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Sample records for density lipoproteins ldl

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

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    Doosty M

    1999-06-01

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

  2. Biochemical and cytotoxic characteristics of an in vivo circulating oxidized low density lipoprotein (LDL-).

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    Hodis, H N; Kramsch, D M; Avogaro, P; Bittolo-Bon, G; Cazzolato, G; Hwang, J; Peterson, H; Sevanian, A

    1994-04-01

    Using ion exchange high pressure liquid chromatography, total plasma low density lipoprotein (LDL) from 30 hypercholesterolemic and 10 normocholesterolemic cynomolgus monkeys was subfractionated into unmodified LDL (n-LDL) and more negatively charged LDL (LDL-). In hypercholesterolemic monkeys, the absolute LDL-cholesterol level was 16.54 +/- 2.82 mg/dl (mean +/- SE) whereas in normocholesterolemic monkeys it was 2.39 +/- 0.12 mg/dl (P < 0.0001); the percentage of LDL- was 5.2 +/- 0.71% and 4.9 +/- 0.19% of the total LDL for hypercholesterolemic versus normocholesterolemic monkeys, respectively. LDL- averaged 5% and n-LDL 95% of the total plasma LDL cholesterol. To confirm and further elucidate the oxidative nature of LDL-, cholesterol and cholesterol oxide contents of LDL- and n-LDL were determined by capillary gas chromatography; 53.98 +/- 2.24% (mean +/- SE) of the LDL- cholesterol was oxidized whereas in n-LDL only 10.70 +/- 1.06% of the cholesterol was oxidized (P < 0.00001). The spectrum of oxysterols identified, which was similar for LDL- and n-LDL, suggested a free radical-mediated process for cholesterol oxidation. The principal oxysterols identified were: cholest-5-ene-3 beta, 7 alpha-diol, cholesta-3,5-diene-7-one, cholest-5-ene-3 beta, 7 beta-diol, 5,6 beta-epoxy-5 beta-cholestan-3 beta-ol, 5,6 alpha-epoxy-5 alpha-cholestan-3 beta-ol, 5 alpha-cholestan-3 beta,5,6 beta-triol, 3 beta-hydroxycholest-5-ene-7-one, and cholest-5-ene-3 beta,25-diol. To model one of the steps in the possible mechanism of atherogenesis, the cytotoxicity of LDL- was demonstrated to be greater against subconfluent than confluent aortic endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Cryoprotection effectiveness of low concentrations of natural and lyophilized LDL (low density lipoproteins on canine spermatozoa

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    M.M. Neves

    2014-06-01

    Full Text Available The aim of this study was to evaluate the use of low concentrations of natural and lyophilized low density lipoprotein (LDL from hen's egg yolk for cryopreservation of canine semen. Different ammonium sulphate concentrations were tested to extract LDL from egg yolk. The yolk was centrifuged, and LDL was isolated using 10, 20, 40, 45, or 50% ammonium sulphate solution (ASS. The LDL-rich floating fraction was collected for chemical characterization. Dry matter content was lowest (P<0.05 in the LDL extracted with the 50% ASS. The purification of LDL increased in association with increasing ammonium sulphate concentrations. SDS-PAGE showed that the 50% ASS solution yielded a purer fraction of LDL from egg yolk. For semen cryopreservation, TRIS extender was used replacing 20% egg yolk (control by natural or lyophilized LDL using 1, 2, and 3% (w/v. Semen was centrifuged (755Xg for 7 min, diluted with one of the extenders, packed into 0.5mL straws (100x106 sperm/mL, and placed in a programmable cryopreservation machine. Thawed semen (37°C/ 30s was analyzed for sperm motility, morphology, and by the hypoosmotic and epifluorescence tests (CFDA/ PI. Natural LDL extracted with 50% ASS was as effective as whole egg yolk to preserve canine frozen sperm when using low concentrations. The lyophilized LDL, mainly in the two higher concentrations tested (2 and 3%, was unsuitable to maintain the effectiveness of the LDL cryoprotective effect on dog sperm.

