. Although the liver is the main receptor organ for these metabolites, liver triglyceride content is reduced. Circulating triglycerides and very-low-density lipoprotein (VLDL)-triglyceride levels are highly augmented in the pregnant rat, indicating that liver-synthesized triglycerides are rapidly released into the circulation. Similar increments in circulating VLDL-triglycerides are seen in pregnant women during the third trimester of gestation. This increase is coincident with a decrease in plasma postheparin lipoprotein lipase activity, indicating a reduced removal of circulating triglycerides by maternal tissues or a redistribution in their use among the different tissues. During late gestation in the rat, tissue lipoprotein lipase activity varies in different directions; it decreases in adipose tissue, the liver, and to a smaller extent the heart, but increases in placental and mammary gland tissue. These changes play an important role in the fate of circulating triglycerides, which are diverted from uptake by adipose tissue to uptake by the mammary gland for milk synthesis, and probably by the placenta for hydrolysis and transfer of released nonesterified fatty acids to the fetus. After 24 hours of starvation, lipoprotein lipase activity in the liver greatly increases in the rat in late pregnancy; this change is not seen in virgin animals. This alteration is similar to that seen in liver triglyceride content and plasma ketone body

  12. Considering risk contexts in explaining the paradoxical HIV increase among female sex workers in Mumbai and Thane, India.

    PubMed

    Bandewar, Sunita V S; Bharat, Shalini; Kongelf, Anine; Pisal, Hemlata; Collumbien, Martine

    2016-01-28

    The period 2006-2009 saw intensive scale-up of HIV prevention efforts and an increase in reported safer sex among brothel and street-based sex workers in Mumbai and Thane (Maharashtra, India). Yet during the same period, the prevalence of HIV increased in these groups. A better understanding of sex workers' risk environment is needed to explain this paradox. In this qualitative study we conducted 36 individual interviews, 9 joint interviews, and 10 focus group discussions with people associated with HIV interventions between March and May 2012. Dramatic changes in Mumbai's urban landscape dominated participants' accounts, with dwindling sex worker numbers in traditional brothel areas attributed to urban restructuring. Gentrification and anti-trafficking efforts explained an escalation in police raids. This contributed to dispersal of sex work with the sex-trade management adapting by becoming more hidden and mobile, leading to increased vulnerability. Affordable mobile phone technology enabled independent sex workers to trade in more hidden ways and there was an increased dependence on lovers for support. The risk context has become ever more challenging, with animosity against sex work amplified since the scale up of targeted interventions. Focus on condom use with sex workers inadvertently contributed to the diversification of the sex trade as clients seek out women who are less visible. Sex workers and other marginalised women who sell sex all strictly prioritise anonymity. Power structures in the sex trade continue to pose insurmountable barriers to reaching young and new sex workers. Economic vulnerability shaped women's decisions to compromise on condom use. Surveys monitoring HIV prevalence among 'visible' street and brothel-bases sex workers are increasingly un-representative of all women selling sex and self-reported condom use is no longer a valid measure of risk reduction. Targeted harm reduction programmes with sex workers fail when implemented in

  13. Phytosterols, Phytostanols, and Lipoprotein Metabolism.

    PubMed

    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

  14. MicroRNAs regulating apolipoprotein B-containing lipoprotein production.

    PubMed

    Zhou, Liye; Irani, Sara; Sirwi, Alaa; Hussain, M Mahmood

    2016-12-01

    MicroRNAs (miRs) are small, non-coding RNAs that regulate gene expression and have been implicated in many pathological conditions. Significant progress has been made to unveil their role in lipid metabolism. This review aims at summarizing the role of different miRs that regulate hepatic assembly and secretion of apolipoprotein B (apoB)-containing lipoproteins. Overproduction and/or impaired clearance of these lipoproteins from circulation increase plasma concentrations of lipids enhancing risk for cardiovascular disease. So far, three miRs, miR-122, miR-34a, and miR-30c have been shown to modulate hepatic production of apoB-containing low density lipoproteins. In this review, we will first provide a brief overview of lipid metabolism and apoB-containing lipoprotein assembly to orient readers to different steps that have been shown to be regulated by miRs. Then, we will discuss the role of each miR on plasma lipids and atherosclerotic burden. Furthermore, we will summarize mechanistic studies explaining how these miRs regulate hepatic lipid synthesis, fatty acid oxidation, and lipoprotein secretion. Finally, we will briefly highlight the potential use of each miR as a therapeutic drug for treating cardiovascular diseases. This article is part of a Special Issue entitled: MicroRNAs and lipid/energy metabolism and related diseases edited by Carlos Fernández-Hernando and Yajaira Suárez.

  15. Lipoproteins, atherogenicity, age and risk of myocardial infarction.

    PubMed

    Hensley, W J; Mansfield, C H

    1999-04-01

    To perform basic statistical analysis of laboratory lipoprotein data, i.e. the measures of very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL), to assist in their interpretation. In particular, to find any difference in male and female data that might explain the known difference in atherogenic susceptibility between the sexes. The study subjects were patients of doctors in city and country New South Wales. Statistical methodology to find the inter-relations of the lipoproteins was the construction of the matrix of correlation, then by matrix algebra to display the independent trends in the data. The findings have been an atherogenicity function involving LDL and HDL and a risk function of myocardial infarction (MI) involving LDL, HDL and age, confirmed by reference to the age and sex incidence of MI in the Australian population. The principal conclusion is a simple mathematical model of the incidence of MI. The means given for identification of at-risk individuals before symptoms appear, also the means given of lowering whole population risk of MI by health education and lifestyle change with increased longevity for all. These concepts call for a prospective trial.

  16. Identification of the Functional Variant(s) that Explain the Low-Density Lipoprotein Receptor (LDLR) GWAS SNP rs6511720 Association with Lower LDL-C and Risk of CHD

    PubMed Central

    Palmen, Jutta; Kalea, Anastasia Z.

    2016-01-01

    Background The Low-Density Lipoprotein Receptor (LDLR) SNP rs6511720 (G>T), located in intron-1 of the gene, has been identified in genome-wide association studies (GWAS) as being associated with lower plasma levels of LDL-C and a lower risk of coronary heart disease (CHD). Whether or not rs6511720 is itself functional or a marker for a functional variant elsewhere in the gene is not known. Methods The association of LDLR SNP rs6511720 with incidence of CHD and levels of LDL-C was determined by reference to CARDIoGRAM, C4D and Global lipids genetics consortium (GLGC) data. SNP annotation databases were used to identify possible SNP function and prioritization. Luciferase reporter assays in the liver cell line Huh7 were used to measure the effect of variant genotype on gene expression. Electrophoretic Mobility Shift Assays (EMSAs) were used to identify the Transcription Factors (TFs) involved in gene expression regulation. Results The phenotype-genotype analysis showed that the rs6511720 minor allele is associated with lower level of LDL-C [beta = -0.2209, p = 3.85 x10-262], and lower risk of CHD [log (OR) = 0.1155, p = 1.04 x10-7]. Rs6511720 is in complete linkage. Rs6511720 is in complete linkage disequilibrium (LD) with three intron-1 SNPs (rs141787760, rs60173709, rs57217136). Luciferase reporter assays in Huh7 cells showed that the rare alleles of both rs6511720 and rs57217136 caused a significant increase in LDLR expression compared to the common alleles (+29% and +24%, respectively). Multiplex Competitor-EMSAs (MC-EMSA) identified that the transcription factor serum response element (SRE) binds to rs6511720, while retinoic acid receptor (RAR) and signal transducer and activator of transcription 1 (STAT1) bind to rs57217136. Conclusion Both LDLR rs6511720 and rs57217136 are functional variants. Both these minor alleles create enhancer-binding protein sites for TFs and may contribute to increased LDLR expression, which is consequently associated with reduced

  17. CXC chemokine ligand 16 is increased in gestational diabetes mellitus and preeclampsia and associated with lipoproteins in gestational diabetes mellitus at 5 years follow-up.

    PubMed

    Lekva, Tove; Michelsen, Annika E; Aukrust, Pål; Paasche Roland, Marie Cecilie; Henriksen, Tore; Bollerslev, Jens; Ueland, Thor

    2017-08-01

    Women with a history of gestational diabetes mellitus and preeclampsia are at increased risk of cardiovascular disease later in life, but the mechanism remains unclear. The aim of the study was to evaluate the association between CXC chemokine ligand 16 and indices of glucose metabolism, dyslipidemia and systemic inflammation in gestational diabetes mellitus and preeclampsia. This sub-study of the population-based prospective cohort included 310 women. Oral glucose tolerance test was performed during pregnancy and 5 years later along with lipid analysis. CXC chemokine ligand 16 was measured in plasma (protein) and peripheral blood mononuclear cells (messenger RNA) during pregnancy and at follow-up. Circulating CXC chemokine ligand 16 was higher in gestational diabetes mellitus women early in pregnancy and at follow-up, while higher in preeclampsia women late in pregnancy compared to control women. Messenger RNA of CXC chemokine ligand 16 in peripheral blood mononuclear cells were lower in gestational diabetes mellitus and preeclampsia women compared to control women. Increased circulating CXC chemokine ligand 16 level was associated with a higher apolipoprotein B and low-density lipoprotein cholesterol in gestational diabetes mellitus women but not in normal pregnancy at follow-up. Our study shows that women with gestational diabetes mellitus and preeclampsia had a dysregulated CXC chemokine ligand 16 during pregnancy, and in gestational diabetes mellitus, the increase in CXC chemokine ligand 16 early in pregnancy and after 5 years was strongly associated with their lipid profile.

  18. High-density lipoprotein cholesterol levels increase with age, body mass index, blood pressure and fasting blood glucose in a rural Uygur population in China.

    PubMed

    Yan, Weili; Gu, Dongfeng; Yang, Xiaoyan; Wu, Jun; Kang, Ling; Zhang, Li

    2005-11-01

    To investigate the distribution of the serum high-density lipoprotein cholesterol (HDLC) levels and its relationship with obesity, hypertension and diabetes in a Uygur case-control study on hypertension. A case-control (339 hypertensive cases, 272 normotensive controls) study on hypertension was conducted, and obesity, hypertension, lipid profiles and fasting blood glucose were analyzed. The demographic data, history of disease and lifestyles, including diet, smoking and salt intake, were recorded and three measurements of blood pressure were obtained by trained observers. The fasting serum lipid profiles and glucose were determined. The HDLC levels of hypertensive participants were significantly higher than normotensive participants after adjustment for age and gender (1.145 versus 1.117 mmol/l, P = 0.001, power = 0.867). After adjustment for related variables, the HDLC levels slightly increased with age, body mass index and fasting glucose (all P = 0.001, power > 0.80) in normotensive participants and only increased with age among hypertensive participants (P = 0.0001, power = 0.971). The serum HDLC levels in Uygur normotensive participants increased with age, body mass index, blood pressure and fasting glucose levels. This was inconsistent with the previous studies and the reason remained unclear. Further study is needed to elucidate both the environmental and genetic determinants of the novel distribution of the HDLC levels and their association with coronary heart disease in the Uygur population.

  19. No improvement of high-density lipoprotein (HDL) vasorelaxant effect despite increase in HDL cholesterol concentration in type 2 diabetic patients treated with glitazones.

    PubMed

    Perségol, Laurence; Duvillard, Laurence; Monier, Serge; Brindisi, Marie-Claude; Bouillet, Benjamin; Petit, Jean-Michel; Vergès, Bruno

    2014-10-01

    High-density lipoproteins (HDLs) from type 2 diabetic patients are unable to counteract the inhibitory effect of oxidized low-density lipoproteins (ox-LDLs) on vasorelaxation. We hypothesized that glitazones, which improve glycemic control and dyslipidemia, could correct this abnormality. We compared the ability of HDL from controls (n = 12) and from type 2 diabetic patients before and after 6 months of treatment with either rosiglitazone (n = 11) or pioglitazone (n = 8) to counteract the inhibitory effect of ox-LDL on vasodilatation of rabbit aorta rings. Rosiglitazone induced a decrease in hemoglobin A1c (7.7% ± 1.1% vs 9.8% ± 1.0%, P = .003) and an increase in HDL cholesterol (1.14 ± 0.32 vs 0.98 ± 0.24 mmol/L, P = .033). Pioglitazone induced a decrease in hemoglobin A1c (8.3% ± 2.5% vs 9.5% ± 3.2%, P = .068) and serum triglycerides (1.58 ± 0.89 vs 2.03 ± 0.70 mmol/L, P = .069) and an increase in HDL cholesterol (1.39 ± 0.22 vs 1.14 ± 0.22 mmol/L, P = .018). The triglyceride content of HDL was unchanged by rosiglitazone and was decreased by 25% (P = .068) by pioglitazone. HDL from controls counteracted the inhibitory effect of ox-LDL on vasodilatation (maximal relaxation [Emax] = 74.4% ± 3.5% vs 51.9% ± 3.3%, P = .0029), whereas HDL from type 2 diabetic patients did not (Emax = 51.7% ± 5.8% vs 52.3% ± 4.6% [P = .66] and 52.7% ± 5.5% vs 51.9% ± 4.5% [P = .78] for the rosiglitazone and pioglitazone group, respectively). Rosiglitazone or pioglitazone did not improve Emax (58.6% ± 5.9% vs 52.3% ± 4.6% [P = .15] and 49.3% ± 6.5% vs 51.9% ± 4.5% [P = .48], respectively). Glitazones increased the concentration of HDL cholesterol without restoring the ability of HDL particles to protect the endothelium from oxidative stress-induced dysfunction, meaning that HDL remained dysfunctional with impaired antiatherogenic properties.

  20. Species-specific adaptations explain resilience of herbaceous understorey to increased precipitation variability in a Mediterranean oak woodland.

    PubMed

    Jongen, Marjan; Hellmann, Christine; Unger, Stephan

    2015-10-01

    To date, the implications of the predicted greater intra-annual variability and extremes in precipitation on ecosystem functioning have received little attention. This study presents results on leaf-level physiological responses of five species covering the functional groups grasses, forbs, and legumes in the understorey of a Mediterranean oak woodland, with increasing precipitation variability, without altering total annual precipitation inputs. Although extending the dry period between precipitation events from 3 to 6 weeks led to increased soil moisture deficit, overall treatment effects on photosynthetic performance were not observed in the studied species. This resilience to prolonged water stress was explained by different physiological and morphological strategies to withstand periods below the wilting point, that is, isohydric behavior in Agrostis, Rumex, and Tuberaria, leaf succulence in Rumex, and taproots in Tolpis. In addition, quick recovery upon irrigation events and species-specific adaptations of water-use efficiency with longer dry periods and larger precipitation events contributed to the observed resilience in productivity of the annual plant community. Although none of the species exhibited a change in cover with increasing precipitation variability, leaf physiology of the legume Ornithopus exhibited signs of sensitivity to moisture deficit, which may have implications for the agricultural practice of seeding legume-rich mixtures in Mediterranean grassland-type systems. This highlights the need for long-term precipitation manipulation experiments to capture possible directional changes in species composition and seed bank development, which can subsequently affect ecosystem state and functioning.

  1. Effects of hormones on lipids and lipoproteins

    SciTech Connect

    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.

  2. Genetics Home Reference: familial lipoprotein lipase deficiency

    MedlinePlus

    ... In people with familial lipoprotein lipase deficiency , increased fat levels can also cause neurological features, such as depression, memory loss, and mild intellectual decline (dementia). These problems are ...

  3. Dysfunctional Pro-Inflammatory High Density Lipoproteins Confer Increased Risk for Atherosclerosis in Women with Systemic Lupus Erythematosus

    PubMed Central

    McMahon, Maureen; Grossman, Jennifer; Skaggs, Brian; FitzGerald, John; Sahakian, Lori; Ragavendra, Nagesh; Charles-Schoeman, Christina; Watson, Karol; Wong, Weng Kee; Chen, Weiling; Gorn, Alan; Karpouzas, George; Weisman, Michael; Wallace, Daniel J.; Hahn, Bevra H.

    2009-01-01

    Objective Women with systemic lupus erythematosus (SLE) have increased atherosclerosis. Identification of at-risk patients and the etiology underlying atherosclerosis in SLE remains elusive. Normal HDL lose antioxidant capacity during inflammation, and these dysfunctional HDL might predispose to atherosclerosis. The aim of this study is to determine whether dysfunctional pro-inflammatory HDL (piHDL) is associated with subclinical atherosclerosis in SLE. Methods 276 SLE women had carotid artery ultrasound to identify plaques and measure intima-media thickness (IMT). Antioxidant function of HDL was measured as change in oxidation of LDL after addition of subject HDL. Two anti-inflammatory HDL components, paraoxonase and apolipoprotein A-1, were also measured. Results 48.2% of patients had piHDL. 86.7% of subjects with plaque had piHDL, versus 40.7% without (p<0.001). Patients with piHDL also had higher IMT (p<0.001). After multivariate analysis, the only significant factors associated with plaque were piHDL, (OR 16.1, p<0.001), age (OR 1.2, p<0.001), hypertension (OR 3.0, p=0.04), dyslipidemia (OR 3.4, p=0.04), and mixed racial background (OR 8.3, p=0.04). Factors associated with IMT measurements in the highest quartile were piHDL (OR 2.5, p=0.02), age (OR 1.1, p<0.001), body mass index (OR 1.07, p=0.04), lifetime prednisone dose > 20g (OR 2.8, p=0.04), and African American race (OR 8.3, p=0.001). Conclusions Dysfunctional piHDL greatly increases risk for subclinical atherosclerosis in SLE; they associate with increased prevalence of carotid plaque and with high IMT. The presence of piHDL may help identify patients at risk for atherosclerosis. PMID:19644959

  4. Enhanced bridging function and augmented monocyte adhesion by lipoprotein lipase N9: insights into increased risk of coronary artery disease in N9 carriers.

    PubMed

    Fisher, Rachel M; Benhizia, Ferdaous; Schreiber, Renate; Makoveichuk, Elena; Putt, Wendy; Al-Haideri, Maysoon; Deckelbaum, Richard J; Olivecrona, Gunilla; Humphries, Steve E; Talmud, Philippa J

    2003-02-01

    Lipoprotein lipase (LPL) is central to triacylglycerol (TG) metabolism, having both hydrolytic and bridging functions. The common LPL gene variant D9N is associated with raised TG, reduced HDL-cholesterol concentrations and increased risk of coronary artery disease (CAD). To investigate the functional basis for the phenotype in N9 carriers, CHO K1 cells were stably transfected with wild type (D9) or mutant (N9) LPL cDNA. LPL RNA expression levels, monomer-to-dimer ratios, and dimer specific activities were similar in D9 and N9 cells. Significantly enhanced binding (4.6-fold) and internalisation (2.6-fold) of 125I-LDL by N9 compared with D9 cells was eradicated by pre-treatment with either heparin or heparinase, confirming involvement of LPL and cell surface proteoglycans. N9 cells bound and internalised 3.8- and 4.4-fold more oxidised 125I-LDL, respectively, than D9 cells (both P<0.0001). Binding of monocytes was 7-fold greater to plates coated with purified LPL-N9 dimer compared with LPL-D9 (P<=0.005). Thus once on the cell surface, LPL-N9 enhances bridging, as assessed both by LDL binding and internalisation, and monocyte adhesion. This augmented LPL-N9 bridging provides a mechanism for the reported increased CAD risk in N9 carriers.

  5. Obesity development in neuron-specific lipoprotein lipase deficient mice is not responsive to increased dietary fat content or change in fat composition.

    PubMed

    Wang, Hong; Taussig, Matthew D; DiPatrizio, Nicholas V; Bruce, Kimberley; Piomelli, Daniele; Eckel, Robert H

    2016-07-01

    We have previously reported that mice with neuron-specific LPL deficiency (NEXLPL-/-) become obese by 16weeks of age on chow. Moreover, these mice had reduced uptake of triglyceride (TG)-rich lipoprotein-derived fatty acids and lower levels of n-3 long chain polyunsaturated fatty acids (n-3 PUFAs) in the hypothalamus. Here, we asked whether increased dietary fat content or altered dietary composition could modulate obesity development in NEXLPL-/- mice. Male NEXLPL-/- mice and littermate controls (WT) were randomly assigned one of three synthetic diets; a high carbohydrate diet (HC, 10% fat), a high-fat diet (HF, 45% fat), or a HC diet supplemented with n-3 PUFAs (HCn-3, 10% fat, Lovaza, GSK®). After 42weeks of HC feeding, body weight and fat mass were increased in the NEXLPL-/- mice compared to WT. WT mice fed a HF diet displayed typical diet-induced obesity, but weight gain was only marginal in HF-fed NEXLPL-/- mice, with no significant difference in body composition. Dietary n-3 PUFA supplementation did not prevent obesity in NEXLPL-/- mice, but was associated with differential modifications in hypothalamic gene expression and PUFA concentration compared to WT mice. Our findings suggest that neuronal LPL is involved in the regulation of body weight and composition in response to either the change in quantity (HF feeding) or quality (n-3 PUFA-enriched) of dietary fat. The precise role of LPL in lipid sensing in the brain requires further investigation.

  6. Different Mechanisms Must Be Considered to Explain the Increase in Hippocampal Neural Precursor Cell Proliferation by Physical Activity

    PubMed Central

    Overall, Rupert W.; Walker, Tara L.; Fischer, Tim J.; Brandt, Moritz D.; Kempermann, Gerd

    2016-01-01

    The number of proliferating neural precursor cells in the adult hippocampus is strongly increased by physical activity. The mechanisms through which this behavioral stimulus induces cell proliferation, however, are not yet understood. In fact, even the mode of proliferation of the stem and progenitor cells is not exactly known. Evidence exists for several mechanisms including cell cycle shortening, reduced cell death and stem cell recruitment, but as yet no model can account for all observations. An appreciation of how the cells proliferate, however, is crucial to our ability to model the neurogenic process and predict its behavior in response to pro-neurogenic stimuli. In a recent study, we addressed modulation of the cell cycle length as one possible mode of regulation of precursor cell proliferation in running mice. Our results indicated that the observed increase in number of proliferating cells could not be explained through a shortening of the cell cycle. We must therefore consider other mechanisms by which physical activity leads to enhanced precursor cell proliferation. Here we review the evidence for and against several different hypotheses and discuss the implications for future research in the field. PMID:27536215

  7. Loss of Peripheral Sensory Function Explains Much of the Increase in Postural Sway in Healthy Older Adults.

    PubMed

    Anson, Eric; Bigelow, Robin T; Swenor, Bonnielin; Deshpande, Nandini; Studenski, Stephanie; Jeka, John J; Agrawal, Yuri

    2017-01-01

    Postural sway increases with age and peripheral sensory disease. Whether, peripheral sensory function is related to postural sway independent of age in healthy adults is unclear. Here, we investigated the relationship between tests of visual function (VISFIELD), vestibular function (CANAL or OTOLITH), proprioceptive function (PROP), and age, with center of mass sway area (COM) measured with eyes open then closed on firm and then a foam surface. A cross-sectional sample of 366 community dwelling healthy adults from the Baltimore Longitudinal Study of Aging was tested. Multiple linear regressions examined the association between COM and VISFIELD, PROP, CANAL, and OTOLITH separately and in multi-sensory models controlling for age and gender. PROP dominated sensory prediction of sway across most balance conditions (β's = 0.09-0.19, p's < 0.001), except on foam eyes closed where CANAL function loss was the only significant sensory predictor of sway (β = 2.12, p < 0.016). Age was not a consistent predictor of sway. This suggests loss of peripheral sensory function explains much of the age-associated increase in sway.

  8. Model to explain the effects of halide ions on the increase in surface enhanced Raman spectral intensity over time

    NASA Astrophysics Data System (ADS)

    Cole, Michael A.

    Understanding the mechanisms responsible for the large increase in spectral intensity when molecules are adsorbed to nanoparticle surfaces such as occurs during surface enhanced Raman (SER) spectroscopy will allow scientists to probe ever smaller scales, even allowing single molecule detection. One particular scenario that increased the SER scattering efficiency was the addition of halide ions to Rhodamine 6G (R6G)-ethanol solution. This thesis presents a theoretical model explaining the effects of halide ions on the SER spectral intensity of the Rhodamine 6G (R6G) molecule when co-adsorbed to a silver nanoparticle surface. Glaspell et al. 2005, found a linear correlation between the increase in spectral intensities of selected vibrational normal modes of R6G over time and the polarizabilities of co-adsorbed halide ions. When the R6G molecule co-adsorbs to the silver nanoparticle surface with the halide ions, the molecule is exposed to three external electric fields that add vectorially, creating a total external electric field. Modelling the fields from the halide ions and the silver nanoparticles as electric dipole fields introduces the polarizability of the halide ion linearly into the Raman spectral intensity equation. This model also shows that there is a necessary interaction between the halide ions and the silver nanoparticle surface in order to see the effects as described by Glaspell et al. Furthermore, we will present experimental results that show that there is a necessary interaction between the halide ions and the nanoparticle surface. Without this interaction there was no increase in the SER spectral intensity of R6G or pyridine molecules in solution with the halide ions but without the silver nanoparticles.

  9. Metabolism of lipoproteins by human fetal hepatocytes

    SciTech Connect

    Carr, B.R.

    1987-12-01

    The rate of clearance of lipoproteins from plasma appears to play a role in the development of atherogenesis. The liver may account for as much as two thirds of the removal of low-density lipoprotein and one third of the clearance of high-density lipoprotein in certain animal species and humans, mainly by receptor-mediated pathways. The purpose of the present investigation was to determine if human fetal hepatocytes maintained in vitro take up and degrade lipoproteins. We first determined that the maximal binding capacity of iodine 125-iodo-LDL was approximately 300 ng of low-density lipoprotein protein/mg of membrane protein and an apparent dissociation constant of approximately 60 micrograms low-density lipoprotein protein/ml in membranes prepared from human fetal liver. We found that the maximal uptake of (/sup 125/I)iodo-LDL and (/sup 125/I)iodo-HDL by fetal hepatocytes occurred after 12 hours of incubation. Low-density lipoprotein uptake preceded the appearance of degradation products by 4 hours, and thereafter the degradation of low-density lipoprotein increased linearly for at least 24 hours. In contrast, high-density lipoprotein was not degraded to any extent by fetal hepatocytes. (/sup 125/I)Iodo-LDL uptake and degradation were inhibited more than 75% by preincubation with low-density lipoprotein but not significantly by high-density lipoprotein, whereas (/sup 125/I)iodo-HDL uptake was inhibited 70% by preincubation with high-density lipoprotein but not by low-density lipoprotein. In summary, human fetal hepatocytes take up and degrade low-density lipoprotein by a receptor-mediated process similar to that described for human extrahepatic tissues.

  10. Compared with Powdered Lutein, a Lutein Nanoemulsion Increases Plasma and Liver Lutein, Protects against Hepatic Steatosis, and Affects Lipoprotein Metabolism in Guinea Pigs.

    PubMed

    Murillo, Ana Gabriela; Aguilar, David; Norris, Gregory H; DiMarco, Diana M; Missimer, Amanda; Hu, Siqi; Smyth, Joan A; Gannon, Sarah; Blesso, Christopher N; Luo, Yangchao; Fernandez, Maria Luz

    2016-10-01

    It is not clear how oil-in-water nanoemulsions of lutein may affect bioavailability and consequently alter lipoprotein metabolism, oxidative stress, and inflammation. The bioavailability as well as effects of a powdered lutein (PL) and an oil-in-water lutein nanoemulsion (NANO; particle size: 254.2 nm; polydispersity index: 0.29; and ζ-potential: -65 mV) on metabolic variables in liver, plasma, and adipose tissue in a guinea pig model of hepatic steatosis were evaluated. Twenty-four 2-mo-old male Hartley guinea pigs, weighing 200-300 g (n = 8/group), were fed diets containing 0.25 g cholesterol/100 g to induce liver injury for the duration of the study. They were allocated to control (0 mg lutein), PL (3.5 mg/d), or NANO (3.5 mg/d) groups. After 6 wk, plasma, liver, and adipose tissue were collected for determination of lutein, plasma lipids, tissue cholesterol, and inflammatory cytokines. The NANO group had 2-fold higher concentrations of lutein in plasma (P < 0.001) and 1.6-fold higher concentrations in liver (P < 0.001) than did the PL group, indicating greater bioavailability of this carotenoid. The NANO group also had 24% lower hepatic steatosis scores (P < 0.05), 31% lower hepatic cholesterol accumulation (P < 0.05), and 64% lower plasma alanine aminotransferase (P < 0.05) than did the control group. Hepatic oxidized LDL was 55% lower in both the PL and NANO groups than in the control group (P < 0.05). In plasma, the NANO group had 2-fold higher concentrations of LDL and HDL cholesterol as well as a 2-fold higher number of VLDL, LDL, and HDL particles than did the other 2 groups as evaluated by nuclear magnetic resonance. Furthermore, the NANO group had 15% higher concentrations of free cholesterol in adipose tissue, resulting in higher concentrations of inflammatory markers, than did the other 2 groups. These results indicate that, although this lutein nanoemulsion exerted protective effects against hepatic steatosis, plasma lipoproteins and adipose tissue

  11. Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia.

    PubMed

    Rieg, Timo; Masuda, Takahiro; Gerasimova, Maria; Mayoux, Eric; Platt, Kenneth; Powell, David R; Thomson, Scott C; Koepsell, Hermann; Vallon, Volker

    2014-01-01

    In the kidney, the sodium-glucose cotransporters SGLT2 and SGLT1 are thought to account for >90 and ∼3% of fractional glucose reabsorption (FGR), respectively. However, euglycemic humans treated with an SGLT2 inhibitor maintain an FGR of 40-50%, mimicking values in Sglt2 knockout mice. Here, we show that oral gavage with a selective SGLT2 inhibitor (SGLT2-I) dose dependently increased urinary glucose excretion (UGE) in wild-type (WT) mice. The dose-response curve was shifted leftward and the maximum response doubled in Sglt1 knockout (Sglt1-/-) mice. Treatment in diet with the SGLT2-I for 3 wk maintained 1.5- to 2-fold higher urine glucose/creatinine ratios in Sglt1-/- vs. WT mice, associated with a temporarily greater reduction in blood glucose in Sglt1-/- vs. WT after 24 h (-33 vs. -11%). Subsequent inulin clearance studies under anesthesia revealed free plasma concentrations of the SGLT2-I (corresponding to early proximal concentration) close to the reported IC50 for SGLT2 in mice, which were associated with FGR of 64 ± 2% in WT and 17 ± 2% in Sglt1-/-. Additional intraperitoneal application of the SGLT2-I (maximum effective dose in metabolic cages) increased free plasma concentrations ∼10-fold and reduced FGR to 44 ± 3% in WT and to -1 ± 3% in Sglt1-/-. The absence of renal glucose reabsorption was confirmed in male and female Sglt1/Sglt2 double knockout mice. In conclusion, SGLT2 and SGLT1 account for renal glucose reabsorption in euglycemia, with 97 and 3% being reabsorbed by SGLT2 and SGLT1, respectively. When SGLT2 is fully inhibited by SGLT2-I, the increase in SGLT1-mediated glucose reabsorption explains why only 50-60% of filtered glucose is excreted.

  12. Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia

    PubMed Central

    Rieg, Timo; Masuda, Takahiro; Gerasimova, Maria; Mayoux, Eric; Platt, Kenneth; Powell, David R.; Thomson, Scott C.; Koepsell, Hermann

    2013-01-01

    In the kidney, the sodium-glucose cotransporters SGLT2 and SGLT1 are thought to account for >90 and ∼3% of fractional glucose reabsorption (FGR), respectively. However, euglycemic humans treated with an SGLT2 inhibitor maintain an FGR of 40–50%, mimicking values in Sglt2 knockout mice. Here, we show that oral gavage with a selective SGLT2 inhibitor (SGLT2-I) dose dependently increased urinary glucose excretion (UGE) in wild-type (WT) mice. The dose-response curve was shifted leftward and the maximum response doubled in Sglt1 knockout (Sglt1−/−) mice. Treatment in diet with the SGLT2-I for 3 wk maintained 1.5- to 2-fold higher urine glucose/creatinine ratios in Sglt1−/− vs. WT mice, associated with a temporarily greater reduction in blood glucose in Sglt1−/− vs. WT after 24 h (−33 vs. −11%). Subsequent inulin clearance studies under anesthesia revealed free plasma concentrations of the SGLT2-I (corresponding to early proximal concentration) close to the reported IC50 for SGLT2 in mice, which were associated with FGR of 64 ± 2% in WT and 17 ± 2% in Sglt1−/−. Additional intraperitoneal application of the SGLT2-I (maximum effective dose in metabolic cages) increased free plasma concentrations ∼10-fold and reduced FGR to 44 ± 3% in WT and to −1 ± 3% in Sglt1−/−. The absence of renal glucose reabsorption was confirmed in male and female Sglt1/Sglt2 double knockout mice. In conclusion, SGLT2 and SGLT1 account for renal glucose reabsorption in euglycemia, with 97 and 3% being reabsorbed by SGLT2 and SGLT1, respectively. When SGLT2 is fully inhibited by SGLT2-I, the increase in SGLT1-mediated glucose reabsorption explains why only 50–60% of filtered glucose is excreted. PMID:24226519

  13. Decreasing Efficacy of Antimalarial Combination Therapy in Uganda Explained by Decreasing Host Immunity Rather than Increasing Drug Resistance

    PubMed Central

    Greenhouse, Bryan; Slater, Madeline; Njama-Meya, Denise; Nzarubara, Bridget; Maiteki-Sebuguzi, Catherine; Clark, Tamara D.; Staedke, Sarah G.; Kamya, Moses R.; Hubbard, Alan; Rosenthal, Philip J.; Dorsey, Grant

    2009-01-01

    Background Improved control efforts are reducing the burden of malaria in Africa, but may result in decreased antimalarial immunity. Methods A cohort of 129 children aged 1–10 years in Kampala, Uganda were treated with amodiaquine+sulfadoxine-pyrimethamine for 396 episodes of uncomplicated malaria over a 29 month period as part of a longitudinal clinical trial. Results The risk of treatment failure increased over the course of the study from 5% to 21% (HR=2.4/yr, 95%CI=1.3–4.3). Parasite genetic polymorphisms were associated with an increased risk of failure, but their prevalence did not change over time. Three markers of antimalarial immunity were associated with a decreased risk of treatment failure: increased age (HR=0.5/5yrs, 95%CI=0.2–1.2), living in an area of higher malaria incidence (HR=0.26, 95%CI=0.11–0.64), and recent asymptomatic parasitemia (HR=0.06, 95%CI=0.01–0.36). In multivariate analysis, adjustment for recent asymptomatic parasitemia, but not parasite polymorphisms, removed the association between calendar time and the risk of treatment failure (HR=1.5/yr, 95%CI=0.7–3.4), suggesting that worsening treatment efficacy was best explained by decreasing host immunity. Conclusion Declining immunity in our study population appeared to be the primary factor underlying decreased efficacy of amodiaquine+sulfadoxine-pyrimethamine. With improved malaria control efforts, decreasing immunity may unmask resistance to partially efficacious drugs. PMID:19199542

  14. Exercise significantly increases plasma adrenaline and oxidized low-density lipoprotein in normal healthy subjects but not in persons with spinal cord injury.

    PubMed

    Mitsui, Toshihito; Nakamura, Takeshi; Ito, Tomoyuki; Umemoto, Yasunori; Sakamoto, Keiko; Kinoshita, Tokio; Nakagawa, Masafumi; Tajima, Fumihiro

    2012-04-01

    To compare plasma concentrations of oxidized low-density lipoprotein (oxLDL) and adrenaline during exercise between persons with spinal cord injury (SCI) and able-bodied (AB) individuals. Randomized controlled study. Human laboratory at a medical university. Persons with SCI (n=7) and AB individuals (n=9). Two-hour arm crank ergometer exercise at 60% maximum oxygen consumption. Plasma oxLDL and adrenaline levels. Exercise significantly increased plasma adrenaline levels in AB persons (mean ± SD: rest, 45.4±32.2 pg/mL; exercise, 200.9±113.7 pg/mL; P<.05) and persons with SCI; however; the magnitude of the increase in those with SCI was attenuated (mean ± SD: rest, 45.4±14.0 pg/mL; exercise, 83.0±55.8 pg/mL; P<.05). Exercise also significantly increased plasma oxLDL levels in AB persons (mean ± SD: rest, 102.2±30.2 U/L; exercise, 179.7±60.0 U/L; P<.05), but not in persons with SCI (mean ± SD: rest, 124.3±66.0 U/L; exercise, 138.9±59.5 U/L). The results suggest that increases in plasma adrenaline levels during exercise contribute to the increase in plasma oxLDL levels. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  15. Higher serum triglyceride to high-density lipoprotein cholesterol ratio was associated with increased cardiovascular mortality in female patients on peritoneal dialysis.

    PubMed

    Wu, H; Xiong, L; Xu, Q; Wu, J; Huang, R; Guo, Q; Mao, H; Yu, X; Yang, X

    2015-08-01

    High serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been found to be an independent predictor for cardiovascular events in the general population. We aimed to evaluate whether a high TG/HDL-C ratio was associated with an increased risk of mortality in patients on continuous ambulatory peritoneal dialysis (CAPD). In this single-center retrospective cohort study, 1170 incident patients on peritoneal dialysis (PD) from 1 January 2007 to 31 December 2011 were recruited and followed up until 31 December 31 2013. The mean age was 47.4 ± 15.2 years, and 24.7% were diabetic. During a median of the 34.5-month follow-up period, 213 (18.2%) deaths occurred, 121 of which (56.8%) were caused by cardiovascular disease (CVD). The serum median TG/HDL-C ratio at baseline was 2.57 (range: 0.06-39.39). On multivariate Cox regression analysis, the highest quartile of the TG/HDL-C ratio (≥4.19) was associated with increased risk of all-cause mortality (hazard ratio (HR) 1.98, 95% confidence interval (CI), 1.17-3.36; P = 0.011) and CVD mortality (HR 2.28, 95% CI, 1.16-4.47; P = 0.017). For female patients, each one-unit higher baseline TG/HDL-C was associated with 13% (95% CI 1.06-1.22; P = 0.001) increased risk of CVD mortality, whereas such an association was not observed for male patients, (HR 1.00, 95% CI 0.92-1.08; P = 0.977). A higher serum TG/HDL-C ratio was associated with an increased risk of all-cause and CVD mortality in PD patients. Moreover, the increased risk of CVD mortality was significantly higher in female than male PD patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Interferon-Free Treatment of Hepatitis C Virus in HIV/Hepatitis C Virus-Coinfected Subjects Results in Increased Serum Low-Density Lipoprotein Concentration

    PubMed Central

    Townsend, Kerry; Meissner, Eric G.; Sidharthan, Sreetha; Sampson, Maureen; Remaley, Alan T.; Tang, Lydia; Kohli, Anita; Osinusi, Anu; Masur, Henry

    2016-01-01

    Abstract Chronic hepatitis C virus (HCV) infection is associated with lower serum concentration of low-density lipoprotein (LDL-C), the primary cholesterol metabolite targeted pharmaceutically to modulate cardiovascular risk. Chronic infection with human immunodeficiency virus (HIV) and treatment with antiretrovirals (ARVs) are associated with dyslipidemia and increased risk of cardiovascular disease. In subjects coinfected with HIV and HCV, lipid abnormalities associated with either infection alone are often attenuated. Treatment of chronic HCV infection in HIV/HCV-coinfected subjects is now possible with interferon (IFN)-free regimens composed of directly acting antivirals (DAAs). We previously observed a marked increase in serum LDL-C in HCV-monoinfected subjects treated with sofosbuvir and ribavirin (SOF/RBV) that correlated with viral decline in serum, suggesting a direct influence of HCV clearance on serum cholesterol. In the present study, we assessed longitudinal changes in cholesterol in HIV/HCV-coinfected subjects during treatment of HCV genotype-1 (GT1) infection with combination DAA therapy. We report a rapid increase in LDL-C and LDL particle size by week 2 of treatment that was sustained during and after treatment in HIV/HCV-coinfected subjects. No change in serum LDL-C was observed at day 3 of treatment, in spite of a marked reduction in serum HCV viral load, suggesting LDL-C increases do not directly reflect HCV clearance as measured in peripheral blood. After effective DAA therapy for HCV, an increase in LDL should be anticipated in HIV/HCV-coinfected subjects. PMID:26559180

  17. Mechanism of hypertriglyceridemia in human apolipoprotein (apo) CIII transgenic mice. Diminished very low density lipoprotein fractional catabolic rate associated with increased apo CIII and reduced apo E on the particles.

    PubMed Central

    Aalto-Setälä, K; Fisher, E A; Chen, X; Chajek-Shaul, T; Hayek, T; Zechner, R; Walsh, A; Ramakrishnan, R; Ginsberg, H N; Breslow, J L

    1992-01-01

    Hypertriglyceridemia is common in the general population, but its mechanism is largely unknown. In previous work human apo CIII transgenic (HuCIIITg) mice were found to have elevated triglyceride levels. In this report, the mechanism for the hypertriglyceridemia was studied. Two different HuCIIITg mouse lines were used: a low expressor line with serum triglycerides of approximately 280 mg/dl, and a high expressor line with serum triglycerides of approximately 1,000 mg/dl. Elevated triglycerides were mainly in VLDL. VLDL particles were 1.5 times more triglyceride-rich in high expressor mice than in controls. The total amount of apo CIII (human and mouse) per VLDL particle was 2 and 2.5 times the normal amount in low and high expressors, respectively. Mouse apo E was decreased by 35 and 77% in low and high expressor mice, respectively. Under electron microscopy, VLDL particles from low and high expressor mice were found to have a larger mean diameter, 55.2 +/- 16.6 and 58.2 +/- 17.8 nm, respectively, compared with 51.0 +/- 13.4 nm from control mice. In in vivo studies, radiolabeled VLDL fractional catabolic rate (FCR) was reduced in low and high expressor mice to 2.58 and 0.77 pools/h, respectively, compared with 7.67 pools/h in controls, with no significant differences in the VLDL production rates. In an attempt to explain the reduced VLDL FCR in transgenic mice, tissue lipoprotein lipase (LPL) activity was determined in control and high expressor mice and no differences were observed. Also, VLDLs obtained from control and high expressor mice were found to be equally good substrates for purified LPL. Thus excess apo CIII in HuCIIITg mice does not cause reduced VLDL FCR by suppressing the amount of extractable LPL in tissues or making HuCIIITg VLDL a bad substrate for LPL. Tissue uptake of VLDL was studied in hepatoma cell cultures, and VLDL from transgenic mice was found to be taken up much more slowly than control VLDL (P < 0.0001), indicating that HuCIIITg VLDL is

  18. Dietary Tuna Dark Muscle Protein Attenuates Hepatic Steatosis and Increases Serum High-Density Lipoprotein Cholesterol in Obese Type-2 Diabetic/Obese KK-A(y) Mice.

    PubMed

    Maeda, Hayato; Hosomi, Ryota; Fukuda, Mari; Ikeda, Yuki; Yoshida, Munehiro; Fukunaga, Kenji

    2017-05-01

    Tuna muscle consists of light and dark muscle in approximately equal proportions. However, besides for the light muscle of tuna, cod, sardine, and salmon, few researches have assessed the health-promoting functions of fish protein. Therefore, we evaluated the mechanisms underlying the alteration of lipid storage and cholesterol metabolism following the intake of tuna dark muscle protein (TDMP) by obese type-2 diabetic/obese mice. Four-week-old male KK-A(y) mice were separated into 2 dietary groups, with one group receiving a casein-based diet and the other receiving a diet with the substitution of part of the protein (50%, w/w) by TDMP (TDMP diet) for 4 wk. The TDMP diet significantly increased the content of serum high-density lipoprotein cholesterol, partly due to the reduction of the expression of scavenger receptor class B member 1 in epididymal white adipose tissue. In addition, dietary TDMP decreased the content of hepatic triacylglycerol, which could be due to the enhancement of carnitine palmitoyltransferase-2 activity through the activation of the expression of the peroxisome proliferative activated receptor-α in the liver. These results suggest that TDMP could have the potential to prevent the development of obesity-related diseases by suppressing the storage of hepatic triacylglycerol and cholesterol. © 2017 Institute of Food Technologists®.

  19. In vitro Increased Respiratory Activity of Selected Oral Bacteria May Explain Competitive and Collaborative Interactions in the Oral Microbiome

    PubMed Central

    Hernandez-Sanabria, Emma; Slomka, Vera; Herrero, Esteban R.; Kerckhof, Frederiek-Maarten; Zaidel, Lynette; Teughels, Wim; Boon, Nico

    2017-01-01

    Understanding the driving forces behind the shifts in the ecological balance of the oral microbiota will become essential for the future management and treatment of periodontitis. As the use of competitive approaches for modulating bacterial outgrowth is unexplored in the oral ecosystem, our study aimed to investigate both the associations among groups of functional compounds and the impact of individual substrates on selected members of the oral microbiome. We employed the Phenotype Microarray high-throughput technology to analyse the microbial cellular phenotypes of 15 oral bacteria. Multivariate statistical analysis was used to detect respiratory activity triggers and to assess similar metabolic activities. Carbon and nitrogen were relevant for the respiration of health-associated bacteria, explaining competitive interactions when grown in biofilms. Carbon, nitrogen, and peptides tended to decrease the respiratory activity of all pathobionts, but not significantly. None of the evaluated compounds significantly increased activity of pathobionts at both 24 and 48 h. Additionally, metabolite requirements of pathobionts were dissimilar, suggesting that collective modulation of their respiratory activity may be challenging. Flow cytometry indicated that the metabolic activity detected in the Biolog plates may not be a direct result of the number of bacterial cells. In addition, damage to the cell membrane may not influence overall respiratory activity. Our methodology confirmed previously reported competitive and collaborative interactions among bacterial groups, which could be used either as marker of health status or as targets for modulation of the oral environment. PMID:28638806

  20. In vitro Increased Respiratory Activity of Selected Oral Bacteria May Explain Competitive and Collaborative Interactions in the Oral Microbiome.

    PubMed

    Hernandez-Sanabria, Emma; Slomka, Vera; Herrero, Esteban R; Kerckhof, Frederiek-Maarten; Zaidel, Lynette; Teughels, Wim; Boon, Nico

    2017-01-01

    Understanding the driving forces behind the shifts in the ecological balance of the oral microbiota will become essential for the future management and treatment of periodontitis. As the use of competitive approaches for modulating bacterial outgrowth is unexplored in the oral ecosystem, our study aimed to investigate both the associations among groups of functional compounds and the impact of individual substrates on selected members of the oral microbiome. We employed the Phenotype Microarray high-throughput technology to analyse the microbial cellular phenotypes of 15 oral bacteria. Multivariate statistical analysis was used to detect respiratory activity triggers and to assess similar metabolic activities. Carbon and nitrogen were relevant for the respiration of health-associated bacteria, explaining competitive interactions when grown in biofilms. Carbon, nitrogen, and peptides tended to decrease the respiratory activity of all pathobionts, but not significantly. None of the evaluated compounds significantly increased activity of pathobionts at both 24 and 48 h. Additionally, metabolite requirements of pathobionts were dissimilar, suggesting that collective modulation of their respiratory activity may be challenging. Flow cytometry indicated that the metabolic activity detected in the Biolog plates may not be a direct result of the number of bacterial cells. In addition, damage to the cell membrane may not influence overall respiratory activity. Our methodology confirmed previously reported competitive and collaborative interactions among bacterial groups, which could be used either as marker of health status or as targets for modulation of the oral environment.

  1. Pioglitazone-induced increase in the stearoyl-CoA desaturation index and fat accumulation in rat muscles are not related to lipoprotein lipase activity.

    PubMed

    Ochiai, Masaru; Matsuo, Tatsuhiro

    2013-01-01

    Muscular insulin resistance is a characteristic of obesity and type 2 diabetes, but little is known about fatty acid (FA) metabolism in insulin-resistant skeletal muscle. In this study, we investigated the effects of the repeated administration of the PPAR-γ agonist pioglitazone on fat accumulation, FA composition, and stearoyl-CoA desaturase (SCD) index in rat tissues. Seventeen 4-week-old male Wistar rats were divided into control (C, n = 9) and pioglitazone treatment (P, n = 8) groups, and all the rats were fed a high-fat and high-sucrose diet for 8 weeks. Vehicle or pioglitazone (3 mg/kg) was orally administered daily to rats in the C group and P group, respectively. In the eighth week of the test period, an oral glucose tolerance test (OGTT) was performed after 12 h fasting. At the end of the test period, serum, liver, perirenal adipose tissue, and skeletal muscles were removed after 12 h fasting. The fasting serum and plasma glucose concentrations and OGTT glucose and insulin levels were significantly lower, while the serum adiponectin concentration was significantly higher in the P group than in the C group. Pioglitazone administration increased fat accumulation in the various muscle types examined, perirenal adipose tissue, and brown adipose tissue (BAT), but decreased fat accumulation in the liver. Pioglitazone administration increased the SCD indices for the muscles, perirenal adipose tissue, and liver, but not those of BAT. The lipoprotein lipase (LPL) activity of the BAT and perirenal adipose tissue, but not the muscles, was higher in the P group than in the C group. These results indicate that pioglitazone administration improved glucose tolerance and increased fat accumulation and SCD indices in the muscles and adipose tissues of rats. The increased fat accumulation was closely correlated with LPL activity in both adipose tissues, but not in the muscles.

  2. Consumption of wonderful variety pomegranate juice and extract by diabetic patients increases paraoxonase 1 association with high-density lipoprotein and stimulates its catalytic activities.