  4. Oxidized low density lipoprotein (LDL) affects hyaluronan synthesis in human aortic smooth muscle cells.

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    Viola, Manuela; Bartolini, Barbara; Vigetti, Davide; Karousou, Evgenia; Moretto, Paola; Deleonibus, Sara; Sawamura, Tatsuya; Wight, Thomas N; Hascall, Vincent C; De Luca, Giancarlo; Passi, Alberto

    2013-10-11

    Thickening of the vessel in response to high low density lipoprotein(s) (LDL) levels is a hallmark of atherosclerosis, characterized by increased hyaluronan (HA) deposition in the neointima. Human native LDL trapped within the arterial wall undergoes modifications such as oxidation (oxLDL). The aim of our study is to elucidate the link between internalization of oxLDL and HA production in vitro, using human aortic smooth muscle cells. LDL were used at an effective protein concentration of 20-50 μg/ml, which allowed 80% cell viability. HA content in the medium of untreated cells was 28.9 ± 3.7 nmol HA-disaccharide/cell and increased after oxLDL treatment to 53.9 ± 5.6. OxLDL treatments doubled the transcripts of HA synthase HAS2 and HAS3. Accumulated HA stimulated migration of aortic smooth muscle cells and monocyte adhesiveness to extracellular matrix. The effects induced by oxLDL were inhibited by blocking LOX-1 scavenger receptor with a specific antibody (10 μg/ml). The cholesterol moiety of LDL has an important role in HA accumulation because cholesterol-free oxLDL failed to induce HA synthesis. Nevertheless, cholesterol-free oxLDL and unmodified cholesterol (20 μg/ml) induce only HAS3 transcription, whereas 22,oxysterol affects both HAS2 and HAS3. Moreover, HA deposition was associated with higher expression of endoplasmic reticulum stress markers (CHOP and GRP78). Our data suggest that HA synthesis can be induced in response to specific oxidized sterol-related species delivered through oxLDL.

  5. Influence of oxidized low-density lipoproteins (LDL) on the viability of osteoblastic cells.

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    Brodeur, Mathieu R; Brissette, Louise; Falstrault, Louise; Ouellet, Pascale; Moreau, Robert

    2008-02-15

    Cardiovascular diseases have recently been noted as potential risk factors for osteoporosis development. Although it is poorly understood how these two pathologies are related, it is a known fact that oxidized low-density lipoproteins (OxLDL) constitute potential determinants for both of them. The current study investigated the metabolism of OxLDL by osteoblasts and its effect on osteoblastic viability. The results obtained show that OxLDL are internalized but not degraded by osteoblasts while they can selectively transfer their CE to these cells. It is also demonstrated that OxLDL induce proliferation at low concentrations but cell death at high concentrations. This reduction of osteoblast viability was associated with lysosomal membrane damage caused by OxLDL as demonstrated by acridine orange relocalization. Accordingly, chloroquine, an inhibitor of lysosomal activity, accentuated cell death induced by OxLDL. Finally, we demonstrate that osteoblasts have the capacity to oxidize LDL and thereby potentially increase the local concentration of OxLDL. Overall, the current study confirms the potential role of OxLDL in the development of osteoporosis given its influence on osteoblastic viability.

  6. Oxidized low-density lipoprotein (Oxidized LDL) and the risk of preeclampsia.

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    Qiu, C; Phung, T T T; Vadachkoria, S; Muy-Rivera, M; Sanchez, S E; Williams, M A

    2006-01-01

    Oxidative stress plays an important role in the pathophysiology of preeclampsia. In a case-control study of 99 women with preeclampsia and 99 controls, we assessed maternal plasma oxidized low-density lipoprotein (oxidized LDL) in relation to preeclampsia risk. Logistic regression procedures were used to derive odds ratios (OR) and 95 % confidence intervals (CI). Plasma oxidized LDL was determined using enzyme immunoassay. Maternal plasma oxidized LDL was significantly positively correlated with lipids in both cases and controls. After adjusting for nulliparity, pre-pregnancy body mass index, physical inactivity, family history of chronic hypertension and plasma vitamin C concentrations, women who had elevated oxidized LDL concentrations ( > or = 50 U/l) experienced a 2.9-fold increased risk of preeclampsia when compared with women having lower oxidized LDL concentrations (95 % CI 1.4-5.9). The risk of preeclampsia was markedly increased in women who had both elevated oxidized LDL and elevated triglyceride concentrations (OR=8.9, 95 % CI 3.1-26.2). Women with both elevated oxidized LDL and low vitamin C concentrations experienced a 9.8-fold increased risk of preeclampsia (95 % CI 3.0-32.2). Our results confirm the role of oxidative stress in the pathogenesis of preeclampsia. Prospective studies are needed to determine if elevated oxidized LDL concentrations can predict the occurrence of preeclampsia.

  7. Oxidized low-density lipoprotein (Ox-LDL) impacts on erythrocyte viscoelasticity and its molecular mechanism.

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    Wang, Xiang; Yang, Li; Liu, Yao; Gao, Wei; Peng, Weiyan; Sung, K-L Paul; Sung, Lanping Amy

    2009-10-16

    The oxidized low-density lipoprotein (Ox-LDL) plays an important role in atherosclerosis, yet it remains unclear if it damages circulating erythrocytes. In this study, erythrocyte deformability and its membrane proteins after Ox-LDL incubations are investigated by micropipette aspiration, thiol radical measurement, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Results show that Ox-LDL incubation reduces the erythrocyte deformability, decreases free thiol radical contents in erythrocytes, and induces the cross-linking among membrane proteins. SDS-PAGE analysis reveals a high molecular weight (HMW) complex as well as new bands between spectrins and band 3 and reduced ratios between band 3 and other major membrane skeletal proteins. Analyses indicate that Ox-LDL makes erythrocytes harder to deform through a molecular mechanism by which the oxidation of free thiol radicals forms disulfide bonds among membrane skeletal proteins.

  8. CD36 binds oxidized low density lipoprotein (LDL) in a mechanism dependent upon fatty acid binding.

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    Jay, Anthony G; Chen, Alexander N; Paz, Miguel A; Hung, Justin P; Hamilton, James A

    2015-02-20

    The association of unesterified fatty acid (FA) with the scavenger receptor CD36 has been actively researched, with focuses on FA and oxidized low density lipoprotein (oxLDL) uptake. CD36 has been shown to bind FA, but this interaction has been poorly characterized to date. To gain new insights into the physiological relevance of binding of FA to CD36, we characterized FA binding to the ectodomain of CD36 by the biophysical method surface plasmon resonance. Five structurally distinct FAs (saturated, monounsaturated (cis and trans), polyunsaturated, and oxidized) were pulsed across surface plasmon resonance channels, generating association and dissociation binding curves. Except for the oxidized FA HODE, all FAs bound to CD36, with rapid association and dissociation kinetics similar to HSA. Next, to elucidate the role that each FA might play in CD36-mediated oxLDL uptake, we used a fluorescent oxLDL (Dii-oxLDL) live cell assay with confocal microscopy imaging. CD36-mediated uptake in serum-free medium was very low but greatly increased when serum was present. The addition of exogenous FA in serum-free medium increased oxLDL binding and uptake to levels found with serum and affected CD36 plasma membrane distribution. Binding/uptake of oxLDL was dependent upon the FA dose, except for docosahexaenoic acid, which exhibited binding to CD36 but did not activate the uptake of oxLDL. HODE also did not affect oxLDL uptake. High affinity FA binding to CD36 and the effects of each FA on oxLDL uptake have important implications for protein conformation, binding of other ligands, functional properties of CD36, and high plasma FA levels in obesity and type 2 diabetes.