    PubMed

    Rock, Wasseem; Rosenblat, Mira; Miller-Lotan, Rachel; Levy, Andrew P; Elias, Mazen; Aviram, Michael

    2008-09-24

    Association of paraoxonase 1 (PON1) with high-density lipoprotein (HDL) stabilizes the enzyme. In diabetic patients, PON1 dissociates from HDL and, as a consequence, is less biologically active. Our aim was to investigate the effects of Wonderful variety pomegranate juice (WPJ) and pomegranate polyphenol extract (WPOMxl) consumption on PON1 association with HDL in diabetic patients. Thirty patients with type 2 diabetes mellitus participated in the study. Ten male patients and 10 female patients received concentrated WPJ (50 mL/day for 4 weeks), while another group of 10 male patients received WPOMxl (5 mL/day for 6 weeks). There were no significant effects of WPJ or WPOMxl consumption on fasting blood glucose or hemoglobin A1c levels. After 4 weeks of WPJ consumption by male patients, basal serum oxidative stress was significantly decreased by 35%, whereas serum concentrations of thiol groups significantly increased by 25%. Moreover, HDL-associated PON1 arylesterase, paraoxonase, and lactonase activities increased significantly after WPJ consumption by 34-45%, as compared to the baseline levels. PON1 protein binding to HDL was significantly increased by 30% following WPJ consumption, and the enzyme became more stable. In male patients that consumed WPOMxl and in female patients that consumed PJ, a similar pattern was observed, although to a lesser extent. We conclude that WPJ as well as WPOMxl consumption by diabetic patients does not worsen their diabetic parameters. Furthermore, WPJ as well as WPOMxl consumption contribute to PON1 stabilization, increased association with HDL, and enhanced catalytic activities. These beneficial effects of pomegranate consumption on serum PON1 stability and activity could lead to retardation of atherosclerosis development in diabetic patients.

  3. A germ-line-selective advantage rather than an increased mutation rate can explain some unexpectedly common human disease mutations.

    PubMed

    Choi, Soo-Kyung; Yoon, Song-Ro; Calabrese, Peter; Arnheim, Norman

    2008-07-22

    Two nucleotide substitutions in the human FGFR2 gene (C755G or C758G) are responsible for virtually all sporadic cases of Apert syndrome. This condition is 100-1,000 times more common than genomic mutation frequency data predict. Here, we report on the C758G de novo Apert syndrome mutation. Using data on older donors, we show that spontaneous mutations are not uniformly distributed throughout normal testes. Instead, we find foci where C758G mutation frequencies are 3-4 orders of magnitude greater than the remaining tissue. We conclude this nucleotide site is not a mutation hot spot even after accounting for possible Luria-Delbruck "mutation jackpots." An alternative explanation for such foci involving positive selection acting on adult self-renewing Ap spermatogonia experiencing the rare mutation could not be rejected. Further, the two youngest individuals studied (19 and 23 years old) had lower mutation frequencies and smaller foci at both mutation sites compared with the older individuals. This implies that the mutation frequency of foci increases as adults age, and thus selection could explain the paternal age effect for Apert syndrome and other genetic conditions. Our results, now including the analysis of two mutations in the same set of testes, suggest that positive selection can increase the relative frequency of premeiotic germ cells carrying such mutations, although individuals who inherit them have reduced fitness. In addition, we compared the anatomical distribution of C758G mutation foci with both new and old data on the C755G mutation in the same testis and found their positions were not correlated with one another.

  4. Krill oil supplementation lowers serum triglycerides without increasing low-density lipoprotein cholesterol in adults with borderline high or high triglyceride levels.

    PubMed

    Berge, Kjetil; Musa-Veloso, Kathy; Harwood, Melody; Hoem, Nils; Burri, Lena

    2014-02-01

    The aim of the study was to explore the effects of 12 weeks daily krill oil supplementation on fasting serum triglyceride (TG) and lipoprotein particle levels in subjects whose habitual fish intake is low and who have borderline high or high fasting serum TG levels (150-499 mg/dL). We hypothesized that Krill oil lowers serum TG levels in subjects with borderline high or high fasting TG levels. To test our hypothesis 300 male and female subjects were included in a double-blind, randomized, multi-center, placebo-controlled study with five treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil. Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks. Due to a high intra-individual variability in TG levels, data from all subjects in the four krill oil groups were pooled to increase statistical power, and a general time- and dose-independent one-way analysis of variance was performed to assess efficacy. Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups relative to the placebo group. The outcome of the pooled analysis suggests that krill oil is effective in reducing a cardiovascular risk factor. However, owing to the individual fluctuations of TG concentrations measured, a study with more individual measurements per treatment group is needed to increase the confidence of these findings. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Increased alertness, better than posture prioritization, explains dual-task performance in prosthesis users and controls under increasing postural and cognitive challenge.

    PubMed

    Howard, Charla L; Perry, Bonnie; Chow, John W; Wallace, Chris; Stokic, Dobrivoje S

    2017-08-31

    Sensorimotor impairments after limb amputation impose a threat to stability. Commonly described strategies for maintaining stability are the posture first strategy (prioritization of balance) and posture second strategy (prioritization of concurrent tasks). The existence of these strategies was examined in 13 below-knee prosthesis users and 15 controls during dual-task standing under increasing postural and cognitive challenge by evaluating path length, 95% sway area, and anterior-posterior and medial-lateral amplitudes of the center of pressure. The subjects stood on two force platforms under usual (hard surface/eyes open) and difficult (soft surface/eyes closed) conditions, first alone and while performing a cognitive task without and then with instruction on cognitive prioritization. During standing alone, sway was not significantly different between groups. After adding the cognitive task without prioritization instruction, prosthesis users increased sway more under the dual-task than single-task standing (p ≤ 0.028) during both usual and difficult conditions, favoring the posture second strategy. Controls, however, reduced dual-task sway under a greater postural challenge (p ≤ 0.017), suggesting the posture first strategy. With prioritization of the cognitive task, sway was unchanged or reduced in prosthesis users, suggesting departure from the posture second strategy, whereas controls maintained the posture first strategy. Individual analysis of dual tasking revealed that greater postural demand in controls and greater cognitive challenge in prosthesis users led to both reduced sway and improved cognitive performance, suggesting cognitive-motor facilitation. Thus, activation of additional resources through increased alertness, rather than posture prioritization, may explain dual-task performance in both prosthesis users and controls under increasing postural and cognitive challenge.

  6. Integration between Glycolysis and Glutamate-Glutamine Cycle Flux May Explain Preferential Glycolytic Increase during Brain Activation, Requiring Glutamate.

    PubMed

    Hertz, Leif; Chen, Ye

    2017-01-01

    The 1988 observation by Fox et al. (1988) that brief intense brain activation increases glycolysis (pyruvate formation from glucose) much more than oxidative metabolism has been abundantly confirmed. Specifically glycolytic increase was unexpected because the amount of ATP it generates is much smaller than that formed by subsequent oxidative metabolism of pyruvate. The present article shows that preferential glycolysis can be explained by metabolic processes associated with activation of the glutamate-glutamine cycle. The flux in this cycle, which is essential for production of transmitter glutamate and GABA, equals 75% of brain glucose utilization and each turn is associated with utilization of ~1 glucose molecule. About one half of the association between cycle flux and glucose metabolism occurs during neuronal conversion of glutamine to glutamate in a process similar to the malate-aspartate shuttle (MAS) except that glutamate is supplied from glutamine, not formed from α-ketoglutarate (αKG) as during operation of conventional MAS. Regular MAS function is triggered by one oxidative process in the cytosol during glycolysis causing NAD(+) reduction to NADH. Since NADH cannot cross the mitochondrial membrane (MEM) for oxidation NAD(+) is re-generated by conversion of cytosolic oxaloacetate (OAA) to malate, which enters the mitochondria for oxidation and in a cyclic process regenerates cytosolic OAA. Therefore MAS as well as the "pseudo-MAS" necessary for neuronal glutamate formation can only operate together with cytosolic reduction of NAD(+) to NADH. The major process causing NAD(+) reduction is glycolysis which therefore also must occur during neuronal conversion of glutamine to glutamate and may energize vesicular glutamate uptake which preferentially uses glycolytically derived energy. Another major contributor to the association between glutamate-glutamine cycle and glucose utilization is the need for astrocytic pyruvate to generate glutamate. Although some

  7. Integration between Glycolysis and Glutamate-Glutamine Cycle Flux May Explain Preferential Glycolytic Increase during Brain Activation, Requiring Glutamate

    PubMed Central

    Hertz, Leif; Chen, Ye

    2017-01-01

    The 1988 observation by Fox et al. (1988) that brief intense brain activation increases glycolysis (pyruvate formation from glucose) much more than oxidative metabolism has been abundantly confirmed. Specifically glycolytic increase was unexpected because the amount of ATP it generates is much smaller than that formed by subsequent oxidative metabolism of pyruvate. The present article shows that preferential glycolysis can be explained by metabolic processes associated with activation of the glutamate-glutamine cycle. The flux in this cycle, which is essential for production of transmitter glutamate and GABA, equals 75% of brain glucose utilization and each turn is associated with utilization of ~1 glucose molecule. About one half of the association between cycle flux and glucose metabolism occurs during neuronal conversion of glutamine to glutamate in a process similar to the malate-aspartate shuttle (MAS) except that glutamate is supplied from glutamine, not formed from α-ketoglutarate (αKG) as during operation of conventional MAS. Regular MAS function is triggered by one oxidative process in the cytosol during glycolysis causing NAD+ reduction to NADH. Since NADH cannot cross the mitochondrial membrane (MEM) for oxidation NAD+ is re-generated by conversion of cytosolic oxaloacetate (OAA) to malate, which enters the mitochondria for oxidation and in a cyclic process regenerates cytosolic OAA. Therefore MAS as well as the “pseudo-MAS” necessary for neuronal glutamate formation can only operate together with cytosolic reduction of NAD+ to NADH. The major process causing NAD+ reduction is glycolysis which therefore also must occur during neuronal conversion of glutamine to glutamate and may energize vesicular glutamate uptake which preferentially uses glycolytically derived energy. Another major contributor to the association between glutamate-glutamine cycle and glucose utilization is the need for astrocytic pyruvate to generate glutamate. Although some

  8. Increased Remnant Cholesterol Explains Part of Residual Risk of All-Cause Mortality in 5414 Patients with Ischemic Heart Disease.

    PubMed

    Jepsen, Anne-Marie K; Langsted, Anne; Varbo, Anette; Bang, Lia E; Kamstrup, Pia R; Nordestgaard, Børge G

    2016-04-01

    concentrations of measured LDL cholesterol. This suggests that increased concentrations of remnant cholesterol explain part of the residual risk of all-cause mortality in patients with ischemic heart disease. © 2016 American Association for Clinical Chemistry.

  9. Reconfiguring health workforce: a case-based comparative study explaining the increasingly diverse professional roles in Europe.

    PubMed

    de Bont, Antoinette; van Exel, Job; Coretti, Silvia; Ökem, Zeynep Güldem; Janssen, Maarten; Hope, Kristin Lofthus; Ludwicki, Tomasz; Zander, Britta; Zvonickova, Marie; Bond, Christine; Wallenburg, Iris

    2016-11-08

    Over the past decade the healthcare workforce has diversified in several directions with formalised roles for health care assistants, specialised roles for nurses and technicians, advanced roles for physician associates and nurse practitioners and new professions for new services, such as case managers. Hence the composition of health care teams has become increasingly diverse. The exact extent of this diversity is unknown across the different countries of Europe, as are the drivers of this change. The research questions guiding this study were: What extended professional roles are emerging on health care teams? How are extended professional roles created? What main drivers explain the observed differences, if any, in extended roles in and between countries? We performed a case-based comparison of the extended roles in care pathways for breast cancer, heart disease and type 2 diabetes. We conducted 16 case studies in eight European countries, including in total 160 interviews with physicians, nurses and other health care professionals in new roles and 600+ hours of observation in health care clinics. The results show a relatively diverse composition of roles in the three care pathways. We identified specialised roles for physicians, extended roles for nurses and technicians, and independent roles for advanced nurse practitioners and physician associates. The development of extended roles depends upon the willingness of physicians to delegate tasks, developments in medical technology and service (re)design. Academic training and setting a formal scope of practice for new roles have less impact upon the development of new roles. While specialised roles focus particularly on a well-specified technical or clinical domain, the generic roles concentrate on organising and integrating care and cure. There are considerable differences in the number and kind of extended roles between both countries and care pathways. The main drivers for new roles reside in the technological

  10. High-density lipoprotein cholesterol increases following a short-term yoga-based lifestyle intervention: a non-pharmacological modulation.

    PubMed

    Yadav, Raj Kumar; Magan, Dipti; Yadav, Rashmi; Sarvottam, Kumar; Netam, Ritesh

    2014-10-01

    The objective of the study was to assess the effect of a brief but comprehensive yoga-based lifestyle intervention on high-density lipoprotein cholesterol (HDL-c). This prospective interventional study was performed at the Integral Health Clinic (IHC), an outpatient facility at All India Institute of Medical Sciences, New Delhi, a tertiary health care centre, conducting yoga-based lifestyle intervention programmes for prevention and management of chronic diseases. The study included apparently healthy normal weight, overweight and obese subjects who underwent a pretested 10-day yoga-based programme including asanas (postures), pranayama (breathing exercises), meditation, group discussions, lectures and individualized advice on stress management and healthy diet. The primary outcome measure was change in serum HDL-c at day 10 versus day 0. 238 participants (147 women, 91 men, 38.81±11.40 years) were included in the study. There was a significant increase in HDL-c levels from baseline to day 10 (42.93±5.00 vs 43.52±5.07 mg/dL, P = 0.043). Notably, HDL-c was significantly improved in those for whom the baseline HDL-c levels were lower than the recommended values. Also, there was a reduction in blood pressure, fasting blood glucose, and improvement in other lipid profile variables. This yoga-based lifestyle intervention significantly increased HDL-c levels in a short duration of 10 days. This has additional clinical relevance as HDL-c is suggested to be one of the strongest statistically independent predictors of major cardiovascular events.

  11. Phospholipase D-modified low density lipoprotein is taken up by macrophages at increased rate. A possible role for phosphatidic acid.

    PubMed Central

    Aviram, M; Maor, I

    1993-01-01

    Macrophage uptake of modified forms of LDL leads to cellular cholesterol accumulation. Upon incubation of LDL with phospholipase D (PLase D), a time- and enzyme dose-dependent production of phosphatidic acid (PA), paralleled by a rapid reduction in LDL phosphatidyl choline content (up to 65% within 15 min of incubation) was noted. No lipid peroxidation could be found in PLase D-modified LDL. Upon in vitro incubation of PLase D-LDL with copper ions, however, this modified LDL was substantially oxidized. The addition of 100 micrograms PA/ml to native LDL for the period of its in vitro oxidation resulted in a 63% elevation in the lipoprotein peroxides content. Incubation of PLase D-LDL with J-774A.1 macrophage-like cell line resulted in an increase in its cellular binding and degradation (up to 91 and 110%, respectively) in comparison with native LDL (via the LDL receptor). When PA was added to LDL before its incubation with the macrophages, a PA dose-dependent elevation in the cellular uptake of LDL (by up to twofold) was noted in comparison with LDL that was incubated without PA, suggesting that PA production in PLase D-LDL may be involved in the increased cellular uptake of PLase D-LDL. PLase D activity towards LDL was demonstrated in J-774A.1 macrophages. Human plasma was also shown to possess PLase D activity. Thus, PLase D modification of LDL may take place under certain pathological conditions and PLase D-LDL interaction with arterial wall macrophages can potentially lead to foam cell formation. PMID:8486764

  12. Use of plasma triglyceride/high-density lipoprotein cholesterol ratio to identify increased cardio-metabolic risk in young, healthy South Asians.

    PubMed

    Flowers, Elena; Molina, César; Mathur, Ashish; Reaven, Gerald M

    2015-01-01

    Prevalence of insulin resistance and associated dyslipidaemia [high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations] are increased in South Asian individuals; likely contributing to their increased risk of type-2 diabetes and cardiovascular disease. The plasma concentration ratio of TG/HDL-C has been proposed as a simple way to identify apparently healthy individuals at high cardio-metabolic risk. This study was carried out to compare the cardio-metabolic risk profiles of high-risk South Asian individuals identified by an elevated TG/HDL-C ratio versus those with a diagnosis of the metabolic syndrome. Body mass index, waist circumference, blood pressure, and fasting plasma glucose, insulin, TG, and HDL-C concentrations were determined in apparently healthy men (n=498) and women (n=526). The cardio-metabolic risk profile of "high risk" individuals identified by TG/HDL-C ratios in men (≥ 3.5) and women (≥2.5) was compared to those identified by a diagnosis of the metabolic syndrome. More concentrations of all cardio-metabolic risk factors were significantly higher in "high risk" groups, identified by either the TG/HDL-C ratio or a diagnosis of the metabolic syndrome. TG, HDL-C, and insulin concentrations were not significantly different in "high risk" groups identified by either criterion, whereas plasma glucose and blood pressure were higher in those with the metabolic syndrome. Apparently healthy South Asian individuals at high cardio-metabolic risk can be identified using either the TG/HDL-C ratio or the metabolic syndrome criteria. The TG/HDL-C ratio may be used as a simple marker to identify such individuals.

  13. Dietary non-tocopherol antioxidants present in extra virgin olive oil increase the resistance of low density lipoproteins to oxidation in rabbits.

    PubMed

    Wiseman, S A; Mathot, J N; de Fouw, N J; Tijburg, L B

    1996-02-01

    Consumption of a range of dietary antioxidants may be beneficial in protecting low density lipoprotein (LDL) against oxidative modification, as studies have demonstrated that antioxidants other than vitamin E may also function against oxidation of LDL in vitro. In the present study, the effect of polyphenol antioxidants on the susceptibility of LDL to copper-mediated oxidation was investigated after feeding semi-purified diets to 3 groups of New Zealand white (NZW) rabbits. All diets comprised 40% energy as fat with 17% energy as oleic acid. Dietary fatty acid compositions were identical. Oils with different polyphenol contents were used to provide the dietary source of oleic acid-refined olive oil, extra virgin olive oil and Trisun high oleic sunflower seed oil. Polyphenolic compounds (hydroxytyrosol and p-tyrosol) could only be detected in the extra virgin olive oil. Vitamin E was equalised in all diets. LDL oxidizability in vitro was determined by continuously monitoring the copper-induced formation of conjugated dienes after 6 weeks of experimental diet feeding. The lag phase before demonstrable oxidation occurred was significantly increased in the high polyphenol, extra virgin olive oil group (P < 0.05) when compared with combined results from the low polyphenol group (refined olive oil and Trisun), even though the LDL vitamin E concentration in the high polyphenol group was significantly lower. The rate of conjugated diene formation was not influenced by the presence of dietary polyphenols. Results demonstrate that antioxidants, possibly phenolic compounds which are present only in extra virgin olive oil, may contribute to the endogenous antioxidant capacity of LDL, resulting in an increased resistance to oxidation as determined in vitro.

  14. Effect of atorvastatin on postcardiac transplant increase in low-density lipoprotein cholesterol reduces development of intimal hyperplasia and progression of endothelial dysfunction.

    PubMed

    See, Vincent Y; DeNofrio, David; Goldberg, Lee; Chang, Gene; Sasseen, Brett; Kolansky, Daniel M; Pickering, Faith; Kao, Andrew; Loh, Evan; Wilensky, Robert L

    2003-07-01

    Following cardiac transplantation, accelerated coronary disease limits long-term survival. Because statins may reduce the progression of the disease in part by their anti-inflammatory effects, this study was designed to assess if atorvastatin prevented neointimal hyperplasia and endothelial dysfunction independently of baseline cholesterol levels. Patients were randomized to usual therapy (n = 13) or to 10 to 20 mg of atorvastatin (n = 12). Control subjects received niacin when their low-density lipoprotein (LDL) cholesterol levels were >130 mg/dl (n = 4). Neointimal hyperplasia by intracoronary ultrasonography, endothelial dependent vascular reactivity, and coronary flow reserve were measured at baseline and 1 year. Control group total cholesterol (203 +/- 11 to 200 +/- 13 mg/dl) and LDL (116 +/- 10 to 119 +/- 11 mg/dl) remained stable, whereas there was a nonsignificant reduction at 12 months in the atorvastatin group (total cholesterol 216 +/- 28 to 178 +/- 21 mg/dl; LDL 126 +/- 17 to 100 +/- 18 mg/dl). At 2 to 3 months there was a significant increase in total cholesterol and LDL cholesterol that was reduced with atorvastatin. At 1 year, patients taking atorvastatin showed a decrease in new or progressing lesions (2.5 +/- 1.7 vs 4.2 +/- 1.8 lesions/patient, p = 0.02), progression of maximal intimal thickness (0.12 +/- 0.07 vs 0.52 +/- 0.17 mm, p = 0.04), and percent area stenosis (5.9 +/- 2.2% vs 19.0 +/- 5.5%, p = 0.04). Atorvastatin ameliorated progressive endothelial dysfunction, whereas coronary flow reserve was unchanged in both groups. Atorvastatin administered to patients with normal or mild hypercholesterolemia in the initial year after transplant reduced the initial increase in LDL cholesterol, and, by doing so, prevented the development and progression of coronary artery lesions and endothelial dysfunction with only mild long-term decreases in cholesterol levels.

  15. Low physical activity is associated with proinflammatory high-density lipoprotein and increased subclinical atherosclerosis in women with systemic lupus erythematosus.

    PubMed

    Volkmann, Elizabeth R; Grossman, Jennifer M; Sahakian, Lori J; Skaggs, Brian J; FitzGerald, John; Ragavendra, Nagesh; Charles-Schoeman, Christina; Chen, Weiling; Gorn, Alan; Karpouzas, George; Weisman, Michael; Wallace, Daniel J; Hahn, Bevra H; McMahon, Maureen

    2010-02-01

    To investigate the association between physical activity, functional activity of high-density lipoprotein (HDL), and subclinical cardiovascular disease in patients with systemic lupus erythematosus (SLE). A total of 242 SLE patients (all women) participated in this cross-sectional study from February 2004 to February 2008. Carotid plaque and intima-media thickness (IMT), antioxidant function of HDL, and traditional cardiac risk factors were measured. Physical activity was assessed from self-reports by calculating the metabolic equivalents (METS) per week and by the physical function domain of the Medical Outcomes Study Short Form 36 (SF-36). Data were analyzed using bivariate and multivariate regression analyses. Number of METS per week spent performing strenuous exercise was negatively correlated with IMT (r = -0.4, P = 0.002) and number of plaques (r = -0.30, P = 0.0001). Physical function as assessed by the SF-36 was also negatively correlated with IMT (r = -0.14, P = 0.03) and number of plaques (r = -0.14, P = 0.04). In multivariate analyses, number of strenuous exercise METS was significantly associated with IMT (t = -2.2, P = 0.028) and number of plaques (t = -2.5, P = 0.014) when controlling for markers of SLE disease activity and damage, but not after controlling for traditional cardiac risk factors. Low physical activity, defined as <225 total METS per week, was associated with the presence of proinflammatory HDL (P = 0.03). Low physical activity is associated with increased subclinical atherosclerosis and proinflammatory HDL in patients with SLE. Increased strenuous exercise may reduce the risk of atherosclerosis in SLE.

  16. Hepatic very-low-density lipoprotein and apolipoprotein B production are increased following in vivo induction of betaine–homocysteine S-methyltransferase

    PubMed Central

    Sparks, Janet D.; Collins, Heidi L.; Chirieac, Doru V.; Cianci, Joanne; Jokinen, Jenny; Sowden, Mark P.; Galloway, Chad A.; Sparks, Charles E.

    2006-01-01

    We have previously reported a positive correlation between the expression of BHMT (betaine–homocysteine S-methyltransferase) and ApoB (apolipoprotein B) in rat hepatoma McA (McArdle RH-7777) cells [Sowden, Collins, Smith, Garrow, Sparks and Sparks (1999) Biochem. J. 341, 639–645]. To examine whether a similar relationship occurs in vivo, hepatic BHMT expression was induced by feeding rats a Met (L-methionine)-restricted betaine-containing diet, and parameters of ApoB metabolism were evaluated. There were no generalized metabolic abnormalities associated with Met restriction for 7 days, as evidenced by control levels of serum glucose, ketones, alanine aminotransferase and L-homocysteine levels. Betaine plus the Met restriction resulted in lower serum insulin and non-esterified fatty acid levels. Betaine plus Met restriction induced hepatic BHMT 4-fold and ApoB mRNA 3-fold compared with Met restriction alone. No changes in percentage of edited ApoB mRNA were observed on the test diets. An increase in liver ApoB mRNA correlated with an 82% and 46% increase in ApoB and triacylglycerol production respectively using in vivo Triton WR 1339. Increased secretion of VLDL (very-low-density lipoprotein) with Met restriction plus betaine was associated with a 45% reduction in liver triacylglycerol compared with control. Nuclear run-off assays established that transcription of both bhmt and apob genes was also increased in Met-restricted plus betaine diets. No change in ApoB mRNA stability was detected in BHMT-transfected McA cells. Hepatic ApoB and BHMT mRNA levels were also increased by 1.8- and 3-fold respectively by betaine supplementation of Met-replete diets. Since dietary betaine increased ApoB mRNA, VLDL ApoB and triacylglycerol production and decreased hepatic triacylglycerol, results suggest that induction of apob transcription may provide a potential mechanism for mobilizing hepatic triacylglycerol by increasing ApoB available for VLDL assembly and secretion

  17. Hepatic very-low-density lipoprotein and apolipoprotein B production are increased following in vivo induction of betaine-homocysteine S-methyltransferase.

    PubMed

    Sparks, Janet D; Collins, Heidi L; Chirieac, Doru V; Cianci, Joanne; Jokinen, Jenny; Sowden, Mark P; Galloway, Chad A; Sparks, Charles E

    2006-04-15

    We have previously reported a positive correlation between the expression of BHMT (betaine-homocysteine S-methyltransferase) and ApoB (apolipoprotein B) in rat hepatoma McA (McArdle RH-7777) cells [Sowden, Collins, Smith, Garrow, Sparks and Sparks (1999) Biochem. J. 341, 639-645]. To examine whether a similar relationship occurs in vivo, hepatic BHMT expression was induced by feeding rats a Met (L-methionine)-restricted betaine-containing diet, and parameters of ApoB metabolism were evaluated. There were no generalized metabolic abnormalities associated with Met restriction for 7 days, as evidenced by control levels of serum glucose, ketones, alanine aminotransferase and L-homocysteine levels. Betaine plus the Met restriction resulted in lower serum insulin and non-esterified fatty acid levels. Betaine plus Met restriction induced hepatic BHMT 4-fold and ApoB mRNA 3-fold compared with Met restriction alone. No changes in percentage of edited ApoB mRNA were observed on the test diets. An increase in liver ApoB mRNA correlated with an 82% and 46% increase in ApoB and triacylglycerol production respectively using in vivo Triton WR 1339. Increased secretion of VLDL (very-low-density lipoprotein) with Met restriction plus betaine was associated with a 45% reduction in liver triacylglycerol compared with control. Nuclear run-off assays established that transcription of both bhmt and apob genes was also increased in Met-restricted plus betaine diets. No change in ApoB mRNA stability was detected in BHMT-transfected McA cells. Hepatic ApoB and BHMT mRNA levels were also increased by 1.8- and 3-fold respectively by betaine supplementation of Met-replete diets. Since dietary betaine increased ApoB mRNA, VLDL ApoB and triacylglycerol production and decreased hepatic triacylglycerol, results suggest that induction of apob transcription may provide a potential mechanism for mobilizing hepatic triacylglycerol by increasing ApoB available for VLDL assembly and secretion.

  18. IMMUNOLOGIC STUDIES OF HUMAN HIGH DENSITY LIPOPROTEINS

    PubMed Central

    DeLalla, Louis; Levine, Lawrence; Brown, Ray K.

    1957-01-01

    High density serum lipoprotein underwent serologic and physicochemical alterations on aging during storage at 0°C. for 1 month, as judged by decrease of diffusion coefficient and increase of C' fixation. Ultracentrifugation, dialysis, and high concentrations of sodium chloride did not cause these changes. A protein sedimenting at density 1.24 in the ultracentrifuge reacted with antiserum to high density lipoprotein. Probably it was the protein portion of α lipoprotein dissociated from the lipide during ultracentrifugation. Although the antiserum to high density lipoprotein did not react with low density lipoprotein prepared from normal serum, it reacted with similarly prepared lipoproteins from the serum of a patient with biliary cirrhosis. PMID:13449236

  19. trans-10,cis-12 Conjugated linoleic acid inhibits lipoprotein lipase but increases the activity of lipogenic enzymes in adipose tissue from hamsters fed an atherogenic diet.

    PubMed

    Zabala, Amaia; Churruca, Itziar; Fernández-Quintela, Alfredo; Rodríguez, Víctor M; Macarulla, M Teresa; Martínez, J Alfredo; Portillo, María P

    2006-06-01

    The aim of the present work was to investigate the effects of trans-10,cis-12 conjugated linoleic acid (CLA) on the activity and expression of lipogenic enzymes and lipoprotein lipase (LPL), as well as on the expression of transcriptional factors controlling these enzymes, in adipose tissue from hamsters, and to evaluate the involvement of these changes in the body fat-reducing effect of this CLA isomer. Thirty male hamsters were divided into three groups and fed atherogenic diets supplemented with 0 (linoleic group), 5 or 10 g trans-10,cis-12 CLA/kg diet, for 6 weeks. Body and adipose tissue weights, food intake and serum insulin were measured. Total and heparin-releasable LPL and lipogenic enzyme activities (acetyl-CoA carboxylase (ACC); fatty acid synthase (FAS); glucose-6-phosphate dehydrogenase (G6PDH); and malic enzyme (ME)) were assessed. ACC, FAS, LPL, sterol regulatory element-binding proteins (SREBP-1a), SREBP-1c and PPARgamma mRNA levels were also determined by real-time PCR. CLA did not modify food intake, body weight and serum insulin level. CLA feeding reduced adipose tissue weight, LPL activity and expression, and increased lipogenic enzyme activities, despite a significant reduction in ACC and FAS mRNA levels. The expression of the three transcriptional factors analysed (SREBP-1a, SREBP-1c and PPARgamma) was also reduced. These results appear to provide a framework for partially understanding the reduction in body fat induced by CLA. Inhibition of LPL activity seems to be an important mechanism underlying body fat reduction in hamsters. Further research is needed to better characterize the effects of CLA on lipogenesis and the role of these effects in CLA action.

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

    PubMed Central

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

    2016-01-01

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

  1. Lipoprotein(a) metabolism

    USDA-ARS?s Scientific Manuscript database

    Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein. The metabolism of this lipoprotein is still not well understood. It has long been known that the plasma concentration of Lp(a) is highly heritable, with its genetic determinants located in the apo(a) locus and regulating the rate of hepatic apo(a...

  2. Exhaustive exercise increases plasma/serum total oxidation resistance in moderately trained men and women, whereas their VLDL + LDL lipoprotein fraction is more susceptible to oxidation.

    PubMed

    Kaikkonen, J; Porkkala-Sarataho, E; Tuomainen, T P; Nyyssönen, K; Kosonen, L; Ristonmaa, U; Lakka, H M; Salonen, R; Korpela, H; Salonen, J T

    2002-01-01

    exhaustive exercise can increase plasma/serum total resistance towards oxidation, the oxidation resistance of the atherogenic lipoprotein fraction might be diminished. On the basis of these results, several in vitro measurements of lipid peroxidation assessing both water and lipid soluble plasma fractions are needed if a true perspective of the plasma redox status is to be obtained.

  3. Increased beta-amyloid levels in the choroid plexus following lead exposure and the involvement of low-density lipoprotein receptor protein-1.

    PubMed

    Behl, Mamta; Zhang, Yanshu; Monnot, Andrew D; Jiang, Wendy; Zheng, Wei

    2009-10-15

    The choroid plexus, a barrier between the blood and cerebrospinal fluid (CSF), is known to accumulate lead (Pb) and also possibly function to maintain brain's homeostasis of Abeta, an important peptide in the etiology of Alzheimer's disease. This study was designed to investigate if Pb exposure altered Abeta levels at the blood-CSF barrier in the choroid plexus. Rats received ip injection of 27 mg Pb/kg. Twenty-four hours later, a FAM-labeled Abeta (200 pmol) was infused into the lateral ventricle and the plexus tissues were removed to quantify Abeta accumulation. Results revealed a significant increase in intracellular Abeta accumulation in the Pb-exposed animals compared to controls (p<0.001). When choroidal epithelial Z310 cells were treated with 10 microM Pb for 24 h and 48 h, Abeta (2 microM in culture medium) accumulation was significantly increased by 1.5 fold (p<0.05) and 1.8 fold (p<0.05), respectively. To explore the mechanism, we examined the effect of Pb on low-density lipoprotein receptor protein-1 (LRP1), an intracellular Abeta transport protein. Following acute Pb exposure with the aforementioned dose regimen, levels of LRP1 mRNA and proteins in the choroid plexus were decreased by 35% (p<0.05) and 31.8% (p<0.05), respectively, in comparison to those of controls. In Z310 cells exposed to 10 microM Pb for 24 h and 48 h, a 33.1% and 33.4% decrease in the protein expression of LRP1 was observed (p<0.05), respectively. Knocking down LRP1 resulted in even more substantial increases of cellular accumulation of Abeta, from 31% in cells without knockdown to 72% in cells with LRP1 knockdown (p<0.05). Taken together, these results suggest that the acute exposure to Pb results in an increased accumulation of intracellular Abeta in the choroid plexus; the effect appears to be mediated, at least in part, via suppression of LRP1 production following Pb exposure.

  4. Increased {beta}-amyloid levels in the choroid plexus following lead exposure and the involvement of low-density lipoprotein receptor protein-1

    SciTech Connect

    Behl, Mamta; Zhang Yanshu; Monnot, Andrew D.; Jiang, Wendy; Zheng Wei

    2009-10-15

    The choroid plexus, a barrier between the blood and cerebrospinal fluid (CSF), is known to accumulate lead (Pb) and also possibly function to maintain brain's homeostasis of A{beta}, an important peptide in the etiology of Alzheimer's disease. This study was designed to investigate if Pb exposure altered A{beta} levels at the blood-CSF barrier in the choroid plexus. Rats received ip injection of 27 mg Pb/kg. Twenty-four hours later, a FAM-labeled A{beta} (200 pmol) was infused into the lateral ventricle and the plexus tissues were removed to quantify A{beta} accumulation. Results revealed a significant increase in intracellular A{beta} accumulation in the Pb-exposed animals compared to controls (p < 0.001). When choroidal epithelial Z310 cells were treated with 10 {mu}M Pb for 24 h and 48 h, A{beta} (2 {mu}M in culture medium) accumulation was significantly increased by 1.5 fold (p < 0.05) and 1.8 fold (p < 0.05), respectively. To explore the mechanism, we examined the effect of Pb on low-density lipoprotein receptor protein-1 (LRP1), an intracellular A{beta} transport protein. Following acute Pb exposure with the aforementioned dose regimen, levels of LRP1 mRNA and proteins in the choroid plexus were decreased by 35% (p < 0.05) and 31.8% (p < 0.05), respectively, in comparison to those of controls. In Z310 cells exposed to 10 {mu}M Pb for 24 h and 48 h, a 33.1% and 33.4% decrease in the protein expression of LRP1 was observed (p < 0.05), respectively. Knocking down LRP1 resulted in even more substantial increases of cellular accumulation of A{beta}, from 31% in cells without knockdown to 72% in cells with LRP1 knockdown (p < 0.05). Taken together, these results suggest that the acute exposure to Pb results in an increased accumulation of intracellular A{beta} in the choroid plexus; the effect appears to be mediated, at least in part, via suppression of LRP1 production following Pb exposure.

  5. Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism

    PubMed Central

    Kersten, Sander

    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 mediates the effect of dietary fatty acids and certain drugs on plasma lipoproteins are the peroxisome proliferator activated receptors (PPARs). Three PPAR isotypes can be distinguished, all of which have a major role in regulating lipoprotein metabolism. PPARα is the molecular target for the fibrate class of drugs. Activation of PPARα in mice and humans markedly reduces hepatic triglyceride production and promotes plasma triglyceride clearance, leading to a clinically significant reduction in plasma triglyceride levels. In addition, plasma high-density lipoprotein (HDL)-cholesterol levels are increased upon PPARα activation in humans. PPARγ is the molecular target for the thiazolidinedione class of drugs. Activation of PPARγ in mice and human is generally associated with a modest increase in plasma HDL-cholesterol and a decrease in plasma triglycerides. The latter effect is caused by an increase in lipoprotein lipase-dependent plasma triglyceride clearance. Analogous to PPARα, activation of PPARβ/δ leads to increased plasma HDL-cholesterol and decreased plasma triglyceride levels. In this paper, a fresh perspective on the relation between PPARs and lipoprotein metabolism is presented. The emphasis is on the physiological role of PPARs and the mechanisms underlying the effect of synthetic PPAR agonists on plasma lipoprotein levels. PMID:18288277

  6. Fat utilization during exercise: adaptation to a fat-rich diet increases utilization of plasma fatty acids and very low density lipoprotein-triacylglycerol in humans

    PubMed Central

    Helge, Jørn W; Watt, Peter W; Richter, Erik A; Rennie, Michael J; Kiens, Bente

    2001-01-01

    This study was carried out to test the hypothesis that the greater fat oxidation observed during exercise after adaptation to a high-fat diet is due to an increased uptake of fat originating from the bloodstream. Of 13 male untrained subjects, seven consumed a fat-rich diet (62% fat, 21% carbohydrate) and six consumed a carbohydrate-rich diet (20% fat, 65% carbohydrate). After 7 weeks of training and diet, 60 min of bicycle exercise was performed at 68 ± 1% of maximum oxygen uptake. During exercise [1-13C]palmitate was infused, arterial and venous femoral blood samples were collected, and blood flow was determined by the thermodilution technique. Muscle biopsy samples were taken from the vastus lateralis muscle before and after exercise. During exercise, the respiratory exchange ratio was significantly lower in subjects consuming the fat-rich diet (0.86 ± 0.01, mean ±s.e.m.) than in those consuming the carbohydrate-rich diet (0.93 ± 0.02). The leg fatty acid (FA) uptake (183 ± 37 vs. 105 ± 28 μmol min−1) and very low density lipoprotein-triacylglycerol (VLDL-TG) uptake (132 ± 26 vs. 16 ± 21 μmol min−1) were both higher (each P < 0.05) in the subjects consuming the fat-rich diet. Whole-body plasma FA oxidation (determined by comparison of 13CO2 production and blood palmitate labelling) was 55-65% of total lipid oxidation, and was higher after the fat-rich diet than after the carbohydrate-rich diet (13.5 ± 1.2 vs. 8.9 ± 1.1 μmol min−1 kg−1; P < 0.05). Muscle glycogen breakdown was significantly lower in the subjects taking the fat-rich diet than those taking the carbohydrate-rich diet (2.6 ± 0.5 vs. 4.8 ± 0.5 mmol (kg dry weight)−1 min−1, respectively; P < 0.05), whereas leg glucose uptake was similar (1.07 ± 0.13 vs. 1.15 ± 0.13 mmol min−1). In conclusion, plasma VLDL-TG appears to be an important substrate source during aerobic exercise, and in combination with the higher plasma FA uptake it accounts for the increased fat oxidation

  7. A Computational Model for the Analysis of Lipoprotein Distributions in the Mouse: Translating FPLC Profiles to Lipoprotein Metabolism

    PubMed Central

    Sips, Fianne L. P.; Tiemann, Christian A.; Oosterveer, Maaike H.; Groen, Albert K.; Hilbers, Peter A. J.; van Riel, Natal A. W.

    2014-01-01

    Disturbances of lipoprotein metabolism are recognized as indicators of cardiometabolic disease risk. Lipoprotein size and composition, measured in a lipoprotein profile, are considered to be disease risk markers. However, the measured profile is a collective result of complex metabolic interactions, which complicates the identification of changes in metabolism. In this study we aim to develop a method which quantitatively relates murine lipoprotein size, composition and concentration to the molecular mechanisms underlying lipoprotein metabolism. We introduce a computational framework which incorporates a novel kinetic model of murine lipoprotein metabolism. The model is applied to compute a distribution of plasma lipoproteins, which is then related to experimental lipoprotein profiles through the generation of an in silico lipoprotein profile. The model was first applied to profiles obtained from wild-type C57Bl/6J mice. The results provided insight into the interplay of lipoprotein production, remodelling and catabolism. Moreover, the concentration and metabolism of unmeasured lipoprotein components could be determined. The model was validated through the prediction of lipoprotein profiles of several transgenic mouse models commonly used in cardiovascular research. Finally, the framework was employed for longitudinal analysis of the profiles of C57Bl/6J mice following a pharmaceutical intervention with a liver X receptor (LXR) agonist. The multifaceted regulatory response to the administration of the compound is incompletely understood. The results explain the characteristic changes of the observed lipoprotein profile in terms of the underlying metabolic perturbation and resultant modifications of lipid fluxes in the body. The Murine Lipoprotein Profiler (MuLiP) presented here is thus a valuable tool to assess the metabolic origin of altered murine lipoprotein profiles and can be applied in preclinical research performed in mice for analysis of lipid fluxes and

  8. A computational model for the analysis of lipoprotein distributions in the mouse: translating FPLC profiles to lipoprotein metabolism.

    PubMed

    Sips, Fianne L P; Tiemann, Christian A; Oosterveer, Maaike H; Groen, Albert K; Hilbers, Peter A J; van Riel, Natal A W

    2014-05-01

    Disturbances of lipoprotein metabolism are recognized as indicators of cardiometabolic disease risk. Lipoprotein size and composition, measured in a lipoprotein profile, are considered to be disease risk markers. However, the measured profile is a collective result of complex metabolic interactions, which complicates the identification of changes in metabolism. In this study we aim to develop a method which quantitatively relates murine lipoprotein size, composition and concentration to the molecular mechanisms underlying lipoprotein metabolism. We introduce a computational framework which incorporates a novel kinetic model of murine lipoprotein metabolism. The model is applied to compute a distribution of plasma lipoproteins, which is then related to experimental lipoprotein profiles through the generation of an in silico lipoprotein profile. The model was first applied to profiles obtained from wild-type C57Bl/6J mice. The results provided insight into the interplay of lipoprotein production, remodelling and catabolism. Moreover, the concentration and metabolism of unmeasured lipoprotein components could be determined. The model was validated through the prediction of lipoprotein profiles of several transgenic mouse models commonly used in cardiovascular research. Finally, the framework was employed for longitudinal analysis of the profiles of C57Bl/6J mice following a pharmaceutical intervention with a liver X receptor (LXR) agonist. The multifaceted regulatory response to the administration of the compound is incompletely understood. The results explain the characteristic changes of the observed lipoprotein profile in terms of the underlying metabolic perturbation and resultant modifications of lipid fluxes in the body. The Murine Lipoprotein Profiler (MuLiP) presented here is thus a valuable tool to assess the metabolic origin of altered murine lipoprotein profiles and can be applied in preclinical research performed in mice for analysis of lipid fluxes and

  9. Lipoprotein-inspired nanoparticles for cancer theranostics.

    PubMed

    Ng, Kenneth K; Lovell, Jonathan F; Zheng, Gang

    2011-10-18

    Over hundreds of millions of years, animals have evolved endogenous lipoprotein nanoparticles for shuttling hydrophobic molecules to different parts of the body. In the last 70 years, scientists have developed an understanding of lipoprotein function, often in relationship to lipid transport and heart disease. Such biocompatible, lipid-protein complexes are also ideal for loading and delivering cancer therapeutic and diagnostic agents, which means that lipoprotein and lipoprotein-inspired nanoparticles also offer opportunities for cancer theranostics. By mimicking the endogenous shape and structure of lipoproteins, the nanocarrier can remain in circulation for an extended period of time, while largely evading the reticuloendothelial cells in the body's defenses. The small size (less than 30 nm) of the low-density (LDL) and high-density (HDL) classes of lipoproteins allows them to maneuver deeply into tumors. Furthermore, lipoproteins can be targeted to their endogenous receptors, when those are implicated in cancer, or to other cancer receptors. In this Account, we review the field of lipoprotein-inspired nanoparticles related to the delivery of cancer imaging and therapy agents. LDL has innate cancer targeting potential and has been used to incorporate diverse hydrophobic molecules and deliver them to tumors. Nature's method of rerouting LDL in atherosclerosis provides a strategy to extend the cancer targeting potential of lipoproteins beyond its narrow purview. Although LDL has shown promise as a drug nanocarrier for cancer imaging and therapy, increasing evidence indicates that HDL, the smallest lipoprotein, may also be of use for drug targeting and uptake into cancer cells. We also discuss how synthetic HDL-like nanoparticles, which do not include human or recombinant proteins, can deliver molecules directly to the cytoplasm of certain cancer cells, effectively bypassing the endosomal compartment. This strategy could allow HDL-like nanoparticles to be used to

  10. Four Statin Benefit Groups Defined by The 2013 ACC/AHA New Cholesterol Guideline are Characterized by Increased Plasma Level of Electronegative Low-Density Lipoprotein

    PubMed Central

    Chu, Chih-Sheng; Ke, Liang-Yin; Chan, Hua-Chen; Chan, Hsiu-Chua; Chen, Chih-Chieh; Cheng, Kai-Hung; Lee, Hsiang-Chun; Kuo, Hsuan-Fu; Chang, Ching-Tang; Chang, Kuan-Cheng; Sheu, Sheng-Hsiung; Chen, Chu-Huang; Lai, Wen-Ter

    2016-01-01

    Background Significantly higher cytotoxic and thrombogenic human electronegative low-density lipoprotein (LDL), or L5, has been found in patients with stable coronary artery disease and acute coronary syndrome. We hypothesized that the statin-benefit groups (SBGs) defined by the new cholesterol guideline were of higher electronegative L5. Methods In total, 62 hyperlipidemia patients (mean age 59.4 ± 10.5, M/F 40/22) were retrospectively divided into SBGs (n = 44) and N-SBGs (n = 18). The levels of complete basic lipid panel, biochemical profile and electronegative L5 of each individual were obtained before and after rosuvastatin 10 mg/day for 3 months. Results After 3 months’ statin therapy, significant reduction of total cholesterol, LDL-C and triglyceride were demonstrated (all p-values < 0.05), with 38.4% LDL-C reduction. The percentage of L5 was significantly reduced by 40.9% (from 4.4% to 2.6%) after statin therapy (p = 0.001). Regarding absolute L5 concentration, derived from L5% multiplied by LDL-C, there was approximate 63.8% reduction (from 6.3 mg/dL to 2.3 mg/dL) of absolute L5 (p < 0.001) after statin treatment. Notably, while plasma LDL-C levels were similar between SBGs and N-SBGs (152.8 ± 48.6 vs. 146.9 ± 35.0 mg/dL), the SBGs had significantly elevated L5% (5.2 ± 7.4% vs. 2.6 ± 1.9%, p = 0.031) and higher absolute L5 concentration (7.4 ± 10.4 vs. 3.7 ± 3.1 mg/dL, p = 0.036). Linear regression showed the significantly positive correlation between the plasma L5 concentration and the 10-year cardiovascular risk by pooled cohort equation (r = 0.297, p < 0.05). Conclusions The four SBGs defined by the 2013 ACC/AHA new cholesterol guideline tend to have increased atherogenic electronegative L5. Statin therapy can effectively reduce the electronegative L5 of these four major SBGs. PMID:27899853

  11. Lipoproteins of Bacterial Pathogens▿

    PubMed Central

    Kovacs-Simon, A.; Titball, R. W.; Michell, S. L.

    2011-01-01

    Bacterial lipoproteins are a set of membrane proteins with many different functions. Due to this broad-ranging functionality, these proteins have a considerable significance in many phenomena, from cellular physiology through cell division and virulence. Here we give a general overview of lipoprotein biogenesis and highlight examples of the roles of lipoproteins in bacterial disease caused by a selection of medically relevant Gram-negative and Gram-positive pathogens: Mycobacterium tuberculosis, Streptococcus pneumoniae, Borrelia burgdorferi, and Neisseria meningitidis. Lipoproteins have been shown to play key roles in adhesion to host cells, modulation of inflammatory processes, and translocation of virulence factors into host cells. As such, a number of lipoproteins have been shown to be potential vaccines. This review provides a summary of some of the reported roles of lipoproteins and of how this knowledge has been exploited in some cases for the generation of novel countermeasures to bacterial diseases. PMID:20974828

  12. Explaining the increase in family financial pressures from medical bills between 2003 and 2007: do affordability thresholds change over time?

    PubMed

    Cunningham, Peter J

    2011-06-01

    This study examines whether affordability thresholds for medical care as defined by families change over time. The results from two nationally representative surveys show that while financial stress from medical bills--defined as the percent with problems paying medical bills--increased between 2003 and 2007, greater out-of-pocket spending accounted for this increase only for higher-income persons with employer-sponsored insurance coverage. Increased spending did not account for an increase in medical bill problems among lower-income persons. Moreover, the increase in medical bill problems among low-income persons occurred at relatively low levels of out-of-pocket spending rather than at higher levels. The results suggest that "affordability thresholds" for medical care as defined by individuals and families are not stable over time, especially for lower-income persons, which has implications for setting affordability standards in health reform.

  13. Serum Sialic Acid Concentration and Content in ApoB-Containing Lipoproteins in Liver Diseases.

    PubMed

    Gudowska, Monika; Gruszewska, Ewa; Cylwik, Bogdan; Panasiuk, Anatol; Filisiak, Robert; Szmitkowski, Maciej; Chrostek, Lech

    2016-01-01

    The great significance for the metabolism of lipoproteins is the composition of carbohydrate chain of apolipoproteins, where sialic acid (SA) is located. In VILDL and LDL sialic acid is attached to apolipoprotein B. The sialylation of serum proteins including apolipoprotein B can be affected in the course of liver diseases. Therefore, the aim of this study was to assess the effect of liver diseases on the concentration and content of SA in ApoB-containing lipoproteins. The tested group consisted of 165 patients (118 males, 47 females) with liver diseases: alcoholic cirrhosis, non-alcoholic cirrhosis, chronic hepatitis, toxic hepatitis, chronic viral hepatitis, and liver cancer. ApoB-containing lipoproteins were isolated by a turbidimetric procedure and SA concentration was measured according to an enzymatic method. There was a significant increase in the serum concentration of SA in ApoB-containing lipoproteins in viral hepatitis. Although the serum concentration of ApoB was not significantly different between specific liver diseases, the serum levels of SA in ApoB-containing lipoproteins appeared to be different. There is an association between SA concentration and triglycerides in alcoholic cirrhosis and viral hepatitis. Also, in viral hepatitis SA concentration correlated negatively with HDL-cholesterol. The content of SA in ApoB-containing lipoproteins in alcoholic cirrhosis and viral hepatitis was significantly higher than that in the control group, but did not differ between diseases. This study may explain the variations in serum lipids and lipoproteins in liver diseases. It seems that the reason for these abnormalities is the changes in the concentration of sialic acid in ApoB-containing lipoproteins.

  14. Decoupling of soil carbon and nitrogen turnover partly explains increased net ecosystem production in response to nitrogen fertilization

    PubMed Central

    Ehtesham, Emad; Bengtson, Per

    2017-01-01

    During the last decade there has been an ongoing controversy regarding the extent to which nitrogen fertilization can increase carbon sequestration and net ecosystem production in forest ecosystems. The debate is complicated by the fact that increased nitrogen availability caused by nitrogen deposition has coincided with increasing atmospheric carbon dioxide concentrations. The latter could further stimulate primary production but also result in increased allocation of carbon to root exudates, which could potentially ‘prime’ the decomposition of soil organic matter. Here we show that increased input of labile carbon to forest soil caused a decoupling of soil carbon and nitrogen cycling, which was manifested as a reduction in respiration of soil organic matter that coincided with a substantial increase in gross nitrogen mineralization. An estimate of the magnitude of the effect demonstrates that the decoupling could potentially result in an increase in net ecosystem production by up to 51 kg C ha−1 day−1 in nitrogen fertilized stands during peak summer. Even if the effect is several times lower on an annual basis, the results still suggest that nitrogen fertilization can have a much stronger influence on net ecosystem production than can be expected from a direct stimulation of primary production alone. PMID:28406242

  15. Decoupling of soil carbon and nitrogen turnover partly explains increased net ecosystem production in response to nitrogen fertilization

    NASA Astrophysics Data System (ADS)

    Ehtesham, Emad; Bengtson, Per

    2017-04-01

    During the last decade there has been an ongoing controversy regarding the extent to which nitrogen fertilization can increase carbon sequestration and net ecosystem production in forest ecosystems. The debate is complicated by the fact that increased nitrogen availability caused by nitrogen deposition has coincided with increasing atmospheric carbon dioxide concentrations. The latter could further stimulate primary production but also result in increased allocation of carbon to root exudates, which could potentially ‘prime’ the decomposition of soil organic matter. Here we show that increased input of labile carbon to forest soil caused a decoupling of soil carbon and nitrogen cycling, which was manifested as a reduction in respiration of soil organic matter that coincided with a substantial increase in gross nitrogen mineralization. An estimate of the magnitude of the effect demonstrates that the decoupling could potentially result in an increase in net ecosystem production by up to 51 kg C ha-1 day-1 in nitrogen fertilized stands during peak summer. Even if the effect is several times lower on an annual basis, the results still suggest that nitrogen fertilization can have a much stronger influence on net ecosystem production than can be expected from a direct stimulation of primary production alone.

  16. Can increases in capillarization explain the early adaptations in metabolic regulation in human muscle to short-term training?

    PubMed

    Green, Howard J; Burnett, Margaret; Kollias, Helen; Ouyang, Jing; Smith, Ian; Tupling, Susan

    2012-05-01

    To investigate the hypothesis that increases in fibre capillary density would precede increases in oxidative potential following training onset, tissue was extracted from the vastus lateralis prior to (0 days) and following 3 and 6 consecutive days of submaximal cycle exercise (2 h·day(-1)). Participants were untrained males (age = 21.4 ± 0.58 years; peak oxygen consumption = 46.2 ± 1.6 mL·kg(-1)·min(-1); mean ± standard error (SE)). Tissue was assessed for succinic dehydrogenase activity (SDH) by microphotometry and indices of capillarization based on histochemically assessed area and capillary counts (CC) in specific fibre types. Three days of training (n = 13) resulted in a generalized decrease (p < 0.05) in fibre area (-14.2% ± 3.0%; mean ± SE) and increase (p < 0.05) in CC/Area (20.4% ± 2.7%) and no change in either CC or SDH activity. Following 6 days of treatment (n = 6), increases (p < 0.05) in CC (18.2% ± 4.2%), CC/Area (28.9% ± 3.2%), and SDH activity (22.9% ± 6.0%) occurred that was not specific to major fibre type. No changes in either fibre area or fibre-type distribution were observed with additional training. We conclude that increases in angiogenic-based capillary density and oxidative potential occur coincidentally following training onset, while increases in capillary density, mediated by reductions in fibre area, represent an initial isolated response, the significance of which may be linked to the metabolic alterations that also result.

  17. Mass incarceration can explain population increases in TB and multidrug-resistant TB in European and central Asian countries

    PubMed Central

    Stuckler, David; Basu, Sanjay; McKee, Martin; King, Lawrence

    2008-01-01

    Several microlevel studies have pinpointed prisons as an important site for tuberculosis (TB) and multidrug-resistant TB in European and central Asian countries. To date, no comparative analyses have examined whether rises in incarceration rates can account for puzzling differences in TB trends among overall populations. Using longitudinal TB and cross-sectional multidrug-resistant TB data for 26 eastern European and central Asian countries, we examined whether and to what degree increases in incarceration account for differences in population TB and multidrug-resistant TB burdens. We find that each percentage point increase in incarceration rates relates to an increased TB incidence of 0.34% (population attributable risk, 95% C.I.: 0.10–0.58%, P < 0.01), after controlling for TB infrastructure; HIV prevalence; and several surveillance, economic, demographic, and political indicators. Net increases in incarceration account for a 20.5% increase in TB incidence or nearly three-fifths of the average total increase in TB incidence in the countries studied from 1991 to 2002. Although the number of prisoners is a significant determinant of differences in TB incidence and multidrug-resistant TB prevalence among countries, the rate of prison growth is a larger determinant of these outcomes, and its effect is exacerbated but not confounded by HIV. Differences in incarceration rates are a major determinant of differences in population TB outcomes among eastern European and central Asian countries, and treatment expansion alone does not appear to resolve the effect of mass incarceration on TB incidence. PMID:18728189

  18. Mass incarceration can explain population increases in TB and multidrug-resistant TB in European and central Asian countries.

    PubMed

    Stuckler, David; Basu, Sanjay; McKee, Martin; King, Lawrence

    2008-09-09

    Several microlevel studies have pinpointed prisons as an important site for tuberculosis (TB) and multidrug-resistant TB in European and central Asian countries. To date, no comparative analyses have examined whether rises in incarceration rates can account for puzzling differences in TB trends among overall populations. Using longitudinal TB and cross-sectional multidrug-resistant TB data for 26 eastern European and central Asian countries, we examined whether and to what degree increases in incarceration account for differences in population TB and multidrug-resistant TB burdens. We find that each percentage point increase in incarceration rates relates to an increased TB incidence of 0.34% (population attributable risk, 95% C.I.: 0.10-0.58%, P < 0.01), after controlling for TB infrastructure; HIV prevalence; and several surveillance, economic, demographic, and political indicators. Net increases in incarceration account for a 20.5% increase in TB incidence or nearly three-fifths of the average total increase in TB incidence in the countries studied from 1991 to 2002. Although the number of prisoners is a significant determinant of differences in TB incidence and multidrug-resistant TB prevalence among countries, the rate of prison growth is a larger determinant of these outcomes, and its effect is exacerbated but not confounded by HIV. Differences in incarceration rates are a major determinant of differences in population TB outcomes among eastern European and central Asian countries, and treatment expansion alone does not appear to resolve the effect of mass incarceration on TB incidence.

  19. Large increases in adipose triacylglycerol flux in Cushingoid CRH-Tg mice are explained by futile cycling

    PubMed Central

    Roohk, Donald J.; Fitch, Mark; Boudignon, Benjamin M.; Halloran, Bernard P.; Hellerstein, Marc K.

    2013-01-01

    Glucocorticoids are extremely effective anti-inflammatory therapies, but their clinical use is limited due to severe side effects, including osteoporosis, muscle wasting, fat redistribution, and skin thinning. Here we use heavy water labeling and mass spectrometry to measure fluxes through metabolic pathways impacted by glucocorticoids. We combine these methods with measurements of body composition in corticotropin-releasing hormone (CRH)-transgenic (Tg)+ mice that have chronically elevated, endogenously produced corticosterone and a phenotype that closely mimics Cushing's disease in humans. CRH-Tg+ mice had increased adipose mass, adipose triglyceride synthesis, and greatly increased triglyceride/fatty acid cycling in subcutaneous and abdominal fat depots and increased de novo lipogenesis in the abdominal depot. In bone, CRH-Tg+ mice had decreased bone mass, absolute collagen synthesis rates, and collagen breakdown rate. In skin, CRH-Tg+ mice had decreased skin thickness and absolute collagen synthesis rates but no decrease in the collagen breakdown rate. In muscle, CRH-Tg+ mice had decreased muscle mass and absolute protein synthesis but no decrease in the protein breakdown rate. We conclude that chronic exposure to endogenous glucocorticoid excess in mice is associated with ongoing decreases in bone collagen, skin collagen, and muscle protein synthesis without compensatory reduction (coupling) of breakdown rates in skin and muscle. Both of these actions contribute to reduced protein pool sizes. We also conclude that increased cycling between triglycerides and free fatty acids occurs in both abdominal and subcutaneous fat depots in CRH-Tg+ mice. CRH-Tg mice have both increased lipolysis and increased triglyceride synthesis in adipose tissue. PMID:23211515

  20. Increased transmissibility explains the third wave of infection by the 2009 H1N1 pandemic virus in England

    PubMed Central

    Dorigatti, Ilaria; Cauchemez, Simon; Ferguson, Neil M.

    2013-01-01

    In the 2009 H1N1 pandemic, the United Kingdom experienced two waves of infection, the first in the late spring and the second in the autumn. Given the low level of susceptibility to the pandemic virus expected to be remaining in the population after the second wave, it was a surprise that a substantial third epidemic occurred in the UK population between November 2010 and February 2011, despite no evidence for any significant antigenic evolution of the pandemic virus. Here, we use a mathematical model of influenza transmission embedded within a Bayesian synthesis inferential framework to jointly analyze syndromic, virological, and serological surveillance data collected in England in 2009–2011 and thereby assess epidemiological mechanisms which might have generated the third wave. We find that substantially increased transmissibility of the H1N1pdm09 virus is required to reproduce the third wave, suggesting that the virus evolved and increased fitness in the human host by the end of 2010, or that the very cold weather experienced in the United Kingdom at that time enhanced transmission rates. We also find some evidence that the preexisting heterologous immunity which reduced attack rates in adults during 2009 had substantially decayed by the winter of 2010, thus increasing the susceptibility of the adult population to infection. Finally, our analysis suggests that a pandemic vaccination campaign targeting adults and school-age children could have mitigated or prevented the third wave even at moderate levels of coverage. PMID:23882078

  1. Cohort effects explain the increase in autism diagnosis among children born from 1992 to 2003 in California

    PubMed Central

    Keyes, Katherine M; Susser, Ezra; Cheslack-Postava, Keely; Fountain, Christine; Liu, Kayuet; Bearman, Peter S

    2012-01-01

    Background The incidence and prevalence of autism have dramatically increased over the last 20 years. Decomposition of autism incidence rates into age, period and cohort effects disentangle underlying domains of causal factors linked to time trends. We estimate an age-period-cohort effect model for autism diagnostic incidence overall and by level of functioning. Methods Data are drawn from sequential cohorts of all 6 501 262 individuals born in California from 1992 to 2003. Autism diagnoses from 1994 to 2005 were ascertained from the California Department of Development Services Client Development and Evaluation Report. Results Compared with those born in 1992, each successively younger cohort has significantly higher odds of an autism diagnosis than the previous cohort, controlling for age and period effects. For example, individuals born in 2003 have 16.6 times the odds of an autism diagnosis compared with those born in 1992 [95% confidence interval (CI) 7.8–35.3]. The cohort effect observed in these data is stronger for high than for low-functioning children with an autism diagnosis. Discussion Autism incidence in California exhibits a robust and linear positive cohort effect that is stronger among high-functioning children with an autism diagnosis. This finding indicates that the primary drivers of the increases in autism diagnoses must be factors that: (i) have increased linearly year-to-year; (ii) aggregate in birth cohorts; and (iii) are stronger among children with higher levels of functioning. PMID:22253308

  2. Binding of anthracycline derivatives to human serum lipoproteins.

    PubMed

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

    1994-01-01

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

  3. Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging.

    PubMed

    Martín-Guerrero, Idoia; de Prado, Elena; Lopez-Lopez, Elixabet; Ardanaz, Maite; Vitoria, Juan Carlos; Parada, Luis A; García-Orad, Cristina; García-Orad, Africa

    2014-01-01

    Chromosome translocations are especially frequent in human lymphomas and leukemias but are insufficient to drive carcinogenesis. Indeed, several of the so-called tumor specific translocations have been detected in peripheral blood of healthy individuals, finding a higher frequency of some of them with aging. The inappropriate repair of DNA double strand breaks by the nonhomologous end joining (NHEJ) pathway is one of the reasons for a translocation to occur. Moreover, fidelity of this pathway has been shown to decline with age. Although the mechanism underlying this inefficacy is unknown, other repair pathways are inactivated by methylation with aging. In this study, we analyzed the implication of NHEJ genes methylation in the increase of translocations with the age. To this aim, we determined the relationship between translocations and aging in 565 Spanish healthy individuals and correlated these data with the methylation status of 11 NHEJ genes. We found higher frequency of BCL2-JH and BCR-ABL (major) translocations with aging. In addition, we detected that two NHEJ genes (LIG4 and XRCC6) presented age-dependent promoter methylation changes. However, we did not observe a correlation between the increase of translocations and methylation, indicating that other molecular mechanisms are involved in the loss of NHEJ fidelity with aging.

  4. Arachnid lipoproteins: comparative aspects.

    PubMed

    Cunningham, Mónica; Garcia, Fernando; Pollero, Ricardo J

    2007-01-01

    Findings on hemolymph lipoproteins in the class Arachnida are reviewed in relation to their lipid and protein compositions, hydrated densities, the capacity of apoproteins to bind lipids, and the influence of xenobiotics on their structures and functionality. The occurrence of hemolymphatic lipoproteins in arachnids has been reported in species belonging to the orders Araneida, Scorpionida, Solpugida and Acarina. However, lipoproteins were properly characterized in only three species, Eurypelma californicum, Polybetes pythagoricus and Latrodectus mirabilis. Like insect and crustaceans the arachnids examined contain high density lipoproteins (HDLs) as predominant circulating lipoproteins. Although in most arachnids these particles resemble those of insect HDLs called "lipophorins", in two arachnid species they differ from lipophorins in their apoproteins, total mass and lipid composition. The hemolymph of P. pythagoricus and L. mirabilis contains another HDL of higher density, while P. pythagoricus and E. californicum hemolymph contain a third lipoprotein of very high density (VHDL). Composition of arachnid lipoproteins regarding apoprotein classes as well as lipid classes differ among species. Hemocyanin, in addition to the classical role of this protein as respiratory pigment, is presented here performing the function of apolipoprotein in some arachnid species. Reports on experiments demonstrating the capacity of hemocyanin to bind neutral and polar lipid classes, including ecdysteroids, are commented. Recent works about the changes evoked by a phosphorous pesticide on the structures and functionality of spider lipoproteins are also reviewed.

  5. Insulin response dysregulation explains abnormal fat storage and increased risk of diabetes mellitus type 2 in Cohen Syndrome.

    PubMed

    Limoge, Floriane; Faivre, Laurence; Gautier, Thomas; Petit, Jean-Michel; Gautier, Elodie; Masson, David; Jego, Gaëtan; El Chehadeh-Djebbar, Salima; Marle, Nathalie; Carmignac, Virginie; Deckert, Valérie; Brindisi, Marie-Claude; Edery, Patrick; Ghoumid, Jamal; Blair, Edward; Lagrost, Laurent; Thauvin-Robinet, Christel; Duplomb, Laurence

    2015-12-01

    Cohen Syndrome (CS) is a rare autosomal recessive disorder, with defective glycosylation secondary to mutations in the VPS13B gene, which encodes a protein of the Golgi apparatus. Besides congenital neutropenia, retinopathy and intellectual deficiency, CS patients are faced with truncal obesity. Metabolism investigations showed abnormal glucose tolerance tests and low HDL values in some patients, and these could be risk factors for the development of diabetes mellitus and/or cardiovascular complications. To understand the mechanisms involved in CS fat storage, we used two models of adipogenesis differentiation: (i) SGBS pre-adipocytes with VPS13B invalidation thanks to siRNA delivery and (ii) CS primary fibroblasts. In both models, VPS13B invalidation led to accelerated differentiation into fat cells, which was confirmed by the earlier and increased expression of specific adipogenic genes, consequent to the increased response of cells to insulin stimulation. At the end of the differentiation protocol, these fat cells exhibited decreased AKT2 phosphorylation after insulin stimulation, which suggests insulin resistance. This study, in association with the in-depth analysis of the metabolic status of the patients, thus allowed us to recommend appropriate nutritional education to prevent the occurrence of diabetes mellitus and to put forward recommendations for the follow-up of CS patients, in particular with regard to the development of metabolic syndrome. We also suggest replacing the term obesity by abnormal fat distribution in CS, which should reduce the number of inappropriate diagnoses in patients who are referred only on the basis of intellectual deficiency associated with obesity.

  6. The association between advanced maternal and paternal ages and increased adult mortality is explained by early parental loss

    PubMed Central

    Elo, Irma T.; Kohler, Iliana; Martikainen, Pekka

    2015-01-01

    The association between advanced maternal and paternal ages at birth and increased mortality among adult offspring is often attributed to parental reproductive ageing, e.g., declining oocyte or sperm quality. Less attention has been paid to alternative mechanisms, including parental socio-demographic characteristics or the timing of parental death. Moreover, it is not known if the parental age-adult mortality association is mediated by socioeconomic attainment of the children, or if it varies over the lifecourse of the adult children. We used register-based data drawn from the Finnish 1950 census (sample size 89,737; mortality follow-up 1971–2008) and discrete-time survival regression with logit link to analyze these alternative mechanisms in the parental age-offspring mortality association when the children were aged 35–49 and 50–72. Consistent with prior literature, we found that adult children of older parents had increased mortality relative to adults whose parents were aged 25–29 at the time of birth. For example, maternal and paternal ages 40–49 were associated with mortality odds ratios (ORs)of 1.31 (p<.001) and 1.22 (p<.01), respectively, for offspring mortality at ages 35–49. At ages 50–72 advanced parental age also predicted higher mortality, though not as strongly. Adjustment for parental socio-demographic characteristics (education, occupation, family size, household crowding, language) weakened the associations only slightly. Adjustment for parental survival, measured by whether the parents were alive when the child reached age 35, reduced the advanced parental age coefficients substantially and to statistically insignificant levels. These results indicate that the mechanism behind the advanced parental age-adult offspring mortality association is mainly social, reflecting early parental loss and parental characteristics, rather than physiological mechanisms reflecting reproductive ageing. PMID:24997641

  7. Development of Behavioral Control and Associated vmPFC-DLPFC Connectivity Explains Children's Increased Resistance to Temptation in Intertemporal Choice.

    PubMed

    Steinbeis, Nikolaus; Haushofer, Johannes; Fehr, Ernst; Singer, Tania

    2016-01-01

    Human civilization is based on the successful pursuit of long-term goals, requiring the ability to forego immediate pleasure for the sake of larger future rewards. This ability improves with age, but the precise cognitive and neural mechanisms underlying its development remain elusive. The developmental changes could result either from younger children valuing immediate rewards more strongly or because older children become better at controlling their impulses. By implementing 2 tasks, a choice-independent valuation task and an intertemporal choice task, both behaviorally and using fMRI in twenty 6- to 13-year old children, we show developmental improvements in behavioral control to uniquely account for age-related changes in temporal discounting. We show further that overcoming temptation during childhood occurs as a function of an age-related increase in functional coupling between value signals in the ventromedial prefrontal cortex and brain regions dedicated to behavioral control, such as left dorsolateral prefrontal cortex during choice. These findings can help to devise measures that reduce the substantial costs of impatience to society. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Increased human immunodeficiency virus loads in active methamphetamine users are explained by reduced effectiveness of antiretroviral therapy.

    PubMed

    Ellis, Ronald J; Childers, Meredith E; Cherner, Mariana; Lazzaretto, Deborah; Letendre, Scott; Grant, Igor

    2003-12-15

    Abuse of methamphetamine (METH) is a frequent comorbidity among individuals infected with human immunodeficiency virus (HIV) type 1. In cell cultures and animal models, METH accelerates retroviral replication. To determine whether METH increases HIV replication in humans, we evaluated HIV loads in HIV-positive METH users and nonusers. We studied 3 groups: Tox+, active METH use and positive urine toxicology results; METH(+)Tox-, previous METH dependence/abuse and negative urine toxicology results; METH(-)Tox-, no METH dependence/abuse and negative urine toxicology results. Tox+ subjects' plasma virus loads were significantly higher than METH(+)Tox- and METH(-)Tox- subjects'; cerebrospinal fluid virus loads showed a similar but nonsignificant trend. Stratification by use of highly active antiretroviral therapy (HAART) revealed that virus loads were higher only in those Tox+ subjects who reported receiving HAART. In contrast, abstinent former METH abusers (METH(+)Tox-) receiving HAART effectively suppressed viral replication. These data suggest that abstinence programs are a key component of effective treatment of HIV in METH-abusing populations.

  9. Increased conspicuousness can explain the match between visual sensitivities and blue plumage colours in fairy-wrens.

    PubMed

    Delhey, Kaspar; Hall, Michelle; Kingma, Sjouke A; Peters, Anne

    2013-01-07

    Colour signals are expected to match visual sensitivities of intended receivers. In birds, evolutionary shifts from violet-sensitive (V-type) to ultraviolet-sensitive (U-type) vision have been linked to increased prevalence of colours rich in shortwave reflectance (ultraviolet/blue), presumably due to better perception of such colours by U-type vision. Here we provide the first test of this widespread idea using fairy-wrens and allies (Family Maluridae) as a model, a family where shifts in visual sensitivities from V- to U-type eyes are associated with male nuptial plumage rich in ultraviolet/blue colours. Using psychophysical visual models, we compared the performance of both types of visual systems at two tasks: (i) detecting contrast between male plumage colours and natural backgrounds, and (ii) perceiving intraspecific chromatic variation in male plumage. While U-type outperforms V-type vision at both tasks, the crucial test here is whether U-type vision performs better at detecting and discriminating ultraviolet/blue colours when compared with other colours. This was true for detecting contrast between plumage colours and natural backgrounds (i), but not for discriminating intraspecific variability (ii). Our data indicate that selection to maximize conspicuousness to conspecifics may have led to the correlation between ultraviolet/blue colours and U-type vision in this clade of birds.

  10. Increased conspicuousness can explain the match between visual sensitivities and blue plumage colours in fairy-wrens

    PubMed Central

    Delhey, Kaspar; Hall, Michelle; Kingma, Sjouke A.; Peters, Anne

    2013-01-01

    Colour signals are expected to match visual sensitivities of intended receivers. In birds, evolutionary shifts from violet-sensitive (V-type) to ultraviolet-sensitive (U-type) vision have been linked to increased prevalence of colours rich in shortwave reflectance (ultraviolet/blue), presumably due to better perception of such colours by U-type vision. Here we provide the first test of this widespread idea using fairy-wrens and allies (Family Maluridae) as a model, a family where shifts in visual sensitivities from V- to U-type eyes are associated with male nuptial plumage rich in ultraviolet/blue colours. Using psychophysical visual models, we compared the performance of both types of visual systems at two tasks: (i) detecting contrast between male plumage colours and natural backgrounds, and (ii) perceiving intraspecific chromatic variation in male plumage. While U-type outperforms V-type vision at both tasks, the crucial test here is whether U-type vision performs better at detecting and discriminating ultraviolet/blue colours when compared with other colours. This was true for detecting contrast between plumage colours and natural backgrounds (i), but not for discriminating intraspecific variability (ii). Our data indicate that selection to maximize conspicuousness to conspecifics may have led to the correlation between ultraviolet/blue colours and U-type vision in this clade of birds. PMID:23118438

  11. Glycosaminoglycan-lipoprotein interaction.

    PubMed

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

    2001-10-01

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

  12. Increased Back-Bonding Explains Step-Edge Reactivity and Particle Size Effect for CO Activation on Ru Nanoparticles.

    PubMed

    Foppa, Lucas; Copéret, Christophe; Comas-Vives, Aleix

    2016-12-28

    Carbon monoxide is a ubiquitous molecule, a key feedstock and intermediate in chemical processes. Its adsorption and activation, typically carried out on metallic nanoparticles (NPs), are strongly dependent on the particle size. In particular, small NPs, which in principle contain more corner and step-edge atoms, are surprisingly less reactive than larger ones. Hereby, first-principles calculations on explicit Ru NP models (1-2 nm) show that both small and large NPs can present step-edge sites (e.g., B5 and B6 sites). However, such sites display strong particle-size-dependent reactivity because of very subtle differences in local chemical bonding. State-of-the-art crystal orbital Hamilton population analysis allows a detailed molecular orbital picture of adsorbed CO on step-edges, which can be classified as flat (η(1) coordination) and concave (η(2) coordination) sites. Our analysis shows that the CO π-metal dπ hybrid band responsible for the electron back-donation is better represented by an oxygen lone pair on flat sites, whereas it is delocalized on both C and O atoms on concave sites, increasing the back-bonding on these sites compared to flat step-edges or low-index surface sites. The bonding analysis also rationalizes why CO cleavage is easier on step-edge sites of large NPs compared to small ones irrespective of the site geometry. The lower reactivity of small NPs is due to the smaller extent of the Ru-O interaction in the η(2) adsorption mode, which destabilizes the η(2) transition-state structure for CO direct cleavage. Our findings provide a molecular understanding of the reactivity of CO on NPs, which is consistent with the observed particle size effect.

  13. Heavy-resistance exercise-induced increases in jump performance are not explained by changes in neuromuscular function.

    PubMed

    Thomas, K; Toward, A; West, D J; Howatson, G; Goodall, S

    2017-01-01

    Post-activation potentiation (PAP) is the increased involuntary muscle twitch response to stimulation following strong contraction. The enhancement to whole-body explosive muscular performance (PE) after heavy-resistance exercise is often attributed to modulations in neuromuscular function that are proposed to reflect PAP, but the evidence to support this is equivocal. We assessed the neuromuscular basis of PE using transcranial magnetic stimulation (TMS) of the primary motor cortex, and electrical stimulation of the femoral nerve. Eleven male athletes performed heavy-resistance exercise with measures of countermovement jump (CMJ) pre- and 8 min post-exercise. Pre-exercise and after the final CMJ, single- and paired-pulse TMS were delivered during submaximal isometric knee-extensor contractions to measure corticospinal excitability, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF), with motor evoked potentials recorded from rectus femoris. Twitch responses to motor nerve stimulation during and post maximum-knee-extensor contractions were studied to quantify voluntary activation (VA) and potentiated twitch (Qtw,pot ). The experimental protocol successfully induced PE (+4 ± 1% change in CMJ, P = 0.01), but no changes were observed for maximum voluntary force, VA, corticospinal excitability, SICI or ICF (all P > 0.05), and Qtw,pot declined (P < 0.001). An enhancement of muscular performance after heavy-resistance exercise was not accompanied by PAP, or changes in measures of neuromuscular function. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. The affective reactivity of psychotic speech: The role of internal source monitoring in explaining increased thought disorder under emotional challenge.

    PubMed

    de Sousa, Paulo; Sellwood, William; Spray, Amy; Bentall, Richard P

    2016-04-01

    Thought disorder (TD) has been shown to vary in relation to negative affect. Here we examine the role internal source monitoring (iSM, i.e. ability to discriminate between inner speech and verbalized speech) in TD and whether changes in iSM performance are implicated in the affective reactivity effect (deterioration of TD when participants are asked to talk about emotionally-laden topics). Eighty patients diagnosed with schizophrenia-spectrum disorder and thirty healthy controls received interviews that promoted personal disclosure (emotionally salient) and interviews on everyday topics (non-salient) on separate days. During the interviews, participants were tested on iSM, self-reported affect and immediate auditory recall. Patients had more TD, poorer ability to discriminate between inner and verbalized speech, poorer immediate auditory recall and reported more negative affect than controls. Both groups displayed more TD and negative affect in salient interviews but only patients showed poorer performance on iSM. Immediate auditory recall did not change significantly across affective conditions. In patients, the relationship between self-reported negative affect and TD was mediated by deterioration in the ability to discriminate between inner speech and speech that was directed to others and socially shared (performance on the iSM) in both interviews. Furthermore, deterioration in patients' performance on iSM across conditions significantly predicted deterioration in TD across the interviews (affective reactivity of speech). Poor iSM is significantly associated with TD. Negative affect, leading to further impaired iSM, leads to increased TD in patients with psychosis. Avenues for future research as well as clinical implications of these findings are discussed.

  15. [Lipid and lipoprotein profile in psoriasis].

    PubMed

    Deiana, L; Pes, G M; Carru, C; Tidore, M; Cherchi, G M

    1992-12-01

    Psoriasis is a common relapsing dermatosis characterized by an increased epidermal cell proliferation. In this work we studied the lipid and lipoprotein pattern in 17 patients affected by long-standing psoriasis and in 20 normal controls. Total cholesterol, triglyceride, HDL-cholesterol and Apolipoprotein AI and B levels were measured; VLDL, LDL and HDL chemical composition was assessed by preparative ultracentrifugation. Plasma lipid and lipoprotein levels were significantly lower in the patient group; chemical analysis of the main lipoprotein classes showed compositional abnormalities consistent with an accelerated turnover of these particles. We believe that epidermal cell proliferation can play a role in determining these changes.

  16. [Metabolism of lipoproteins in rats treated with ethinyl estradiol].

    PubMed

    Tvorogova, M G; Titov, V N

    1986-01-01

    Effect of ethinyl-estradiol on metabolism of lipoproteins was studied in rat blood. Administration of ethinyl-estradiol at a dose of 50 micrograms/kg of body mass led to hypocholesterolemia and to hypertriglyceridemia in blood of experimental animals as well as the hormone impaired lipid composition of all the lipoprotein classes. These alterations in lipid composition of lipoproteins occurred as a result of an increase in biosynthesis and secretion of very low density lipoproteins as well as due to impairments of lipoprotein transformation in blood serum caused by a decrease in activity of main enzymes responsible for the transformation of lipoproteins in circulation--lipoprotein lipase, liver triglyceride lipase and lecithin-cholesterol acyltransferase.

  17. [The high content of palmitinic fatty acid in food as a major cause of increase of concentration of cholesterol and low density lipoproteins and atheromatous plaques of arteries' intima].

    PubMed

    Titov, V N

    2013-02-01

    The positioning of individual triglycerides of blood serum in palmitinic and oleic lipoproteins ofvery low density in the order ofincrease of the rate constant of their hydrolysis under action of post-heparin lipoprotein leads to the sequence as follows: palmitoil-palmitoil-palmitate-->palmitoil-palmitoil-oleate-->palmitoil-oleil-palmitat-->oleil-palmitoil-palmitate-->oleil-palmitate-palmitate-->oleil-oleil-palmitate-->oleil-oleil-oleate. The shift to the left and to the right is discerned with this spectrum of isoforms of triglycerides. The shift to the left into direction of palmitinicc triglycerides occurs in case of eating of animal food (i.e. beef andfoodstuf of fat saw milk) when the content of palmitinic saturated fatty acid supersedes 15% of fatty acids total and under the development of endogenic syndrome of insulin resistance. The content of low density lipoproteins cholesterol is high in blood The shift to the right with prevalence of oleinic triglycerides occurs in case of low content of beef and foodstuff of fat saw milk in food, fish eating, seafood and olive oil. The physiologic levels of carbohydrates in food and insulin function are present too. The shift to the right initiates the action of insulin, ometa-3 essential polyenic fatty acids, glytazones and fibrates. They increase the activity of delta9-stearil-KoA-desaturase-2 and the transformation of palmitine saturated fatty acid into mono unsaturated oleinic fatty acid. The shift to the left forms the palmitine alternative of metabolism of substrate to supply cells with energy. The shift to the right is a more effective oleinic alternative.

  18. Do working conditions explain the increased risks of disability pension among men and women with low education? A follow-up of Swedish cohorts.

    PubMed

    Falkstedt, Daniel; Backhans, Mona; Lundin, Andreas; Allebeck, Peter; Hemmingsson, Tomas

    2014-09-01

    Rates of disability pension are greatly increased among people with low education. This study examines the extent to which associations between education and disability pensions might be explained by differences in working conditions. Information on individuals at age 13 years was used to assess confounding of associations. Two nationally representative samples of men and women born in 1948 and 1953 in Sweden (22 889 participants in total) were linked to information from social insurance records on cause (musculoskeletal, psychiatric, and other) and date (from 1986-2008) of disability pension. Education data were obtained from administrative records. Occupation data were used for measurement of physical strain at work and job control. Data on paternal education, ambition to study, and intellectual performance were collected in school. Women were found to have higher rates of disability pension than men, regardless of diagnosis, whereas men had a steeper increase in disability pension by declining educational level. Adjustment of associations for paternal education, ambition to study, and intellectual performance at age 13 had a considerable attenuating effect, also when disability pension with a musculoskeletal diagnosis was the outcome. Despite this, high physical strain at work and low job control both contributed to explain the associations between low education and disability pensions in multivariable models. Working conditions seem to partly explain the increased rate of disability pension among men and women with lower education even though this association does reflect considerable selection effects based on factors already present in late childhood.

  19. Lipoprotein profile, lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients.

    PubMed

    Rolla, Roberta; De Mauri, Andreana; Valsesia, Ambra; Vidali, Matteo; Chiarinotti, Doriana; Bellomo, Giorgio

    2015-12-01

    Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients; the increased risk of cardiovascular disease is due to accelerated atherosclerosis, inflammation and impaired lipoprotein metabolism. We aimed to evaluate lipoprotein-associated phospholipase A2 (Lp-PLA2) and some pro-inflammatory aspects of the lipoprotein profile in dialyzed patients in order to evaluate the relationship with the accelerated atherosclerosis and vascular accidents. In 102 dialysis patients and 40 non-uremic controls, we investigated the lipoprotein plasma profile, high sensitivity C-reactive protein (CRP), ceruloplasmin and serum amyloid A protein (SAA), and followed patients for 1 year to analyze the risk of acute cardiovascular events. Total cholesterol, low-density lipoprotein and high-density lipoprotein plasma levels were significantly lower in uremic patients than controls, whereas CRP, SAA, ceruloplasmin, Lp-PLA2 and their ratio with apolipoprotein A1 were significantly higher. Patients with Lp-PLA2 levels >194 nmol/min/ml had more acute cardiovascular events than patients with lower values. Our results show that in dialysis subjects: (1) low-density lipoproteins show a more atherogenic phenotype than in the general population; (2) high-density lipoproteins are less anti-inflammatory; (3) Lp-PLA2 could potentially be used to evaluate cardiovascular risk.

  20. Familial lipoprotein lipase deficiency

    MedlinePlus

    ... Coronary artery disease References Hegele RA. Lipoprotein and lipid metabolism. In: Rimoin D, Korf B, eds. Emery ... Semenkovich CF, Goldberg AC, Goldberg IJ. Disorders of lipid metabolism. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg ...

  1. Protein Kinase C-α–Mediated Regulation of Low-Density Lipoprotein Receptor–Related Protein and Urokinase Increases Astrocytoma Invasion

    PubMed Central

    Amos, Samson; Mut, Melike; diPierro, Charles G.; Carpenter, Joan E.; Xiao, Aizhen; Kohutek, Zachary A.; Redpath, Gerard T.; Zhao, Yunge; Wang, Jiahu; Shaffrey, Mark E.; Hussaini, Isa M.

    2008-01-01

    Aggressive and infiltrative invasion is one of the hallmarks of glioblastoma. Low-density lipoprotein receptor–related protein (LRP) is expressed by glioblastoma, but the role of this receptor in astrocytic tumor invasion remains poorly understood. We show that activation of protein kinase C-α (PKC-α) phosphorylated and down-regulated LRP expression. Pretreatment of tumor cells with PKC inhibitors, phosphoinositide 3-kinase (PI3K) inhibitor, PKC-α small interfering RNA (siRNA), and short hairpin RNA abrogated phorbol 12-myristate 13-acetate–induced down-regulation of LRP and inhibited astrocytic tumor invasion in vitro. In xenograft glioblastoma mouse model and in vitro transmembrane invasion assay, LRP-deficient cells, which secreted high levels of urokinase-type plasminogen activator (uPA), invaded extensively the surrounding normal brain tissue, whereas the LRP-overexpressing and uPA-deficient cells did not invade into the surrounding normal brain. siRNA, targeted against uPA in LRP-deficient clones, attenuated their invasive potential. Taken together, our results strongly suggest the involvement of PKC-α/PI3K signaling pathways in the regulation of LRP-mediated astrocytoma invasion. Thus, a strategy of combining small molecule inhibitors of PKC-α and PI3K could provide a new treatment paradigm for glioblastomas. PMID:17974965

  2. Acute changes in lipoprotein subclasses during exercise.

    PubMed

    Søndergaard, Esben; Poulsen, Marianne K; Jensen, Michael D; Nielsen, Søren

    2014-01-01

    Lipids are important substrates for oxidation in the basal fasting state and during exercise. Studies have demonstrated beneficial changes in lipoprotein subclass composition the day after an exercise bout. However, the acute effect of exercise on TG concentration and lipoprotein subclass composition remains unclear. Sixteen lean, healthy individuals (8 men and 8 women) were recruited (age 20-30 years, BMI<25 kg/m(2)). The subjects were studied during basal fasting conditions as well as during and after 90 min of cycling at 50% of VO2peak. Lipoprotein subclass composition was measured with (1)H NMR spectroscopy. During exercise, LDL and HDL particle concentration increased significantly (p<0.05) despite lower total TG concentration. In addition, exercise resulted in a shift towards smaller VLDL particles in men (p<0.05), but VLDL-TG concentration was unaltered. Acute exercise induces beneficial changes in lipoprotein subclass composition. These changes are similar to the effects of exercise training. © 2013.

  3. Familial defective apolipoprotein B-100 and increased low-density lipoprotein cholesterol and coronary artery calcification in the old order amish.

    PubMed

    Shen, Haiqing; Damcott, Coleen M; Rampersaud, Evadnie; Pollin, Toni I; Horenstein, Richard B; McArdle, Patrick F; Peyser, Patricia A; Bielak, Lawrence F; Post, Wendy S; Chang, Yen-Pei C; Ryan, Kathleen A; Miller, Michael; Rumberger, John A; Sheedy, Patrick F; Shelton, John; O'Connell, Jeffrey R; Shuldiner, Alan R; Mitchell, Braxton D

    2010-11-08

    Elevated low-density lipoprotein cholesterol (LDL-C) levels are a major cardiovascular disease risk factor. Genetic factors are an important determinant of LDL-C levels. To identify single nucleotide polymorphisms associated with LDL-C and subclinical coronary atherosclerosis, we performed a genome-wide association study of LDL-C in 841 asymptomatic Amish individuals aged 20 to 80 years, with replication in a second sample of 663 Amish individuals. We also performed scanning for coronary artery calcification (CAC) in 1018 of these individuals. From the initial genome-wide association study, a cluster of single nucleotide polymorphisms in the region of the apolipoprotein B-100 gene (APOB) was strongly associated with LDL-C levels (P < 10(-68)). Additional genotyping revealed the presence of R3500Q, the mutation responsible for familial defective apolipoprotein B-100, which was also strongly associated with LDL-C in the replication sample (P < 10(-36)). The R3500Q carrier frequency, previously reported to be 0.1% to 0.4% in white European individuals, was 12% in the combined sample of 1504 Amish participants, consistent with a founder effect. The mutation was also strongly associated with CAC in both samples (P < 10(-6) in both) and accounted for 26% and 7% of the variation in LDL-C levels and CAC, respectively. Compared with noncarriers, R3500Q carriers on average had LDL-C levels 58 mg/dL higher, a 4.41-fold higher odds (95% confidence interval, 2.69-7.21) of having detectable CAC, and a 9.28-fold higher odds (2.93-29.35) of having extensive CAC (CAC score ≥400). The R3500Q mutation in APOB is a major determinant of LDL-C levels and CAC in the Amish.

  4. Increase in the oxidised low-density lipoprotein level by smoking and the possible inhibitory effect of statin therapy in patients with cardiovascular disease: a retrospective study

    PubMed Central

    Ogawa, Kazuo; Tanaka, Toshikazu; Nagoshi, Tomohisa; Sekiyama, Hiroshi; Arase, Satoshi; Minai, Kosuke; Ogawa, Takayuki; Yoshimura, Michihiro

    2015-01-01

    Objectives Malondialdehyde-modified low-density lipoprotein (MDA-LDL) level is a marker of oxidative stress and is linked to progression of arteriosclerosis; however, the clinical factors affecting the oxidised LDL level have not been elucidated. We investigate various factors to identify correlation with MDA-LDL level in high-risk patients requiring catheter intervention. Setting Secondary care (cardiology), single-centre study. Participants 600 patients who were admitted to our hospital and underwent cardiac catheterisation. Primary and secondary outcome measures Blood samples were obtained to measure lipid profiles and MDA-LDL level. Results With regard to smoking status, MDA-LDL level was significantly higher in ex-smokers/current smokers compared with non-smokers. Of note, there was no improvement of MDA-LDL level even in patients who had quit smoking. Multiple regression analysis showed that MDA-LDL level was positively correlated with LDL-cholesterol (LDL-C) level, Brinkman index and male gender. The correlation between smoking status and either MDA-LDL or LDL-C level was investigated in two groups: namely, patients with and patients without statin treatment. In the non-statin group, MDA-LDL level and MDA-LDL/LDL-C ratio were significantly higher in ex-smokers/current smokers compared with non-smokers, while no significant correlation was observed between smoking status and LDL-C level. In contrast, in the statin group, there were no significant correlations between smoking status and any of the cholesterol parameters. Conclusions We found that MDA-LDL level was affected by multiple factors, such as smoking status, LDL-C level and male gender. The present findings give additional evidence that smoking should be prohibited from a MDA-LDL standpoint. Furthermore, statin therapy might have a beneficial effect on the reduction of MDA-LDL level. PMID:25609666

  5. Insulin resistance contributes more to the increased risk for diabetes development in subjects with low lipoprotein(a) level than insulin secretion.

    PubMed

    Rhee, Eun-Jung; Cho, Jung Hwan; Lee, Da Young; Kwon, Hyemi; Park, Se Eun; Park, Cheol-Young; Oh, Ki-Won; Park, Sung-Woo; Lee, Won-Young

    2017-01-01

    Recent studies suggest an association between Lipoprotein(a) [Lp(a)] and the development of diabetes mellitus. We analyzed the association between baseline Lp(a) levels and diabetes development after 4 years of follow-up, in a population of apparently healthy Korean subjects. A total of 2,536 non-diabetic participants (mean age: 41 years, men: 92%) of a health checkup program were included in the study. Diabetes development was defined by fasting blood glucose ≥126 mg/dL, HbA1c ≥6.5%, and self-reported treatment of diabetes. Homeostasis model assessment (HOMA) indices were used to assess insulin resistance (IR) and insulin secretion (IS). Presence of IR and impaired IS was defined by being in the highest quartile of HOMA-IR and in the lowest quartile HOMA-IS. After four years, 3.4% of the participants developed diabetes. The odds ratio (OR) of developing diabetes was lowest in the 4th quartile group of baseline Lp(a) (0.323 [95% CI 0.153-0.685])with the 1st quartile group as the reference. The subjects with both IR & impaired IS plus baseline Lp(a)<50 mg/dL showed the higher OR for diabetes development compared with those without IR and normal IS as the reference (67.277 [20.218-223.871], and those with IR plus Lp(a)<50 mg/dL showed higher OR for diabetes than in those with impaired IS and Lp(a)<50 mg/dL (3.811 [1.938-7.495] vs. 3.452 [1.620-7.353]). The subjects with low baseline Lp(a) level showed higher risk for development of diabetes compared with high baseline Lp(a) level, and this was prominent in those with IR than in those with impaired IS.

  6. Effect of omega-3 fatty acid ethyl esters on the oxylipin composition of lipoproteins in hypertriglyceridemic, statin-treated subjects.

    PubMed

    Newman, John W; Pedersen, Theresa L; Brandenburg, Verdayne R; Harris, William S; Shearer, Gregory C

    2014-01-01

    Oxylipins mediate inflammation, vascular tension, and more. Their presence in lipoproteins could explain why lipoproteins mediate nearly identical activities. To determine how oxylipins are distributed in the lipoproteins of hypertriglyceridemic subjects, and whether omega-3 fatty acids alter them in a manner consistent with improved cardiovascular health, we recruited 15 dyslipidemic subjects whose levels of low density lipoprotein cholesterol (LDL-C) were at goal but who remained hypertriglyceridemic (200-499 mg/dL). They were treated them with the indicated dose of 4 g/d omega-3 acid ethyl esters (P-OM3) for 8 weeks. Measured oxylipins included mid-chain alcohols (HETEs, HEPEs and HDoHEs), ketones (KETEs), epoxides (as EpETrEs, EpETEs, and EpDPEs). At baseline, arachidonate-oxylipins (HETEs, KETEs, and EpETrEs) were most abundant in plasma with the greatest fraction of total abundance (mean |95% CI|) being carried in high density lipoproteins (HDL); 42% |31, 57| followed by very low density lipoproteins (VLDL); 27% |20, 36|; and LDL 21% |16, 28|. EPA- and DHA-derived oxylipins constituted less than 11% of total. HDL carried alcohols and epoxides but VLDL was also rich in ketones. Treatment decreased AA-derived oxylipins across lipoprotein classes (-23% |-33, -12|, p = 0.0003), and expanded EPA-(322% |241, 422|, p<0.0001) and DHA-derived oxylipins (123% |80, 176|, p<0.0001). Each lipoprotein class carries a unique oxylipin complement. P-OM3 treatment alters the oxylipin content of all classes, reducing pro-inflammatory and increasing anti-inflammatory species, consistent with the improved inflammatory and vascular status associated with the treatment. ClinicalTrials.gov NCT00959842.

  7. Effect of Omega-3 Fatty Acid Ethyl Esters on the Oxylipin Composition of Lipoproteins in Hypertriglyceridemic, Statin-Treated Subjects

    PubMed Central

    Newman, John W.; Pedersen, Theresa L.; Brandenburg, Verdayne R.; Harris, William S.; Shearer, Gregory C.

    2014-01-01

    Background Oxylipins mediate inflammation, vascular tension, and more. Their presence in lipoproteins could explain why lipoproteins mediate nearly identical activities. Methods To determine how oxylipins are distributed in the lipoproteins of hypertriglyceridemic subjects, and whether omega-3 fatty acids alter them in a manner consistent with improved cardiovascular health, we recruited 15 dyslipidemic subjects whose levels of low density lipoprotein cholesterol (LDL-C) were at goal but who remained hypertriglyceridemic (200–499 mg/dL). They were treated them with the indicated dose of 4 g/d omega-3 acid ethyl esters (P-OM3) for 8 weeks. Measured oxylipins included mid-chain alcohols (HETEs, HEPEs and HDoHEs), ketones (KETEs), epoxides (as EpETrEs, EpETEs, and EpDPEs). Results At baseline, arachidonate-oxylipins (HETEs, KETEs, and EpETrEs) were most abundant in plasma with the greatest fraction of total abundance (mean |95% CI|) being carried in high density lipoproteins (HDL); 42% |31, 57| followed by very low density lipoproteins (VLDL); 27% |20, 36|; and LDL 21% |16, 28|. EPA- and DHA-derived oxylipins constituted less than 11% of total. HDL carried alcohols and epoxides but VLDL was also rich in ketones. Treatment decreased AA-derived oxylipins across lipoprotein classes (−23% |−33, −12|, p = 0.0003), and expanded EPA−(322% |241, 422|, p<0.0001) and DHA-derived oxylipins (123% |80, 176|, p<0.0001). Conclusions Each lipoprotein class carries a unique oxylipin complement. P-OM3 treatment alters the oxylipin content of all classes, reducing pro-inflammatory and increasing anti-inflammatory species, consistent with the improved inflammatory and vascular status associated with the treatment. Trial Registration ClinicalTrials.gov NCT00959842 PMID:25393536

  8. Postprandial Hyperlipidemia and Remnant Lipoproteins

    PubMed Central

    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

  9. Postprandial Hyperlipidemia and Remnant Lipoproteins.

    PubMed

    Masuda, Daisaku; Yamashita, Shizuya

    2017-02-01

    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.

  10. Thermal stability of human plasma electronegative low-density lipoprotein: A paradoxical behavior of low-density lipoprotein aggregation

    PubMed Central

    Rull, Anna; Jayaraman, Shobini; Gantz, Donald L.; Rivas-Urbina, Andrea; Pérez-Cuellar, Montserrat; Ordóñez-Llanos, Jordi; Sánchez-Quesada, Jose Luis; Gursky, Olga

    2017-01-01

    Low-density lipoprotein (LDL) aggregation is central in triggering atherogenesis. A minor fraction of electronegative plasma LDL, termed LDL(−), plays a special role in atherogenesis. To better understand this role, we analyzed the kinetics of aggregation, fusion and disintegration of human LDL and its fractions, LDL(+) and LDL(−). Thermal denaturation of LDL was monitored by spectroscopy and electron microscopy. Initially, LDL(−) aggregated and fused faster than LDL(+), but later the order reversed. Most LDL(+) disintegrated and precipitated upon prolonged heating. In contrast, LDL(−) partially retained lipoprotein morphology and formed soluble aggregates. Biochemical analysis of all fractions showed no significant degradation of major lipids, mild phospholipid oxidation, and anincrease in non-esterified fatty acid (NEFA) upon thermal denaturation. The main baseline difference between LDL subfractions was higher content of NEFA in LDL(−). Since NEFA promote lipoprotein fusion, increased NEFA content can explain rapid initial aggregation and fusion of LDL(−) but not its resistance to extensive disintegration. Partial hydrolysis of apoB upon heating was similar in LDL subfractions, suggesting that minor proteins importantly modulate LDL disintegration. Unlike LDL(+), LDL(−) contains small amounts of apoA-I and apoJ. Addition of exogenous apoA-I to LDL(+) hampered lipoprotein aggregation, fusion and precipitation, while depletion of endogenous apoJ had an opposite effect. Therefore, the initial rapid aggregation of LDL(−) is apparently counterbalanced by the stabilizing effects of minor proteins such as apoA-I and apoJ. These results help identify key determinants for LDL aggregation, fusion and coalescence into lipid droplets in vivo. PMID:27233433

  11. Triacylglycerol-rich lipoproteins protect lipoprotein lipase from inactivation by ANGPTL3 and ANGPTL4.

    PubMed

    Nilsson, Stefan K; Anderson, Fredrick; Ericsson, Madelene; Larsson, Mikael; Makoveichuk, Elena; Lookene, Aivar; Heeren, Joerg; Olivecrona, Gunilla

    2012-10-01

    Lipoprotein lipase (LPL) is important for clearance of triacylglycerols (TG) from plasma both as an enzyme and as a bridging factor between lipoproteins and receptors for endocytosis. The amount of LPL at the luminal side of the capillary endothelium determines to what extent lipids are taken up. Mechanisms to control both the activity of LPL and its transport to the endothelial sites are regulated, but poorly understood. Angiopoietin-like proteins (ANGPTLs) 3 and 4 are potential control proteins for LPL, but plasma concentrations of ANGPTLs do not correlate with plasma TG levels. We investigated the effects of recombinant human N-terminal (NT) ANGPTLs3 and 4 on LPL-mediated bridging of TG-rich lipoproteins to primary mouse hepatocytes and found that the NT-ANGPTLs, in concentrations sufficient to cause inactivation of LPL in vitro, were unable to prevent LPL-mediated lipoprotein uptake. We therefore investigated the effects of lipoproteins (chylomicrons, VLDL and LDL) on the inactivation of LPL in vitro by NT-ANGPTLs3 and 4 and found that LPL activity was protected by TG-rich lipoproteins. In vivo, postprandial TG protected LPL from inactivation by recombinant NT-ANGPTL4 injected to mice. We conclude that lipoprotein-bound LPL is stabilized against inactivation by ANGPTLs. The levels of ANGPTLs found in blood may not be sufficient to overcome this stabilization. Therefore it is likely that the prime site of action of ANGPTLs on LPL is in subendothelial compartments where TG-rich lipoprotein concentration is lower than in blood. This could explain why the plasma levels of TG and ANGPTLs do not correlate. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Is the recent rise in type 2 diabetes incidence from 1984 to 2007 explained by the trend in increasing BMI?: evidence from a prospective study of British men.

    PubMed

    Hardoon, Sarah L; Morris, Richard W; Thomas, Mary C; Wannamethee, S Goya; Lennon, Lucy T; Whincup, Peter H

    2010-07-01

    To estimate the extent to which increasing BMI may explain the rise in type 2 diabetes incidence in British men from 1984 to 2007. A representative cohort ratio of 6,460 British men was followed-up for type 2 diabetes incidence between 1984 (aged 45-65 years) and 2007 (aged 67-89 years). BMI was ascertained at regular intervals before and during the follow-up. Between 1984-1992 and 1999-2007, the age-adjusted hazard of type 2 diabetes more than doubled (hazard ratio 2.33 [95% CI 1.75-3.10]). Mean BMI rose by 1.42 kg/m(2) (95% CI 1.10-1.74) between 1984 and 1999; this could explain 26% (95% CI 17-38) of the type 2 diabetes increase. An appreciable portion of the rise in type 2 diabetes can be attributed to BMI changes. A substantial portion remains unexplained, possibly associated with other determinants such as physical activity. This merits further research.

  13. Increased serum soluble lectin-like oxidized low-density lipoprotein receptor-1 levels in patients with biopsy-proven nonalcoholic fatty liver disease

    PubMed Central

    Ozturk, Oguzhan; Colak, Yasar; Senates, Ebubekir; Yilmaz, Yusuf; Ulasoglu, Celal; Doganay, Levent; Ozkanli, Seyma; Oltulu, Yasemin Musteri; Coskunpinar, Ender; Tuncer, Ilyas

    2015-01-01

    AIM: To analyze the relationship between the serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) levels and clinical and histopathological features of biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) patients. METHODS: Fifty-three consecutive, biopsy-proven NAFLD patients (31 males and 22 females, mean age 42.5 ± 9.6 years) and 26 age- and gender-matched, healthy controls (14 males and 12 females, mean age 39 ± 10.7 years) were included. The patients with NAFLD were consecutive patients who had been admitted to the hepatology outpatient clinic within the last year and had been diagnosed with NAFLD as the result of liver biopsy. The healthy controls were individuals who attended the outpatient clinic for routine health control and had no known chronic illnesses. The histological evaluation was conducted according to the NAFLD activity scoring system recommended by The National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. The serum LOX-1 levels were measured using an ELISA kit (Life Science Inc. USCN. Wuhan, Catalog No. E1859Hu) in both patients and healthy controls. A receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff value of LOX-1 and thereby distinguish between patients with nonalcoholic steatohepatitis (NASH) and healthy controls. A P-value < 0.05 was considered statistically significant. RESULTS: NAFLD and healthy control groups were similar in terms of age and sex. NAFLD patients consisted of 8 patients with simple steatosis (15%), 27 with borderline NASH (51%) and 18 with definitive NASH (34%). Metabolic syndrome was found in 62.2% of the patients with NAFLD. The mean serum LOX-1 level in biopsy-proven NAFLD patients was 8.49 ± 6.43 ng/mL compared to 4.08 ± 4.32 ng/mL in healthy controls (P = 0.001). The LOX-1 levels were significantly different between controls, simple steatosis and NASH (borderline+definite) cases (4

  14. Human ABCA1 BAC transgenic mice show increased high density lipoprotein cholesterol and ApoAI-dependent efflux stimulated by an internal promoter containing liver X receptor response elements in intron 1.

    PubMed

    Singaraja, R R; Bocher, V; James, E R; Clee, S M; Zhang, L H; Leavitt, B R; Tan, B; Brooks-Wilson, A; Kwok, A; Bissada, N; Yang, Y Z; Liu, G; Tafuri, S R; Fievet, C; Wellington, C L; Staels, B; Hayden, M R

    2001-09-07

    By using BAC transgenic mice, we have shown that increased human ABCA1 protein expression results in a significant increase in cholesterol efflux in different tissues and marked elevation in high density lipoprotein (HDL)-cholesterol levels associated with increases in apoAI and apoAII. Three novel ABCA1 transcripts containing three different transcription initiation sites that utilize sequences in intron 1 have been identified. In BAC transgenic mice there is an increased expression of ABCA1 protein, but the distribution of the ABCA1 product in different cells remains similar to wild type mice. An internal promoter in human intron 1 containing liver X response elements is functional in vivo and directly contributes to regulation of the human ABCA1 gene in multiple tissues and to raised HDL cholesterol, apoAI, and apoAII levels. A highly significant relationship between raised protein levels, increased efflux, and level of HDL elevation is evident. These data provide proof of the principle that increased human ABCA1 efflux activity is associated with an increase in HDL levels in vivo.

  15. New roles of low density lipoproteins and vitamin E in the pathogenesis of atherosclerosis.

    PubMed

    Ozer, N K; Boscoboinik, D; Azzi, A

    1995-01-01

    Accumulation of oxidized low density lipoproteins in macrophages and smooth muscle cells causes foam cell formation, an initial step in atherosclerosis. Active oxygen species are considered important in the pathogenesis of the disease. Antioxidants, such as tocopherols and tocotrienols have been considered to prevent the deleterious effects of active oxygen species. We found native low density lipoproteins can stimulate directly smooth muscle cell proliferation, it is associated with an increase of protein kinase C activity. d-alpha-Tocopherol, biologically most active form of vitamin E, inhibits both cell proliferation and protein kinase C activity. The effect of d-alpha-tocopherol is not related to its radical scavenging properties. Transforming growth factor-beta secreted by smooth muscle cells as growth inhibitor. Low density lipoproteins decrease the release of transforming growth factor-beta from smooth muscle cells thus activating growth. d-alpha-Tocopherol activates the cellular release of transforming growth factor-beta. These new aspects explain the important role of low density lipoproteins and vitamin E in increasing and decreasing the risk of atherosclerosis, respectively.

  16. Does material disadvantage explain the increased risk of adverse health, educational, and behavioural outcomes among children in lone parent households in Britain? A cross sectional study.

    PubMed

    Spencer, Nick

    2005-02-01

    To test the hypothesis that material disadvantage explains the increased risk among children and young people of adverse health, educational, and behavioural problems associated with living in lone parent households in Britain Secondary analysis of a cross sectional survey of a representative sample of British households with children and youthMain outcomes: Parent reported fair/poor health, longstanding illness and disability, statement of special educational needs, suspension and/or expulsion from school, and in trouble with the police. Data were available on 15 636 (8049 boys and 7587 girls) aged 0-18 years in 8541 households in the third sweep (2001) of the British government's families and children study Lone parenthood was associated with increased risk of health and educational problems, and antisocial behaviour among boys and girls in a logistic regression model adjusting for child's age alone. Adding age of main carer, number of dependent children, and child's rank in the household made little difference to the associations. Addition of housing tenure, household hardship index, and an interaction term for lone parenthood and hardship eliminated the relation with lone parenthood for all outcomes except parent reported health among girls. Similar results were obtained for households headed by lone parents for at least a year. An interaction effect of lone parenthood with hardship for parent reported health and statement of special educational needs was noted. Adverse effects of lone parenthood on health, education, and antisocial behaviour were apparently explained by material disadvantage in this cross sectional sample of British households with children and youth.

  17. Progressive decline in tacrolimus clearance after renal transplantation is partially explained by decreasing CYP3A4 activity and increasing haematocrit

    PubMed Central

    de Jonge, Hylke; Vanhove, Thomas; de Loor, Henriëtte; Verbeke, Kristin; Kuypers, Dirk R J

    2015-01-01

    Aims The long-term disposition of tacrolimus following kidney transplantation is characterized by a gradual decrease in dose requirements and increase in dose-corrected exposure. This phenomenon has been attributed to a progressive decline in cytochrome P450 3A4 (CYP3A4) activity, although this has never been demonstrated in vivo. Methods Sixty-five tacrolimus- and 10 cyclosporine-treated renal transplant recipients underwent pharmacokinetic testing at day 7 and months 1, 3, 6 and 12 after transplantation, including 8-h area under the concentration-time curve (AUC) for tacrolimus or cyclosporine and assessment of CYP3A4 activity using oral and intravenous midazolam (MDZ) drug probes. Results Tacrolimus clearance decreased gradually throughout the entire first year but only in CYP3A5*3/*3 homozygous recipients (25.6 ± 11.1 l h–1 at day 7; 17 ± 9.1 l h–1 at month 12; P < 0.001). In mixed model analysis, decreasing CYP3A4 activity, measured by apparent oral MDZ clearance (924 ± 443 ml min–1 at day 7 vs. 730 ± 344 ml min–1 at month 1; P < 0.001), explained 55.4% of the decline in tacrolimus clearance in the first month. CYP3A4 activity decreased by 18.9 ml min–1 for every milligram of methylprednisolone dose tapering within the first month; beyond this point it remained stable. A gradual rise in haematocrit throughout the entire first year explained 31.7% of the decrease in tacrolimus clearance in the first month and 23.6% of the decrease between months 1 and 12. Cyclosporine clearance did not change over time. Conclusions The maturation of tacrolimus disposition in the first year after renal transplantation observed in CYP3A5*3/*3 homozygous patients can partly be explained by a (steroid tapering-related) decline in CYP3A4 activity and a progressive increase in haematocrit. PMID:26114223

  18. Progressive decline in tacrolimus clearance after renal transplantation is partially explained by decreasing CYP3A4 activity and increasing haematocrit.

    PubMed

    de Jonge, Hylke; Vanhove, Thomas; de Loor, Henriëtte; Verbeke, Kristin; Kuypers, Dirk R J

    2015-09-01

    The long-term disposition of tacrolimus following kidney transplantation is characterized by a gradual decrease in dose requirements and increase in dose-corrected exposure. This phenomenon has been attributed to a progressive decline in cytochrome P450 3A4 (CYP3A4) activity, although this has never been demonstrated in vivo. Sixty-five tacrolimus- and 10 cyclosporine-treated renal transplant recipients underwent pharmacokinetic testing at day 7 and months 1, 3, 6 and 12 after transplantation, including 8-h area under the concentration-time curve (AUC) for tacrolimus or cyclosporine and assessment of CYP3A4 activity using oral and intravenous midazolam (MDZ) drug probes. Tacrolimus clearance decreased gradually throughout the entire first year but only in CYP3A5*3/*3 homozygous recipients (25.6 ± 11.1 l h(-1) at day 7; 17 ± 9.1 l h(-1) at month 12; P < 0.001). In mixed model analysis, decreasing CYP3A4 activity, measured by apparent oral MDZ clearance (924 ± 443 ml min(-1) at day 7 vs. 730 ± 344 ml min(-1) at month 1; P < 0.001), explained 55.4% of the decline in tacrolimus clearance in the first month. CYP3A4 activity decreased by 18.9 ml min(-1) for every milligram of methylprednisolone dose tapering within the first month; beyond this point it remained stable. A gradual rise in haematocrit throughout the entire first year explained 31.7% of the decrease in tacrolimus clearance in the first month and 23.6% of the decrease between months 1 and 12. Cyclosporine clearance did not change over time. The maturation of tacrolimus disposition in the first year after renal transplantation observed in CYP3A5*3/*3 homozygous patients can partly be explained by a (steroid tapering-related) decline in CYP3A4 activity and a progressive increase in haematocrit. © 2015 The British Pharmacological Society.

  19. Astronomy Explained

    NASA Astrophysics Data System (ADS)

    North, Gerald

    Every year large numbers of people take up the study of astronomy, mostly at amateur level. There are plenty of elementary books on the market, full of colourful photographs, but lacking in proper explanations of how and why things are as they are. Many people eventually wish to go beyond the 'coffee-table book' stage and study this fascinating subject in greater depth. This book is written for them. In addition, many people sit for public examinations in this subject each year and this book is also intended to be of use to them. All the topics from the GCSE syllabus are covered here, with sample questions at the end of each chapter. Astronomy Explained provides a comprehensive treatment of the subject in more depth than is usually found in elementary works, and will be of interest to both amateur astronomers and students of astronomy.

  20. Revisiting the Gram-negative lipoprotein paradigm.

    PubMed

    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.

  1. Revisiting the Gram-Negative Lipoprotein Paradigm

    PubMed Central

    LoVullo, Eric D.; Wright, Lori F.; Isabella, Vincent; Huntley, Jason F.

    2015-01-01

    ABSTRACT 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. IMPORTANCE 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. PMID:25755189

  2. Lipoproteins and lipoprotein mimetics for imaging and drug delivery.

    PubMed

    Thaxton, C Shad; Rink, Jonathan S; Naha, Pratap C; Cormode, David P

    2016-11-15

    Lipoproteins are a set of natural nanoparticles whose main role is the transport of fats within the body. While much work has been done to develop synthetic nanocarriers to deliver drugs or contrast media, natural nanoparticles such as lipoproteins represent appealing alternatives. Lipoproteins are biocompatible, biodegradable, non-immunogenic and are naturally targeted to some disease sites. Lipoproteins can be modified to act as contrast agents in many ways, such as by insertion of gold cores to provide contrast for computed tomography. They can be loaded with drugs, nucleic acids, photosensitizers or boron to act as therapeutics. Attachment of ligands can re-route lipoproteins to new targets. These attributes render lipoproteins attractive and versatile delivery vehicles. In this review we will provide background on lipoproteins, then survey their roles as contrast agents, in drug and nucleic acid delivery, as well as in photodynamic therapy and boron neutron capture therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. A Mediterranean-style, low-glycemic-load diet decreases atherogenic lipoproteins and reduces lipoprotein (a) and oxidized low-density lipoprotein in women with metabolic syndrome.

    PubMed

    Jones, Jennifer L; Comperatore, Michael; Barona, Jacqueline; Calle, Mariana C; Andersen, Catherine; McIntosh, Mark; Najm, Wadie; Lerman, Robert H; Fernandez, Maria Luz

    2012-03-01

    The objective was to assess the impact of a Mediterranean-style, low-glycemic-load diet (control group, n = 41) and the same diet plus a medical food (MF) containing phytosterols, soy protein, and extracts from hops and Acacia (MF group, n = 42) on lipoprotein atherogenicity in women with metabolic syndrome. Plasma lipids, apolipoproteins (apos), lipoprotein subfractions and particle size, low-density lipoprotein (LDL) oxidation, and lipoprotein (a) were measured at baseline, week 8, and week 12 of the intervention. Three-day dietary records were collected at the same time points to assess compliance. Compared with baseline, women decreased energy intake from carbohydrate (P < .001) and fat (P < .001), whereas they increased energy intake from protein (P < .001). A significant increase in energy from monounsaturated fatty acids was also observed as well as increases in eicosapentaenoic acid and docosahexaenoic acid, whereas trans-fatty acid intake was reduced (P < .00001). The atherogenic lipoproteins, large very low-density lipoprotein (P < .0001) and small LDL (P < .0001), were reduced, whereas the ratio of large high-density lipoprotein to smaller high-density lipoprotein particles was increased (P < .0001). Apolipoprotein B was reduced for all women (P < .0001), with a greater reduction in the MF group (P < .025). Oxidized LDL (P < .05) and lipoprotein (a) (P < .001) were reduced in both groups at the end of the intervention. Consumption of a Mediterranean-style diet reduces the risk for cardiovascular disease by decreasing atherogenic lipoproteins, oxidized LDL, and apo B. Inclusion of an MF may have an additional effect in reducing apo B. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Role for circulating lipoproteins in protection from endotoxin toxicity.

    PubMed Central

    Feingold, K R; Funk, J L; Moser, A H; Shigenaga, J K; Rapp, J H; Grunfeld, C

    1995-01-01

    Previous studies have shown that endotoxin (lipopolysaccharide [LPS])-induced death can be prevented by preincubating LPS with lipoproteins in vitro or by infusing large quantities of lipids into animals prior to LPS administration. In the present study we determined whether physiological levels of lipids also provide protection. Serum lipid levels were decreased by two different mechanisms: administration of 4-aminopyrolo-(3,4-D)pyrimide, which prevents the hepatic secretion of lipoproteins, and administration of pharmacological doses of estradiol, which increases the number of hepatic low-density lipoprotein receptors, leading to increased lipoprotein clearance. In both hypolipidemic models, LPS-induced mortality is markedly increased compared with that of controls with normal serum lipid levels. In both hypolipidemic models, administration of exogenous lipoproteins, which increase levels of serum lipids into the physiological range, reduces the increased mortality to levels similar to that seen in normal animals. In normal lipidemic animals, 63% of 125I-LPS in plasma is associated with lipoproteins, where it would not be capable of stimulating cytokine production. In contrast, in hypolipidemic animals, very little LPS (12 to 17%) is associated with lipoproteins. Rather, more LPS is in the lipoprotein-free plasma compartment, where it could exert biological effects. In both hypolipidemic models, LPS produces a greater increase in serum tumor necrosis factor levels than it does in controls (three- to fivefold increase), and administration of exogenous lipoproteins prevents this increase. Cytokines, in particular tumor necrosis factor, are responsible for most of the toxic effects of LPS. These data provide evidence that physiological levels of serum lipids protect animals from LPS toxicity. Thus, lipoproteins, in addition to playing a role in lipid transport, may have protective functions. Moreover, as part of the immune response, cytokine-induced increases in

  5. High-Density Lipoprotein, Lecithin: Cholesterol Acyltransferase, and Atherosclerosis

    PubMed Central

    Ossoli, Alice; Pavanello, Chiara

    2016-01-01

    Epidemiological data clearly show the existence of a strong inverse correlation between plasma high-density lipoprotein cholesterol (HDL-C) concentrations and the incidence of coronary heart disease. This relation is explained by a number of atheroprotective properties of HDL, first of all the ability to promote macrophage cholesterol transport. HDL are highly heterogeneous and are continuously remodeled in plasma thanks to the action of a number of proteins and enzymes. Among them, lecithin:cholesterol acyltransferase (LCAT) plays a crucial role, being the only enzyme able to esterify cholesterol within lipoproteins. LCAT is synthetized by the liver and it has been thought to play a major role in reverse cholesterol transport and in atheroprotection. However, data from animal studies, as well as human studies, have shown contradictory results. Increased LCAT concentrations are associated with increased HDL-C levels but not necessarily with atheroprotection. On the other side, decreased LCAT concentration and activity are associated with decreased HDL-C levels but not with increased atherosclerosis. These contradictory results confirm that HDL-C levels per se do not represent the functionality of the HDL system. PMID:27302716

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

    PubMed

    Lamon-Fava, Stefania; Asztalos, Bela F; Howard, Timothy D; Reboussin, David M; Horvath, Katalin V; Schaefer, Ernst J; Herrington, David M

    2010-02-01

    A high degree of inter-individual variability in plasma lipid level response to hormone therapy (HT) has been reported. Variations in the oestrogen receptor alpha gene (ESR1) and in genes involved in lipid metabolism may explain some of the variability in response to HT. Subjects Postmenopausal Caucasian women (n = 208) participating in a placebo-controlled randomized trial of 3.2 years of hormone therapy (HT). Plasma triglyceride (TG), remnant lipoprotein cholesterol (RLP-C), and high-density lipoprotein cholesterol (HDL-C) levels and HDL subpopulations were assessed at baseline and at follow up. Single nucleotide polymorphisms (SNPs) in ESR1 and in the ATP binding cassette A1 (ABCA1), cholesteryl ester transfer protein (CETP), hepatic lipase (LIPC), lipoprotein lipase (LPL), and scavenger receptor class B type I (SRB1) genes were assessed for their association with baseline plasma levels and HT-related changes in levels of RLP-C and HDL subpopulations. Carriers of the ESR1 PvuII or IVS1-1505 variants had lower plasma TG concentrations and higher plasma HDL-C and alpha-1 and prealpha-1 HDL particle levels at baseline and showed greater increases in HDL-C, apo A-I and alpha-1 particle levels after HT than wild-type carriers. Carriers of the N291S and D9N variants in the LPL gene had significantly higher remnant lipoproteins and lower alpha-2 HDL particle levels at baseline. The CETP TaqIB SNP was a significant determinant of baseline plasma HDL-C and HDL subpopulation profile. Single nucleotide polymorphisms in ESR1, CETP and LPL had significant effects on baseline plasma levels of TG-rich and HDL subpopulations. With the exception of ESR1 SNPs, variation in genes involved in lipid metabolism has a very modest effect on lipoprotein response to HT.

  7. Pharmacokinetics cannot explain the increased effective dose requirement for morphine and midazolam in rats during their extended administration alone or in combination.

    PubMed

    Schaller, Stefan J; Alam, Saad M; Mao, Jianren; Zhao, Yanli; Blobner, Manfred; Greenblatt, David J; Martyn, J A Jeevendra

    2017-01-01

    Chronic administration of morphine and midazolam, alone or in combination, can induce tolerance to their effects. Data showed that co-administration of morphine and midazolam increased effective dose requirement of morphine, exceeding that observed with morphine alone. To elucidate the pharmacokinetic component to the tolerance, we administered midazolam (2 mg/kg) and morphine (10 mg/kg) alone or their combination daily to rats for 12 days followed by a pharmacokinetic study on day 13. On the study day, each animal received a single bolus dose of 5 mg/kg morphine, and 2 mg/kg of midazolam 30 s later. Multiple blood samples were obtained for 6 h. Plasma drug concentrations were assayed by mass spectrometry optimized for small samples. Mean morphine clearance was as follows: 22.2, 27.2, 26.0 and 23.4 l/h per kg in the saline-saline, saline-midazolam, saline-morphine and midazolam-morphine groups, respectively. Corresponding midazolam clearances were 32.8, 23.0, 22.2 and 31.1 l/h per kg. ANOVA indicated no significant differences among the four groups in the clearances, half-lives, and volumes of distribution. Morphine and midazolam clearances were significantly correlated (R(2) = 0.48, P < 0.001). This animal model suggests that altered pharmacokinetics cannot explain tolerance evidenced as increased dose requirement for morphine or midazolam, when administered alone or combination, for extended periods. © 2016 Royal Pharmaceutical Society.

  8. Radiation Dose Associated with Renal Failure Mortality: A Potential Pathway to Partially Explain Increased Cardiovascular Disease Mortality Observed after Whole-Body Irradiation

    PubMed Central

    Adams, Michael Jacob; Grant, Eric J.; Kodama, Kazunori; Shimizu, Yukiko; Kasagi, Fumiyoshi; Suyama, Akihiko; Sakata, Ritsu; Akahoshi, Masazumi

    2012-01-01

    Whole-body and thoracic ionizing radiation exposure are associated with increased cardiovascular disease (CVD) risk. In atomic bomb survivors, radiation dose is also associated with increased hypertension incidence, suggesting that radiation dose may be associated with chronic renal failure (CRF), thus explaining part of the mechanism for increased CVD. Multivariate Poisson regression was used to evaluate the association of radiation dose with various definitions of chronic kidney disease (CKD) mortality in the Life Span Study (LSS) of atomic bomb survivors. A secondary analysis was performed using a subsample for whom self-reported information on hypertension and diabetes, the two biggest risk factors for CRF, had been collected. We found a significant association between radiation dose and only our broadest definition of CRF among the full cohort. A quadratic dose excess relative risk model [ERR/Gy2 = 0.091 (95% CI: 0.05, 0.198)] fit minimally better than a linear model. Within the subsample, association was also observed only with the broadest CRF definition [ERR/Gy2 = 0.15 (95% CI: 0.02, 0.32)]. Adjustment for hypertension and diabetes improved model fit but did not substantially change the ERR/Gy2 estimate, which was 0.17 (95% CI: 0.04, 0.35). We found a significant quadratic dose relationship between radiation dose and possible chronic renal disease mortality that is similar in shape to that observed between radiation and incidence of hypertension in this population. Our results suggest that renal dysfunction could be part of the mechanism causing increased CVD risk after whole-body irradiation, a hypothesis that deserves further study. PMID:22149958

  9. [Hormonal regulation of lipoprotein metabolism: the role in pathogenesis of coronary heart disease].

    PubMed

    Sokolov, E I; Metel'skaia, V A; Perova, N V; Shchukina, G N

    2006-01-01

    The character and role of hormonal dysregulation of lipoprotein metabolism during postprandial hyperlipemia were studied in patients with coronary heart disease (CHD) and hyperthyroidism as compared with healthy subjects. Pronounced hypertriglyceridemia alongside with the decreased high density lipoprotein cholesterol (HDL C) after standard fat load were associated with increased level of insulin and decreased level of cortisol. Moreover, in CHD patients fasting hyperinsulinemia becoming even stronger postprandially resulted in prevalence of antilipolytic action of insulin over lipid-mobilizing effect of cortisol; and an extended postprandial hypertriglyceridemia took place. Patients with hyperthyroidism and low cholesterol level both in atherogenic LDL and antiatherogenic HDL, demonstrated decreased level of apo AI (as in CHD patients) and apo B (three times lower than in CHD patients). Very low ratio of apo B/AI in patients with hyperthyroidism both in fasting and postprandial state was a clear indication of their lipoprotein profile antiatherogeneity. Thus, in patients with hyperthyroidism despite of low HDL C and apo AI levels, antiatherogenic properties of lipoprotein profile are probably determined by very low apo B/AI ratio induced by thyroid hormones, and might be explained by the influence of thyroid hormones on the expression of genes coding these apoproteins.

  10. Increased proximal reflux in a hypersensitive esophagus might explain symptoms resistant to proton pump inhibitors in patients with gastroesophageal reflux disease.

    PubMed

    Rohof, Wout O; Bennink, Roelof J; de Jonge, Hugo; Boeckxstaens, Guy E

    2014-10-01

    Approximately 30% of patients with gastroesophageal reflux disease have symptoms resistant to treatment with proton pump inhibitors (PPIs). Several mechanisms such as esophageal hypersensitivity, increased mucosal permeability, and possibly the position of the gastric acid pocket might underlie a partial response to PPIs. To what extent these mechanisms interact and contribute to PPI-resistant symptoms, however, has not been investigated previously. In 18 gastroesophageal reflux disease patients (9 PPI responders and 9 PPI partial responders), esophageal sensitivity, mucosal permeability, and postprandial reflux parameters were determined during PPI use. Esophageal sensitivity for distension was measured by gradual balloon inflation at 5 and 15 cm above the lower esophageal sphincter. The mucosal permeability of 4 esophageal biopsy specimens per patient was determined in Ussing chambers by measuring the transepithelial electrical resistance and transmucosal flux of fluorescein. Postprandial reflux parameters were determined using concurrent high-resolution manometry/pH impedance after a standardized meal. In addition, the acid pocket was visualized using scintigraphy. No difference in the rate of postprandial acid reflux, in the pH of the acid pocket (PPI responders 3.7 ± 0.7 vs PPI partial responders 4.2 ± 0.4; P = .54), or in the position of the acid pocket was observed in PPI partial responders compared with PPI responders. In addition, the permeability of the esophageal mucosa was similar in both groups, as shown by a similar transepithelial electrical resistance and flux of fluorescein. PPI partial responders had more reflux episodes with a higher mean proximal extent, compared with PPI responders, and were more sensitive to balloon distension, both in the upper and lower esophagus. PPI-resistant symptoms most likely are explained by increased proximal reflux in a hypersensitive esophagus and less likely by increased mucosal permeability or the position of

  11. Lipoprotein electrostatic properties regulate hepatic lipase association and activity.

    PubMed

    Boucher, Jonathan G; Nguyen, Trang; Sparks, Daniel L

    2007-12-01

    The effect of lipoprotein electrostatic properties on the catalytic regulation of hepatic lipase (HL) was investigated. Enrichment of serum or very low density lipoprotein (VLDL) with oleic acid increased lipoprotein negative charge and stimulated lipid hydrolysis by HL. Similarly, enrichment of serum or isolated lipoproteins with the anionic phospholipids phosphatidylinositol (PI), phosphatidic acid, or phosphatidylserine also increased lipoprotein negative charge and stimulated hydrolysis by HL. Anionic lipids had a small effect on phospholipid hydrolysis, but significantly stimulated triacylglyceride (TG) hydrolysis. High density lipoprotein (HDL) charge appears to have a specific effect on lipolysis. Enrichment of HDL with PI significantly stimulated VLDL-TG hydrolysis by HL. To determine whether HDL charge affects the association of HL with HDL and VLDL, HL-lipoprotein interactions were probed immunochemically. Under normal circumstances, HL associates with HDL particles, and only small amounts bind to VLDL. PI enrichment of HDL blocked the binding of HL with HDL. These data indicate that increasing the negative charge of HDL stimulates VLDL-TG hydrolysis by reducing the association of HL with HDL. Therefore, HDL controls the hydrolysis of VLDL by affecting the interlipoprotein association of HL. Lipoprotein electrostatic properties regulate lipase association and are an important regulator of the binding and activity of lipolytic enzymes.

  12. Lipoprotein marker for hypertriglyceridemia

    DOEpatents

    Cubicciotti, Roger S.; Karu, Alexander E.; Krauss, Ronald M.

    1986-01-01

    Methods and compositions are provided for the detection of a particular low density lipoprotein which has been found to be a marker for patients suffering from type IV hypertriglyceridemia. A monoclonal antibody capable of specifically binding to a characteristic epitopic site on this LDL subspecies can be utilized in a wide variety of immunoassays. Hybridoma cell line SPL.IVA5A1 was deposited at the American Type Culture Collection on Mar. 29, 1984, and granted accession no. HB 8535.

  13. Explaining global increases in water use efficiency: why have we overestimated responses to rising atmospheric CO(2) in natural forest ecosystems?

    PubMed

    Silva, Lucas C R; Horwath, William R

    2013-01-01

    The analysis of tree-ring carbon isotope composition (δ(13)C) has been widely used to estimate spatio-temporal variations in intrinsic water use efficiency (iWUE) of tree species. Numerous studies have reported widespread increases in iWUE coinciding with rising atmospheric CO(2) over the past century. While this could represent a coherent global response, the fact that increases of similar magnitude were observed across biomes with no apparent effect on tree growth raises the question of whether iWUE calculations reflect actual physiological responses to elevated CO(2) levels. Here we use Monte Carlo simulations to test if an artifact of calculation could explain observed increases in iWUE. We show that highly significant positive relationships between iWUE and CO(2) occur even when simulated data (randomized δ(13)C values spanning the observed range) are used in place of actual tree-ring δ(13)C measurements. From simulated data sets we calculated non-physiological changes in iWUE from 1900 to present and across a 4000 m altitudinal range. This generated results strikingly similar to those reported in recent studies encompassing 22 species from tropical, subtropical, temperate, boreal and mediterranean ecosystems. Only 6 of 49 surveyed case studies showed increases in iWUE significantly higher than predicted from random values. Our results reveal that increases in iWUE estimated from tree-ring δ(13)C occur independently of changes in (13)C discrimination that characterize physiological responses to elevated CO(2). Due to a correlation with CO(2) concentration, which is used as an independent factor in the iWUE calculation, any tree-ring δ(13)C data set would inevitably generate increasing iWUE over time. Therefore, although consistent, previously reported trends in iWUE do not necessarily reflect a coherent global response to rising atmospheric CO(2). We discuss the significance of these findings and suggest ways to distinguish real from artificial responses

  14. Beneficial effects of weight loss associated with moderate calorie/carbohydrate restriction, and increased proportional intake of protein and unsaturated fat on serum urate and lipoprotein levels in gout: a pilot study

    PubMed Central

    Dessein, P; Shipton, E; Stanwix, A; Joffe, B; Ramokgadi, J

    2000-01-01

    OBJECTIVES—Insulin resistance (IR) has been increasingly implicated in the pathogenesis of gout. The lipoprotein abnormalities described in hyperuricaemic subjects are similar to those associated with IR, and insulin influences renal urate excretion. In this study it was investigated whether dietary measures, reported to be beneficial in IR, have serum uric acid (SU) and lipid lowering effects in gout.
METHODS—Thirteen non-diabetic men (median age 50, range 38-62) were enrolled. Each patient had had at least two gouty attacks during the four months before enrolment. Dietary recommendations consisted of calorie restriction to 6690 kJ (1600 kcal) a day with 40% derived from carbohydrate, 30% from protein, and 30% from fat; replacement of refined carbohydrates with complex ones and saturated fats with mono- and polyunsaturated ones. At onset and after 16 weeks, fasting blood samples were taken for determination of SU, serum cholesterol (C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TGs). Results were expressed as median (SD).
RESULTS—At onset, the body mass index (BMI) was 30.5 (8.1) kg/m2. Dietary measures resulted in weight loss of 7.7 (5.4) kg (p=0.002) and a decrease in the frequency of monthly attacks from 2.1 (0.8) to 0.6 (0.7) (p=0.002). The SU decreased from 0.57 (0.10) to 0.47 (0.09) mmol/l (p=0.001) and normalised in 7 (58%) of the 12 patients with an initially raised level. Serum cholesterol decreased from 6.0 (1.7) to 4.7 (0.9) mmol/l (p=0.002), LDL-C from 3.5 (1.2) to 2.7 (0.8) mmol/l (p=0.004), TGs from 4.7 (4.2) to 1.9 (1.0) mmol/l (p=0.001), and C:HDL-C ratios from 6.7 (1.7) to 5.2 (1.0) (p=0.002). HDL-C levels increased insignificantly. High baseline SU, frequency of attacks, total cholesterol, LDL-C and TG levels, and total C:HDL-C ratios correlated with higher decreases in the respective variables upon dietary intervention (p<0.05).

  15. Explaining happiness.

    PubMed

    Easterlin, Richard A

    2003-09-16

    What do social survey data tell us about the determinants of happiness? First, that the psychologists' setpoint model is questionable. Life events in the nonpecuniary domain, such as marriage, divorce, and serious disability, have a lasting effect on happiness, and do not simply deflect the average person temporarily above or below a setpoint given by genetics and personality. Second, mainstream economists' inference that in the pecuniary domain "more is better," based on revealed preference theory, is problematic. An increase in income, and thus in the goods at one's disposal, does not bring with it a lasting increase in happiness because of the negative effect on utility of hedonic adaptation and social comparison. A better theory of happiness builds on the evidence that adaptation and social comparison affect utility less in the nonpecuniary than pecuniary domains. Because individuals fail to anticipate the extent to which adaptation and social comparison undermine expected utility in the pecuniary domain, they allocate an excessive amount of time to pecuniary goals, and shortchange nonpecuniary ends such as family life and health, reducing their happiness. There is need to devise policies that will yield better-informed individual preferences, and thereby increase individual and societal well-being.

  16. Explaining happiness

    PubMed Central

    Easterlin, Richard A.

    2003-01-01

    What do social survey data tell us about the determinants of happiness? First, that the psychologists' setpoint model is questionable. Life events in the nonpecuniary domain, such as marriage, divorce, and serious disability, have a lasting effect on happiness, and do not simply deflect the average person temporarily above or below a setpoint given by genetics and personality. Second, mainstream economists' inference that in the pecuniary domain “more is better,” based on revealed preference theory, is problematic. An increase in income, and thus in the goods at one's disposal, does not bring with it a lasting increase in happiness because of the negative effect on utility of hedonic adaptation and social comparison. A better theory of happiness builds on the evidence that adaptation and social comparison affect utility less in the nonpecuniary than pecuniary domains. Because individuals fail to anticipate the extent to which adaptation and social comparison undermine expected utility in the pecuniary domain, they allocate an excessive amount of time to pecuniary goals, and shortchange nonpecuniary ends such as family life and health, reducing their happiness. There is need to devise policies that will yield better-informed individual preferences, and thereby increase individual and societal well-being. PMID:12958207

  17. Can differences in the type, nature or amount of polysubstance use explain the increased risk of non-fatal overdose among psychologically distressed people who inject drugs?

    PubMed

    Betts, Kim S; McIlwraith, Fairlie; Dietze, Paul; Whittaker, Elizabeth; Burns, Lucy; Cogger, Shelley; Alati, Rosa

    2015-09-01

    This study investigates whether the type, nature or amount of polysubstance use can explain the increased risk of non-fatal overdose among people who inject drugs with severe psychological distress. Data came from three years (2011-2013) of the Illicit Drug Reporting System (IDRS), an annual sentinel sample of injecting drug users across Australia (n=2673). Structural Equation Modelling (SEM) was used on 14 drug types to construct five latent factors, each representing a type of polysubstance use. Tests of measurement invariance were carried out to determine if polysubstance use profiles differed between those with and without severe psychological distress. Next, we regressed non-fatal overdose on the polysubstance use factors with differences in the relationships tested between groups. Among those with severe psychological distress a polysubstance use profile characterised by heroin, oxycodone, crystal methamphetamine and cocaine use was associated with greater risk of non-fatal overdose. Among those without severe psychological distress, two polysubstance use profiles, largely characterised by opioid substitution therapies and prescription drugs, were protective against non-fatal overdose. The types of polysubstance use profiles did not differ between people who inject drugs with and without severe psychological distress. However, the nature of use of one particular polysubstance profile placed the former group at a strongly increased risk of non-fatal overdose, while the nature of polysubstance use involving opioid substitution therapies was protective only among the latter group. The findings identify polysubstance use profiles of importance to drug-related harms among individuals with psychological problems. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Decreased concentrations of the lipoprotein lipase inhibitor angiopoietin-like protein 4 and increased serum triacylglycerol are associated with increased neonatal fat mass in pregnant women with gestational diabetes mellitus.

    PubMed

    Ortega-Senovilla, Henar; Schaefer-Graf, Ute; Meitzner, Katrin; Abou-Dakn, Michael; Herrera, Emilio

    2013-08-01

    Angiopoietin-like protein 4 (ANGPTL4) is an extracellular inhibitor of lipoprotein lipase (LPL) activity. No studies have been done in pregnancy in which hypertriglyceridemia and tissue-specific changes in LPL activity are present. The objective of the study was to determine the relationship between neonatal fat mass (FM) and concentrations of ANGPTL4 and triacylglycerols (TAG) in maternal and cord serum of pregnant women with gestational diabetes mellitus (GDM) compared with controls. Maternal blood samples (control, n = 90, and GDM, n= 80) and umbilical cord blood were drawn before and after vaginal delivery, respectively. Control and GDM subjects were grouped separately into 3 subgroups, according to neonatal FM: 0-25th percentiles, 25th-75th percentiles, and 75th-100th percentiles. Glucose, insulin, TAG, nonesterified fatty acids (NEFAs), and ANGPTL4 were determined in maternal and neonatal serum. Age and pregestational body mass index did not differ between GDM and control women in any subgroups. Maternal serum of GDM pregnant women who delivered the newborn with the highest FM showed the highest concentrations of TAG and NEFAs and lowest concentration of ANGPTL4, despite glucose and insulin concentrations being independent of changes in neonatal FM. However, cord serum of neonates of GDM patients with the highest FM showed higher concentrations of insulin and lower concentrations of TAG than those with lower neonatal FM but no significant differences in NEFAs or ANGPTL4 concentrations. In well-controlled GDM pregnancies, decreased maternal ANGPTL4 concentrations and a gradient of TAG toward the fetus are related with higher neonatal FM. However, in GDM fetuses with the highest FM, the potential effect of ANGPTL4 inhibiting adipose tissue LPL activity could be overcome by their hyperinsulinemia.

  19. A Cross-Sectional Study Demonstrating Increased Serum Amyloid A Related Inflammation in High-Density Lipoproteins from Subjects with Type 1 Diabetes Mellitus and How this Association Was Augmented by Poor Glycaemic Control.

    PubMed

    McEneny, Jane; Daniels, Jane-Ann; McGowan, Anne; Gunness, Anjuli; Moore, Kevin; Stevenson, Michael; Young, Ian S; Gibney, James

    2015-01-01

    Inflammatory atherosclerosis is increased in subjects with type 1 diabetes mellitus (T1DM). Normally high-density lipoproteins (HDL) protect against atherosclerosis; however, in the presence of serum amyloid-A- (SAA-) related inflammation this property may be reduced. Fasting blood was obtained from fifty subjects with T1DM, together with fifty age, gender and BMI matched control subjects. HDL was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. Serum-hsCRP and serum-, HDL2-, and HDL3-SAA were measured by ELISAs. Compared to control subjects, SAA was increased in T1DM subjects, nonsignificantly in serum (P = 0.088), and significantly in HDL2(P = 0.003) and HDL3(P = 0.005). When the T1DM group were separated according to mean HbA1c (8.34%), serum-SAA and HDL3-SAA levels were higher in the T1DM subjects with HbA1c ≥ 8.34%, compared to when HbA1c was <8.34% (P < 0.05). Furthermore, regression analysis illustrated, that for every 1%-unit increase in HbA1c, SAA increased by 20% and 23% in HDL2 and HDL3, respectively, independent of BMI. HsCRP did not differ between groups (P > 0.05). This cross-sectional study demonstrated increased SAA-related inflammation in subjects with T1DM that was augmented by poor glycaemic control. We suggest that SAA is a useful inflammatory biomarker in T1DM, which may contribute to their increased atherosclerosis risk.

  20. A Cross-Sectional Study Demonstrating Increased Serum Amyloid A Related Inflammation in High-Density Lipoproteins from Subjects with Type 1 Diabetes Mellitus and How This Association Was Augmented by Poor Glycaemic Control

    PubMed Central

    McEneny, Jane; Daniels, Jane-Ann; McGowan, Anne; Gunness, Anjuli; Moore, Kevin; Stevenson, Michael; Young, Ian S.; Gibney, James

    2015-01-01

    Inflammatory atherosclerosis is increased in subjects with type 1 diabetes mellitus (T1DM). Normally high-density lipoproteins (HDL) protect against atherosclerosis; however, in the presence of serum amyloid-A- (SAA-) related inflammation this property may be reduced. Fasting blood was obtained from fifty subjects with T1DM, together with fifty age, gender and BMI matched control subjects. HDL was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. Serum-hsCRP and serum-, HDL2-, and HDL3-SAA were measured by ELISAs. Compared to control subjects, SAA was increased in T1DM subjects, nonsignificantly in serum (P = 0.088), and significantly in HDL2(P = 0.003) and HDL3(P = 0.005). When the T1DM group were separated according to mean HbA1c (8.34%), serum-SAA and HDL3-SAA levels were higher in the T1DM subjects with HbA1c ≥ 8.34%, compared to when HbA1c was <8.34% (P < 0.05). Furthermore, regression analysis illustrated, that for every 1%-unit increase in HbA1c, SAA increased by 20% and 23% in HDL2 and HDL3, respectively, independent of BMI. HsCRP did not differ between groups (P > 0.05). This cross-sectional study demonstrated increased SAA-related inflammation in subjects with T1DM that was augmented by poor glycaemic control. We suggest that SAA is a useful inflammatory biomarker in T1DM, which may contribute to their increased atherosclerosis risk. PMID:26557720

  1. Softness of atherogenic lipoproteins: a comparison of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) using elastic incoherent neutron scattering (EINS).

    PubMed

    Mikl, Christian; Peters, Judith; Trapp, Marcus; Kornmueller, Karin; Schneider, Wolfgang J; Prassl, Ruth

    2011-08-31

    Apolipoprotein B100 (apoB100)-containing plasma lipoproteins (LDL and VLDL) supply tissues and cells with cholesterol and fat. During lipolytic conversion from VLDL to LDL the size and chemical composition of the particles change, but the apoB100 molecule remains bound to the lipids and regulates the receptor mediated uptake. The molecular physical parameters which control lipoprotein remodeling and enable particle stabilization by apoB100 are largely unknown. Here, we have compared the molecular dynamics and elasticities of VLDL and LDL derived by elastic neutron scattering temperature scans. We have determined thermal motions, dynamical transitions, and molecular fluctuations, which reflect the temperature-dependent motional coupling between lipid and protein. Our results revealed that lipoprotein particles are extremely soft and flexible. We found substantial differences in the molecular resiliences of lipoproteins, especially at higher temperatures. These discrepancies not only can be explained in terms of lipid composition and mobility but also suggest that apoB100 displays different dynamics dependent on the lipoprotein it is bound to. Hence, we suppose that the inherent conformational flexibility of apoB100 permits particle stabilization upon lipid exchange, whereas the dynamic coupling between protein and lipids might be a key determinant for lipoprotein conversion and atherogenicity.

  2. Reversible and irreversible interactions between elastin and plasma lipoproteins.

    PubMed

    Winlove, C P; Parker, K H; Ewins, A R

    1985-03-08

    The interactions between radiolabeled, human plasma lipoproteins and elastin derived from bovine ligamentum nuchae were investigated using a washout technique. The interaction was characterised by Ki, a coefficient of irreversible binding, and Kr, the reversible partition coefficient. For both low-density lipoproteins (LDL) and high-density lipoproteins (HDL) the Ki values decreased as total lipoprotein concentration increased, suggesting that the binding is saturable, and were similar in magnitude to those measured by other workers using elastin derived from the human aorta. For both LDL and HDL the Kr values were independent of lipoprotein concentration in the range 0.1 microgram/ml-1.5 micrograms/ml. At a total protein concentration of 1.5 mg/ml in the incubation medium, the reversible interactions were comparable in magnitude to the irreversible.

  3. Microchip-based human serum atherogenic lipoprotein profile analysis.

    PubMed

    Wang, Hua; Zhang, Wei; Wan, Jun; Liu, Weiwei; Yu, Bo; Jin, Qinghui; Guan, Ming

    2014-12-15

    Owing to the mounting evidence of serum lipid changes in atherosclerosis, there has been increasing interest in developing new methods for analyzing atherogenic lipoprotein profiles. The separation of lipoprotein and lipoprotein subclasses has been demonstrated using a microchip capillary electrophoresis (CE) system [Chromatographia 74 (2011) 799-805]. In contrast to this previous study, the current report demonstrates that sdLDL peak efficiencies can be improved dramatically by adding gold nanoparticles (AuNPs) to the sample. Moreover, NBD C6-ceramide was identified as a satisfactory dye for specific labeling and quantitation of individual serum lipoproteins. The accuracy of the method was evaluated by comparison with ultracentrifuge separated small, dense, low-density lipoprotein (sdLDL). A high correlation was observed between these two methods for sdLDL cholesterol. Lipid levels were investigated between atherosclerotic patients and healthy controls. The variation of serum atherogenic lipoprotein profiles for atherosclerotic patients pre- and post-treatment was assessed by microchip CE. This method has potential for the rapid and sensitive detection of different lipoprotein classes as well as their subclasses and, therefore, is suitable for routine clinical applications. Microchip-based atherogenic lipoprotein profile assays will greatly improve the analysis of risk factors in atherosclerosis and will provide useful information for monitoring the effect of therapies on atherosclerotic disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Distributions of serum lipoproteins in children by repeated measurements.

    PubMed

    Cresanta, J L; Srinivasan, S R; Foster, T A; Webber, L S; Berenson, G S

    1983-07-01

    Serum lipids and lipoproteins were measured three times over 6 years in a total-community study of children in Bogalusa, Louisiana. Interrelationships and changes in the distributions of serum lipoprotein cholesterol levels were examined in terms of variability and precision of the laboratory measurements. Although distributions of serum lipoprotein cholesterol variables shifted among the three surveys, precision increased markedly as indicated by a decrease in the coefficient of variation for measurement error for total cholesterol, alpha-lipoprotein cholesterol, and triglycerides between Year 1 and Year 4 and then stabilized. Pre-beta-lipoprotein cholesterol was the most difficult variable to measure. The range and magnitude of correlation coefficients between lipid and lipoprotein variables were very similar. Despite quality controls, efforts to standardize laboratory analyses, and adherence to protocols, fluctuations in distributions of lipids and lipoproteins occurred when the same population was restudied. Long-term studies for coronary artery disease prevention should include laboratory safeguards that help to distinguish modest population changes in serum lipids and lipoproteins from laboratory drift.

  5. Oxidized lipoprotein lipids and atherosclerosis.

    PubMed

    Ahotupa, Markku

    2017-04-01

    Plasma lipoproteins contain variable amounts of lipid oxidation products (LOP), which are known to impair normal physiological functions and stimulate atherosclerotic processes. Recent evidence indicates that plasma lipoproteins are active carriers of LOP, low-density lipoprotein (LDL) directing transport toward peripheral tissues, and high-density lipoprotein (HDL) being active in the reverse transport. It has been proposed that the lipoprotein-specific transport of LOP could play a role in atherosclerosis-related effects of LDL and HDL. This article gives an overview of the present knowledge of lipoprotein LOP transport and its association with the risk of atherosclerosis and cardiovascular diseases (CVD). Evidence of the significance of lipoprotein LOP transport comes mainly from studies of physiological oxidative stress and is supported by studies of the functionality apolipoprotein A-1 mimetic peptides. A large body of data has accumulated indicating that lipoprotein LOP transport is connected to the risk of atherosclerosis. While high levels of LOP carried by LDL are indicative of elevated risk, high LOP level in HDL appears to associate with protection. If confirmed, the proposed lipoprotein LOP transport function would affect conception of the etiology of atherosclerosis, but would not conflict current views of the pathophysiological mechanisms. It could open new perspectives, such as the dietary origin of LOP, and the protective function of HDL in clearance of LOP. Focusing on LOP could give additional tools especially for prevention and diagnosis, but would not radically change the management of atherosclerosis and CVD.

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

    SciTech Connect

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

    2011-03-15

    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) {alpha}, {beta}, and {gamma} 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.

  7. Release of endothelial cell lipoprotein lipase by plasma lipoproteins and free fatty acids

    SciTech Connect

    Saxena, U.; Witte, L.D.; Goldberg, I.J.

    1989-03-15

    Lipoprotein lipase (LPL) bound to the lumenal surface of vascular endothelial cells is responsible for the hydrolysis of triglycerides in plasma lipoproteins. Studies were performed to investigate whether human plasma lipoproteins and/or free fatty acids would release LPL which was bound to endothelial cells. Purified bovine milk LPL was incubated with cultured porcine aortic endothelial cells resulting in the association of enzyme activity with the cells. When the cells were then incubated with media containing chylomicrons or very low density lipoproteins (VLDL), a concentration-dependent decrease in the cell-associated LPL enzymatic activity was observed. In contrast, incubation with media containing low density lipoproteins or high density lipoproteins produced a much smaller decrease in the cell-associated enzymatic activity. The addition of increasing molar ratios of oleic acid:bovine serum albumin to the media also reduced enzyme activity associated with the endothelial cells. To determine whether the decrease in LPL activity was due to release of the enzyme from the cells or inactivation of the enzyme, studies were performed utilizing radioiodinated bovine LPL. Radiolabeled LPL protein was released from endothelial cells by chylomicrons, VLDL, and by free fatty acids (i.e. oleic acid bound to bovine serum albumin). The release of radiolabeled LPL by VLDL correlated with the generation of free fatty acids from the hydrolysis of VLDL triglyceride by LPL bound to the cells. Inhibition of LPL enzymatic activity by use of a specific monoclonal antibody, reduced the extent of release of /sup 125/I-LPL from the endothelial cells by the added VLDL. These results demonstrated that LPL enzymatic activity and protein were removed from endothelial cells by triglyceride-rich lipoproteins (chylomicrons and VLDL) and oleic acid.

  8. Colistin-Resistant, Lipopolysaccharide-Deficient Acinetobacter baumannii Responds to Lipopolysaccharide Loss through Increased Expression of Genes Involved in the Synthesis and Transport of Lipoproteins, Phospholipids, and Poly-β-1,6-N-Acetylglucosamine

    PubMed Central

    Henry, Rebekah; Vithanage, Nuwan; Harrison, Paul; Seemann, Torsten; Coutts, Scott; Moffatt, Jennifer H.; Nation, Roger L.; Li, Jian; Harper, Marina; Adler, Ben

    2012-01-01

    We recently demonstrated that colistin resistance in Acinetobacter baumannii can result from mutational inactivation of genes essential for lipid A biosynthesis (Moffatt JH, et al., Antimicrob. Agents Chemother. 54:4971–4977). Consequently, strains harboring these mutations are unable to produce the major Gram-negative bacterial surface component, lipopolysaccharide (LPS). To understand how A. baumannii compensates for the lack of LPS, we compared the transcriptional profile of the A. baumannii type strain ATCC 19606 to that of an isogenic, LPS-deficient, lpxA mutant strain. The analysis of the expression profiles indicated that the LPS-deficient strain showed increased expression of many genes involved in cell envelope and membrane biogenesis. In particular, upregulated genes included those involved in the Lol lipoprotein transport system and the Mla-retrograde phospholipid transport system. In addition, genes involved in the synthesis and transport of poly-β-1,6-N-acetylglucosamine (PNAG) also were upregulated, and a corresponding increase in PNAG production was observed. The LPS-deficient strain also exhibited the reduced expression of genes predicted to encode the fimbrial subunit FimA and a type VI secretion system (T6SS). The reduced expression of genes involved in T6SS correlated with the detection of the T6SS-effector protein AssC in culture supernatants of the A. baumannii wild-type strain but not in the LPS-deficient strain. Taken together, these data show that, in response to total LPS loss, A. baumannii alters the expression of critical transport and biosynthesis systems associated with modulating the composition and structure of the bacterial surface. PMID:22024825

  9. Genetics of non-conventional lipoprotein fractions

    USDA-ARS?s Scientific Manuscript database

    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...

  10. Triacylglycerol composition of human endogenous lipoproteins.

    PubMed

    Lajos, S; Katalin, R; László, T; Miklós, M; István, K; László, R

    1995-01-01

    The intact triacylglycerol profiles for VLDL and LDL of healthy and primary hypertriglyceridemic patients were obtained by high temperature capillary gas chromatography. The data were treated by the methods of computerized analysis. Marked individual heterogeneity was found. This can be explained by either genetic polymorphism or multiple lipoprotein triacylglycerol pools within one density class. Suspecting genetic polymorphism and determination type IV (familial hypertriglyceridemia) seems to be a pure overproduction of endogenous VLDL, while in type II B (familial combined hyperlipidemia) an altered mechanism of triacyglycerol synthesis can be supposed.

  11. Intima-media thickness of the carotid artery and the distribution of lipoprotein subclasses in men aged 40 to 49 years between whites in the United States and the Japanese in Japan for the ERA JUMP study.

    PubMed

    Sekikawa, Akira; Ueshima, Hirotsugu; Sutton-Tyrrell, Kim; Kadowaki, Takashi; El-Saed, Aiman; Okamura, Tomonori; Takamiya, Tomoko; Ueno, Yoshiki; Evans, Rhobert W; Nakamura, Yasuyuki; Edmundowicz, Daniel; Kashiwagi, Atsunori; Maegawa, Hiroshi; Kuller, Lewis H

    2008-02-01

    In men in the post-World War II birth cohort, that is, men aged 40 to 49 years, whites in the United States had significantly higher levels of intima-media thickness of the carotid arteries (IMT) than the Japanese in Japan (Electron-Beam Tomography and Risk Assessment Among Japanese and US Men in the Post World War II Birth Cohort [ERA JUMP] study). The difference remained after adjusting for traditional risk factors. Primary genetic effects are unlikely, given the degree to which IMT is increased in the Japanese who migrated to the United States. We investigated whether the differences in the distributions of lipoprotein subclasses explain the difference in IMT between the 2 populations. We examined population-based samples of 466 randomly selected men aged 40 to 49 years (215 whites from Allegheny County, Pennsylvania, and 241 Japanese from Kusatsu, Shiga, Japan). Lipoprotein subclasses were determined by nuclear magnetic resonance (NMR) spectroscopy. The whites had significantly higher levels of large very low-density lipoprotein particles and significantly lower levels of large high-density lipoprotein particles than the Japanese, whereas the 2 populations had similar levels of small low-density lipoprotein particles. The 2 populations had similar associations of IMT with NMR lipoproteins. Adjusting for NMR lipoproteins did not attenuate the significant difference in IMT between the 2 populations (0.671 +/- 0.006 mm for the whites and 0.618 +/- 0.006 mm for the Japanese, P = .01, mean +/- SE). Differences in the distributions of NMR lipoproteins between the 2 populations did not explain the higher IMT in the whites.

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

    PubMed

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

    2014-09-05

    Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease.

    PubMed

    Varbo, Anette; Benn, Marianne; Smith, George Davey; Timpson, Nicholas J; Tybjaerg-Hansen, Anne; Nordestgaard, Børge G

    2015-02-13

    Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. To test the hypothesis that the increased IHD risk because of obesity is mediated through lipoproteins, blood pressure, glucose, and C-reactive protein. Approximately 90 000 participants from Copenhagen were included in a Mendelian randomization design with mediation analyses. Associations were examined using conventional measurements of body mass index and intermediate variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood pressure, and possibly also through elevated nonfasting glucose levels; however, reduced high-density lipoprotein cholesterol and elevated C-reactive protein levels were not mediators in genetic analyses. The 3 intermediate variables that explained the highest excess risk of IHD from genetically determined obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. The increased IHD risk because of obesity was partly mediated through elevated levels of nonfasting remnant and low-density lipoprotein cholesterol and through elevated blood pressure. Our results suggest that there may be benefit to gain by reducing levels of these risk factors in obese individuals not able to achieve sustained weight loss. © 2014 American Heart Association, Inc.

  14. Changes in Underlying Determinants Explain Rapid Increases in Child Linear Growth in Alive & Thrive Study Areas between 2010 and 2014 in Bangladesh and Vietnam.

    PubMed

    Nguyen, Phuong Hong; Headey, Derek; Frongillo, Edward A; Tran, Lan Mai; Rawat, Rahul; Ruel, Marie T; Menon, Purnima

    2017-03-01

    Background: Child linear growth sometimes improves in both intervention and comparison groups in evaluations of nutrition interventions, possibly because of spillover intervention effects to nonintervention areas or improvements in underlying determinants of nutritional change in both areas.Objective: We aimed to understand what changes in underlying socioeconomic characteristics and behavioral factors are important in explaining improvements in child linear growth.Methods: Baseline (2010) and endline (2014) surveys from the Alive & Thrive impact evaluation were used to identify the underlying determinants of height-for-age z scores (HAZs) among children aged 24-48 mo in Bangladesh (n = 4311) and 24-59 mo in Vietnam (n = 4002). Oaxaca-Blinder regression decompositions were used to examine which underlying determinants contributed to HAZ changes over time.Results: HAZs improved significantly between 2010 and 2014 in Bangladesh (∼0.18 SDs) and Vietnam (0.25 SDs). Underlying determinants improved substantially over time and were larger in Vietnam than in Bangladesh. Multiple regression models revealed significant associations between changes in HAZs and socioeconomic status (SES), food security, maternal education, hygiene, and birth weight in both countries. Changes in HAZs were significantly associated with maternal nutrition knowledge and child dietary diversity in Bangladesh, and with prenatal visits in Vietnam. Improvements in maternal nutrition knowledge in Bangladesh accounted for 20% of the total HAZ change, followed by maternal education (13%), SES (12%), hygiene (10%), and food security (9%). HAZ improvements in Vietnam were accounted for by changes in SES (26%), prenatal visits (25%), hygiene (19%), child birth weight (10%), and maternal education (7%). The decomposition models in both countries performed well, explaining >75% of the HAZ changes.Conclusions: Decomposition is a useful and simple technique for analyzing nonintervention drivers of

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

    SciTech Connect

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

    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.

  16. Human intestinal lipoproteins. Studies in chyluric subjects.

    PubMed

    Green, P H; Glickman, R M; Saudek, C D; Blum, C B; Tall, A R

    1979-07-01

    To explore the role of the human intestine as a source of apolipoproteins, we have studied intestinal lipoproteins and apoprotein secretion in two subjects with chyluria (mesenteric lymphatic-urinary fistulae). After oral corn oil, apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II) output in urine increased in parallel to urinary triglyceride. One subject, on two occasions, after 40 g of corn oil, excreted 8.4 and 8.6 g of triglyceride together with 196 and 199 mg apoA-I and on one occasion, 56 mg apoA-II. The other subject, after 40 g corn oil, excreted 0.3 g triglyceride and 17.5 mg apoA-I, and, after 100 g of corn oil, excreted 44.8 mg apoA-I and 5.8 mg apoA-II. 14.5+/-2.1% of apoA-I and 17.7+/-4.3% of apoA-II in chylous urine was in the d < 1.006 fraction (chylomicrons and very low density lipoprotein). Calculations based on the amount of apoA-I and apoA-II excreted on triglyceride-rich lipoproteins revealed that for these lipid loads, intestinal secretion could account for 50 and 33% of the calculated daily synthetic rate of apoA-I and apoA-II, respectively. Similarly, subject 2 excreted 48-70% and 14% of the calculated daily synthetic rate of apoA-I and apoA-II, respectively. Chylous urine contained chylomicrons, very low density lipoproteins and high density lipoproteins, all of which contained apoA-I. Chylomicrons and very low density lipoproteins contained a previously unreported human apoprotein of 46,000 mol wt. We have called this apoprotein apoA-IV because of the similarity of its molecular weight and amino acid composition to rat apoA-IV. In sodium dodecyl sulfate gels, chylomicron apoproteins consisted of apoB 3.4+/-0.7%, apoA-IV 10.0+/-3.3%, apoE 4.4+/-0.3%, apoA-I 15.0+/-1.8%, and apoC and apoA-II 43.3+/-11.3%. Very low density lipoprotein contained more apoB and apoA-IV and less apoC than chylomicrons. Ouchterlony immunodiffusion of chylomicron apoproteins revealed the presence of apoC-I, apoC-II, and apoC-III. In contrast, plasma

  17. Lipoprotein-associated phospholipase A2 decreases oxidized lipoprotein cellular association by human macrophages and hepatocytes.

    PubMed

    Yang, Ming; Chu, Eugene M; Caslake, Muriel J; Edelstein, Celina; Scanu, Angelo M; Hill, John S

    2010-02-01

    We investigated whether the presence of endogenous or exogenous lipoprotein-associated phospholipase A2 (Lp-PLA2) can modify the cellular association of oxidized low density lipoprotein (oxLDL) and oxidized lipoprotein(a) (oxLp(a)) by human monocyte-derived macrophages (MDM) and hepatocytes (HepG2). Purified recombinant Lp-PLA2 was used as a source of exogenous enzyme whereas Pefabloc (serine esterase inhibitor) was used to inhibit the endogenous Lp-PLA2 activity associated with isolated lipoproteins. Cellular association studies were performed with DiI-labeled oxLDL or oxLp(a) and human monocyte-derived macrophages and HepG2 cells. Active Lp-PLA2 decreased the cellular association of oxLDL and oxLp(a) in macrophages and HepG2 cells by approximately 30-40%, whereas the inactive enzyme did not significantly change oxidized lipoprotein cellular association by either cell type. OxLDL pretreated by Pefabloc increased oxLDL cellular association by MDM and HepG2 cells compared to untreated oxLDL. Therefore, unlike some lipases, Lp-PLA2 did not appear to have any catalytic independent function in oxLDL cellular association. To assess whether the reduced cellular association mediated by Lp-PLA2 was due to the hydrolysis of oxidized phosphatidylcholine (oxPC), we measured the concentration of lysophosphatidylcholine (lysoPC) in lipoprotein fractions after Lp-PLA2 treatment. LysoPC was increased by 20% (0.4 microM) and 87% (0.7 microM) by active Lp-PLA2 compared to inactive Lp-PLA2 for oxLDL and Lp(a), respectively. LysoPC at higher concentration dose-dependently increased the cellular association of oxLDL and oxLp(a) in MDM and HepG2 cells. We conclude that Lp-PLA2 mediates a decrease in oxidized lipoprotein cellular association in human macrophages and HepG2 cells by reducing the concentration of oxPC within these lipoproteins.

  18. High-density lipoprotein cholesterol: current perspective for clinicians.

    PubMed

    Whayne, Thomas F

    2009-01-01

    High-density lipoproteins are regarded as ''good guys'' but not always. Situations involving high-density lipoproteins are discussed and medication results are considered. Clinicians usually consider high-density lipoprotein cholesterol. Nicotinic acid is the best available medication to elevate high-density lipoprotein cholesterol and this appears beneficial for cardiovascular risk. The major problem with nicotinic acid is that many patients do not tolerate the associated flushing. Laropiprant decreases this flushing and has an approval in Europe but not in the United States. The most potent medications for increasing high-density lipoprotein cholesterol are cholesteryl ester transfer protein inhibitors. The initial drug in this class, torcetrapib, was eliminated by excess cardiovascular problems. Two newer cholesteryl ester transfer protein inhibitors, R1658 and anacetrapib, initially appear promising. High-density lipoprotein cholesterol may play an important role in improving cardiovascular risk in the 60% of patients who do not receive cardiovascular mortality/morbidity benefit from low-density lipoproteins reduction by statins.

  19. Consuming a buttermilk drink containing lutein-enriched egg yolk daily for 1 year increased plasma lutein but did not affect serum lipid or lipoprotein concentrations in adults with early signs of age-related macular degeneration.

    PubMed

    van der Made, Sanne M; Kelly, Elton R; Berendschot, Tos T J M; Kijlstra, Aize; Lütjohann, Dieter; Plat, Jogchum

    2014-09-01

    Dietary lutein intake is postulated to interfere with the development of age-related macular degeneration (AMD). Because egg yolk-derived lutein has a high bioavailability, long-term consumption of lutein-enriched eggs might be effective in preventing AMD development, but alternatively might increase cardiovascular disease risk. Here, we report the effect of 1-y daily consumption of a buttermilk drink containing 1.5 lutein-rich egg yolks on serum lipid and lipoprotein and plasma lutein concentrations. Additionally, subgroups that could potentially benefit the most from the intervention were identified. Men and women who had early signs of AMD in at least 1 eye, but were otherwise healthy, participated in a 1-y randomized, placebo-controlled parallel intervention trial. At the start of the study, 101 participants were included: 52 in the experimental (Egg) group and 49 in the control (Con) group. Final analyses were performed with 45 participants in the Egg group and 43 participants in the Con group. As expected, the increase in plasma lutein concentrations in the Egg group was 83% higher than that in the Con group (P < 0.001). Changes in serum total, HDL, and LDL cholesterol, as well as the ratio of total cholesterol to HDL cholesterol, were not different between the 2 groups. Interestingly, participants classified as cholesterol absorbers had higher serum HDL cholesterol concentrations than participants classified as cholesterol synthesizers or participants with average campesterol-to-lathosterol ratios (P < 0.05) at baseline. In addition, cholesterol absorbers had a 229% higher increase in plasma lutein concentrations than participants who were classified as having an average campesterol-to-lathosterol ratio upon consumption of the lutein-enriched egg yolk drink (P < 0.05). Moreover, the change in serum HDL cholesterol upon consumption was significantly different between these 3 groups (P < 0.05). We suggest that cholesterol absorbers particularly might benefit

  20. Effect of dietary modification by calorie restriction on cholesterol levels in lipoprotein(a) and other lipoprotein classes.

    PubMed

    Hirowatari, Yuji; Manita, Daisuke; Kamachi, Keiko; Tanaka, Akira

    2017-09-01

    Background Dietary habits are associated with obesity which is a risk factor for coronary heart disease. The objective is to estimate the change of lipoprotein(a) and other lipoprotein classes by calorie restriction with obesity index and Framingham risk score. Methods Sixty females (56 ± 9 years) were recruited. Their caloric intakes were reduced during the six-month period, and the calorie from fat was not more than 30%. Lipoprotein profiles were estimated at baseline and after the six-month period of calorie restriction. Cholesterol levels in six lipoprotein classes (HDL, LDL, IDL, VLDL, chylomicron and lipoprotein(a)) were analysed by anion-exchange liquid chromatography. The other tests were analysed by general methods. Additionally, Framingham risk score for predicting 10-year coronary heart disease risk was calculated. Results Body mass index, waist circumference, insulin resistance, Framingham risk score, total cholesterol, LDL-cholesterol and IDL-cholesterol were significantly decreased by the calorie restriction, and the protein and cholesterol levels of lipoprotein(a) were significantly increased. The change of body mass index was significantly correlated with those of TC, VLDL-cholesterol and chylomicron-cholesterol, and that of waist circumference was significantly correlated with that of chylomicron-cholesterol. The change of Framingham risk score was significantly correlated with the change of IDL-C. Conclusion Obesity indexes and Framingham risk score were reduced by the dietary modification. Lipoprotein profile was improved with the reduction of obesity indexes, but lipoprotein(a) was increased. The changes of obesity indexes and Framingham risk score were related with those of triglyceride-rich lipoproteins, e.g. IDL, VLDL and CM.

  1. Multiple aberrations in shared inflammatory and oxidative & nitrosative stress (IO&NS) pathways explain the co-association of depression and cardiovascular disorder (CVD), and the increased risk for CVD and due mortality in depressed patients.

    PubMed

    Maes, Michael; Ruckoanich, Piyanuj; Chang, Young Seun; Mahanonda, Nithi; Berk, Michael

    2011-04-29

    There is evidence that there is a bidirectional relationship between major depression and cardiovascular disorder (CVD): depressed patients are a population at risk for increased cardiac morbidity and mortality, and depression is more frequent in patients who suffer from CVD. There is also evidence that inflammatory and oxidative and nitrosative stress (IO&NS) pathways underpin the common pathophysiology of both CVD and major depression. Activation of these pathways may increase risk for both disorders and contribute to shared risk. The shared IO&NS pathways that may contribute to CVD and depression comprise the following: increased levels of pro-inflammatory cytokines, like interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-α, and interferon-γ; T cell activation; increased acute phase proteins, like C-reactive protein, haptoglobin, fibrinogen and α1-antitrypsin; complement factors; increased LPS load through bacterial translocation and subsequent gut-derived inflammation; induction of indoleamine 2,3-dioxygenase with increased levels of tryptophan catabolites; decreased levels of antioxidants, like coenzyme Q10, zinc, vitamin E, glutathione and glutathione peroxidase; increased O&NS characterized by oxidative damage to low density lipoprotein (LDL) and phospholipid inositol, increased malondialdehyde, and damage to DNA and mitochondria; increased nitrosative stress; and decreased ω3 polyunsaturated fatty acids (PUFAs). The complex interplay between the abovementioned IO&NS pathways in depression results in pro-atherogenic effects and should be regarded as a risk factor to future clinical CVD and due mortality. We suggest that major depression should be added as a risk factor to the Charlson "comorbidity" index. It is advised that patients with (sub)chronic or recurrent major depression should routinely be assessed by serology tests to predict if they have an increased risk to cardiovascular disorders.

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

    PubMed Central

    Bilen, Ozlem; Kamal, Ayeesha; Virani, Salim S

    2016-01-01

    South Asians have a high prevalence of coronary heart disease (CHD) and suffer from early-onset CHD compared to other ethnic groups. Conventional risk factors may not fully explain this increased CHD risk in this population. Indeed, South Asians have a unique lipid profile which may predispose them to premature CHD. Dyslipidemia in this patient population seems to be an important contributor to the high incidence of coronary atherosclerosis. The dyslipidemia in South Asians is characterized by elevated levels of triglycerides, low levels of high-density lipoprotein (HDL) cholesterol, elevated lipoprotein(a) levels, and a higher atherogenic particle burden despite comparable low-density lipoprotein cholesterol levels compared with other ethnic subgroups. HDL particles also appear to be smaller, dysfunctional, and proatherogenic in South Asians. Despite the rapid expansion of the current literature with better understanding of the specific lipid abnormalities in this patient population, studies with adequate sample sizes are needed to assess the significance and contribution of a given lipid parameter on overall cardiovascular risk in this population. Specific management goals and treatment thresholds do not exist for South Asians because of paucity of data. Current treatment recommendations are mostly extrapolated from Western guidelines. Lastly, large, prospective studies with outcomes data are needed to assess cardiovascular benefit associated with various lipid-lowering therapies (including combination therapy) in this patient population. PMID:27022456

  3. Explaining the increased health care expenditures associated with gastroesophageal reflux disease among elderly Medicare beneficiaries with chronic obstructive pulmonary disease: a cost-decomposition analysis

    PubMed Central

    Ajmera, Mayank; Raval, Amit D; Shen, Chan; Sambamoorthi, Usha

    2014-01-01

    Objective To estimate excess health care expenditures associated with gastroesophageal reflux disease (GERD) among elderly individuals with chronic obstructive pulmonary disease (COPD) and examine the contribution of predisposing characteristics, enabling resources, need variables, personal health care practices, and external environment factors to the excess expenditures, using the Blinder–Oaxaca linear decomposition technique. Methods This study utilized a cross-sectional, retrospective study design, using data from multiple years (2006–2009) of the Medicare Current Beneficiary Survey linked with fee-for-service Medicare claims. Presence of COPD and GERD was identified using diagnoses codes. Health care expenditures consisted of inpatient, outpatient, prescription drugs, dental, medical provider, and other services. For the analysis, t-tests were used to examine unadjusted subgroup differences in average health care expenditures by the presence of GERD. Ordinary least squares regressions on log-transformed health care expenditures were conducted to estimate the excess health care expenditures associated with GERD. The Blinder–Oaxaca linear decomposition technique was used to determine the contribution of predisposing characteristics, enabling resources, need variables, personal health care practices, and external environment factors, to excess health care expenditures associated with GERD. Results Among elderly Medicare beneficiaries with COPD, 29.3% had co-occurring GERD. Elderly Medicare beneficiaries with COPD/GERD had 1.5 times higher ($36,793 vs $24,722 [P<0.001]) expenditures than did those with COPD/no GERD. Ordinary least squares regression revealed that individuals with COPD/GERD had 36.3% (P<0.001) higher expenditures than did those with COPD/no GERD. Overall, 30.9% to 43.6% of the differences in average health care expenditures were explained by differences in predisposing characteristics, enabling resources, need variables, personal health care

  4. IMMUNOCHEMICAL STUDIES ON HUMAN PLASMA LIPOPROTEINS

    PubMed Central

    Aladjem, Frederick; Lieberman, Miriam; Gofman, John W.

    1957-01-01

    Low density human plasma lipoproteins Sf 17+, Sf 13, and Sf 6, high density lipoproteins 2 and 3, and a lipoprotein-free plasma protein fraction were isolated from human plasma by ultracentrifugal methods. It was found that human plasma lipoproteins are immunochemically distinct from the non-lipoprotein containing plasma protein fraction. Lipoprotein fractions of a given hydrated density, isolated from different individuals, were found to be immunochemically indistinguishable by qualitative absorption tests. Qualitative antigenic differences were shown to exist between low density lipoproteins and high density lipoproteins. Quantitative precipitin reactions showed that low density lipoproteins Sf 6 and Sf 13 were immunochemically very similar. However, they differed with respect to the amount of antigen nitrogen required for maximum precipitation. Agar diffusion analyses were performed; the results suggest heterogeneity of lipoproteins by this criterion. PMID:13385406

  5. Bath and Shower Effects in the Rat Parotid Gland Explain Increased Relative Risk of Parotid Gland Dysfunction After Intensity-Modulated Radiotherapy

    SciTech Connect

    Luijk, Peter van Faber, Hette; Schippers, Jacobus M.; Brandenburg, Sytze; Langendijk, Johannes A.; Meertens, Harm; Coppes, Robert P.

    2009-07-15

    Purpose: To assess in a rat model whether adding a subtolerance dose in a region adjacent to a high-dose irradiated subvolume of the parotid gland influences its response (bath-and-shower effect). Methods and Materials: Irradiation of the whole, cranial 50%, and/or the caudal 50% of the parotid glands of Wistar rats was performed using 150-MeV protons. To determine suitable (i.e., subtolerance) dose levels for a bath-dose, both whole parotid glands were irradiated with 5 to 25 Gy. Subsequently groups of Wistar rats received 30 Gy to the caudal 50% (shower) and 0 to 10 Gy to the cranial 50% (bath) of both parotid glands. Stimulated saliva flow rate (function) was measured before and up to 240 days after irradiation. Results: Irradiation of both glands up to a dose of 10 Gy did not result in late loss of function and is thus regarded subtolerance. Addition of a dose bath of 1 to 10 Gy to a high-dose in the caudal 50% of the glands resulted in enhanced function loss. Conclusion: Similar to the spinal cord, the parotid gland demonstrates a bath and shower effect, which may explain the less-than-expected sparing of function after IMRT.

  6. Increased temperature tolerance of the air-breathing Asian swamp eel Monopterus albus after high-temperature acclimation is not explained by improved cardiorespiratory performance.

    PubMed

    Lefevre, S; Findorf, I; Bayley, M; Huong, D T T; Wang, T

    2016-01-01

    This study investigated the hypothesis that in the Asian swamp eel Monopterus albus, an air-breathing fish from south-east Asia that uses the buccopharyngeal cavity for oxygen uptake, the upper critical temperature (TU) is increased by acclimation to higher temperature, and that the increased TU is associated with improved cardiovascular and respiratory function. Monopterus albus were therefore acclimated to 27° C (current average) and 32° C (current maximum temperature as well as projected average within 100-200 years), and both the effect of acclimation and acute temperature increments on cardiovascular and respiratory functions were investigated. Two weeks of heat acclimation increased upper tolerated temperature (TU ) by 2° C from 36·9 ± 0·1° C to 38·9 ± 0·1° C (mean ± s.e.). Oxygen uptake (M˙O2) increased with acclimation temperature, accommodated by increases in both aerial and aquatic respiration. Overall, M˙O2 from air (M˙O2a ) was predominant, representing 85% in 27° C acclimated fish and 80% in 32° C acclimated fish. M˙O2 increased with acute increments in temperature and this increase was entirely accommodated by an increase in air-breathing frequency and M˙O2a . Monopterus albus failed to upregulate stroke volume; rather, cardiac output was maintained through increased heart rate with rising temperature. Overall, acclimation of M. albus to 32° C did not improve its cardiovascular and respiratory performance at higher temperatures, and cardiovascular adaptations, therefore, do not appear to contribute to the observed increase in TU.

  7. Synthetic Lipoproteins as Carriers for Drug Delivery.

    PubMed

    Huang, Gangliang; Liu, Yang; Huang, Hualiang

    2016-01-01

    Synthetic lipoprotein is an effective carrier of targeted delivery for drugs. It has the very small size, good biocompatibility, suitable half-life, and specific lipoprotein receptorbinding capacity. Compared with the traditional natural lipoprotein, synthetic lipoprotein not only retains the original biological characteristics and functions, but also exhibits the excellent characteristics in drug delivery. Herein, the advantages, development, applications, and prospect of synthetic lipoproteins as drug carriers were summarized.

  8. Fungal-mediated mortality explains the different effects of dung leachates on the germination response of grazing increaser and decreaser species

    NASA Astrophysics Data System (ADS)

    Carmona, Carlos P.; Navarro, Elena; Peco, Begoña

    2016-01-01

    Depending on their response to grazing, grassland species can be categorized as grazing increasers or decreasers. Grazing by livestock includes several different activities that can impact species differently. Recent evidence suggest that one of these actions, dung deposition, can reduce the germinative performance of decreaser species, thus favouring increasers. The present study tested the hypothesis that decreased germinative success of decreaser species is caused by a greater activity of fungal pathogens under the influence of dung leachates. We performed a phytotron experiment analysing the germination and fungal infections of fourteen species from Mediterranean grasslands. Species were grouped into phylogenetically-related pairs, composed of an increaser and a decreaser species. Seeds of each species were germinated under four different treatments (control, dung leachate addition, fungicide addition and dung leachate and fungicide addition), and the differences in germination percentage, germination speed and infection rate between each increaser species and its decreaser counterpart were analysed. Decreaser species were more affected by mortality than increaser ones, and these differences were higher under the presence of dung leachates. The differences in germinative performance after excluding the effect of seed mortality did not differ between treatments, showing that the main mechanism by which dung leachates favour increaser species is through increased mortality of the seeds of decreaser species. Drastic reductions in the number of dead seeds in the treatments including fungicide addition further revealed that fungal pathogens are responsible for these differences between species with different grazing response. The different vulnerabilities of increaser and decreaser species to the increased activity of fungal pathogens under the presence of dung leachates seems the main reason behind the differential effect of these leachates on species with

  9. [Analysis of lipoprotein metabolism in alcoholics].

    PubMed

    Mizukami, Yuki; Okazaki, Mitsuyo; Usui, Shinichi; Hosaki, Seijin; Maruyama, Katsuya; Hosokawa, Yu

    2008-04-01

    High density lipoprotein (HDL) is increased by exercise and drinking and is well known as a negative risk factor of coronary heart disease. We analyzed serum lipids of alcoholics from the view points of biochemical examination, remnant like particle (RLP) and particle size of lipoprotein for the purpose of estimated effect of serum lipids, especially HDL quality in alcoholics. Serum levels of total cholesterol, free glycerol, RLP-C and RLP-TG were significantly decreased after hospitalization. The condition of RLP-C/RLP-TG on admission revealed cholesterol-rich composition. In case of HDL-C, the longer period from last drinking to hospitalization affected its decrease. From analytical study of particle size of lipoprotein, quantities of HDL-C in very large size and large size were significantly decreased after hospitalization which means that HDL composition at hospitalization is cholesterol-rich. So, it is speculated that increased serum level of HDL in alcoholics may be caused by expanded cholesterol ester and its quality may be different from that of healthy people. In this meaning, the study of arteriosclerosis in alcoholics will be necessary in relation to high level of serum HDL-C.

  10. Excessive centrifugal fields damage high density lipoprotein[S

    PubMed Central

    Munroe, William H.; Phillips, Martin L.; Schumaker, Verne N.

    2015-01-01

    HDL is typically isolated ultracentrifugally at 40,000 rpm or greater, however, such high centrifugal forces are responsible for altering the recovered HDL particle. We demonstrate that this damage to HDL begins at approximately 30,000 rpm and the magnitude of loss increases in a rotor speed-dependent manner. The HDL is affected by elevated ultracentrifugal fields resulting in a lower particle density due to the shedding of associated proteins. To circumvent the alteration of the recovered HDL, we utilize a KBr-containing density gradient and a lowered rotor speed of 15,000 rpm to separate the lipoproteins using a single 96 h centrifugation step. This recovers the HDL at two density ranges; the bulk of the material has a density of about 1.115 g/ml, while lessor amounts of material are recovered at >1.2 g/ml. Thus, demonstrating the isolation of intact HDL is possible utilizing lower centrifuge rotor speeds. PMID:25910941

  11. Regulation of hepatic lipase activity by sphingomyelin in plasma lipoproteins.

    PubMed

    Yang, Peng; Subbaiah, Papasani V

    2015-10-01

    Hepatic lipase (HL) is an important enzyme in the clearance of triacylglycerol (TAG) from the circulation, and has been proposed to have pro-atherogenic as well as anti-atherogenic properties. It hydrolyzes both phospholipids and TAG of lipoproteins, and its activity is negatively correlated with HDL levels. Although it is known that HL acts preferentially on HDL lipids, the basis for this specificity is not known, since it does not require any specific apoprotein for activity. In this study, we tested the hypothesis that sphingomyelin (SM), whose concentration is much higher in VLDL and LDL compared to HDL, is an inhibitor of HL, and that this could explain the lipoprotein specificity of the enzyme. The results presented show that the depletion of SM from normal lipoproteins activated the HL roughly in proportion to their SM content. SM depletion stimulated the hydrolysis of both phosphatidylcholine (PC) and TAG, although the PC hydrolysis was stimulated more. In the native lipoproteins, HL showed specificity for PC species containing polyunsaturated fatty acids at sn-2 position, and produced more unsaturated lyso PC species. The enzyme also showed preferential hydrolysis of certain TAG species over others. SM depletion affected the specificity of the enzyme towards PC and TAG species modestly. These results show that SM is a physiological inhibitor of HL activity in lipoproteins and that the specificity of the enzyme towards HDL is at least partly due to its low SM content. Published by Elsevier B.V.

  12. Regulation of hepatic lipase activity by sphingomyelin in plasma lipoproteins

    PubMed Central

    Yang, Peng; Subbaiah, Papasani V.

    2015-01-01

    Hepatic lipase (HL) is an important enzyme in the clearance of triacylglycerol (TAG) from the circulation, and has been proposed to have pro-atherogenic as well as anti-atherogenic properties. It hydrolyzes both phospholipids and TAG of lipoproteins, and its activity is negatively correlated with HDL levels. Although it is known that HL acts preferentially on HDL lipids, the basis for this specificity is not known, since it does not require any specific apoprotein for activity. In this study, we tested the hypothesis that sphingomyelin (SM), whose concentration is much higher in VLDL and LDL compared to HDL, is an inhibitor of HL, and that this could explain the lipoprotein specificity of the enzyme. The results presented show that the depletion of SM from normal lipoproteins activated the HL roughly in proportion to their SM content. SM depletion stimulated the hydrolysis of both phosphatidylcholine (PC) and TAG, although the PC hydrolysis was stimulated more. In the native lipoproteins, HL showed specificity for PC species containing polyunsaturated fatty acids at sn-2 position, and produced more unsaturated lyso PC species. The enzyme also showed preferential hydrolysis of certain TAG species over others. SM depletion affected the specificity of the enzyme towards PC and TAG species modestly. These results show that SM is a physiological inhibitor of HL activity in lipoproteins and that the specificity of the enzyme towards HDL is at least partly due to its low SM content. PMID:26193433

  13. Can behavior change explain increases in the proportion of genital ulcers attributable to herpes in sub-Saharan Africa? A simulation modeling study.

    PubMed

    Korenromp, Eline L; Bakker, Roel; De Vlas, Sake J; Robinson, N Jamie; Hayes, Richard; Habbema, J Dik F

    2002-04-01

    The proportion of cases of genital ulcer disease attributable to herpes simplex virus type 2 (HSV-2) appears to be increasing in sub-Saharan Africa. To assess the contributions of HIV disease and behavioral response to the HIV epidemic to the increasing proportion of genital ulcer disease (GUD) attributable to HSV-2 in sub-Saharan Africa. Simulations of the transmission dynamics of ulcerative sexually transmitted diseases (STDs) and HIV with use of the model STDSIM. In simulations, 28% of GUD was caused by HSV-2 before a severe HIV epidemic. If HIV disease was assumed to double the duration and frequency of HSV-2 recurrences, this proportion rose to 35% by year 2000. If stronger effects of HIV were assumed, this proportion rose further, but because of increased HSV-2 transmission this would shift the peak in HSV-2 seroprevalence to an unrealistically young age. A simulated 25% reduction in partner-change rates increased the proportion of GUD caused by HSV-2 to 56%, following relatively large decreases in chancroid and syphilis. Behavioral change may make an important contribution to relative increases in genital herpes.

  14. Does Increasing Reliance on Student Debt Explain Declines in Entrepreneurial Activity? Posing the Question, Gathering Evidence, Considering Policy Options. Research Report

    ERIC Educational Resources Information Center

    Baum, Sandy

    2015-01-01

    In recent years, concerns have emerged both about declines in entrepreneurial activity, and about increases in the amount students borrow to finance postsecondary education--in the aggregate as well as on average. Because the financial obligations associated with student debt could limit access to credit for individuals seeking to start…

  15. Does increased endogenous formation of N-nitroso compounds in the human colon explain the association between red meat and colon cancer?

    PubMed

    Bingham, S A; Pignatelli, B; Pollock, J R; Ellul, A; Malaveille, C; Gross, G; Runswick, S; Cummings, J H; O'Neill, I K

    1996-03-01

    High red meat diets have been linked with risk of sporadic colorectal cancer; but their effects on mutations which occur in this cancer are unknown. G-->A transitions in K-ras occur in colorectal cancer and are characteristic of the effects of alkylating agents such as N-nitroso compounds (NOC). We studied th effect of red meat consumption on faecal NOC levels in eight male volunteers who consumed diets low or high in meat (60 or 600 g/day), as beef, lamb or pork, whilst living in a metabolic suite. Increased intake of red meat induced a significant (P<0.024) 3-fold increase from 40 + or - 7 to ab average of 113 + or - 25 microgram/day NOC, a range of exposure in faeces similar to that from tobacco-specific NOC in cigarette smoke. THe diets were isoenergetic and contained equal amounts of fat, but concentrations of heterocyclic amines were low. Faecal excretion of the promotor ammonia was significantly increased to 6.5 + or - 1.08 mmol/day. When the high red meat diets were supplemented with 20 g phytate-free wheat bran in six volunteers there was no reduction in NOC levels (mean 138 + or - 41 microgram/day NOC), but faecal weight increased. Higher starch and non-starch polysaccharide intakes reduced intraluminal cross-linking in microcapsules (r=-0.77) and reduced faecal pH (r=-0.64). In two volunteers there was no effect of 600 g white meat and fish o faecal NOC (mean low white meat diet 68 + or - 10 microgram/day, high white meat 56 + or -6 microgram/day nor on faecal nitrate, nitrite and iron. Faecal nitrite levels increased on changing from a white to red meat diet (mean high white meat diet 46 + or - 7 mg/day, high red meat diet mean 80 + or - 7 mg/day.) Increased endogenous production of NOC and precursors from increased red meat, but not white meat and fish, consumption may be relevant to the aetiology of colorectal cancer.

  16. Identification of low density lipoprotein as a regulator of Fc receptor-mediated phagocytosis.

    PubMed Central

    Bigler, R D; Khoo, M; Lund-Katz, S; Scerbo, L; Esfahani, M

    1990-01-01

    Optimal expression of the high-affinity Fc receptor for IgG (FcRI) by the human monocyte cell line U-937 requires the presence of low density lipoprotein (LDL), and neither cholesterol nor high density lipoprotein can provide the component necessary for optimal FcRI expression. Here we show that FcR-mediated phagocytosis also requires LDL. U-937 cells were cultured in medium containing interferon gamma and either fetal calf serum (FCS) or delipidated FCS (DLFCS). The phagocytosis of IgG-coated erythrocytes was measured by a colorimetric assay. U-937 cells cultured in DLFCS medium had less than 16% of the phagocytic activity of cells cultured in normal FCS medium. Phagocytosis of IgG-coated erythrocytes could be inhibited 85% by the addition of murine IgG2a myeloma protein (5 micrograms/ml). U-937 cells cultured in DLFCS medium supplemented with pure cholesterol in ethanol (10 micrograms/ml) had only 30% of the phagocytic activity of cells grown in FCS medium. Addition of very low density lipoprotein (0.2 mg of protein per ml) to DLFCS medium also failed to increase phagocytosis. However, the addition of LDL (0.2 mg of protein per ml) to DLFCS medium restored 90% of the phagocytic activity. Since neither pure cholesterol nor very low density lipoprotein restored normal phagocytic function to U-937 cells despite a normalization of cellular cholesterol content, the restoration of phagocytosis observed with LDL replacement cannot be explained by mere delivery of cholesterol by LDL. Thus, LDL is required for the expression of FcRI and FcR-mediated phagocytosis by U-937 cells and may be an important regulator of phagocytic activity of monocytes and macrophages in vivo. PMID:2367519

  17. [Very low density lipoproteins and subclasses of intermediate density lipoproteins in postmenopausal women].

    PubMed

    Berg, G; Halperín, H; Siseles, N; Wikinski, R

    1996-01-01

    Post menopausal women present an increase of cardiovascular risk associated with the atherogenic plasma lipoproteins IDL and LDL. Our purpose was to study the composition of VLDL, IDL and the subfractions IDL-1 and IDL-2, and the Lipoprotein Lipase and Hepatic Lipase activities in a group of twelve healthy post menopausal women as compared with eleven fertile controls. The mean values of total cholesterol and LDL cholesterol were significantly increased in the post menopausal group compared to the controls (p < 0.005 and p < 0.001 respectively). The contribution of the HDL-cholesterol plasma concentration to total cholesterol was lower in the postmenopausal women (p < 0.02) although no one had HDL-cholesterol lower than 35 mg/dl and the mean value was 50 mg/dl. Postmenopausal women had increased concentrations of VLDL, total IDL and IDL-2 compared to controls (p < 0.05, p < 0.005 and p < 0.001 respectively). Plasma concentrations of total IDL was increased in postmenopausal women (33.6 +/- 3.4 vs 22.6 +/- 0.8 mg/dl, p < 0.005). The increase in total IDL was due to IDL-2 (19.9 +/- 1.7 vs 11.5 +/- 0.8 mg/dl, p < 0.001, in postmenopausal women vs controls). The IDL-2 subfraction was 60 +/- 2.6% of total IDL in postmenopausal women and 51 +/- 2.0% in controls (p < 0.02). In postmenopausal women and in controls the ratio triglyceride/protein (which indicates particles size) was significantly higher in IDL-1 than in IDL-2 (p < 0.005 and p < 0.01 respectively), but this ratio did not show differences when VLDL, total IDL and IDL-2 were compared between postmenopausal and control women. Then, the increased plasma concentration of these lipoproteins would show an increased number of particles in the postmenopausal women vs controls. There were no differences in the Lipoprotein Lipase and Hepatic Lipase activities between both groups. Lipoprotein Lipase vs total IDL-triglycerides and IDL-2-triglycerides showed a significant inverse correlation in controls (p < 0.05) but not

  18. A mechanistic study explaining the synergistic viscosity increase obtained from polyethylene oxide (PEO) and {beta}-naphthalene sulfonate (BNS) in shotcrete

    SciTech Connect

    Pickelmann, J.; Plank, J.

    2012-11-15

    In shotcrete, a combination of polyethylene oxide (PEO) and {beta}-naphthalene sulfonate (BNS) is commonly applied to reduce rebound. Here, the mechanism for the synergistic viscosity increase resulting from this admixture combination was investigated via x-ray diffraction (XRD), infrared and nuclear magnetic resonance (NMR) spectroscopy. It was found that the electron-rich aromatic rings present in BNS donate electrons to the alkyl protons of PEO and thus increase the electron density there. This rare interaction is known as CH-{pi} interaction and leads to the formation of a supramolecular structure whereby PEO chains bind weakly to BNS molecules. Through this mechanism a polymer network exhibiting exceptionally high molecular weight and thus viscosity is formed. Among polycondensates, sulfanilic acid-phenol-formaldehyde (SPF) provides even higher synergy with PEO than BNS while melamine (PMS), acetone (AFS) or polycarboxylate (PCE) based superplasticizers do not work at all. Effectiveness of lignosulfonates is dependent on their degree of sulfonation.

  19. Nutrigenetics of the lipoprotein metabolism.

    PubMed

    Garcia-Rios, Antonio; Perez-Martinez, Pablo; Delgado-Lista, Javier; Lopez-Miranda, Jose; Perez-Jimenez, Francisco

    2012-01-01

    It is well known that lipid metabolism is a cornerstone in the development of the commonest important chronic diseases worldwide, such as obesity, cardiovascular disease, or metabolic syndrome. In this regard, the area of lipid and lipoprotein metabolism is one of the areas in which the understanding of the development and progression of those metabolic disorders has been studied in greater depth. Thus, growing evidence has demonstrated that while universal recommendations might be appropriate for the general population, in this area there is great variability among individuals, related to a combination of environmental and genetic factors. Moreover, the interaction between genetic and dietary components has helped in understanding this variability. Therefore, with further study into the interaction between the most important genetic markers or single-nucleotide polymorphisms (SNPs) and diet, it may be possible to understand the variability in lipid metabolism, which could lead to an increase in the use of personalized nutrition as the best support to combat metabolic disorders. This review discusses some of the evidence in which candidate SNPs can affect the key players of lipid metabolism and how their phenotypic manifestations can be modified by dietary intake. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Resting energy expenditure and thermal balance during isothermic and thermoneutral haemodialysis--heat production does not explain increased body temperature during haemodialysis.

    PubMed

    Horácek, Jirí; Sulková, Sylvie Dusilová; Fortová, Magdalena; Lopot, Frantisek; Kalousová, Marta; Sobotka, Lubos; Chaloupka, Jirí; Tesar, Vladimír; Zák, Ales; Zima, Tomás

    2007-12-01

    During routine haemodialysis (HD) body temperature increases, which contributes to haemodynamic instability. The relative roles of increased heat production and/or incomplete heat transfer are not fully elucidated. Concomitant measurement of heat production and heat transfer may help to assess the factors determining thermal balance during HD. Thirteen stable non-diabetic maintenance HD patients were investigated during two HD procedures (isothermic, dT = 0, no change of body temperature; thermoneutral, dE = 0, no energy transfer between blood and dialysate), using a blood temperature monitor (BTM) in active mode. Energy transfer, blood and dialysate temperature, and relative blood volume change (dBV) were continuously recorded, and resting energy expenditure (REE; Deltatrac Datex) was measured repeatedly during each procedure. Fourteen healthy persons served as controls for REE comparison. In isothermic HD, median energy removal was 218 kJ/4 h HD (= heat flow -15.1 W). This cooling correlated with dBV induced by ultrafiltration (rho = 0.731, P < 0.01). There was no difference in dBV between isothermic (7.7%) and thermoneutral (8.1%) HD. Predialysis REE was 82.8 W/1.73 m(2), not different from controls. No variation in REE during HD was observed, except a small and transient increase after a light meal (5 and 4%). In the time course of REE, no difference between the procedures was found. Our findings suggest that stable maintenance HD patients have REE not different from healthy controls, that HD procedure per se does not significantly increase REE and that neither isothermic nor thermoneutral regimen has any influence on metabolic rate. Therefore, body temperature elevation during routine HD may rather be due to decreased heat removal. With the use of BTM in active mode, body temperature can be kept stable (isothermic HD), which requires active cooling. This negative energy transfer is proportional to decrease in blood volume induced by ultrafiltration.

  1. Searching for events in Chinese ancient records to explain the increase in 14C from AD 774-775 and AD 993-994

    NASA Astrophysics Data System (ADS)

    Chai, Ya-Ting; Zou, Yuan-Chuan

    2015-09-01

    According to analysis of the 14C content in two Japanese trees, that grew over a period of approximately 3000 years, with high time resolution, Miyake et al. found a rapid increase at AD 774-775 and another one at AD 993-994. These increases correspond to high-energy events that happened within those years and radiated γ-ray energy of about 7×1024 erg toward the Earth. The origin of these events is a mystery. Such strong events should have an unusual optical counterpart, and have been recorded in historical literatures. We searched Chinese historical materials around AD 744-775 and AD 993-994, but no remarkable event was found except for a violent thunderstorm in AD 775. However, the possibility of a thunderstorm containing so much energy is unlikely. We conclude that the events, which caused the 14C increase, are still unclear. These events most probably had no optical counterpart, and a short gamma-ray burst, giant flare of a soft gamma-ray repeater or a terrestrial γ-ray flash could all be candidates.

  2. Increase in dance imprecision with decreasing foraging distance in the honey bee Apis mellifera L. is partly explained by physical constraints.

    PubMed

    Beekman, Madeleine; Doyen, Laurent; Oldroyd, Benjamin P

    2005-12-01

    Honey bee foragers communicate the direction and distance of both food sources and new nest sites to nest mates by means of a symbolic dance language. Interestingly, the precision by which dancers transfer directional information is negatively correlated with the distance to the advertised food source. The 'tuned-error' hypothesis suggests that colonies benefit from this imprecision as it spreads recruits out over a patch of constant size irrespective of the distance to the advertised site. An alternative to the tuned-error hypothesis is that dancers are physically incapable of dancing with great precision for nearby sources. Here we revisit the tuned-error hypothesis by studying the change in dance precision with increasing foraging distance over relatively short distances while controlling for environmental influences. We show that bees indeed increase their dance precision with the increase in foraging distance. However, we also show that dance performed by swarm-scouts for a nearby (30 m) nest site, where there could be no benefit to imprecision, are either without or with only limited directional information. This result suggests that imprecision in dance communication is caused primarily by physical constraints in the ability of dancers to turn around quickly enough when the advertised site is nearby.

  3. Disaster-related prenatal maternal stress explains increasing amounts of variance in body composition through childhood and adolescence: Project Ice Storm.

    PubMed

    Liu, Guan Ting; Dancause, Kelsey N; Elgbeili, Guillaume; Laplante, David P; King, Suzanne

    2016-10-01

    The increasing prevalence of childhood obesity worldwide has become a public health issue. While many factors are involved in the development of obesity, stress during pregnancy has been linked to adiposity. However, research involving stressors that are independent of pregnant women's socioeconomic and psychological characteristics is rare. The present study made use of a natural disaster (1998 Quebec ice storm) to determine which aspect of the women's disaster experience (objective hardship, subjective stress, and/or cognitive appraisal) were associated with body mass index levels and/or waist to height ratio across childhood and adolescence. Measure of objective hardship, subjective stress, and cognitive appraisal were obtained following the 1998 Quebec ice storm. We measured height, weight, and waist circumference in children at ages 5½, 8½, 11½, 13½, and 15½. Our results show that higher prenatal maternal stress was associated with higher body mass index levels and central adiposity in children of ages 5½, 8½, 13½, and 15½. The effects of prenatal maternal stress on anthropometric measurements tend to increase as the children grew older. The findings of this study highlight the long-lasting effect of prenatal stress on body composition, and are compatible with the current theory of fetal programming. Hopefully, our increased knowledge of the effects of prenatal stress on the fetus will lead to improved awareness and the creation of early intervention programs, ultimately improving women's and children's health in the future. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. What are lipoproteins doing in the brain?

    PubMed

    Wang, Hong; Eckel, Robert H

    2014-01-01

    Lipoproteins in plasma transport lipids between tissues, however, only high-density lipoproteins (HDL) appear to traverse the blood-brain barrier (BBB); thus, lipoproteins found in the brain must be produced within the central nervous system. Apolipoproteins E (ApoE) and ApoJ are the most abundant apolipoproteins in the brain, are mostly synthesized by astrocytes, and are found on HDL. In the hippocampus and other brain regions, lipoproteins help to regulate neurobehavioral functions by processes that are lipoprotein receptor-mediated. Moreover, lipoproteins and their receptors also have roles in the regulation of body weight and energy balance, acting through lipoprotein lipase (LPL) and the low-density lipoprotein (LDL) receptor-related protein (LRP). Thus, understanding lipoproteins and their metabolism in the brain provides a new opportunity with potential therapeutic relevance. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. [Effect of rations with an increased sunflower seed oil level on the rate of very low-density lipoprotein formation in the liver, secretion into the blood and composition in the blood].

    PubMed

    Liapkov, B G

    1978-01-01

    Feeding of rats on a ration with an excessive content of sunflower-oil (60 per cent of the total calorific value of the ration) for a period of 30 days resulted in lowering the rate of the apoproteins, prolipoproteins synthesis in the liver and in their loading with triglycerides and cholesterol. As a consequence of this it diminished secretion of endogenously formed tryglycerides and cholesterol from the liver into the blood and a changed lipid composition of lipoproteins of a very low density in the blood.

  6. Lipoproteins: When size really matters

    PubMed Central

    German, J. Bruce; Smilowitz, Jennifer T.; Zivkovic, Angela M.

    2010-01-01

    The field of nanoscience is extending the applications of physics, chemistry and biology into previously unapproached infinitesimal length scales. Understanding the behavior and manipulating the positions and properties of single atoms and molecules hold great potential to improve areas of science as disparate as medicine and computation, and communication and orbiting satellites. Yet, in the race to develop novel, previously unavailable nanoparticles, there is an opportunity for scientists in this field to digress and to apply their growing understanding of nanoscience and the tools of nanotechnology to one of the most pressing problems in all of human biology—diseases related to lipoproteins. Although not appreciated outside the field of lipoprotein biology, variations in the compositions, structures and properties of these nanoscale-sized, blood-borne particles are responsible for most of the variations in health, morbidity and mortality in the Western world. If the lipoproteins could be understood at the nanometer length scale with precise details of their structures and functions, scientists could understand a wide range of perplexing physiological processes and also address the dysfunctions in normal lipoprotein biology that lead to such diseases as hypercholesterolemia, heart disease, stroke and neurodegenerative diseases. Furthermore, if the capabilities of nanoscience to assemble and manipulate nanometer-sized particles could be recruited to studies of lipoproteins, these biological particles would provide a new dimension to therapeutic agents, and these natural particles could be designed to carry out many specialized beneficial tasks. PMID:20592953

  7. Constitutive androstane receptor activation decreases plasma apolipoprotein B-containing lipoproteins and atherosclerosis in low-density lipoprotein receptor-deficient mice.

    PubMed

    Sberna, Anne-Laure; Assem, Mahfoud; Xiao, Rui; Ayers, Steve; Gautier, Thomas; Guiu, Boris; Deckert, Valérie; Chevriaux, Angélique; Grober, Jacques; Le Guern, Naig; Pais de Barros, Jean-Paul; Moore, David D; Lagrost, Laurent; Masson, David

    2011-10-01

    The goal of this study was to determine the impact of the nuclear receptor constitutive androstane receptor (CAR) on lipoprotein metabolism and atherosclerosis in hyperlipidemic mice. Low-density lipoprotein receptor-deficient (Ldlr(-/-)) and apolipoprotein E-deficient (ApoE(-/-)) mice fed a Western-type diet were treated weekly with the Car agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) or the vehicle only for 8 weeks. In Ldlr(-/-) mice, treatment with TCPOBOP induced a decrease in plasma triglyceride and intermediate-density lipoprotein/low-density lipoprotein cholesterol levels (≈30% decrease in both cases after 2 months, P<0.01). These mice also showed a significant reduction in the production of very-low-density lipoproteins associated with a decrease in hepatic triglyceride content and the repression of several genes involved in lipogenesis. TCPOBOP treatment also induced a marked increase in the very-low-density lipoprotein receptor in the liver, which probably contributed to the decrease in intermediate-density lipoprotein/low-density lipoprotein levels. Atherosclerotic lesions in the aortic valves of TCPOBOP-treated Ldlr(-/-) mice were also reduced (-60%, P<0.001). In ApoE(-/-) mice, which lack the physiological apoE ligand for the very-low-density lipoprotein receptor, the effect of TCPOBOP on plasma cholesterol levels and the development of atherosclerotic lesions was markedly attenuated. CAR is a potential target in the prevention and treatment of hypercholesterolemia and atherosclerosis.

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

    PubMed

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

    2011-04-01

    Elevated levels of lipoprotein(a) are associated with an increased risk of myocardial infarction. Our study aimed to test whether genetic data are consistent with this association being causal. Accordingly, we developed a high-throughput realtime PCR assay to genotype for the lipoprotein(a) kringle IV type 2 (KIV-2) repeat polymorphism in the LPA gene in > 40,000 individuals. The LPA KIV-2 genotype associated with plasma levels of lipoprotein(a) (trend p < 0.001), and the LPA KIV-2 genotype associated with risk of myocardial infarction (trend p < 0.001 to 0.03) in a manner consistent with its effect on plasma levels of lipoprotein(a). The association of LPA KIV-2 genotypes raising plasma levels of lipoprotein(a) with increased risk of myocardial infarction strongly supports a causal association of lipoprotein(a) with risk of myocardial infarction.

  9. Alterations of intestinal lipoprotein metabolism in diabetes mellitus and metabolic syndrome.

    PubMed

    Arca, Marcello

    2015-02-01

    Diabetes and metabolic syndrome are associated with abnormal postprandial lipoprotein metabolism, with a significant delay in the clearance of many lipid parameters, including triglycerides and chylomicrons. Abnormal concentrations of plasma lipids can result from changes in the production, conversion, or catabolism of lipoprotein particles. Whereas the liver is involved in controlling serum lipid levels through synthesis of liver derived triglyceride-rich lipoproteins and low-density lipoprotein metabolism, the intestine also has a major role in lipoprotein production. Postprandial lipemia results from increases in apoB-48 availability, lipogenesis, and the synthesis and absorption of cholesterol in the enterocytes. Increased intestinal lipoprotein production prolongs postprandial lipemia in patients with diabetes and MetS, and may contribute directly to atherogenesis in these patients. © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Remnant Lipoprotein Cholesterol and Mortality After Acute Myocardial Infarction: Further Evidence for a Hypercholesterolemia Paradox From the TRIUMPH Registry.

    PubMed

    Martin, Seth S; Faridi, Kamil F; Joshi, Parag H; Blaha, Michael J; Kulkarni, Krishnaji R; Khokhar, Arif A; Maddox, Thomas M; Havranek, Edward P; Toth, Peter P; Tang, Fengming; Spertus, John A; Jones, Steven R

    2015-11-01

    Remnants are partially hydrolyzed, triglyceride-rich lipoproteins that, like other apolipoprotein B-containing lipoproteins, are atherogenic. Prior observational studies suggest paradoxically better outcomes in hypercholesterolemic patients who sustain an acute myocardial infarction (AMI), one of several known recurrent risk paradoxes. To date, the association of directly measured remnant lipoprotein cholesterol (RLP-C) with survival after an AMI has not been examined. Higher RLP-C levels may be paradoxically associated with lower mortality. We examined 2465 AMI survivors in a prospective, 24-center US study of AMI outcomes. Lipoprotein cholesterol subfractions were directly measured by ultracentrifugation. RLP-C was defined as intermediate-density lipoprotein cholesterol (IDL-C) + very-low-density lipoprotein cholesterol subfraction 3 (VLDL3 -C). Given a linear relationship between RLP-C and mortality, we examined RLP-C by tertiles and continuously. Cox regression hazard ratios (HRs) were adjusted for the Global Registry of Acute Coronary Events (GRACE) score and 23 other covariates. Participants were age 58 ± 12 years (mean ± SD), and 68% were men. After 2 years of follow-up, 226 (9%) participants died. The mortality proportion was 12.4% in the lowest tertile of RLP-C (0-15 mg/dL), 8.5% in the middle tertile (16-23 mg/dL), and 6.8% in the highest tertile (24-120 mg/dL; P < 0.001). A 1-SD increase in RLP-C (11 mg/dL) predicted a 24% lower adjusted risk of 2-year mortality (HR: 0.76, 95% confidence interval [CI]: 0.64-0.91). Similar results were found for a 1-SD increase in IDL-C (HR per 8 mg/dL: 0.80, 95% CI: 0.67-0.96), VLDL3 -C (HR per 4 mg/dL: 0.74, 95% CI: 0.61-0.89), and very-low-density lipoprotein cholesterol (VLDL-C; HR per 8 mg/dL: 0.69, 95% CI: 0.55-0.85). Higher RLP-C levels were associated with lower mortality 2 years after AMI despite rigorous adjustment for known confounders. Unknown protective factors or a lead-time bias likely explains the

  11. The Prevalence of Erosive Esophagitis Is Not Significantly Increased in a Healthy Korean Population - Could It Be Explained?: A Multi-center Prospective Study

    PubMed Central

    Seo, Geom Seog; Jeon, Byung Jun; Chung, Jin Soo; Joo, Young-Eun; Kim, Dae Yong; Shin, Jeong Eun; Kim, Heung Up; Park, Hyun Kyung; Kim, Nayoung

    2013-01-01

    Background/Aims Researches on the potential risk factors for the development of erosive esophagitis have been conducted extensively, however, the results are conflicting. The aim of this multicenter study was to identify the prevalence rate and risk factors of erosive esophagitis and their interactions with residency status. Methods A total of 4,023 eligible subjects at 8 tertiary health care centers were evaluated using questionnaires, laboratory tests and endoscopy. Univariate and multivariate analyses were conducted to identify independent risk factors for erosive esophagitis. Results The prevalence rate of reflux esophagitis was 8.8%. Los Angeles grade A was common type of erosive esophagitis. Residence in a large urban areas was negatively associated with the development of erosive esophagitis (OR, 0.60; 95% CI, 0.40-0.90). The high body mass index (≥ 25 kg/m2) was more frequent in residents of small and medium-sized cities than those in big cities (38.8% and 26.9%, respectively; P < 0.001). Seronegativity of Helicobacter pylori was associated with increased erosive esophagitis (OR, 1.91; 95% CI, 1.48-2.46). Triglyceride ≥ 150 mg/dL (OR, 1.65; 95% CI, 1.08-2.07), fasting glucose level ≥ 126 mg/dL (OR, 1.73; 95% CI, 1.06-2.81), and hiatal hernia (OR, 3.11; 95% CI, 1.87-5.16) were also associated with erosive esophagitis. Conclusions The prevalence rate of erosive esophagitis and its risk factors in this study were similar to the result of 8.0% of nationwide study in 2006. Residency and obesity are more important independent risk factors than H. pylori infection status for development of erosive esophagitis in Korea. These results suggest that the prevalence rate of erosive esophagitis in Korea might not increase as in the Western countries. PMID:23350050

  12. Cotinine exposure increases Fallopian tube PROKR1 expression via nicotinic AChRalpha-7: a potential mechanism explaining the link between smoking and tubal ectopic pregnancy.

    PubMed

    Shaw, Julie L V; Oliver, Elizabeth; Lee, Kai-Fai; Entrican, Gary; Jabbour, Henry N; Critchley, Hilary O D; Horne, Andrew W

    2010-11-01

    Tubal ectopic pregnancy (EP) is the most common cause of maternal mortality in the first trimester of pregnancy; however, its etiology is uncertain. In EP, embryo retention within the Fallopian tube (FT) is thought to be due to impaired smooth muscle contractility (SMC) and alterations in the tubal microenvironment. Smoking is a major risk factor for EP. FTs from women with EP exhibit altered prokineticin receptor-1 (PROKR1) expression, the receptor for prokineticins (PROK). PROK1 is angiogenic, regulates SMC, and is involved in intrauterine implantation. We hypothesized that smoking predisposes women to EP by altering tubal PROKR1 expression. Sera/FT were collected at hysterectomy (n=21). Serum levels of the smoking metabolite, cotinine, were measured by enzyme-linked immunosorbent assay. FTs were analyzed by q-RT-PCR, immunohistochemistry, and Western blotting for expression of PROKR1 and the predicted cotinine receptor, nicotinic acetylcholine receptor α-7 (AChRα-7). FT explants (n=4) and oviductal epithelial cells (cell line OE-E6/E7) were treated with cotinine and an nAChRα-7 antagonist. PROKR1 transcription was higher in FTs from smokers (P<0.01). nAChRα-7 expression was demonstrated in FT epithelium. Cotinine treatment of FT explants and OE-E6/E7 cells increased PROKR1 expression (P<0.05), which was negated by cotreatment with nAChRα-7 antagonist. Smoking targets human FTs via nAChRα-7 to increase tubal PROKR1, leading to alterations in the tubal microenvironment that could predispose to EP.

  13. Classifying lipoproteins based on their polar profiles.

    PubMed

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

    2016-01-01

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

  14. Low-density lipoprotein apheresis: an overview.

    PubMed

    Bambauer, Rolf; Schiel, Ralf; Latza, Reinhard

    2003-08-01

    Atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lpa) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL adsorption and LDL hemoperfusion. Regarding the different LDL apheresis systems used, there is no significant difference with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein (HDL), or triglyceride concentrations. With respect to elevated Lpa levels, however, the immunoadsorption method seems to be the most effective. In 45 patients (25 women, 20 men) suffering from familial hypercholesterolemia resistant to diet and lipid lowering drugs, low-density lipoprotein (LDL) apheresis was performed over 95.6 +/- 44.7 months. Four different systems (Liposorber, 32 of 45, Kaneka, Osaka, Japan; Therasorb, 6 of 45, Baxter, Munich, Germany; Lipopak, 2 of 45, Pocard, Moscow, Russia; and Dali, 5 of 45, Fresenius, St. Wendel, Germany) were used. With all methods, average reductions of 57% for total cholesterol, 55.9% for LDL, 75.8% for lipoprotein a (Lpa), and 45.9% for triglycerides, and an average increase of 14.3% for HDL were reached. Severe side-effects such as shock or allergic reactions were very rare (0.3%) in all methods. In the course of treatment, an improvement

  15. Enhanced Botrytis cinerea Resistance of Arabidopsis Plants Grown in Compost May Be Explained by Increased Expression of Defense-Related Genes, as Revealed by Microarray Analysis

    PubMed Central

    Segarra, Guillem; Santpere, Gabriel; Elena, Georgina; Trillas, Isabel

    2013-01-01

    Composts are the products obtained after the aerobic degradation of different types of organic matter waste and can be used as substrates or substrate/soil amendments for plant cultivation. There is a small but increasing number of reports that suggest that foliar diseases may be reduced when using compost, rather than standard substrates, as growing medium. The purpose of this study was to examine the gene expression alteration produced by the compost to gain knowledge of the mechanisms involved in compost-induced systemic resistance. A compost from olive marc and olive tree leaves was able to induce resistance against Botrytis cinerea in Arabidopsis, unlike the standard substrate, perlite. Microarray analyses revealed that 178 genes were differently expressed, with a fold change cut-off of 1, of which 155 were up-regulated and 23 were down-regulated in compost-grown, as against perlite-grown plants. A functional enrichment study of up-regulated genes revealed that 38 Gene Ontology terms were significantly enriched. Response to stress, biotic stimulus, other organism, bacterium, fungus, chemical and abiotic stimulus, SA and ABA stimulus, oxidative stress, water, temperature and cold were significantly enriched, as were immune and defense responses, systemic acquired resistance, secondary metabolic process and oxireductase activity. Interestingly, PR1 expression, which was equally enhanced by growing the plants in compost and by B. cinerea inoculation, was further boosted in compost-grown pathogen-inoculated plants. Compost triggered a plant response that shares similarities with both systemic acquired resistance and ABA-dependent/independent abiotic stress responses. PMID:23405252

  16. Enhanced Botrytis cinerea resistance of Arabidopsis plants grown in compost may be explained by increased expression of defense-related genes, as revealed by microarray analysis.

    PubMed

    Segarra, Guillem; Santpere, Gabriel; Elena, Georgina; Trillas, Isabel

    2013-01-01

    Composts are the products obtained after the aerobic degradation of different types of organic matter waste and can be used as substrates or substrate/soil amendments for plant cultivation. There is a small but increasing number of reports that suggest that foliar diseases may be reduced when using compost, rather than standard substrates, as growing medium. The purpose of this study was to examine the gene expression alteration produced by the compost to gain knowledge of the mechanisms involved in compost-induced systemic resistance. A compost from olive marc and olive tree leaves was able to induce resistance against Botrytis cinerea in Arabidopsis, unlike the standard substrate, perlite. Microarray analyses revealed that 178 genes were differently expressed, with a fold change cut-off of 1, of which 155 were up-regulated and 23 were down-regulated in compost-grown, as against perlite-grown plants. A functional enrichment study of up-regulated genes revealed that 38 Gene Ontology terms were significantly enriched. Response to stress, biotic stimulus, other organism, bacterium, fungus, chemical and abiotic stimulus, SA and ABA stimulus, oxidative stress, water, temperature and cold were significantly enriched, as were immune and defense responses, systemic acquired resistance, secondary metabolic process and oxireductase activity. Interestingly, PR1 expression, which was equally enhanced by growing the plants in compost and by B. cinerea inoculation, was further boosted in compost-grown pathogen-inoculated plants. Compost triggered a plant response that shares similarities with both systemic acquired resistance and ABA-dependent/independent abiotic stress responses.

  17. Ion mobility analysis of lipoproteins

    DOEpatents

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

    2007-08-21

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

  18. Aerosol preparation of intact lipoproteins

    DOEpatents

    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.

  19. Lipoprotein subfractions highly associated with renal damage in familial lecithin:cholesterol acyltransferase deficiency.

    PubMed

    Kuroda, Masayuki; Holleboom, Adriaan G; Stroes, Erik S G; Asada, Sakiyo; Aoyagi, Yasuyuki; Kamata, Kouju; Yamashita, Shizuya; Ishibashi, Shun; Saito, Yasushi; Bujo, Hideaki

    2014-08-01

    In familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD), deposition of abnormal lipoproteins in the renal stroma ultimately leads to renal failure. However, fish-eye disease (FED) does not lead to renal damage although the causative mutations for both FLD and FED lie within the same LCAT gene. This study was performed to identify the lipoproteins important for the development of renal failure in genetically diagnosed FLD in comparison with FED, using high-performance liquid chromatography with a gel filtration column. Lipoprotein profiles of 9 patients with LCAT deficiency were examined. Four lipoprotein fractions specific to both FLD and FED were identified: (1) large lipoproteins (>80 nm), (2) lipoproteins corresponding to large low-density lipoprotein (LDL), (3) lipoproteins corresponding to small LDL to large high-density lipoprotein, and (4) to small high-density lipoprotein. Contents of cholesteryl ester and triglyceride of the large LDL in FLD (below detection limit and 45.8±3.8%) and FED (20.7±6.4% and 28.0±6.5%) were significantly different, respectively. On in vitro incubation with recombinant LCAT, content of cholesteryl ester in the large LDL in FLD, but not in FED, was significantly increased (to 4.2±1.4%), whereas dysfunctional high-density lipoprotein was diminished in both FLD and FED. Our novel analytic approach using high-performance liquid chromatography with a gel filtration column identified large LDL and high-density lipoprotein with a composition specific to FLD, but not to FED. The abnormal lipoproteins were sensitive to treatment with recombinant LCAT and thus may play a causal role in the renal pathology of FLD. © 2014 American Heart Association, Inc.

  20. Intravenous Glucose Acutely Stimulates Intestinal Lipoprotein Secretion in Healthy Humans.

    PubMed

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

    2016-07-01

    Increased production of intestinal triglyceride-rich lipoproteins (TRLs) contributes to dyslipidemia and increased risk of atherosclerotic cardiovascular disease in insulin resistance and type 2 diabetes. We have previously demonstrated that enteral glucose enhances lipid-stimulated intestinal lipoprotein particle secretion. Here, we assessed whether glucose delivered systemically by intravenous infusion also enhances intestinal lipoprotein particle secretion in humans. On 2 occasions, 4 to 6 weeks apart and in random order, 10 healthy men received a constant 15-hour intravenous infusion of either 20% glucose to induce hyperglycemia or normal saline as control. Production of TRL-apolipoprotein B48 (apoB48, primary outcomes) and apoB100 (secondary outcomes) was assessed during hourly liquid-mixed macronutrient formula ingestion with stable isotope enrichment and multicompartmental modeling, under pancreatic clamp conditions to limit perturbations in pancreatic hormones (insulin and glucagon) and growth hormone. Compared with saline infusion, glucose infusion induced both hyperglycemia and hyperinsulinemia, increased plasma triglyceride levels, and increased TRL-apoB48 concentration and production rate (P<0.05), without affecting TRL-apoB48 fractional catabolic rate. No significant effect of hyperglycemia on TRL-apoB100 concentration and kinetic parameters was observed. Short-term intravenous infusion of glucose stimulates intestinal lipoprotein production. Hyperglycemia may contribute to intestinal lipoprotein overproduction in type 2 diabetes. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02607839. © 2016 American Heart Association, Inc.

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

    PubMed

    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

  2. Lipoprotein metabolism in nonalcoholic fatty liver disease

    PubMed Central

    Jiang, Zhenghui Gordon; Robson, Simon C.; Yao, Zemin

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD), an escalating health problem worldwide, covers a spectrum of pathologies characterized by fatty accumulation in hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extracellular role in lipid transport between vital organs through circulation, but also play an important intracellular role in hepatic lipoprotein assembly and secretion. The liver functions as the central hub for lipoprotein metabolism, as it dictates lipoprotein production and to a significant extent modulates lipoprotein clearance. Lipoprotein metabolism is an integral component of hepatocellular lipid homeostasis and is implicated in the pathogenesis, potential diagnosis, and treatment of NAFLD. PMID:23554788

  3. Single-Particle Tracking of Human Lipoproteins.

    PubMed

    de Messieres, Michel; Ng, Abby; Duarte, Cornelio J; Remaley, Alan T; Lee, Jennifer C

    2016-01-05

    Lipoproteins, such as high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low density lipoprotein (VLDL), play a critical role in heart disease. Lipoproteins vary in size and shape as well as in their apolipoprotein content. Here, we developed a new experimental framework to study freely diffusing lipoproteins from human blood, allowing analysis of even the smallest HDL with a radius of 5 nm. In an easily constructed confinement chamber, individual HDL, LDL, and VLDL particles labeled with three distinct fluorophores were simultaneously tracked by wide-field fluorescence microscopy and their sizes were determined by their motion. This technique enables studies of individual lipoproteins in solution and allows characterization of the heterogeneous properties of lipoproteins which affect their biological function but are difficult to discern in bulk studies.

  4. What are Lipoproteins doing in the Brain?

    PubMed Central

    Wang, Hong; Eckel, Robert H.

    2014-01-01

    Lipoproteins in plasma transport lipids between tissues, however, only high density lipoproteins (HDL) appear to traverse the blood brain barrier; thus, lipoproteins found in the brain must be produced within the central nervous system. Apolipoproteins E (ApoE) and ApoJ are the most abundant apolipoproteins in the brain, are mostly synthesized by astrocytes and are found on HDL. In the hippocampus and other brain regions lipoproteins help regulate neurobehavioral functions by processes that are lipoprotein receptor-mediated. Moreover, lipoproteins and their receptors also have roles in the regulation of body weight and energy balance, i.e. through lipoprotein lipase (LPL) and the LDL receptor-related protein (LRP). Thus, understanding lipoproteins and their metabolism in the brain provides a new opportunity with potential therapeutic relevance. PMID:24189266

  5. Comparison of the mechanisms proposed to explain the hypocholesterolemic effect of soybean protein versus casein in experimental animals.

    PubMed

    Beynen, A C

    1990-10-01

    Diets containing soybean protein generally induce low levels of serum cholesterol in experimental animals, when compared with diets containing casein. The hypocholesterolemia in animals fed soybean protein is associated with increased rates of fecal excretion of bile acids and neutral steroids, low liver cholesterol concentrations, increased numbers of hepatic apo B/E receptors, increased rates of hepatic cholesterol synthesis, increased rates of bile acid synthesis and decreased rates of lipoprotein cholesterol output by the liver. In this communication the development of the hypocholesterolemia induced by soybean protein is described. The various mechanisms that have been proposed to explain the hypocholesterolemic effect of soybean protein are scrutinized, compared and contrasted.

  6. Explaining Increases in Higher Education Costs

    ERIC Educational Resources Information Center

    Archibald, Robert B.; Feldman, David H.

    2008-01-01

    The real cost of higher education per full-time equivalent student has grown substantially over the last 75 years, and the rapid rise since the early 1980s is a cause of considerable public concern. Opinion surveys consistently find that how much one has to pay for a college education is a serious national issue. In his July 1996 congressional…

  7. Explaining Increases in Higher Education Costs

    ERIC Educational Resources Information Center

    Archibald, Robert B.; Feldman, David H.

    2008-01-01

    The real cost of higher education per full-time equivalent student has grown substantially over the last 75 years, and the rapid rise since the early 1980s is a cause of considerable public concern. Opinion surveys consistently find that how much one has to pay for a college education is a serious national issue. In his July 1996 congressional…

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

    PubMed

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

    2016-09-01

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

  9. Characterization of metabolic interrelationships and in silico phenotyping of lipoprotein particles using self-organizing maps[S

    PubMed Central

    Kumpula, Linda S.; Mäkelä, Sanna M.; Mäkinen, Ville-Petteri; Karjalainen, Anna; Liinamaa, Johanna M.; Kaski, Kimmo; Savolainen, Markku J.; Hannuksela, Minna L.; Ala-Korpela, Mika

    2010-01-01

    Plasma lipid concentrations cannot properly account for the complex interactions prevailing in lipoprotein (patho)physiology. Sequential ultracentrifugation (UCF) is the gold standard for physical lipoprotein isolations allowing for subsequent analyses of the molecular composition of the particles. Due to labor and cost issues, however, the UCF-based isolations are usually done only for VLDL, LDL, and HDL fractions; sometimes with the addition of intermediate density lipoprotein (IDL) particles and the fractionation of HDL into HDL2 and HDL3 (as done here; n = 302). We demonstrate via these data, with the lipoprotein lipid concentration and composition information combined, that the self-organizing map (SOM) analysis reveals a novel data-driven in silico phenotyping of lipoprotein metabolism beyond the experimentally available classifications. The SOM-based findings are biologically consistent with several well-known metabolic characteristics and also explain some apparent contradictions. The novelty is the inherent emergence of complex lipoprotein associations; e.g., the metabolic subgrouping of the associations between plasma LDL cholesterol concentrations and the structural subtypes of LDL particles. Importantly, lipoprotein concentrations cannot pinpoint lipoprotein phenotypes. It would generally be beneficial to computationally enhance the UCF-based lipoprotein data as illustrated here. Particularly, the compositional variations within the lipoprotein particles appear to be a fundamental issue with metabolic and clinical corollaries. PMID:19734566

  10. Revisiting the gram-negative lipoprotein paradigm

    USDA-ARS?s Scientific Manuscript database

    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...

  11. Capillary isotachophoresis study of lipoprotein network sensitive to apolipoprotein E phenotype. 1. ApoE distribution between lipoproteins.

    PubMed

    Dergunov, Alexander D; Ponthieux, Anne; Mel'kin, Maxim V; Lambert, Daniel; Visvikis-Siest, Sophie; Siest, Gerard

    2009-05-01

    Sixteen patients differing widely in plasma triglyceride content were divided into three groups by their apolipoprotein E (apoE) phenotype-E33 homozygotes, E23, and E34 heterozygotes. The plasma lipid and apoE distribution between individual lipoproteins was followed by capillary isotachophoresis (CITP) of plasma samples pre-stained with lipid fluorescent probe NBD-C6-ceramide and by fluorescein-labeled apoE, respectively. Among 12 peaks visualized by ceramide staining, an individual peak with very low density lipoproteins (VLDL) was identified. The VLDL cholesterol and apoE content determined by CITP directly in whole plasma were significantly related to their content as determined by conventional analysis with isolated VLDL. The ceramide distribution among lipoprotein pools was insensitive to apoE phenotype (49-53 : 7-11 : 39-43% for HDL, VLDL, and IDL/LDL, respectively) while the preferential binding of apoE to VLDL was observed in E34 patients compared to E33 (62 : 19 : 20 vs. 70 : 9 : 22%). In a study of apoE/F displacement from lipoproteins at plasma titration by apoC-III in vitro, apoE was found to bind more tightly to VLDL from E34 compared to E33 patients as evidenced by both the increased non-displaceable apoE pool, the increased VLDL sorbtion capacity for apoE, and the decreased displacement parameter in a "container" model of lipoprotein binding. Two different types of apoE package in a whole lipoprotein profile were observed. ApoE structure in a particular lipoprotein may underlie the phenotype-sensitive apoE distribution and apoC-III interference in hypertriglyceridemia.

  12. Regulation of high density lipoprotein levels

    SciTech Connect

    Krauss, R.M.

    1982-03-01

    An increasing awareness of the physiologic and pathologic importance of serum high density lipoproteins (HDL) has led to a large number of observations regarding factors which influence their concentrations. HDL consists of a heterogeneous collection of macromolecules with diverse physical properties and chemical constituents. While laboratory techniques have made it possible to measure HDL and their individual components, there are as yet large gaps in our knowledge of the biochemical mechanisms and clinical significance of changes in these laboratory parameters. In this review, current concepts of the structure and metabolism of HDL will be briefly summarized, and the factors influencing their levels in humans will be surveyed. 313 references.

  13. [Intermediate-density lipoproteins and liver lipase in postmenopausal women].

    PubMed

    Halperin, H; Berg, G; Aisemberg, L; Brites, F; Siseles, N; Wikinski, R

    1992-01-01

    In order to evaluate atherogenic lipoproteins in post-menopause, we studied 73 healthy women, 49 to 65 years old (Post-menopausal Group), with 1 to 10 years of amenorrhea and body mass index below 27 Kg/m2, and 20 young women (Control Group). We have determined plasma cholesterol concentration in the lipoproteins of intermediate density in addition to the classical lipoprotein parameters: total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and fractionation of lipoproteins by electrophoresis. In 63 women from the Post-menopausal Group and 16 from the Control Group we studied the activity of hepatic lipase. Among these patients we selected at random 25 post-menopausal women and 13 controls to add measurements of triglycerides in the lipoproteins of intermediate density. Table 1 shows that the average plasma concentration of total cholesterol in the Post-menopausal Group was higher than that of the Controls (p < 0.001). The same was found for LDL-cholesterol (p < 0.001) and for triglycerides (p < 0.001) whereas the average concentration of HDL-cholesterol did not show significant differences. The Post-menopausal Group had high values of plasma lipoproteins of intermediate density, even with normal phenotypes (Table 2). Cholesterol but also triglycerides (Fig. 1) were responsible for this increase. A triglyceride rich lipoprotein subspecies of intermediate density was predominant in 73% of Post-menopausal women vs 23% of the Controls (p < 0.01, Table 3). No differences in hepatic lipase activity were seen between the two groups (Table 4), and non statistic correlation between the enzyme activity and IDL-triglycerides or HDL-cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Expression of scavenger receptor-BI and low-density lipoprotein receptor and differential use of lipoproteins to support early steroidogenesis in luteinizing macaque granulosa cells.

    PubMed

    Cherian-Shaw, Mary; Puttabyatappa, Muraly; Greason, Erin; Rodriguez, Annabelle; VandeVoort, Catherine A; Chaffin, Charles L

    2009-02-01

    An ovulatory hCG stimulus to rhesus macaques undergoing controlled ovarian stimulation protocols results in a rapid and sustained increase in progesterone synthesis. The use of lipoproteins as a substrate for progesterone synthesis remains unclear, and the expression of lipoprotein receptors [very-low-density lipoprotein receptor (VLDLR), low-density lipoprotein receptor (LDLR), and scavenger receptor-BI (SR-BI)] soon after human chorionic gonadotropin (hCG) (<12 h) has not been characterized. This study investigated lipoprotein receptor expression and lipoprotein (VLDL, LDL, and HDL) support of steroidogenesis during luteinization of macaque granulosa cells. Granulosa cells were aspirated from rhesus monkeys undergoing controlled ovarian stimulation before or up to 24 h after an ovulatory hCG stimulus. The expression of VLDLR decreased within 3 h of hCG, whereas LDLR and SR-BI increased at 3 and 12 h, respectively. Granulosa cells isolated before hCG were cultured for 24 h in the presence of FSH or FSH plus hCG with or without VLDL, LDL, or HDL. Progesterone levels increased in the presence of hCG regardless of lipoprotein addition, although LDL, but not HDL, further augmented hCG-induced progesterone. Other cells were cultured with FSH or FSH plus hCG without an exogenous source of lipoprotein for 24 h, followed by an additional 24 h culture with or without lipoproteins. Cells treated with hCG in the absence of any lipoprotein were unable to maintain progesterone levels through 48 h, whereas LDL (but not HDL) sustained progesterone synthesis. These data suggest that an ovulatory stimulus rapidly mobilizes stored cholesterol esters for use as a progesterone substrate and that as these are depleted, new cholesterol esters are obtained through an LDLR- and/or SR-BI-mediated mechanism.

  15. Linkage of low-density lipoprotein size to the lipoprotein lipase gene in heterozygous lipoprotein lipase deficiency.

    PubMed Central

    Hokanson, J E; Brunzell, J D; Jarvik, G P; Wijsman, E M; Austin, M A

    1999-01-01

    Small low-density lipoprotein (LDL) particles are a genetically influenced coronary disease risk factor. Lipoprotein lipase (LpL) is a rate-limiting enzyme in the formation of LDL particles. The current study examined genetic linkage of LDL particle size to the LpL gene in five families with structural mutations in the LpL gene. LDL particle size was smaller among the heterozygous subjects, compared with controls. Among heterozygous subjects, 44% were classified as affected by LDL subclass phenotype B, compared with 8% of normal family members. Plasma triglyceride levels were significantly higher, and high-density lipoprotein cholesterol (HDL-C) levels were lower, in heterozygous subjects, compared with normal subjects, after age and sex adjustment. A highly significant LOD score of 6.24 at straight theta=0 was obtained for linkage of LDL particle size to the LpL gene, after adjustment of LDL particle size for within-genotype variance resulting from triglyceride and HDL-C. Failure to adjust for this variance led to only a modest positive LOD score of 1.54 at straight theta=0. Classifying small LDL particles as a qualitative trait (LDL subclass phenotype B) provided only suggestive evidence for linkage to the LpL gene (LOD=1. 65 at straight theta=0). Thus, use of the quantitative trait adjusted for within-genotype variance, resulting from physiologic covariates, was crucial for detection of significant evidence of linkage in this study. These results indicate that heterozygous LpL deficiency may be one cause of small LDL particles and may provide a potential mechanism for the increase in coronary disease seen in heterozygous LpL deficiency. This study also demonstrates a successful strategy of genotypic specific adjustment of complex traits in mapping a quantitative trait locus. PMID:9973300

  16. New insights into the role of lipoprotein(a)-associated lipoprotein-associated phospholipase A2 in atherosclerosis and cardiovascular disease.

    PubMed

    Tsimikas, Sotirios; Tsironis, Loukas D; Tselepis, Alexandros D

    2007-10-01

    Lipoprotein(a) [Lp(a)] plays an important role in atherosclerosis. The biological effects of Lp(a) have been attributed either to apolipoprotein(a) or to its low-density lipoprotein-like particle. Lp(a) contains platelet-activating factor acetylhydrolase, an enzyme that exhibits a Ca2+-independent phospholipase A2 activity and is complexed to lipoproteins in plasma; thus, it is also referred to as lipoprotein-associated phospholipase A2. Substrates for lipoprotein-associated phospholipase A2 include phospholipids containing oxidatively fragmented residues at the sn-2 position (oxidized phospholipids; OxPLs). OxPLs may play important roles in vascular inflammation and atherosclerosis. Plasma levels of OxPLs present on apolipoprotein B-100 particles (OxPL/apolipoprotein B) are correlated with coronary artery, carotid, and peripheral arterial disease. Furthermore, OxPL/apolipoprotein B levels in plasma are strongly correlated with Lp(a) levels, are preferentially sequestered on Lp(a), and thus are potentially subjected to degradation by the Lp(a)-associated lipoprotein-associated phospholipase A2. The present review article focuses specifically on the characteristics of the lipoprotein-associated phospholipase A2 associated with Lp(a) and discusses the possible role of this enzyme in view of emerging data showing that OxPLs in plasma are preferentially sequestered on Lp(a) and may significantly contribute to the increased atherogenicity of this lipoprotein.

  17. Relationship between noninvasive scores of nonalcoholic fatty liver disease and nuclear magnetic resonance lipoprotein abnormalities: A focus on atherogenic dyslipidemia.

    PubMed

    Amor, Antonio J; Pinyol, Montserrat; Solà, Elsa; Catalan, Marta; Cofán, Montserrat; Herreras, Zoe; Amigó, Nuria; Gilabert, Rosa; Sala-Vila, Aleix; Ros, Emilio; Ortega, Emilio

    Nonalcoholic fatty liver disease (NAFLD) is an emerging, highly prevalent, cardiovascular risk factor, and lipoprotein proatherogenic disturbances likely explain a large part of this risk. However, information regarding associations between detailed nuclear magnetic resonance (NMR) lipoprotein changes and noninvasive NAFLD scores is lacking. The objective of the study was to investigate the NMR-assessed atherogenic lipoprotein profile according to noninvasive NAFLD status. Lipoprotein profiles by NMR spectroscopy and NAFLD status by fatty liver index (FLI) and Gholam's models. We assessed 173 participants (55% males), mean age 60.8 ± 7.8 years, 87% overweight/obese, 53% with diabetes. An FLI <30, 30 to 60, and >60 was found in 32, 50, and 91 participants, respectively. Individuals with FLI >60 had lower high-density lipoprotein (HDL)-cholesterol (P < .001), higher triglyceride (P < .001), and similar non-HDL-cholesterol (P = .912) concentrations. In NMR analysis, FLI was related with very-low-density lipoprotein (VLDL) and HDL parameters in a dose-dependent manner. VLDL particle number (P < .001) and VLDL size (39.1 ± 0.99, 39.7 ± 0.96, 40.8 ± 1.19 nm, P < .001) increased with increased FLI (<30, 30-60, and >60, respectively). Conversely, although total HDL particle number did not differ by FLI (P = .377), larger HDL particles (P < .001), amount of cholesterol within HDL particles (P < .001), and HDL size (median [p25-p75]: 8.23 [8.08-8.41], 8.12 [8.03-8.29], 8.04 [7.93-8.16] nm, P < .001) decreased as FLI increased. FLI >60 (vs <60) was associated with a higher proportion of small LDL particles (P = .010) and lower LDL size (19.85 ± 0.34 vs 19.98 ± 0.25 nm; P = .005). Similar findings were found for Gholam's model. Simple and noninvasive NAFLD scores are useful to detect many of the proatherogenic changes (especially in VLDL and HDL), beyond conventional lipids parameters that are common in individuals with this high

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

    PubMed

    Ducobu, J

    1997-02-01

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

  19. Lipoprotein metabolism and lipoprotein lipase in severe cystic acne.

    PubMed

    Pigatto, P; Altomare, G F; Negri, M; Finzi, A F; Vigotti, G; Vergani, C

    1985-01-01

    In severe cystic acne we found low levels of high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A (Apo-A) in the presence of normal total lipids. In a larger number of patients, we always observed significantly lower levels of HDL-C and Apo-A than in either age-matched controls or subjects with acne vulgaris. Since lipoprotein lipase is one major determinant of HDL concentration, we assayed the lipase activity in liver and extra-hepatic tissues by the method of Krauss et al. There was highly significant less total and hepatic lipase activity than in age-matched controls. HDL distribution was examined by zonal ultracentrifugation and a decrease in the HDL2 subclass was discovered. Since HDL are inversely correlated to atherosclerosis, cystic acne is one risk factor for atherosclerosis. The linkage between low HDL levels and severe cystic acne should be further investigated.

  20. A lipoprotein characterizing obstructive jaundice. I. Method for quantitative separation and identification of lipoproteins in jaundiced subjects

    PubMed Central

    Seidel, D.; Alaupovic, P.; Furman, R. H.

    1969-01-01

    Three immunochemically and electrophoretically distinct lipoproteins, LP-A, LP-B, and LP-X,1 were isolated from the low density lipoprotein fraction (1.006-1.063 g/ml) in plasma from patients with biliary obstruction by a separation procedure which combines ultracentrifugation, heparin precipitation, and ethanol fractionation. This method, here described, permits the quantitative determination of individual plasma lipoprotein families on the basis of their protein moieties, rather than on the basis of their lipid moieties or density. The chemical composition of the unique lipoprotein, LP-X, was similar to that of an abnormal lipoprotein, OLP, isolated by Russ et al. (29) and by Switzer (30). In obstructive jaundice plasma, the combined LP-X and LP-B accounted for 98% and the LP-A for only 2% of the total protein content of the LDL fraction. This study indicates that the plasma lipoprotein pattern in obstructive jaundice is characterized by (a) a decreased concentration of HDL, (b) an increased concentration of LDL, and (c) the presence in the LDL fraction of varying amounts of a specific lipoprotein, LP-X, immunochemically and chemically distinct from LP-A and LP-B. LP-X, with its characteristically high content of unesterified cholesterol and phospholipids, is primarily responsible for the unusual protein and lipid content of the LDL fraction. Screening tests in 61 patients with various forms of jaundice indicated that a characteristic immunoelectrophoretic precipitin are between plasma samples and purified antibodies to LP-X was observed only in patients with obstructive jaundice. This simple immunochemical test may represent a valuable new tool in the differential diagnosis of obstructive and nonobstructive jaundice. Images PMID:4978447

  1. [Influence of calcic and magnesic sulphurous thermal water on the metabolism of lipoproteins in the rat].

    PubMed

    Toussaint, C; Peuchant, E; Nguyen, B C; Jensen, R; Canellas, J

    1986-06-01

    We have studied in rats fed hypercholesterolemic diet the action of calcic and magnesic sulphurous water from Capvern on the modification of the lipoproteins metabolism caused by hypercholesterolemia. The rats subjected to a hypercholesterolemic diet with thermal water of Capvern was found to have a plasma level of cholesterol significantly less increased (P less than 0.01) compared to those subjected to the same diet with ordinary drinking water (25%). We demonstrated after 105 days of experimentation on tested rats that thermal water may affect the cholesterol catabolism by increased level of cholesterol HDL (52%) and stabilizing level of cholesterol LDL comparatively to the controls. These data suggest that the thermal water from Capvern enhanced the transformation of cholesterol to biliary acids and their biliary secretion. A possible relationship between the influence of the thermal water and the metabolism of lipoproteins would be explained by a possible increase of hepatic receptors which identify apolipoproteins B (LDL) and E (HDLc) on cholesterol fed rats, suggesting a great synthesis of nascent apolipoproteins HDL which are antiatherogenic.

  2. A green tea catechin extract upregulates the hepatic low-density lipoprotein receptor in rats.

    PubMed

    Bursill, Christina A; Roach, Paul D

    2007-07-01

    Green tea extracts have hypocholesterolaemic properties in epidemiological and animal intervention studies. Upregulation of the low-density lipoprotein (LDL) receptor may be one mechanism to explain this as it is the main way cholesterol is removed from the circulation. This study aimed to determine if a green tea extract could upregulate the hepatic LDL receptor in vivo in the rat. A green tea extract (GTE) enriched in its anti-oxidant constituents, the catechins, was fed to rats (n = 6) at concentrations of either 0, 0.5, 1.0 or 2.0% (w/w) mixed in with their normal chow along with 0.25% (w/w) cholesterol for 12 days. Administration of the GTE had no effect on plasma total or LDL cholesterol concentrations but high-density lipoprotein significantly increased (41%; p < 0.05). Interestingly, there was a significant increase in LDL receptor binding activity (2.7-fold) and LDL receptor protein (3.4-fold) in the 2% (w/w) treatment group compared to controls. There were also significant reductions in liver total and unesterified cholesterol (40%). Administration of the GTE significantly reduced cholesterol absorption (24%) but did not affect cholesterol synthesis. These results show that, despite no effect on plasma cholesterol, the GTE upregulated the LDL receptor in vivo. This appears to be via a reduction in liver cholesterol concentration and suggests that the green tea extract was able to increase the efflux of cholesterol from liver cells.

  3. Low-Density Lipoprotein Receptor-Dependent and Low-Density Lipoprotein Receptor-Independent Mechanisms of Cyclosporin A-Induced Dyslipidemia.

    PubMed

    Kockx, Maaike; Glaros, Elias; Leung, Betty; Ng, Theodore W; Berbée, Jimmy F P; Deswaerte, Virginie; Nawara, Diana; Quinn, Carmel; Rye, Kerry-Anne; Jessup, Wendy; Rensen, Patrick C N; Meikle, Peter J; Kritharides, Leonard

    2016-07-01

    Cyclosporin A (CsA) is an immunosuppressant commonly used to prevent organ rejection but is associated with hyperlipidemia and an increased risk of cardiovascular disease. Although studies suggest that CsA-induced hyperlipidemia is mediated by inhibition of low-density lipoprotein receptor (LDLr)-mediated lipoprotein clearance, the data supporting this are inconclusive. We therefore sought to investigate the role of the LDLr in CsA-induced hyperlipidemia by using Ldlr-knockout mice (Ldlr(-/-)). Ldlr(-/-) and wild-type (wt) C57Bl/6 mice were treated with 20 mg/kg per d CsA for 4 weeks. On a chow diet, CsA caused marked dyslipidemia in Ldlr(-/-) but not in wt mice. Hyperlipidemia was characterized by a prominent increase in plasma very low-density lipoprotein and intermediate-density lipoprotein/LDL with unchanged plasma high-density lipoprotein levels, thus mimicking the dyslipidemic profile observed in humans. Analysis of specific lipid species by liquid chromatography-tandem mass spectrometry suggested a predominant effect of CsA on increased very low-density lipoprotein-IDL/LDL lipoprotein number rather than composition. Mechanistic studies indicated that CsA did not alter hepatic lipoprotein production but did inhibit plasma clearance and hepatic uptake of [(14)C]cholesteryl oleate and glycerol tri[(3)H]oleate-double-labeled very low-density lipoprotein-like particles. Further studies showed that CsA inhibited plasma lipoprotein lipase activity and increased levels of apolipoprotein C-III and proprotein convertase subtilisin/kexin type 9. We demonstrate that CsA does not cause hyperlipidemia via direct effects on the LDLr. Rather, LDLr deficiency plays an important permissive role for CsA-induced hyperlipidemia, which is associated with abnormal lipoprotein clearance, decreased lipoprotein lipase activity, and increased levels of apolipoprotein C-III and proprotein convertase subtilisin/kexin type 9. Enhancing LDLr and lipoprotein lipase activity and decreasing

  4. RP105 facilitates macrophage activation by Mycobacterium tuberculosis lipoproteins.

    PubMed

    Blumenthal, Antje; Kobayashi, Toshihiko; Pierini, Lynda M; Banaei, Niaz; Ernst, Joel D; Miyake, Kensuke; Ehrt, Sabine

    2009-01-22

    RP105, phylogenetically related to Toll-like receptor (TLR)-4, is reported to facilitate B cell activation by the TLR4-agonist lipopolysaccharide (LPS)--but to limit LPS-induced cytokine production by antigen-presenting cells. Here, we show that the role of RP105 extends beyond LPS recognition and that RP105 positively regulates macrophage responses to Mycobacterium tuberculosis (Mtb) lipoproteins. Mtb-infected RP105(-/-) mice exhibited impaired proinflammatory cytokine responses associated with enhanced bacterial burden and increased lung pathology. The Mtb 19 kDa lipoprotein induced release of tumor necrosis factor in a manner dependent on both TLR2 and RP105, and macrophage activation by Mtb lacking mature lipoproteins was not RP105 dependent. Thus, mycobacterial lipoproteins are RP105 agonists. RP105 physically interacted with TLR2, and both RP105 and TLR2 were required for optimal macrophage activation by Mtb. Our data identify RP105 as an accessory molecule for TLR2, forming part of the receptor complex for innate immune recognition of mycobacterial lipoproteins.

  5. Structural Stability and Functional Remodeling of High-Density Lipoproteins

    PubMed Central

    Gursky, Olga

    2015-01-01

    Lipoproteins are protein-lipid nanoparticles that transport lipids in circulation and are central in atherosclerosis and other disorders of lipid metabolism. Apolipoproteins form flexible structural scaffolds and important functional ligands on the particle surface and direct lipoprotein metabolism. Lipoproteins undergo multiple rounds of metabolic remodeling that is crucial to lipid transport. Important aspects of this remodeling, including apolipoprotein dissociation and particle fusion, are mimicked in thermal or chemical denaturation and are modulated by free energy barriers. Here we review our biophysical studies that revealed kinetic mechanism of lipoprotein stabilization and unraveled its structural basis. The main focus is on high-density lipoprotein (HDL). An inverse correlation between stability and functions of various HDLs in cholesterol transport suggests functional role of structural disorder. A mechanism for conformational adaptation of the major HDL proteins, apoA-I and apoA-II, to the increasing lipid load is proposed. Together, these studies help understand why HDL form discrete subclasses separated by kinetic barriers, which have distinct composition, conformation and functional properties. Understanding these properties may help improve HDL quality and develop novel therapies for cardiovascular disease. PMID:25749369

  6. Characterization of chick serum lipoproteins isolated by density gradient ultracentrifugation.

    PubMed

    Rodriguez-Vico, F; Lopez, J M; Castillo, M; Zafra, M F; Garcia-Peregrin, E

    1992-01-01

    Serum lipoproteins from 12h fasted male chicks (15-day-old) were separated into 20 fractions by isopycnic density gradient ultracentrifugation. A new procedure was described by collecting the different fractions from the bottom of tube instead of by aspiration from the meniscus of each tube. Analyses of chemical composition of serum lipoproteins have permitted to reevaluate the density limits of major classes: VHDL, d greater than 1.132 g/ml; HDL, d 1.132-1.084 g/ml; LDL, d 1.084-1.038; IDL, d 1.038-1.022; and VLDL d less than 1.022. HDL fractions clearly predominated (approx. 77% of total lipoproteins) while IDL and VLDL were present at low percentage. LDL was the fraction richest in cholesterol; triacylglycerol content clearly increased from HDL to VLDL, while protein content decreased. All the chemical components of chick serum lipoproteins were accumulated in HDL, although triacylglycerol was relatively distributed in all the lipoprotein classes.

  7. Low density lipoproteins mediated nanoplatforms for cancer targeting

    NASA Astrophysics Data System (ADS)

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

    2013-09-01

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

  8. Low levels of high-density lipoprotein cholesterol and increased risk of cardiovascular events in stable ischemic heart disease patients: A post-hoc analysis from the COURAGE Trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation).

    PubMed

    Acharjee, Subroto; Boden, William E; Hartigan, Pamela M; Teo, Koon K; Maron, David J; Sedlis, Steven P; Kostuk, William; Spertus, John A; Dada, Marcin; Chaitman, Bernard R; Mancini, G B John; Weintraub, William S

    2013-11-12

    This study sought to assess the independent effect of high-density lipoprotein-cholesterol (HDL-C) level on cardiovascular risk in patients with stable ischemic heart disease (SIHD) who were receiving optimal medical therapy (OMT). Although low HDL-C level is a powerful and independent predictor of cardiovascular risk, recent data suggest that this may not apply when low-density lipoprotein-cholesterol (LDL-C) is reduced to optimal levels using intensive statin therapy. We performed a post-hoc analysis in 2,193 men and women with SIHD from the COURAGE trial. The primary outcome measure was the composite of death from any cause or nonfatal myocardial infarction (MI). The independent association between HDL-C levels measured after 6 months on OMT and the rate of cardiovascular events after 4 years was assessed. Similar analyses were performed separately in subjects with LDL-C levels below 70 mg/dl (1.8 mmol/l). In the overall population, the rate of death/MI was 33% lower in the highest HDL-C quartile as compared with the lowest quartile, with quartile of HDL-C being a significant, independent predictor of death/MI (p = 0.05), but with no interaction for LDL-C category (p = 0.40). Among subjects with LDL-C levels <70 mg/dl, those in the highest quintile of HDL-C had a 65% relative risk reduction in death or MI as compared with the lowest quintile, with HDL-C quintile demonstrating a significant, inverse predictive effect (p = 0.02). In this post-hoc analysis, patients with SIHD continued to experience incremental cardiovascular risk associated with low HDL-C levels despite OMT during long-term follow-up. This relationship persisted and appeared more prominent even when LDL-C was reduced to optimal levels with intensive dyslipidemic therapy. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  9. Biogenesis and Membrane Targeting of Lipoproteins.

    PubMed

    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. Effects of bariatric surgery on hepatic and intestinal lipoprotein particle metabolism in obese, nondiabetic humans.

    PubMed

    Padilla, Nadège; Maraninchi, Marie; Béliard, Sophie; Berthet, Bruno; Nogueira, Juan-Patricio; Wolff, Estelle; Nicolay, Alain; Bégu, Audrey; Dubois, Noémie; Grangeot, Rachel; Mattei, Catherine; Vialettes, Bernard; Xiao, Changting; Lewis, Gary F; Valéro, René

    2014-10-01

    The dyslipidemia of obesity and other insulin-resistant states is characterized by the elevation of plasma triglyceride-rich lipoproteins (TRL) of both hepatic (apoB-100-containing very low-density lipoprotein) and intestinal (apoB-48-containing chylomicrons) origin. Bariatric surgery is a well-established and effective modality for the treatment of obesity and is associated with improvements in several metabolic abnormalities associated with obesity, including a reduction in plasma triglycerides. Here, we have investigated the effect of bariatric surgery on TRL metabolism. Twenty-two nondiabetic, obese subjects undergoing bariatric surgery: sleeve gastrectomy (n=12) or gastric bypass (n=10) were studied. Each subject underwent 1 lipoprotein turnover study 1 month before surgery followed by a second study, 6 months after surgery, using established stable isotope enrichment methodology, in constant fed state. TRL-apoB-100 concentration was significantly reduced after sleeve gastrectomy, explained by a decrease (P<0.05) in TRL-apoB-100 production rate and an increase (P<0.05) in TRL-apoB-100 fractional catabolic rate. TRL-apoB-48 concentration was also significantly reduced after sleeve gastrectomy, explained by reduction in TRL-apoB-48 production rate (P<0.05). For gastric bypass, although TRL-apoB-100 concentration declined after surgery (P<0.01), without a significant decline in TRL-apoB-48, there was no significant change in either TRL-apoB-100 or TRL-apoB-48 production rate or fractional catabolic rate. The reduction in TRL-apoB-100 concentration was significantly associated with a reduction in plasma apoC-III in the pooled group of patients undergoing bariatric surgery. This is the first human lipoprotein kinetic study to explore the mechanism of improvement of TRL metabolism after bariatric surgery. These effects may contribute to the decrease of cardiovascular mortality after surgery. http://www.ClinicalTrials.gov. Unique identifier: NCT01277068. © 2014

  11. Lipoprotein Metabolism, Dyslipidemia and Nonalcoholic Fatty Liver Disease

    PubMed Central

    Cohen, David E.; Fisher, Edward A.

    2014-01-01

    Cardiovascular disease represents the most common cause of death in patients with non-alcoholic fatty liver disease (NAFLD). NAFLD patients exhibit an atherogenic dyslipidemia that is characterized by an increased plasma concentration of triglycerides, reduced concentration of high density lipoprotein (HDL) cholesterol, and low density lipoprotein (LDL) particles that are smaller and more dense than normal. The pathogenesis of NAFLD-associated atherogenic dyslipidemia is multifaceted, but many aspects are attributable to manifestations of insulin resistance. Here we review the structure, function and metabolism of lipoproteins, which are macromolecular particles of lipids and proteins that transport otherwise insoluble triglyceride and cholesterol molecules within the plasma. We provide a current explanation of the metabolic perturbations that are observed in the setting of insulin resistance. An improved understanding of the pathophysiology of atherogenic dyslipidemia would be expected to guide therapies aimed at reducing morbidity and mortality in NAFLD patients. PMID:24222095

  12. The affection of the disturbance of the hydrodynamics of blood in case of stress on pathological increase of level of low density lipoproteins in blood. The formation of cylindrical plaques, and their participation in the development of acute ischemic disorders of heart and brain.

    PubMed

    Rusanov, S E

    2017-09-01

    In this article is given the new insight about the affection of stress on the increase of level of low density lipoproteins (LDL) in the blood, which is connected with the disturbance of hydrodynamics in the bloodstream, the attention was paid to the cylindrical cholesterol plaque, and it's classification. The disturbance of hydrodynamics of blood under the stress leads to the formation of a cylindrical cholesterol plaque, which repeats the contour of the vessel, and leads to the ischemic disorders of the heart and brain. The cylindrical cholesterol plaque goes through several stages of development: friable, yielding, dense, old. In the case of destruction of friable, fresh cholesterol plaque, releases a big quantity of low-density lipoproteins. This leads to the pathological increase of level of LDL in the blood. In the case of long disturbance of hydrodynamics, occurs the formation of strong links between low-density lipoproteins. Yielding cholesterol plaque is formed. Further maturation of cylindrical cholesterol plaque, leads to it's densifying and damage. We may emphasize, that short periods of strong contraction and expansion of vessels lead to the increase of level of LDL in the blood. Self-dependent restoration of normal level of LDL in blood occurs in the case of restoration of pressure in the limits of numbers, which are specific for particular person, and which don't exceed the physiological standard. Among patients with long duration of stress, the duration of vasospasm increases. LDL, without having a possibility to crumble, begin to stick together and form the yielding cylindrical plaque. It is characterized by having of not so strong connection with the vascular wall, and maintains only at the expanse of iteration of the vascular wall, it has cylindrical shape, is elastic and yellow. The thickness and length of walls depends on the degree of cross-clamping during the time of formation of yielding cylindrical plaque. In the case of stopping of spasm

  13. Extended-release niacin for modifying the lipoprotein profile.

    PubMed

    Guyton, John R

    2004-06-01

    Niacin (nicotinic acid) favourably modifies all aspects of the lipoprotein profile; it raises high-density lipoprotein cholesterol (HDL-C) levels, lowers triglyceride, low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) levels and reduces atherogenic small, dense LDL particles. One large monotherapy trial and multiple trials of niacin in combination with other lipid-modifying drugs show remarkable consistency in the ability of niacin to improve angiographic and clinical outcomes. In practice, however, the use of regular, immediate-release niacin (niacin IR) has been limited by the side effect of flushing. Sustained-release (SR) formulations, developed in order to reduce flushing, were found to cause serious hepatotoxicity at varying frequencies. Extended-release niacin (niacin ER; Niaspan), Kos Pharmaceuticals, Inc.) is a prescription formulation of niacin, administered once-daily at bedtime. Niacin ER is as effective in modifying lipoprotein levels as an equal daily dose of niacin IR and it causes less flushing. In addition, niacin ER administered once-daily is not associated with the increased hepatotoxicity reported with SR formulations. Niacin ER has been studied extensively in combination therapy with statins, including lovastatin in a recently introduced combination tablet. Myopathy has not been a substantial problem in statin/niacin ER combination therapy. Finally, a study of niacin ER given to diabetic patients showed only mild trends towards increased glycosylated haemoglobin concentrations and a need for additional antidiabetic medication. Thus, niacin ER represents an effective and safe option in the management of low levels of HDL-C and other lipoprotein abnormalities in a variety of settings.

  14. [Lipids, lipoproteins, arterial accidents and oral contraceptives].

    PubMed

    Bakir, R; Hilliquin, P

    1986-01-01

    This work reviews lipoprotein metabolism and relationships to atherosclerosis, examines the nature of arterial accidents and lipid modifications that occur with oral contraceptive (OC) use, and assesses the practical consequences for OC prescription. Cholesterol, triglycerides, and phospholipids are not soluble in aqueous milieus, and their transport in plasma is provided by macromolecules comprising a protein part and a lipid part. 5 types of these lipoproteins are distinguished by their relative richness in lipids and protein and by the nature of their proteins. The chylomicrons carry exogenous triglycerides to the peripheral tissues and cholesterol of dietary origin to the liver. Very low density lipoprotein (VLDL) cholesterol is secreted by the liver and transports triglycerides and cholesterol of endogenous origin. Low denisty lipoprotein (LDL) cholesterol originates in the degradation of VLDL cholesterol and transports cholesterol to the cells. High density lipoprotein (HDL) cholesterol is secreted by the liver and intestines or formed in the course of degradation of chylomicrons and VLDL cholesterol. Its role is to carry excess cholesterol in the peripheral tissues to the liver for elimination in the bile. Cholesterol thus follows 2 different pathways in the body: a path from the liver to the peripheral cells, whose markers are LDL and VLDL cholesterol and the plasma apoprotein B, and a path of return of excess cholesterol from the tissues and especially the arteries to the liver, marked by HDL cholesterol and the plasma apoprotein A. Only a proper balance between the 2 flows can prevent an excess of cholesterol in the arteries and the consequent constitution of atherosclerotic lesions. LDL and to a lesser extent VLDL cholesterol are strongly and positively correlated to atherogenic risk, while HDL cholesterol is negatively correlated to risk, independently of other risk factors. Arterial accidents occurring with OC use do not seem to be atheromatous in

  15. Lipoprotein apheresis: present and future uses.

    PubMed

    Moriarty, Patrick M

    2015-12-01

    For the past 40 years, apheresis, in particular, lipoprotein apheresis, has been the therapy of choice to lower LDL-C for familial hypercholesterolemia patients with uncontrolled dyslipidemia and cardiovascular disease. With the advent of recent and future lipid-modifying agents and their ability to lower LDL-C, the question arises on what will be the future of lipoprotein apheresis. Lipoprotein apheresis lowers not only plasma levels of apolipoprotein B lipoproteins but also markers of vascular inflammation and blood rheology. Other vascular diseases, not necessarily associated with familial hypercholesterolemia, such as nephrotic syndrome and peripheral arterial disease have profited from lipoprotein apheresis therapy. In 2013, the Food and Drug Administration approved lipoprotein apheresis therapy for patients with focal segmental glomerulosclerosis. Since 2010, the German healthcare ministry has approved lipoprotein apheresis therapy for patients with an elevated lipoprotein(a) and ongoing cardiovascular disease irrespective of LDL-C levels. Recent and future lipid-modifying therapies will most likely reduce the practice of lipoprotein apheresis therapy for familial hypercholesterolemia patients. Future implications for lipoprotein apheresis will involve vascular diseases that are at present lacking clinically effective therapy, whereas acute and chronic reductions of lipids, vascular inflammation, and/or rheology may improve the clinical outcome.

  16. Lipoprotein metabolism differs between Marek's disease susceptible and resistant chickens.

    PubMed

    Yuan, P; Yu, Y; Luo, J; Tian, F; Zhang, H; Chang, S; Ramachandran, R; Zhang, L; Song, J

    2012-10-01

    Marek's disease (MD) is a lymphoproliferative disease of chickens caused by MD virus and has an important impact on the poultry industry worldwide. There have been reports showing different physiological characteristics between MD susceptible and resistant chickens. However, little is known about whether there are differences in lipid metabolism between MD susceptible and resistant lines of chickens. In this study, we examined the BW and the weight of tissues (abdominal fat, breast muscle with bone, leg muscle with bone, liver, and heart), the lipoprotein-cholesterol concentrations and distributions, and the plasma and tissue levels of adiponectin and its receptors in the highly resistant and susceptible lines during chicken growth. Our data showed that the increase in total cholesterol during growth was mainly due to the elevation of cholesterol in the low-density/very low-density lipoprotein fraction in MD susceptible chickens, whereas the increase of total cholesterol was mainly attributable to the increase in high-density lipoprotein-cholesterol in MD resistant chickens. Meanwhile, the MD resistant line appeared to have increased plasma adiponectin levels compared with MD susceptible chickens during growth. Taken together, our data suggested that lipoprotein-cholesterol and adiponectin metabolism are different between MD susceptible and resistant chickens.

  17. Influence of medium components on the expression of recombinant lipoproteins in Escherichia coli.

    PubMed

    Tseng, Chi-Ling; Leng, Chih-Hsiang

    2012-02-01

    Bacterial lipoproteins are crucial antigens for protective immunity against bacterial pathogens. Expression of exogenous lipoproteins in Escherichia coli at high levels is thought to be an extremely difficult endeavor because it frequently results in incomplete or absent lipid modification. Previously, we identified a fusion sequence (D1) from a Neisseria meningitidis lipoprotein that induced a non-lipidated protein, E3 (the domain III of the dengue virus envelope protein), to become lipidated. However, without optimizing the growth conditions, some of the D1-fusion proteins were not lipidated. Here, we report the influence of medium components on the expression of recombinant lipoproteins in E. coli. For high-level expression of mature lipoproteins in the C43 (DE3) strain, M9 medium was better than M63 and the rich medium. Furthermore, we analyzed the influence of other media factors (including nitrogen and carbon sources, phosphate, ferrous ions, calcium, magnesium, and pH) on the levels of lipoprotein expression. The results showed that excess nitrogen sources and phosphate in M9 medium could increase the amount of immature lipoproteins, and glucose was a better carbon source than glycerol for expressing mature lipoproteins. We also found that lipoproteins tended to be completely processed in the alkaline environment, even in the nutrient-rich medium. Additional constructs expressing different immunogens or lipid signal peptides as targets were also utilized, demonstrating that these targets could be expressed as completely mature lipoproteins in the M9 medium but not in the rich medium. Our results provide the useful information for expressing mature exogenous lipoproteins in E. coli.

  18. Acute alcohol consumption downregulates lipoprotein lipase activity in vivo.

    PubMed

    Zemánková, Kateřina; Makoveichuk, Elena; Vlasáková, Zuzana; Olivecrona, Gunilla; Kovář, Jan

    2015-11-01

    Acute alcohol consumption can induce hypertriglyceridemia. Such an effect could be explained in part by the influence of alcohol on lipoprotein lipase (LPL) - the key enzyme responsible for triglyceride hydrolysis in circulation. Therefore, we have studied the effects of acute moderate alcohol consumption on LPL activity and on the concentrations of angiopoietin-like proteins 3 and 4 (ANGPTL3 and ANGPTL4), which are known to inhibit LPL. Two experiments were carried out in 8 healthy volunteers. They received 25 g of alcohol (vodka) in one experiment and water in the other (control). The in vivo function of LPL was estimated using intravenous fat tolerance tests (IVFTT) carried out before, 2 and 4 hours after alcohol administration. At the end of each experiment, LPL activity and mass were measured in post-heparin plasma (PHP). The concentrations of ANGPTL3 and ANGPTL4 in blood were measured before alcohol consumption and at the end of the experiments. LPL activity, as estimated using the IVFTT, was reduced by 25% and 24% two and four hours after the administration of alcohol, respectively, and was not affected in the control experiment. At the end of the experiment, LPL activity in PHP was 23% lower after alcohol consumption than in the controls. The concentrations of ANGPTL3 and ANGPTL4 had dropped to 67% and 86% of baseline values, respectively, at 280 min after alcohol consumption. These levels were not affected in the control experiment. The levels of ANGPTL4 but not those of ANGPTL3 were increased in PHP compared to both baseline values and values at 280 min. The capacity for triglyceride clearance seemed to be acutely reduced by alcohol consumption and the effect persisted for several hours. The levels of LPL activity in PHP were reduced to a similar extent. This reduction in LPL activity could not be explained by the changes in the levels of ANGPTL3 or ANGPTL4, which both decreased. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    PubMed Central

    Heuck, Claus-Chr.

    2011-01-01

    Polyacrylate (PAA) adsorbents selectively bind low density lipoproteins (LDL) from human plasma and blood, whereas very low density lipoproteins (VLDL) are only minimally adsorbed. The adsorption of cholesterol-rich lipoproteins to PAA adsorbents is related to the molecular weight (mw) of the polyanion ligand. Ca++ and Mg++ inhibit the binding of LDL to PAA adsorbents. The chemical composition of the organic hardgels of the adsorbents does not have an influence on adsorption. The selective adsorption of LDL to PAA adsorbents can be explained to result from their low negative surface charge density and the specific colloid-chemical properties of the surface-bound PAA, which do not prevent LDL from binding to charge-like domains of the ligand. By contrast, VLDL and high density lipoproteins (HDL) are repelled from the adsorbents due to their higher negative surface charge density. PMID:21289994

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

    PubMed

    Heuck, Claus-Chr

    2011-01-24

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

  1. Leukocyte activation by triglyceride-rich lipoproteins.

    PubMed

    Alipour, Arash; van Oostrom, Antonie J H H M; Izraeljan, Alisa; Verseyden, Caroline; Collins, Jennifer M; Frayn, Keith N; Plokker, Thijs W M; Elte, Jan Willem F; Castro Cabezas, Manuel

    2008-04-01

    Postprandial lipemia has been linked to atherosclerosis and inflammation. Because leukocyte activation is obligatory for atherogenesis, leukocyte activation by triglyceride-rich lipoproteins (TRLs) was investigated. The expression of CD11b and CD66b after incubation with glucose and native and artificial TRLs (NTRL and ATRL) in vivo and in vitro was evaluated by flowcytometry. Oral fat loading tests showed an increased expression of CD11b on monocytes and neutrophils and CD66b on neutrophils. In 11 volunteers, postprandial leukocytes became enriched with meal-derived fatty acids ([1-(13)C]16:0) suggesting uptake of exogenous fat. ApoB binding on leukocytes measured by flowcytometry in 65 subjects was highest on neutrophils and monocytes suggesting adherence of apoB-containing lipoproteins. Physiological concentrations of TRLs showed 62% increased neutrophil CD11b and a dose-dependent increased monocyte CD11b up to 84% in vitro. Incubations with lipid emulsions in the hypertriglyceridemic range showed a 5-fold increased monocyte CD11b expression, which was higher than the positive control (fMLP), and a dose-dependent 2- to 3-fold increased neutrophil CD11b and CD66b. The oxidative scavenger DMTU decreased the neutrophil CD66b expression by 36%. Acute hypertriglyceridemia is a leukocyte activator most likely by direct interaction between TRLs and leukocytes and uptake of fatty acids. TG-mediated leukocyte activation is an alternative proinflammatory and proatherogenic mechanism of hypertriglyceridemia in part associated to the generation of oxidative stress.

  2. The impact of the transmission dynamics of the HIV/AIDS epidemic on sexual behaviour: a new hypothesis to explain recent increases in risk taking-behaviour among men who have sex with men.

    PubMed

    Boily, Marie-Claude; Godin, G; Hogben, M; Sherr, L; Bastos, F I

    2005-01-01

    Increases in sexually transmitted infections and related high-risk behaviours have been reported among men who have sex with men (MSM) in industrialised countries when effective antiretroviral therapy against HIV infection has become widely available, in the mid-nineties. The reasons for these increases are not fully understood and often conflicting. Prevention fatigue, relapses to unsafe sex, as well as optimism toward the risk of developing AIDS among people living with HIV are not unique to the era of antiretroviral therapy (ART). This has led researchers to highlight the need to investigate other potential reasons that could explain the increase in high-risk taking following the ART introduction. We put forward the hypothesis that the change in the transmission dynamics of the HIV/AIDS epidemic before and after the introduction of ART has contributed to this change in high-risk behaviour. It is suggested that a decline in sexual risk activities has occurred at the population-level following the initial spread of the HIV/AIDS epidemic because AIDS mortality and severe morbidity disproportionately depleted the pool of high-risk taking individuals. As a result, non-volitional changes may have occurred at the individual-level over time because the depletion of this pool of high-risk individuals made it more difficult for the remaining high-risk taking individuals to find partners to engage in risky sex with. Following its introduction, ART has facilitated the differential replenishment of the pool of individuals willing to engage in high-risk taking behaviours because ART reduces AIDS mortality, and morbidity. Consequently, high-risk taking individuals who had previously reduced their level of risky sex non-volitionally (i.e., as a result of the reduced availability of high-risk partners) were able to resume their initial high-risk practices as the pool of high-risk taking individuals replenished over time. Thus, a fraction of the recently reported increase in high

  3. A More Flexible Lipoprotein Sorting Pathway

    PubMed Central

    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

  4. Recent advances in physiological lipoprotein metabolism.

    PubMed

    Ramasamy, Indra

    2014-12-01

    Research into lipoprotein metabolism has developed because understanding lipoprotein metabolism has important clinical indications. Lipoproteins are risk factors for cardiovascular disease. Recent advances include the identification of factors in the synthesis and secretion of triglyceride rich lipoproteins, chylomicrons (CM) and very low density lipoproteins (VLDL). These included the identification of microsomal transfer protein, the cotranslational targeting of apoproteinB (apoB) for degradation regulated by the availability of lipids, and the characterization of transport vesicles transporting primordial apoB containing particles to the Golgi. The lipase maturation factor 1, glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 and an angiopoietin-like protein play a role in lipoprotein lipase (LPL)-mediated hydrolysis of secreted CMs and VLDL so that the right amount of fatty acid is delivered to the right tissue at the right time. Expression of the low density lipoprotein (LDL) receptor is regulated at both transcriptional and post-transcriptional level. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has a pivotal role in the degradation of LDL receptor. Plasma remnant lipoproteins bind to specific receptors in the liver, the LDL receptor, VLDL receptor and LDL receptor-like proteins prior to removal from the plasma. Reverse cholesterol transport occurs when lipid free apoAI recruits cholesterol and phospholipid to assemble high density lipoprotein (HDL) particles. The discovery of ABC transporters (ABCA1 and ABCG1) and scavenger receptor class B type I (SR-BI) provided further information on the biogenesis of HDL. In humans HDL-cholesterol can be returned to the liver either by direct uptake by SR-BI or through cholesteryl ester transfer protein exchange of cholesteryl ester for triglycerides in apoB lipoproteins, followed by hepatic uptake of apoB containing particles. Cholesterol content in cells is regulated by several

  5. Nanotechnology for Synthetic High Density Lipoproteins

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    1996-04-01

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

  7. [Protective role of high density lipoproteins in sepsis: basic issues and clinical implications].

    PubMed

    Contreras-Duarte, Susana; Varas, Pablo; Awad, Fernanda; Busso, Dolores; Rigotti, Attilio

    2014-02-01

    High density lipoproteins (HDL) are responsible of reverse cholesterol transport and play an important antiatherogenic role. In recent years, several studies suggest that HDL have additional functions, including a possible anti-inflammatory activity in infectious conditions. Furthermore, available evidence indicates that the presence of lipopolysaccharide (LPS) within the circulation during infectious states induced by gram-negative bacteria may be involved in the decrease in HDL cholesterol levels and changes in lipoprotein composition, which have been associated with a higher mortality due to sepsis in animal models and in humans. In this article, we review this subject and also discuss possible mechanisms that explain the positive impact achieved by native HDL, reconstituted HDL, or HDL apolipoprotein peptides on the inflammatory response and mortality in models of endotoxemia. In this regard, it has been proposed that one of the mechanisms by which HDL protect against sepsis may be mediated by its binding ability and/or neutralizing capacity on LPS, avoiding an excessive response of the immune system. Thus, increasing blood levels of HDL and/or parenteral HDL administration may represent a new anti-inflammatory tool for managing septic states in humans.

  8. Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice.

    PubMed Central

    Harris, H W; Grunfeld, C; Feingold, K R; Rapp, J H

    1990-01-01

    Endotoxemia stimulates many physiologic responses including disturbances in lipid metabolism. We hypothesized that this lipemia may be part of a defensive mechanism by which the body combats the toxic effects of circulating endotoxin. We tested the effects of mixtures of endotoxin, lipoproteins, and lipoprotein-free plasma and determined the ability of varying concentrations of human very low density lipoproteins (VLDL) and chylomicrons, as well as low density lipoproteins (LDL) and high density lipoproteins (HDL), and of the synthetic lipid emulsion SOYACAL to prevent endotoxin-induced death in mice. This study demonstrates that the triglyceride-rich VLDL and chylomicrons, as well as cholesterol-rich LDL and HDL, and cholesterol-free SOYACAL can protect against endotoxin-induced death. Protection required small amounts of lipoprotein-free plasma, and depended on the incubation time and the concentration of lipoprotein lipid. Despite stringent techniques to prevent exogenous endotoxin contamination eight of ten duplicate VLDL preparations contained endotoxin (5,755 +/- 3,514 ng endotoxin/mg triglyceride, mean +/- SEM) making the isolation of endotoxin-free VLDL difficult. In contrast, simultaneous preparations of LDL and HDL were relatively free of endotoxin contamination (3 +/- 3 and 320 +/- 319 ng/mg total cholesterol, respectively), suggesting that the contamination of VLDL occurs in vivo and not during the isolation procedure. These observations suggest a possible role for increased triglyceride-rich lipoproteins in the host's defense against endotoxemia and infection. Images PMID:2394827

  9. Serum amyloid A is found on ApoB-containing lipoproteins in obese humans with diabetes.

    PubMed

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

    2013-05-01

    In murine models of obesity/diabetes, there is an increase in plasma serum amyloid A (SAA) levels along with redistribution of SAA from high-density lipoprotein (HDL) to apolipoprotein B (apoB)-containing lipoprotein particles, namely, low-density lipoprotein and very low-density lipoprotein. The goal of this study was to determine if obesity is associated with similar SAA lipoprotein redistribution in humans. Three groups of obese individuals were recruited from a weight loss clinic: healthy obese (n = 14), metabolic syndrome (MetS) obese (n = 8), and obese with type 2 diabetes (n = 6). Plasma was separated into lipoprotein fractions by fast protein liquid chromatography, and SAA was measured in lipid fractions using enzyme-linked immunosorbent assay and Western blotting. Only the obese diabetic group had SAA detectable in apoB-containing lipoproteins, and SAA reverted back to HDL with active weight loss. In human subjects, SAA is found in apoB-containing lipoprotein particles only in obese subjects with type 2 diabetes, but not in healthy obese or obese subjects with MetS. Copyright © 2012 The Obesity Society.

  10. Lipoprotein Changes in HIV-Infected Antiretroviral-Naïve Individuals after Starting Antiretroviral Therapy: ACTG Study A5152s Stein: Lipoprotein Changes on Antiretroviral Therapy.

    PubMed

    Stein, James H; Komarow, Lauren; Cotter, Bruno R; Currier, Judith S; Dubé, Michael P; Fichtenbaum, Carl J; Gerschenson, Mariana; Mitchell, Carol K C; Murphy, Robert L; Squires, Kathleen; Parker, Robert A; Torriani, Francesca J

    2008-12-01

    BACKGROUND: Dyslipidemia is a frequent complication of antiretroviral therapy (ART) for patients with human immunodeficiency virus infection (HIV). The effects of ART on lipoproteins are less well-understood, and have not been investigated in a prospective study where assignment to ART is randomized. OBJECTIVE: To evaluate the effects of three class-sparing ART regimens on lipids and lipoproteins. METHODS: This was a substudy of a prospective, multicenter study treatment-naïve HIV-infected individuals randomly assigned to receive a regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + the non-nucleoside reverse transcriptase inhibitor efavirenz, NRTIs + the protease inhibitor lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. Lipoproteins were measured by nuclear magnetic resonance spectroscopy. RESULTS: Among the 82 participants, total and small low-density lipoprotein concentrations increased (median, interquartile range) by 152 (-49 - +407, p<0.01) and 130 (-98 - +417, p<0.01) nmol/L, respectively, especially in the arms containing lopinavir/ritonavir (p(KW)<0.04). Very low-density lipoproteins also increased (p<0.01), with a larger increase in the arms that contained lopinavir/ritonavir (p=0.022). High-density lipoproteins increased by 6.0 nmol/L (2.8 - 10.4, p<0.01), but differences between arms were not significant (p(KW)=0.069). Changes were not related to changes in markers of insulin/glucose metabolism. CONCLUSIONS: Total and small low-density lipoprotein concentrations increased, especially in the arms containing lopinavir/ritonavir, as did increases in total very low-density lipoproteins. Adverse changes were especially prominent in the arm with efavirenz + lopinavir/ritonavir.

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

    PubMed

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

    1995-04-01

    detrimental lipid profile. Lipoprotein[a] levels were identical among the regions surveyed (mean: 11-15 mg/dl) and displayed the typical distribution with an increased number of individuals with low levels. The 90th percentile value for lipoprotein[a] was about 30 mg/dl for both men and women. Smoking, a major risk factor for heart disease, was very prevalent in the Turkish population, especially in men (50-70% smokers) and women in urban areas (30-40% smokers). Hypertension, defined as a systolic pressure > 140 or a diastolic pressure of > 90 occurred in approximately 17% and 26% of the men and women surveyed, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

  12. LIPOPROTEIN LIPASE RELEASES ESTERIFIED OXYLIPINS FROM VERY LOW-DENSITY LIPOPROTEINS.

    USDA-ARS?s Scientific Manuscript database

    Defects in lipoprotein metabolism alter the lipoprotein distribution of oxidized PUFAs, and we speculate that lipoprotein lipase (LpL) is a determinant in the release of VLDL-associated oxylipins. Here, using 12 wk old normolipidemic (lean) and hyperlipidemic (obese) Zucker-rats, we measured PUFA al...

  13. Low-Density Lipoprotein Apheresis

    PubMed Central

    2007-01-01

    are approximately 765 refractory HTZ FH patients in Ontario, of which 115 are diagnosed and 650 are undiagnosed. Drug therapy is less effective in HMZ FH patients since the effects of the majority of cholesterol-lowering drugs are mediated by the upregulation of LDL receptors, which are often absent or function poorly in HMZ FH patients. Some HMZ FH patients may still benefit from drug therapy, however this rarely reduces LDL-C levels to targeted levels. Existing Technology: Plasma Exchange An option currently available in Ontario for FH patients who do not respond to standard diet and drug therapy is plasma exchange (PE). Patients are treated with this lifelong therapy on a weekly or biweekly basis with concomitant drug therapy. Plasma exchange is nonspecific and eliminates virtually all plasma proteins such as albumin, immunoglobulins, coagulation factors, fibrinolytic factors and HDL-C, in addition to acutely lowering LDL-C by about 50%. Blood is removed from the patient, plasma is isolated, discarded and replaced with a substitution fluid. The substitution fluid and the remaining cellular components of the blood are then returned to the patient. The major limitation of PE is its nonspecificity. The removal of HDL-C prevents successful vascular remodeling of the areas stenosed by atherosclerosis. In addition, there is an increased susceptibility to infections, and costs are incurred by the need for replacement fluid. Adverse events can be expected to occur in 12% of procedures. Other Alternatives Surgical alternatives for FH patients include portocaval shunt, ileal bypass and liver transplantation. However, these are risky procedures and are associated with a high morbidity rate. Results with gene therapy are not convincing to date. The Technology Being Reviewed: LDL Apheresis An alternative to PE is LDL apheresis. Unlike PE, LDL apheresis is a selective treatment that removes LDL-C and other atherogenic lipoproteins from the blood while minimally impacting other

  14. Simultaneous labeling of lipoprotein intracellular trafficking in pigeon monocyte-derived macrophages.

    PubMed Central

    Jones, N. L.

    1997-01-01

    Macrophage foam cell formation resulting from the accumulation of cholesterol and cholesterol esters derived from plasma lipoproteins is important for progression of atherosclerosis. Hypothetically, intracellular processing of lipoproteins that stimulate foam cell formation differs from processing of lipoproteins that do not. To test this, we examined simultaneous subcellular trafficking of lipoproteins in pigeon monocyte-derived macrophages. Pigeon beta-very-low-density lipoprotein (beta-VLDL), low-density lipoprotein (LDL), and acetylated low-density lipoprotein (Ac-LDL), differentially labeled with colloidal gold, were added in pairs to cells at 4 degrees C for 2 hours before uptake at 18 degrees C, 22 degrees C, or 37 degrees C for either 30 minutes or 2 hours. The colloidal gold distribution and percent co-labeling as observed by transmission electron microscopy were determined for organelles of the endocytic pathway. Incubations at 18 degrees C and 22 degrees C blocked lipoprotein trafficking to lysosomes. Incubation at 18 degrees C increased the percent distribution of lipoproteins in the endocytic pathway up to the early cisternal endosomes. Incubations at 22 degrees C resulted in a greater distribution of lipoproteins in the spherical late endosomes and late endosomal-prelysosomal tubular reticular compartment. The distribution in the endocytic pathway was a factor of time and temperature rather than lipoprotein type. The percentage of co-labeling of organelles for the three pairs of lipoproteins examined, Ac-LDL plus beta-VLDL, LDL plus beta-VLDL, and LDL plus Ac-LDL, was similar. Fewer noncoated and clathrin-coated pits and vesicles were co-labeled (average of 6%, maximum of 17%) than the rest of the endocytic pathway, early cisternal endosomes, spherical late endosomes, late endosomal-prelysosomal tubuloreticular compartment, and spherical lysosomes (average of 36%, maximum of 47%). The 36% of co-labeled later endocytic organelles contained an average

  15. Effect of Helicobacter pylori eradication on high-density lipoprotein cholesterol.

    PubMed

    Scharnagl, Hubert; Kist, Manfred; Grawitz, Andrea Busse; Koenig, Wolfgang; Wieland, Heinrich; März, Winfried

    2004-01-15

    We examined the effect of Helicobacter pylori (H. pylori) eradication on lipids and apolipoproteins in 87 patients with duodenal ulcers. A significant increase was observed in high-density lipoprotein (HDL) cholesterol (+24.7%, p <0.001), apolipoprotein AI (+9.0%, p <0.001), and apolipoprotein AII (+11.7%, p <0.001) after eradication. Minor increases occurred in total cholesterol, triglycerides, and apolipoprotein B, whereas low-density lipoprotein cholesterol remained unchanged. Our results suggest that chronic H. pylori infection reduces plasma levels of HDL cholesterol and that eradication improves the lipoprotein pattern.

  16. Effect of proteolysis of low-density serum lipoproteins on their interaction with macrophages

    SciTech Connect

    Karmanskii, I.M.; Kovaleva, G.G.; Viktorova, L.N.; Shpikiter, V.O.

    1987-01-01

    The authors previously postulated, on the basis of changes observed in the structural stability of low-density lipoproteins during treatment with pepsin or aortic cathepsin, that enzymatic modifications may lead to potentiation of the atherogenic properties of the lipoproteins. They also reported that treatment of lipoproteins with trypsin causes an increase in their binding with aortic glycosaminoglycans and to increased degradation by fibroblasts of patients with hereditary hypercholesterolemia. Limited proteolysis of lipoproteins with pepsin facilitated their binding with fibronectin. In this paper the authors investigate the uptake and degradation of low-density lipoproteins by macrophages after their limited hydrolysis by pepsin, an analog of tissue cathepsin D. The lipoproteins were isolated from the serum of healthy blood donors by ultracentrifugation. Iodination of the proteins with I 125 was carried out by the iodine monochloride method. Uptake and retention of the labelled lipoprotein were measured with a gamma counter. The increased uptake of the proteins, partially hydrolized by pepsin, was accompanied by their more intense degradation by macrophages.

  17. Intestinal Lipid Absorption and Lipoprotein Formation

    PubMed Central

    Hussain, M. Mahmood

    2014-01-01

    Purpose of review The purpose of this review is to summarize evidence for the presence of two pathways of lipid absorption and their regulation. Recent findings Lipid absorption involves hydrolysis of dietary fat in the lumen of the intestine followed by the uptake of hydrolyzed products by enterocytes. Lipids are re-synthesized in the endoplasmic reticulum and are either secreted with chylomicrons and high density lipoproteins or stored as cytoplasmic lipid droplets. Lipids in the droplets are hydrolyzed and are secreted at a later time. Secretion of lipids by the chylomicron and HDL pathways are critically dependent on MTP and ABCA1, respectively, and are regulated independently. Gene ablation studies showed that MTP function and chylomicron assembly is essential for the absorption of triglyceride and retinyl esters. Ablation of MTP abolishes triglyceride absorption and results in massive triglyceride accumulation in enterocytes. Although majority of phospholipid, cholesterol and vitamin E are absorbed through the chylomicron pathway, a significant amount of these lipids are also absorbed via the HDL pathway. Chylomicron assembly and secretion is increased by the enhanced availability of fatty acids, whereas HDL pathway is upregulated by LXR agonists. Intestinal insulin resistance increases chylomicron and might reduce HDL production. Summary Triglycerides are exclusively transported via the chylomicron pathway and this process is critically dependent on MTP. Besides chylomicrons, absorption of phospholipids, free cholesterol, retinol, and vitamin E also involves high density lipoproteins. These two pathways are complementary and are regulated independently. They may be targeted to lower lipid absorption in order to control hyperlipidemia, obesity, metabolic syndrome, steatosis, insulin resistance, atherosclerosis and other disorders. PMID:24751933

  18. Lipoprotein binding to cultured human hepatoma cells.

    PubMed Central

    Krempler, F; Kostner, G M; Friedl, W; Paulweber, B; Bauer, H; Sandhofer, F

    1987-01-01

    Binding of various 125I-lipoproteins to hepatic receptors was studied on cultured human hepatoma cells (Hep G2). Chylomicrons, isolated from a chylothorax, chylomicron remnants, hypertriglyceridemic very low-density lipoproteins, normotriglyceridemic very low-density lipoproteins (NTG-VLDL), their remnants, low-density lipoproteins (LDL), and HDL-E (an Apo E-rich high-density lipoprotein isolated from the plasma of a patient with primary biliary cirrhosis) were bound by high-affinity receptors. Chylomicron remnants and HDL-E were bound with the highest affinity. The results, obtained from competitive binding experiments, are consistent with the existence of two distinct receptors on Hep G2 cells: (a) a remnant receptor capable of high-affinity binding of triglyceride-rich lipoproteins and HDL-E, but not of Apo E free LDL, and (b) a LDL receptor capable of high-affinity binding of LDL, NTG-VLDL, and HDL-E. Specific binding of Apo E-free LDL was completely abolished in the presence of 3 mM EDTA, indicating that binding to the LDL receptor is calcium dependent. Specific binding of chylomicron remnants was not inhibited by the presence of even 10 mM EDTA. Preincubation of the Hep G2 cells in lipoprotein-containing medium resulted in complete suppression of LDL receptors but did not affect the remnant receptors. Hep G2 cells seem to be a suitable model for the study of hepatic receptors for lipoprotein in man. Images PMID:3038957

  19. Lipoproteins in bacteria: structures and biosynthetic pathways.

    PubMed

    Nakayama, Hiroshi; Kurokawa, Kenji; Lee, Bok Luel

    2012-12-01

    Bacterial lipoproteins are characterized by the presence of a conserved N-terminal lipid-modified cysteine residue that allows the hydrophilic protein to anchor onto bacterial cell membranes. These proteins play important roles in a wide variety of bacterial physiological processes, including virulence, and induce innate immune reactions by functioning as ligands of the mammalian Toll-like receptor 2. We review recent advances in our understanding of bacterial lipoprotein structure, biosynthesis and structure-function relationships between bacterial lipoproteins and Toll-like receptor 2. Notably, 40 years after the first report of the triacyl structure of Braun's lipoprotein in Escherichia coli, recent intensive MS-based analyses have led to the discovery of three new lipidated structures of lipoproteins in monoderm bacteria: the lyso, N-acetyl and peptidyl forms. Moreover, the bacterial lipoprotein structure is considered to be constant in each bacterium; however, lipoprotein structures in Staphylococcus aureus vary between the diacyl and triacyl forms depending on the environmental conditions. Thus, the lipidation state of bacterial lipoproteins, particularly in monoderm bacteria, is more complex than previously assumed. © 2012 The Authors Journal compilation © 2012 FEBS.

  20. Computational studies of plasma lipoprotein lipids.

    PubMed

    Pan, Lurong; Segrest, Jere P

    2016-10-01

    Plasma lipoproteins are macromolecular assemblies of proteins and lipids found in the blood. The lipid components of lipoproteins are amphipathic lipids such as phospholipids (PLs), and unesterified cholesterols (UCs) and hydrophobic lipids such as cholesteryl esters (CEs) and triglycerides (TGs). Since lipoproteins are soft matter supramolecular assemblies easily deformable by thermal fluctuations and they also exist in varying densities and protein/lipid components, a detailed understanding of their structure/function is experimentally difficult. Molecular dynamics (MD) simulation has emerged as a particularly promising way to explore the structure and dynamics of lipoproteins. The purpose of this review is to survey the current status of computational studies of the lipid components of the lipoproteins. Computational studies aim to explore three levels of complexity for the 3-dimensional structural dynamics of lipoproteins at various metabolic stages: (i) lipoprotein particles consist of protein with minimal lipid; (ii) lipoprotein particles consist of PL-rich discoidal bilayer-like lipid particles; (iii) mature circulating lipoprotein particles consist of CE-rich or TG-rich spheroidal lipid-droplet-like particles. Due to energy barriers involved in conversion between these species, other biomolecules also participate in lipoprotein biological assembly. For example: (i) lipid-poor apolipoprotein A-I (apoA-I) interacts with ATP-binding cassette transporter A1 (ABCA1) to produce nascent discoidal high density lipoprotein (dHDL) particles; (ii) lecithin-cholesterol acyltransferase (LCAT) mediates the conversion of UC to CE in dHDL, driving spheroidal HDL (sHDL) formation; (iii) transfer proteins, cholesterol ester transfer protein (CETP) and phospholipid transfer protein (PLTP), transfer both CE and TG and PL, respectively, between lipoprotein particles. Computational studies have the potential to explore different lipoprotein particles at each metabolic stage in

  1. Lipoprotein lipase, LDL receptors and apo-lipoproteins in human fetal membranes at term.

    PubMed

    Huter, O; Wolf, H J; Schnetzer, A; Pfaller, K

    1997-11-01

    Ultrastructurally, all cells of human fetal membranes strongly exhibit a large amount of lipid deposits throughout pregnancy. Their origin and function is still unknown. The aim of this study was to investigate the localization of key components of lipid metabolism in this tissue. Using immunohistochemical techniques, the distribution of lipoprotein lipase (LPL), low density lipoprotein receptors (LDL receptors), and apo-lipoprotein B and E was investigated in 20 human fetal membranes at term. In addition, electron microscopy was used to study the intracellular localization of lipoprotein-sized particles. Amnionic epithelium and trophoblast cells reacted strongly for LPL. LDL receptors and apo-lipoproteins were present in amnionic epithelium and fibroblasts of the amnion. In none of the investigated cells were lipoprotein-sized particles identified. Similar results were obtained in all 20 cases. The findings indicate that lipoprotein from the amniotic fluid or from the maternal circulation may serve as substrate for lipids in human fetal membranes.

  2. Altered Serum Lipoprotein Profiles in Male and Female Power Lifters Ingesting Anabolic Steroids.

    ERIC Educational Resources Information Center

    Cohen, Jonathan C.; And Others

    1986-01-01

    Serum lipoprotein profiles were measured in nine male and three female weightlifters who were taking anabolic steroids. The profiles suggest that steriod users may face an increased risk of coronary artery disease. (Author/MT)

  3. Altered Serum Lipoprotein Profiles in Male and Female Power Lifters Ingesting Anabolic Steroids.

    ERIC Educational Resources Information Center

    Cohen, Jonathan C.; And Others

    1986-01-01

    Serum lipoprotein profiles were measured in nine male and three female weightlifters who were taking anabolic steroids. The profiles suggest that steriod users may face an increased risk of coronary artery disease. (Author/MT)

  4. The pathophysiology of intestinal lipoprotein production

    PubMed Central

    Giammanco, Antonina; Cefalù, Angelo B.; Noto, Davide; Averna, Maurizio R.

    2015-01-01

    Intestinal lipoprotein production is a multistep process, essential for the absorption of dietary fats and fat-soluble vitamins. Chylomicron assembly begins in the endoplasmic reticulum with the formation of primordial, phospholipids-rich particles that are then transported to the Golgi for secretion. Several classes of transporters play a role in the selective uptake and/or export of lipids through the villus enterocytes. Once secreted in the lymph stream, triglyceride-rich lipoproteins (TRLs) are metabolized by Lipoprotein lipase (LPL), which catalyzes the hydrolysis of triacylglycerols of very low density lipoproteins (VLDLs) and chylomicrons, thereby delivering free fatty acids to various tissues. Genetic mutations in the genes codifying for these proteins are responsible of different inherited disorders affecting chylomicron metabolism. This review focuses on the molecular pathways that modulate the uptake and the transport of lipoproteins of intestinal origin and it will highlight recent findings on TRLs assembly. PMID:25852563

  5. The iron-regulated staphylococcal lipoproteins.

    PubMed

    Sheldon, Jessica R; Heinrichs, David E

    2012-01-01

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

  6. 21 CFR 862.1475 - Lipoprotein test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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...

  7. 21 CFR 862.1475 - Lipoprotein test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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...

  8. 21 CFR 862.1475 - Lipoprotein test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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...

  9. 21 CFR 862.1475 - Lipoprotein test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 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...

  10. Advanced lipoprotein testing for cardiovascular diseases risk assessment: a review of the novel approaches in lipoprotein profiling.

    PubMed

    Clouet-Foraison, Noémie; Gaie-Levrel, Francois; Gillery, Philippe; Delatour, Vincent

    2017-08-28

    With the increasing prevalence of cardiovascular diseases (CVD) worldwide, finding reliable and clinically relevant biomarkers to predict acute cardiovascular events has been a major aim of the scientific and medical community. Improvements of the understanding of the pathophysiological pathways of the disease highlighted the major role of lipoprotein particles, and these past decades have seen the emergence of a number of new methodologies to separate, measure and quantitate lipoproteins. Those methods, also known as advanced lipoprotein testing methods (ALT), have gained acceptance in the field of CVD risk assessment and have proven their clinical relevance. In the context of worldwide standardization and harmonization of biological assays, efforts have been initiated toward standardization of ALT methods. However, the complexity of lipoprotein particles and the multiple approaches and methodologies reported to quantify them have rendered these initiatives a critical issue. In this context and to better understand these challenges, this review presents a summary of the major methods available for ALT with the aim to point out the major differences in terms of procedures and quantities actually measured and to discuss the resulting comparability issues.

  11. Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall: A Key Mechanism Distinguishing Susceptible From Resistant Sites.

    PubMed

    Steffensen, Lasse Bach; Mortensen, Martin Bødtker; Kjolby, Mads; Hagensen, Mette Kallestrup; Oxvig, Claus; Bentzon, Jacob Fog

    2015-09-01

    Atherosclerosis develops initially at branch points and in areas of high vessel curvature. Moreover, experiments in hypercholesterolemic mice have shown that the introduction of disturbed flow in straight, atherosclerosis-resistant arterial segments turns them highly atherosclerosis susceptible. Several biomechanical mechanisms have been proposed, but none has been demonstrated. In the present study, we examined whether a causal link exists between disturbed laminar flow and the ability of the arterial wall to retain lipoproteins. Lipoprotein retention was detected at natural predilection sites of the murine thoracic aorta 18 hours after infusion of fluorescently labeled low-density lipoprotein. To test for causality between blood flow and the ability of these areas to retain lipoproteins, we manipulated blood flow in the straight segment of the common carotid artery using a constrictive collar. Disturbed laminar flow did not affect low-density lipoprotein influx, but increased the ability of the artery wall to bind low-density lipoprotein. Concordantly, disturbed laminar flow led to differential expression of genes associated with phenotypic modulation of vascular smooth muscle cells, increased expression of proteoglycan core proteins associated with lipoprotein retention, and of enzymes responsible for chondroitin sulfate glycosaminoglycan synthesis and sulfation. Blood flow regulates genes associated with vascular smooth muscle cell phenotypic modulation, as well as the expression and post-translational modification of lipoprotein-binding proteoglycan core proteins, and the introduction of disturbed laminar flow vastly augments the ability of a previously resistant, straight arterial segment to retain lipoproteins. © 2015 American Heart Association, Inc.

  12. The expanding role of lipoprotein apheresis in the treatment of raised lipoprotein(a) in ischaemic heart disease and refractory angina

    PubMed Central

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

    2014-01-01

    It is increasingly recognised that lipoprotein(a) [Lp(a)], an inherited, genetically-determined form of LDL-cholesterol, is an independent cardiovascular risk factor and predictor of adverse cardiovascular outcomes. Lp(a) is felt to increase cardiovascular risk via its pro-thrombotic effect and by enhancing intimal lipoprotein deposition. Lipoprotein apheresis is currently the most effective treatment for raised Lp(a). There is a growing body of evidence suggesting that aggressively lowering raised Lp(a) may improve cardiovascular and clinical outcomes, although much more research is required in this field. Angina which is refractory to conventional medical therapy and revascularisation, is extremely challenging to manage. Treatment options for such patients remain very limited. We describe the case of a patient with refractory angina and raised lipoprotein(a) in whom aggressive reduction of Lp(a) with lipoprotein apheresis successfully ameliorated the progression of coronary stenosis and provided effective and durable relief of angina symptoms. In our centre, we are currently conducting a prospective, randomised controlled cross-over study of patients with refractory angina and raised Lp(a), randomised to undergoing lipoprotein apheresis or ‘sham’ apheresis with assessment of myocardial perfusion, carotid atherosclerosis, endothelial vascular function, thrombogenesis, oxidised phospholipids and their antibodies, exercise capacity, angina symptoms and quality of life at the beginning and end of treatment. PMID:25054114

  13. Lipoprotein composition and oxidative modification during therapy with gemfibrozil and lovastatin in patients with combined hyperlipidaemia

    PubMed Central

    Vázquez, M; Zambón, D; Hernández, Y; Adzet, T; Merlos, M; Ros, E; Laguna, J C

    1998-01-01

    Aims To evaluate the resistance to oxidation of human lipoproteins after hypolipidaemic therapy. Methods VLDL and LDL samples were obtained from patients with Familial Combined Hyperlipidaemia included in a randomized, double-blind, cross-over study, with 8 weeks of active treatment (gemfibrozil, 600 mg twice daily, or lovastatin, 40 mg daily) and a 4-week wash-out period. Oxidation related analytes after Cu-induced oxidation of VLDL and LDL have been investigated. Further, in order to relate possible changes in oxidative behaviour to lipoprotein composition, the proportion of the lipid species transported by lipoproteins (triglycerides, phospholipids, and cholesteryl esters), the molar composition of fatty acids for each lipoprotein lipid, and the content of antioxidant vitamins in plasma (vitamin C) and lipoproteins (vitamin E) have been studied. Results Both drugs reduced the plasma concentration of apo-B lipoproteins (−23% gemfibrozil, −26% lovastatin), but whereas lovastatin affected mainly LDL-cholesterol (−30%), gemfibrozil reduced triglycerides (−49%) and VLDL-cholesterol (−48%). Lovastatin treatment had no effect on the lipid and protein composition, the fatty acid profile, or the vitamin E content of either VLDL or LDL; likewise, lipoprotein oxidation markers (Cu-induced conjugated dienes, thiobarbituric acid reactive substances formation, and lysine residues) were similar before and after lovastatin treatment. Gemfibrozil therapy also had no effect on lipoprotein oxidation; nevertheless, it consistently: a) decreased the proportion of LDL-triglycerides (−32%), and b) increased the proportion (molar%) of 18:3 n-6 in VLDL triglycerides (+140%), phospholipids (+363%) and cholesteryl esters (+53%). Conclusions Based on these results, lovastatin and gemfibrozil do not adversely affect lipoprotein oxidation in patients with mixed dyslipidaemia. In the case of gemfibrozil, this occurs in spite of an increased proportion of some polyunsaturated fatty

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

    PubMed

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

    2001-05-01

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

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

    PubMed

    Smith, M B; Back, J F

    1975-05-22

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

  16. Characterization of biophysical properties of baboon lipoproteins: modulation by dietary fat and cholesterol

    SciTech Connect

    Babiak, J.

    1984-04-01

    The serum lipoproteins of baboons fed diets containing differing types and amounts of fat and varying amounts of cholesterol were examined by analytic ultracentrifugation, gradient gel electrophoresis, density gradient ultracentrifugation, sodium dodecyl sulfate-polyacrylamide electrophoresis, electron microscopy, and standard protein and lipid composition assays. These studies characterized the lipoproteins of the baboon, observed how concentrations and physical-chemical properties of the lipoproteins are modulated by dietary fat and cholesterol and described the suitability of the baboon as an animal model of human lipoprotein metabolism. Results indicate that baboon high density lipoproteins (HDL), though higher in total serum concentration than human HDL, are remarkably similar to human HDL. The concentration of baboon HDL is increased by dietary saturated fat but decreased by the addition of cholesterol. While serum concentrations of low density lipoproteins (LDL) tend to be lower in baboons, the physical-chemical properties of the LDL of baboons and humans are comparable. The LDL of both species contains apolipoprotein B as their major apolipoprotein and exhibit considerable polydispersity in particle size. LDL of both species consists of seven discrete subpopulations. The analytical and statistical data presented in this dissertation indicate that the baboon is a good model for studying the role of lipoproteins in the development of atherosclerosis. 125 references, 31 figures, 28 tables.

  17. Patients with Rheumatoid Arthritis Show Altered Lipoprotein Profiles with Dysfunctional High-Density Lipoproteins that Can Exacerbate Inflammatory and Atherogenic Process

    PubMed Central

    Kim, Jae-Yong; Lee, Eun-Young; Park, Jin Kyun; Song, Yeong Wook; Kim, Jae-Ryong; Cho, Kyung-Hyun

    2016-01-01

    Objective In order to identify putative biomarkers in lipoprotein, we compared lipid and lipoprotein properties between rheumatoid arthritis (RA) patients and control with similar age. Methods We analyzed four classes of lipoproteins (VLDL, LDL, HDL2, HDL3) from both male (n = 8, 69±4 year-old) and female (n = 25, 53±7 year-old) rheumatoid arthritis (RA) patients as well as controls with similar age (n = 13). Results Although RA group showed normal levels of total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, and glucose, however, the RA group showed significantly reduced high-density lipoprotein (HDL)-C level and ratio of HDL-C/TC. The RA group showed significantly elevated levels of blood triglyceride (TG), uric acid, and cholesteryl ester transfer protein (CETP) activity. The RA group also showed elevated levels of advanced glycated end (AGE) products in all lipoproteins and severe aggregation of apoA-I in HDL. As CETP activity and TG contents were 2-fold increased in HDL from RA group, paraoxonase activity was reduced upto 20%. Electron microscopy revealed that RA group showed much less HDL2 particle number than control. LDL from the RA group was severely oxidized and glycated with greater fragmentation of apo-B, especially in female group, it was more atherogenic via phagocytosis. Conclusion Lipoproteins from the RA patients showed severely altered structure with impaired functionality, which is very similar to that observed in coronary heart patients. These dysfunctional properties in lipoproteins from the RA patients might be associated with high incidence of cardiovascular events in RA patients. PMID:27736980

  18. Patients with Rheumatoid Arthritis Show Altered Lipoprotein Profiles with Dysfunctional High-Density Lipoproteins that Can Exacerbate Inflammatory and Atherogenic Process.

    PubMed

    Kim, Jae-Yong; Lee, Eun-Young; Park, Jin Kyun; Song, Yeong Wook; Kim, Jae-Ryong; Cho, Kyung-Hyun

    2016-01-01

    In order to identify putative biomarkers in lipoprotein, we compared lipid and lipoprotein properties between rheumatoid arthritis (RA) patients and control with similar age. We analyzed four classes of lipoproteins (VLDL, LDL, HDL2, HDL3) from both male (n = 8, 69±4 year-old) and female (n = 25, 53±7 year-old) rheumatoid arthritis (RA) patients as well as controls with similar age (n = 13). Although RA group showed normal levels of total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, and glucose, however, the RA group showed significantly reduced high-density lipoprotein (HDL)-C level and ratio of HDL-C/TC. The RA group showed significantly elevated levels of blood triglyceride (TG), uric acid, and cholesteryl ester transfer protein (CETP) activity. The RA group also showed elevated levels of advanced glycated end (AGE) products in all lipoproteins and severe aggregation of apoA-I in HDL. As CETP activity and TG contents were 2-fold increased in HDL from RA group, paraoxonase activity was reduced upto 20%. Electron microscopy revealed that RA group showed much less HDL2 particle number than control. LDL from the RA group was severely oxidized and glycated with greater fragmentation of apo-B, especially in female group, it was more atherogenic via phagocytosis. Lipoproteins from the RA patients showed severely altered structure with impaired functionality, which is very similar to that observed in coronary heart patients. These dysfunctional properties in lipoproteins from the RA patients might be associated with high incidence of cardiovascular events in RA patients.

  19. Hydrolysis of bovine and caprine milk fat globules by lipoprotein lipase. Effects of heparin and skim milk on lipase distribution and on lipolysis

    SciTech Connect

    Sundheim, G.; Bengtsson-Olivecrona, G.

    1987-12-01

    Heparin can dissociate lipoprotein lipase from casein micelles, and addition of heparin enhances lipolysis in bovine but not in caprine milk. Heparin shortened the lag-time for binding of lipoprotein lipase to milk fat globules and for lipolysis. Heparin counteracted the inhibitory effects of skim milk on binding of lipase and on lipolysis. Heparin stimulated lipolysis in all bovine milk samples when added before cooling and in spontaneously lipolytic milk samples also when added after cooling. Heparin enhanced lipolysis of isolated milk fat globules. Hence, its effect is not solely due to dissociation of lipoprotein lipase from the casein micelles. Cooling of goat milk caused more marked changes in the distribution of lipase than cooling of bovine milk; the fraction of added /sup 125/I-labeled lipase that bound to cream increased from about 8 to 60%. In addition, caprine skim milk caused less inhibition of lipolysis than bovine skim milk. These observations provide an explanation for the high degree of cold storage lipolysis in goat milk. Heparin had only small effects on the distribution of lipoprotein lipase in caprine milk, which explains why heparin has so little effect on lipolysis in caprine milk. The distribution of /sup 35/S-labeled heparin in bovine milk was studied. In warm milk less than 10% bound to the cream fraction, but when milk was cooled, binding of heparin to cream increased to 45%. These results suggest that there exists in the skim fraction a relatively small amount of a heparin-binding protein, which on cooling of milk adsorbs to the milk fat, or suggests that cooling induces a conformational change in a membrane protein such that its affinity for heparin increases.

  20. Proteomic Analysis of Aortae from Human Lipoprotein(a) Transgenic Mice Shows an Early Metabolic Response Independent of Atherosclerosis

    PubMed Central

    Rodger, Euan J.; Suetani, Rachel J.; Jones, Gregory T.; Kleffmann, Torsten; Carne, Alan; Legge, Michael; McCormick, Sally P. A.

    2012-01-01

    Background Elevated low density lipoprotein (LDL) and lipoprotein(a) are independent risk factors for the development of atherosclerosis. Using a proteomic approach we aimed to determine early changes in arterial protein expression in transgenic mice containing both human LDL and lipoprotein(a) in circulation. Methods and Results Plasma lipid analyses showed the lipoprotein(a) transgenic mice had significantly higher lipid levels than wildtype, including a much increased LDL and high density lipoprotein (HDL) cholesterol. Analysis of aortae from lipoprotein(a) mice showed lipoprotein(a) accumulation but no lipid accumulation or foam cells, leaving the arteries essentially atherosclerosis free. Using two-dimensional gel electrophoresis and mass spectrometry, we identified 34 arterial proteins with significantly altered abundance (P<0.05) in lipoprotein(a) transgenic mice compared to wildtype including 17 that showed a ≥2 fold difference. Some proteins of interest showed a similarly altered abundance at the transcript level. These changes collectively indicated an initial metabolic response that included a down regulation in energy, redox and lipid metabolism proteins and changes in structural proteins at a stage when atherosclerosis had not yet developed. Conclusions Our study shows that human LDL and lipoprotein(a) promote changes in the expression of a unique set of arterial proteins which may be early indicators of the metabolic disturbances preceding atherosclerosis. PMID:22276189

  1. Lipoprotein alterations, abdominal fat distribution and breast cancer.

    PubMed

    Schreier, L E; Berg, G A; Basilio, F M; Lopez, G I; Etkin, A E; Wikinski, R L

    1999-04-01

    Plasma lipid profile and abdominal obesity have been associated with breast cancer risk, however published results have been inconsistent. To clarify these associations we studied lipid and lipoprotein alterations, obesity degree and body fat distribution, in 30 newly diagnosed breast cancer patients without treatment and 30 controls matched by age and menopausal status. Both pre and postmenopausal breast cancer patients presented higher body mass index, waist/hip ratio and insulin levels than their matched controls. An increase in triglycerides and a decrease in HDL-cholesterol, especially in the HDL2 subfraction, were observed in patients with breast cancer. Besides, HDL particle from these patients showed increased apo A1/HDL-cholesterol ratio. These alterations were correlated with waist/hip ratio. The association between lipoprotein alterations and abdominal obesity independent of menopausal status, in untreated newly diagnosed breast cancer patients is reported for the first time in this study.

  2. Breast milk jaundice; the role of lipoprotein lipase and the free fatty acids.

    PubMed

    Constantopoulos, A; Messaritakis, J; Matsaniotis, N

    1980-06-01

    Lipoprotein lipase activity and free fatty acid concentrations were measured in samples of milk collected from mothers of infants without and with prolonged neonatal jaundice. The lipoprotein lipase and free fatty acid values in the milk from mothers of infants without jaundice were found to increase with the duration of breast-feeding until the 12th post-partum day, and then to fall to the original levels. In the group of mothers with jaundiced infants both lipoprotein lipase and free fatty acid values were found within normal limits when measured between 15th and 37th days post-partum. These findings indicate that increased values of lipoprotein lipase and free fatty acids in the milk are not responsible for the development of breast-milk jaundice.

  3. Explaining the Oxbridge Figures.

    ERIC Educational Resources Information Center

    Davies, Bronwyn; Harre, Rom

    1989-01-01

    Rejects sociobiological theories on female academic achievement and bases findings on social structure to explain why undergraduate women at Oxford University (England) achieve fewer first places and more second places in class honors. Bases theory on bipolarity of gender as an organizing principle of society. Claims that the double bind of social…

  4. Explaining Immigrant Naturalization.

    ERIC Educational Resources Information Center

    Yang, Philip Q.

    1994-01-01

    Proposes a broad analytical framework in the study of immigrant naturalization that incorporates an immigrant's individual characteristics with the larger social contexts in the country of origin and the country of destination to explain the likelihood of citizenship acquisition. Results testing of this framework show that such considerations are…

  5. Cellular uptake of lipoproteins and persistent organic compounds-An update and new data

    SciTech Connect

    Hjelmborg, Philip Sebastian; Andreassen, Thomas Kjaergaard; Bonefeld-Jorgensen, Eva Cecilie

    2008-10-15

    There are a number of interactions related to the transport of lipophilic xenobiotic compounds in the blood stream of mammals. This paper will focus on the interactions between lipoproteins and persistent organic pollutants (POPs) and how these particles are taken up by cells. A number of POPs including the pesticide p,p'-dichlorodiphenyltrichloroethane (DDT), and especially its metabolite p,p'-dichlorodiphenyldichloroethene (DDE), interacts with nuclear hormone receptors causing these to malfunction, which in turn results in a range of deleterious health effects in humans. The aim of the present study was to determine the role of lipoprotein receptors in mouse embryonic fibroblast (MEF) cells in conjunction with uptake of DDT-lipoprotein complexes from supplemented media in vitro. Uptake of DDT by MEF cells was investigated using MEF1 cells carrying the receptors low-density lipoprotein receptor-related protein (LRP) and low-density lipoprotein receptor (LDLR) present and MEF4 cells with no LRP and LDLR expression. Cells were incubated together with the complex of low-density lipoproteins (LDL) and [{sup 14}C]DDT. The receptor function was further evaluated by adding the 40 kDa receptor-associated protein (RAP) which blocks receptor activity. The results showed that [{sup 14}C]DDT uptake was decreasing when the LDL concentration was increasing. There was no strong evidence for a receptor-mediated uptake of the [{sup 14}C]DDT-lipoprotein complex. To conclude, DDT travels in the blood stream and can cross cell membranes while being transported as a DDT-lipoprotein complex. The lipoproteins do not need receptors to cross cell membranes since passive diffusion constitutes a major passageway.

  6. Lipoprotein subfractions partly mediate the association between serum uric acid and coronary artery disease.

    PubMed

    Zhang, Yan; Xu, Rui-Xia; Li, Sha; Zhu, Cheng-Gang; Guo, Yuan-Lin; Sun, Jing; Li, Jian-Jun

    2015-02-20

    Serum uric acid (SUA) has been established to be highly associated with coronary artery disease (CAD) susceptibility and lipid metabolism, but the underlying mechanisms are unclear. Recently, lipoprotein subfractions have been proposed to be more valuable in CAD risk evaluation. Hence, we sought to investigate whether the relationship between SUA and CAD is partly mediated by lipoprotein subfractions. A total of 401 consecutive subjects undergoing coronary angiography were enrolled. The baseline clinical data including the SUA level and lipid profiles were collected. The lipoprotein subfractions were determined using the Lipoprint system. In the overall population, the upper SUA quintiles had significantly higher atherogenic lipid parameters and unbalanced lipoprotein subfractions especially higher small dense low-density lipoprotein-cholesterol (sdLDL-C) and lower large high-density lipoprotein-cholesterol (HDL-C) (p<0.05). The levels of SUA and lipoprotein subfractions were dramatically different between male and female. After adjusting for traditional risk factors including gender, multivariate linear regression analysis suggested that SUA was positively associated with sdLDL-C (β=0.113, p=0.013) but negatively related to large HDL-C level (β=-0.152, p=0.002). Given the significant association of the SUA level with lipoprotein subfractions and incident CAD (adjusted OR=1.312, 95% CI 1.069-1.609, p=0.009), we performed the mediation analyses and found that 8.7-10.5% of the effect of SUA on CAD susceptibility was mediated by the increased sdLDL-C or decreased large HDL-C level (p<0.05). The SUA level was proved to be associated with lipoprotein subfractions including sdLDL-C (positive) and large HDL-C (negative), which partly mediated the association between SUA and CAD susceptibility. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    PubMed

    Warnick, G R

    2000-04-01

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

  8. Nanocrystal Core Lipoprotein Biomimetics for Imaging of Lipoproteins and Associated Diseases

    PubMed Central

    Fay, Francois; Sanchez-Gaytan, Brenda L.; Cormode, David P.; Skajaa, Torjus; Fisher, Edward A.; Fayad, Zahi A.

    2013-01-01

    Lipoproteins are natural nanoparticles composed of phospholipids and apolipoproteins that transport lipids throughout the body. As key effectors of lipid homeostasis, the functions of lipoproteins have been demonstrated to be crucial during the development of cardiovascular diseases. Therefore various strategies have been used to study their biology and detect them in vivo. A recent approach has been the production of lipoprotein biomimetic particles loaded with diagnostically active nanocrystals in their core. These include, but are not limited to: quantum dots, iron oxide or gold nanocrystals. Inclusion of these nanocrystals enables the utilization of lipoproteins as probes for a variety of imaging modalities (computed tomography, magnetic resonance imaging, fluorescence) while preserving their biological activity. Furthermore as some lipoproteins naturally accumulate in atherosclerotic plaque or specific tumor tissues, nanocrystal core lipoprotein biomimetics have been developed as contrast agents for early diagnosis of these diseases. PMID:23687557

  9. Low-density lipoprotein density determination by electric conductivity.

    PubMed

    Fernández-Higuero, José A; Salvador, Ana M; Arrondo, José L R; Milicua, José Carlos G

    2011-10-15

    The predominance of small dense low-density lipoprotein (LDL) particles is associated with an increased risk of coronary heart disease. A simple but precise method has been developed, based on electrical conductivity of an isopycnic gradient of KBr, to obtain density values of human LDL fraction. The results obtained can distinguish LDL density populations and their subfractions from different patients. These data were corroborated by Fourier transform infrared spectroscopy (FTIR) (structure) and light-scattering analyses (size).

  10. The majority of lipoprotein lipase in plasma is bound to remnant lipoproteins: A new definition of remnant lipoproteins.

    PubMed

    Sato, Koichi; Okajima, Fumikazu; Miyashita, Kazuya; Imamura, Shigeyuki; Kobayashi, Junji; Stanhope, Kimber L; Havel, Peter J; Machida, Tetsuo; Sumino, Hiroyuki; Murakami, Masami; Schaefer, Ernst; Nakajima, Katsuyuki

    2016-10-01

    Lipoprotein lipase (LPL) is a multifunctional protein and a key enzyme involved in the regulation of lipoprotein metabolism. We determined the lipoproteins to which LPL is bound in the pre-heparin and post-heparin plasma. Tetrahydrolipstatin (THL), a potent inhibitor of serine lipases, was used to block the lipolytic activity of LPL, thereby preventing changes in the plasma lipoproteins due to ex vivo lipolysis. Gel filtration was performed to obtain the LPL elution profiles in plasma and the isolated remnant lipoproteins (RLP). When ex vivo lipolytic activity was inhibited by THL in the post-heparin plasma, majority of the LPL was found in the VLDL elution range, specifically in the RLP as inactive dimers. However, in the absence of THL, most of the LPL was found in the HDL elution range as active dimers. Furthermore, majority of the LPL in the pre-heparin plasma was found in the RLP as inactive form, with broadly diffused lipoprotein profiles in the presence and absence of THL. It is suggested that during lipolysis in vivo, the endothelial bound LPL dimers generates RLP, forming circulating RLP-LPL complexes in an inactive form that subsequently binds and initiates receptor-mediated catabolism. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Understanding Lipoproteins as Transporters of Cholesterol and Other Lipids

    ERIC Educational Resources Information Center

    Biggerstaff, Kyle D.; Wooten, Joshua S.

    2004-01-01

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

  12. Understanding Lipoproteins as Transporters of Cholesterol and Other Lipids

    ERIC Educational Resources Information Center

    Biggerstaff, Kyle D.; Wooten, Joshua S.

    2004-01-01

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

  13. Association between tumour status and serum lipoprotein cholesterol in hemopoietic malignancy.

    PubMed

    Venkatanarayanan, S; Nagarajan, B

    1988-09-01

    Total and lipoprotein cholesterol in serum have been determined in patients with leukemia and lymphoma. Untreated patients were hypocholesterolemic with reduced lipoprotein cholesterol content. On successful chemotherapy most of the patients showed near normal total cholesterol levels with a subsequent increase in LDL cholesterol content. A rapid, sensitive and inexpensive method is reported using agarose electrophoresis and quantitation of cholesterol by Liebermann-Burchard reaction.

  14. Effects of carbon tetrachloride on isolated rat hepatocytes. Inhibition of protein and lipoprotein secretion.

    PubMed Central

    Gravela, E; Albano, E; Dianzani, M U; Poli, G; Slater, T F

    1979-01-01

    The effects of carbon tetrachloride on protein and lipoprotein secretion, and on lipid peroxidation, have been investigated in isolated rat hepatocytes. It was found that although the free-radical scavenger promethazine completely suppressed the increased peroxidation produced by carbon tetrachloride, it had no effect on the inhibitory action of carbon tetrachloride on lipoprotein secretion. In consequence, the latter effect of carbon tetrachloride does not appear to be mediated through a peroxidative stage. PMID:444227

  15. Further characterization of the metabolic properties of triglyceride-rich lipoproteins from human and mouse apoC-III transgenic mice.

    PubMed

    Aalto-Setälä, K; Weinstock, P H; Bisgaier, C L; Wu, L; Smith, J D; Breslow, J L

    1996-08-01

    We previously showed that human apoC-III expression in transgenic mice causes hypertriglyceridemia due to the accumulation of enlarged very low density lipoprotein (VLDL)-like particles, with increased triglycerides and apoC-III and decreased apoE. In vivo turnover studies indicated the metabolic basis was decreased particle fractional catabolic rate. The presence of enlarged triglyceride-rich particles with prolonged residence time in plasma implied defective lipolysis, but in vitro these particles were good substrates for purified lipoprotein lipase (LPL). In the current study we further characterize the metabolic properties of these particles. We show that expression of a mouse apoC-III transgene can also cause hypertriglyceridemia with a similar accumulation of a VLDL-like particle with increased apoC-III and decreased apoE. A vitamin A fat tolerance test was used to show that MoCIIITg and HuCIIITg mice had similarly delayed clearance of triglyceride-rich postprandial particles. Thus, the previously observed hypertriglyceridemia caused by human apoC-III transgene expression was not due interspecies incompatibility but a property of apoC-III. In further experiments we showed VLDL from apoC-III transgenic mice interacted poorly with fibroblast lipoprotein receptors and this could be corrected by adding exogenous apoE. In addition, control VLDL interaction could be decreased by exogenous apoC-III. Moreover, the hypertriglyceridemia of HuCIIITg mice could be normalized by crossbreeding with HuETg mice. Thus, a functionally significant reciprocal relationship of apoC-III and apoE exists, presumably due to competition for space on the surface of triglyceride-rich lipoproteins. Finally, VLDL from HuCIITg and MoCIIITg mice showed decreased binding to heparin-Sepharose. This suggests and additional locus of the defect in these mice could potentially be in the binding of triglyceride-rich lipoproteins to heparan sulfate proteoglycan matrix on the surface of endothelial

  16. Leptin levels and lipoprotein profiles in patients with cholelithiasis.

    PubMed

    Saraç, Serdar; Atamer, Aytaç; Atamer, Yildiz; Can, Ahmet Selçuk; Bilici, Aslan; Taçyildiz, İbrahim; Koçyiğit, Yüksel; Yenice, Necati

    2015-06-01

    To determine the relationships between serum leptin and levels of lipoprotein(a) [Lp(a)], apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) in patients with cholelithiasis. Patients with ultrasound-confirmed cholelithiasis and controls frequency-matched for age, sex, body mass index, fasting blood glucose and haemoglobin A1c levels were recruited. Fasting blood samples from all study participants were assayed for glucose, haemoglobin A1c, total cholesterol, high density lipoprotein-cholesterol (HDL-C) and triglyceride. Serum Lp(a), ApoA-1 and ApoB levels were measured using nephelometric assays; serum leptin was measured using an enzyme-linked immunosorbent assay. A total of 90 patients with cholelithiasis and 50 controls were included in the study. Serum levels of leptin, Lp(a), total cholesterol, triglyceride and ApoB were significantly increased, and levels of ApoA-1 and HDL-C were significantly decreased, in patients with cholelithiasis compared with controls. Serum leptin in patients with cholelithiasis were significantly positively correlated with Lp(a) and ApoB and negatively correlated with ApoA-1. Patients with cholelithiasis have higher leptin levels and an altered lipoprotein profile compared with controls, with increased leptin levels being associated with increased Lp(a) and ApoB levels, and decreased ApoA-1 levels, in those with cholelithiasis. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  17. Lipoprotein subclass metabolism in nonalcoholic steatohepatitis[S

    PubMed Central

    Männistö, Ville T.; Simonen, Marko; Soininen, Pasi; Tiainen, Mika; Kangas, Antti J.; Kaminska, Dorota; Venesmaa, Sari; Käkelä, Pirjo; Kärjä, Vesa; Gylling, Helena; Ala-Korpela, Mika; Pihlajamäki, Jussi

    2014-01-01

    Nonalcoholic steatohepatitis (NASH) is associated with increased synthesis of triglycerides and cholesterol coupled with increased VLDL synthesis in the liver. In addition, increased cholesterol content in the liver associates with NASH. Here we study the association of lipoprotein subclass metabolism with NASH. To this aim, liver biopsies from 116 morbidly obese individuals [age 47.3 ± 8.7 (mean ± SD) years, BMI 45.1 ± 6.1 kg/m2, 39 men and 77 women] were used for histological assessment. Proton NMR spectroscopy was used to measure lipid concentrations of 14 lipoprotein subclasses in native serum samples at baseline and after obesity surgery. We observed that total lipid concentration of VLDL and LDL subclasses, but not HDL subclasses, associated with NASH [false discovery rate (FDR) < 0.1]. More specifically, total lipid and cholesterol concentration of VLDL and LDL subclasses associated with inflammation, fibrosis, and cell injury (FDR < 0.1), independent of steatosis. Cholesterol concentration of all VLDL subclasses also correlated with total and free cholesterol content in the liver. All NASH-related changes in lipoprotein subclasses were reversed by obesity surgery. High total lipid and cholesterol concentration of serum VLDL and LDL subclasses are linked to cholesterol accumulation in the liver and to liver cell injury in NASH. PMID:25344588

  18. The Human Pathogen Streptococcus pyogenes Releases Lipoproteins as Lipoprotein-rich Membrane Vesicles.

    PubMed

    Biagini, Massimiliano; Garibaldi, Manuela; Aprea, Susanna; Pezzicoli, Alfredo; Doro, Francesco; Becherelli, Marco; Taddei, Anna Rita; Tani, Chiara; Tavarini, Simona; Mora, Marirosa; Teti, Giuseppe; D'Oro, Ugo; Nuti, Sandra; Soriani, Marco; Margarit, Immaculada; Rappuoli, Rino; Grandi, Guido; Norais, Nathalie

    2015-08-01

    Bacterial lipoproteins are attractive vaccine candidates because they represent a major class of cell surface-exposed proteins in many bacteria and are considered as potential pathogen-associated molecular patterns sensed by Toll-like receptors with built-in adjuvanticity. Although Gram-negative lipoproteins have been extensively characterized, little is known about Gram-positive lipoproteins. We isolated from Streptococcus pyogenes a large amount of lipoproteins organized in vesicles. These vesicles were obtained by weakening the bacterial cell wall with a sublethal concentration of penicillin. Lipid and proteomic analysis of the vesicles revealed that they were enriched in phosphatidylglycerol and almost exclusively composed of lipoproteins. In association with lipoproteins, a few hypothetical proteins, penicillin-binding proteins, and several members of the ExPortal, a membrane microdomain responsible for the maturation of secreted proteins, were identified. The typical lipidic moiety was apparently not necessary for lipoprotein insertion in the vesicle bilayer because they were also recovered from the isogenic diacylglyceryl transferase deletion mutant. The vesicles were not able to activate specific Toll-like receptor 2, indicating that lipoproteins organized in these vesicular structures do not act as pathogen-associated molecular patterns. In light of these findings, we propose to name these new structures Lipoprotein-rich Membrane Vesicles. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. The Human Pathogen Streptococcus pyogenes Releases Lipoproteins as Lipoprotein-rich Membrane Vesicles*

    PubMed Central

    Biagini, Massimiliano; Garibaldi, Manuela; Aprea, Susanna; Pezzicoli, Alfredo; Doro, Francesco; Becherelli, Marco; Taddei, Anna Rita; Tani, Chiara; Tavarini, Simona; Mora, Marirosa; Teti, Giuseppe; D'Oro, Ugo; Nuti, Sandra; Soriani, Marco; Margarit, Immaculada; Rappuoli, Rino; Grandi, Guido; Norais, Nathalie

    2015-01-01

    Bacterial lipoproteins are attractive vaccine candidates because they represent a major class of cell surface-exposed proteins in many bacteria and are considered as potential pathogen-associated molecular patterns sensed by Toll-like receptors with built-in adjuvanticity. Although Gram-negative lipoproteins have been extensively characterized, little is known about Gram-positive lipoproteins. We isolated from Streptococcus pyogenes a large amount of lipoproteins organized in vesicles. These vesicles were obtained by weakening the bacterial cell wall with a sublethal concentration of penicillin. Lipid and proteomic analysis of the vesicles revealed that they were enriched in phosphatidylglycerol and almost exclusively composed of lipoproteins. In association with lipoproteins, a few hypothetical proteins, penicillin-binding proteins, and several members of the ExPortal, a membrane microdomain responsible for the maturation of secreted proteins, were identified. The typical lipidic moiety was apparently not necessary for lipoprotein insertion in the vesicle bilayer because they were also recovered from the isogenic diacylglyceryl transferase deletion mutant. The vesicles were not able to activate specific Toll-like receptor 2, indicating that lipoproteins organized in these vesicular structures do not act as pathogen-associated molecular patterns. In light of these findings, we propose to name these new structures Lipoprotein-rich Membrane Vesicles. PMID:26018414

  20. Contribution of lipoproteins and lipoprotein processing to endocarditis virulence in Streptococcus sanguinis.

    PubMed

    Das, Sankar; Kanamoto, Taisei; Ge, Xiuchun; Xu, Ping; Unoki, Takeshi; Munro, Cindy L; Kitten, Todd

    2009-07-01

    Streptococcus sanguinis is an important cause of infective endocarditis. Previous studies have identified lipoproteins as virulence determinants in other streptococcal species. Using a bioinformatic approach, we identified 52 putative lipoprotein genes in S. sanguinis strain SK36 as well as genes encoding the lipoprotein-processing enzymes prolipoprotein diacylglyceryl transferase (lgt) and signal peptidase II (lspA). We employed a directed signature-tagged mutagenesis approach to systematically disrupt these genes and screen each mutant for the loss of virulence in an animal model of endocarditis. All mutants were viable. In competitive index assays, mutation of a putative phosphate transporter reduced in vivo competitiveness by 14-fold but also reduced in vitro viability by more than 20-fold. Mutations in lgt, lspA, or an uncharacterized lipoprotein gene reduced competitiveness by two- to threefold in the animal model and in broth culture. Mutation of ssaB, encoding a putative metal transporter, produced a similar effect in culture but reduced in vivo competiveness by >1,000-fold. [(3)H]palmitate labeling and Western blot analysis confirmed that the lgt mutant failed to acylate lipoproteins, that the lspA mutant had a general defect in lipoprotein cleavage, and that SsaB was processed differently in both mutants. These results indicate that the loss of a single lipoprotein, SsaB, dramatically reduces endocarditis virulence, whereas the loss of most other lipoproteins or of normal lipoprotein processing has no more than a minor effect on virulence.

  1. Contribution of Lipoproteins and Lipoprotein Processing to Endocarditis Virulence in Streptococcus sanguinis▿ §

    PubMed Central

    Das, Sankar; Kanamoto, Taisei; Ge, Xiuchun; Xu, Ping; Unoki, Takeshi; Munro, Cindy L.; Kitten, Todd

    2009-01-01

    Streptococcus sanguinis is an important cause of infective endocarditis. Previous studies have identified lipoproteins as virulence determinants in other streptococcal species. Using a bioinformatic approach, we identified 52 putative lipoprotein genes in S. sanguinis strain SK36 as well as genes encoding the lipoprotein-processing enzymes prolipoprotein diacylglyceryl transferase (lgt) and signal peptidase II (lspA). We employed a directed signature-tagged mutagenesis approach to systematically disrupt these genes and screen each mutant for the loss of virulence in an animal model of endocarditis. All mutants were viable. In competitive index assays, mutation of a putative phosphate transporter reduced in vivo competitiveness by 14-fold but also reduced in vitro viability by more than 20-fold. Mutations in lgt, lspA, or an uncharacterized lipoprotein gene reduced competitiveness by two- to threefold in the animal model and in broth culture. Mutation of ssaB, encoding a putative metal transporter, produced a similar effect in culture but reduced in vivo competiveness by >1,000-fold. [3H]palmitate labeling and Western blot analysis confirmed that the lgt mutant failed to acylate lipoproteins, that the lspA mutant had a general defect in lipoprotein cleavage, and that SsaB was processed differently in both mutants. These results indicate that the loss of a single lipoprotein, SsaB, dramatically reduces endocarditis virulence, whereas the loss of most other lipoproteins or of normal lipoprotein processing has no more than a minor effect on virulence. PMID:19395487

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

    PubMed

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

    2006-01-01

    We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on serum lipid profiles and lipoprotein (a) in 64 children with epilepsy (aged between 1 and 15 years) admitted to the child neurology outpatient clinic between July 2000 and July 2002. The children were separated as group 1 (18 children), treated with phenobarbital, 5 mg/kg/day; group 2 (22 children), treated with carbamazepine, 10 to 15 mg/kg/day; and group 3 (24 children), treated with sodium valproate, 20 mg/kg/day. Plasma lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A and apolipoprotein B levels, and liver enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase were determined before the initiation of the treatment and at 3, 6, and 12 months of the treatment period. The mean age of children in group 1 was significantly low compared with those in groups 2 and 3 (P <.05). The mean pretreatment lipid levels among the groups were not significantly increased. The mean lipoprotein (a) levels were significantly increased in all groups at 3, 6, and 12 months of the treatment period (P <.05). The increase in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol at 3, 6, and 12 months was statistically significant in group 1 (P <.05). The higher levels in lipoprotein (a) (mean > 30 mg/dL) were observed only in carbamazepine-treated patients at 6 and 12 months. The percentage of children with lipoprotein (a) levels over 30 mg/dL was 44%, 63%, and 33% in the phenobarbital-, carbamazepine-, and valproate-treated children, respectively. Antiepileptic drugs significantly increase the level of lipoprotein (a), which is a major risk factor for atherosclerosis, and also have variable effects on other lipid parameters

  3. Cholesterol in serum lipoprotein fractions after spaceflight

    NASA Technical Reports Server (NTRS)

    Leach, Carolyn S.; Johnson, Philip C., Jr.; Krauhs, Jane M.; Cintron, Nitza M.

    1988-01-01

    Results are reported from blood-lipid measurements obtained from 125 Space Shuttle crew members before and after space flight. The data are presented in tables and discussed in detail. The main differences noted between preflight and postflight values are a 12.8-percent decrease in high-density lipoproteins on postflight day 1 and significant decreases in total cholesterol and both high- and low-density lipoproteins later in the 23-day postflight period.

  4. Cholesterol in serum lipoprotein fractions after spaceflight

    NASA Technical Reports Server (NTRS)

    Leach, Carolyn S.; Johnson, Philip C., Jr.; Krauhs, Jane M.; Cintron, Nitza M.

    1988-01-01

    Results are reported from blood-lipid measurements obtained from 125 Space Shuttle crew members before and after space flight. The data are presented in tables and discussed in detail. The main differences noted between preflight and postflight values are a 12.8-percent decrease in high-density lipoproteins on postflight day 1 and significant decreases in total cholesterol and both high- and low-density lipoproteins later in the 23-day postflight period.

  5. Lipoprotein subclass profiles in young adults born preterm at very low birth weight.

    PubMed

    Hovi, Petteri; Kajantie, Eero; Soininen, Pasi; Kangas, Antti J; Järvenpää, Anna-Liisa; Andersson, Sture; Eriksson, Johan G; Ala-Korpela, Mika; Wehkalampi, Karoliina

    2013-04-30

    Adults born preterm at very low birth weight (VLBW ≤ 1500g) have increased risk factors for cardiovascular diseases including high blood pressure and impaired glucose regulation. Non-optimal lipoprotein profile is generally also likely to affect the increased cardiovascular risk, but lipoprotein subclass level data on adults born at VLBW are sparse. We studied 162 subjects born at VLBW and 169 term-born controls, aged 19 to 27 years. Total lipid, triglyceride and cholesterol concentrations of 14 lipoprotein subclasses were determined by proton nuclear magnetic resonance spectroscopy in the fasting state and in 2-hour serum samples from an oral glucose tolerance test. In comparison to controls, VLBW subjects had significantly higher fasting concentration of triglycerides in chylomicrons and largest very-low-density lipoprotein particles [XXL-VLDL-TG, difference 0.026 (95% CI: 0.004 to 0.049), P=0.024], and of triglycerides in small high-density lipoprotein particles [S-HDL-TG, 0.026 (95% CI: 0.002 to 0.051), P=0.037]. The seemingly important role of triglycerides was further supported by principal component analysis in which the first component was characterized by multiple lipoprotein triglyceride measures. Young adults born at VLBW and their peers born at term had triglyceride-related differences in both VLDL and HDL subclasses. These differences suggest that the increased risk factors for cardiovascular diseases among the VLBW individuals in adulthood may partly relate to impaired triglyceride metabolism.

  6. Ultrafiltration of lipoproteins through a synthetic membrane

    PubMed Central

    Colton, Clark K.; Friedman, Sigmund; Wilson, Dana E.; Lees, Robert S.

    1972-01-01

    To investigate the interaction of lipoproteins with semipermeable membranes, solutions of low density lipoproteins (LDL), very low density lipoproteins (VLDL), mixtures of the two, and diluted, normal, and hyperlipidemic serum were ultrafiltered through a synthetic membrane (500 A nominal pore diameter) using a stirred laboratory ultrafiltration cell. The pressure dependence of ultrafiltrate flux showed that a concentrated layer of lipoproteins was built up at the membrane surface (concentration polarization) and that VLDL was more subject to polarization than LDL. This phenomenon controlled the observed lipoprotein transport behavior. Whereas true membrane rejection (the fraction of the solute on the membrane surface which does not pass through the membrane) was greater than 0.95 for both LDL and VLDL, observed solute rejection varied from nearly 0 to 1.0, depending upon experimental conditions. If concentration polarization occurs in the arterial system, these results suggest that lipoprotein transport into arterial wall may be influenced not only by arterial blood pressure and the properties of the arterial wall, but also by local hemodynamic conditions and by the relative as well as absolute magnitudes of LDL and VLDL concentration. PMID:4344733

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

    PubMed

    Heckers, H; Platt, D

    1991-06-20

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