  9. Achievement of 2011 European low-density lipoprotein cholesterol (LDL-C) goals of either VOYAGER.

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    Karlson, Björn W; Nicholls, Stephen J; Lundman, Pia; Palmer, Mike K; Barter, Philip J

    2013-05-01

    Guidelines published in 2011 by the European Atherosclerosis Society and the European Society of Cardiology recommend a goal of either low-density lipoprotein cholesterol (LDL-C) VOYAGER individual patient data meta-analysis treated with rosuvastatin 10-40 mg, atorvastatin 10-80 mg or simvastatin 10-80 mg who achieved this goal. We analysed 25,075 patient exposures from high-risk patients. Paired comparisons were made between each rosuvastatin dose and an equal or higher dose of either atorvastatin or simvastatin, with a series of meta-analyses that included only randomised studies that directly compared rosuvastatin and its comparator treatments. As statin dose increased, higher percentages of patients achieved LDL-C VOYAGER highlight the importance of an effective statin at an appropriate dose to achieve treatment goals for LDL-C in patients with very high cardiovascular risk. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Differential regulation of acid sphingomyelinase in macrophages stimulated with oxidized low-density lipoprotein (LDL) and oxidized LDL immune complexes: role in phagocytosis and cytokine release.

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    Truman, Jean-Philip; Al Gadban, Mohammed M; Smith, Kent J; Jenkins, Russell W; Mayroo, Nalini; Virella, Gabriel; Lopes-Virella, Maria F; Bielawska, Alicja; Hannun, Yusuf A; Hammad, Samar M

    2012-05-01

    Oxidized low-density lipoprotein (oxLDL) and oxLDL-containing immune complexes (oxLDL-IC) contribute to the formation of lipid-laden macrophages (foam cells). Fcγ receptors mediate uptake of oxLDL-IC, whereas scavenger receptors internalize oxLDL. We have previously reported that oxLDL-IC, but not free oxLDL, activate macrophages and prolong their survival. Sphingomyelin is a major constituent of cell membranes and lipoprotein particles and acid sphingomyelinase (ASMase) hydrolyses sphingomyelin to generate the bioactive lipid ceramide. ASMase exists in two forms: lysosomal (L-ASMase) and secretory (S-ASMase). In this study we examined whether oxLDL and oxLDL-IC regulate ASMase differently, and whether ASMase mediates monocyte/macrophage activation and cytokine release. The oxLDL-IC, but not oxLDL, induced early and consistent release of catalytically active S-ASMase. The oxLDL-IC also consistently stimulated L-ASMase activity, whereas oxLDL induced a rapid transient increase in L-ASMase activity before it steadily declined below baseline. Prolonged exposure to oxLDL increased L-ASMase activity; however, activity remained significantly lower than that induced by oxLDL-IC. Further studies were aimed at defining the function of the activated ASMase. In response to oxLDL-IC, heat-shock protein 70B' (HSP70B') was up-regulated and localized with redistributed ASMase in the endosomal compartment outside the lysosome. Treatment with oxLDL-IC induced the formation and release of HSP70-containing and IL-1β-containing exosomes via an ASMase-dependent mechanism. Taken together, the results suggest that oxLDL and oxLDL-IC differentially regulate ASMase activity, and the pro-inflammatory responses to oxLDL-IC are mediated by prolonged activation of ASMase. These findings may contribute to increased understanding of mechanisms mediating macrophage involvement in atherosclerosis.

  11. Comparative reactivity of the myeloperoxidase-derived oxidants HOCl and HOSCN with low-density lipoprotein (LDL)

    DEFF Research Database (Denmark)

    Ismael, Fahd O; Proudfoot, Julie M; Brown, Bronwyn E;

    2015-01-01

    Atherosclerosis is characterised by the accumulation of lipids within macrophages in the artery wall. Low-density lipoprotein (LDL) is the source of this lipid, owing to the uptake of oxidised LDL by scavenger receptors. Myeloperoxidase (MPO) released by leukocytes during inflammation produces...

  12. The role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in comparison with whole egg yolk for sperm cryopreservation in rhesus monkeys.

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    Dong, Qiao-Xiang; Rodenburg, Sarah E; Hill, Dana; Vandevoort, Catherine A

    2011-05-01

    Low-density lipoprotein (LDL) extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein (HDL) in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant (glycerol) on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL-sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL-sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in post-thaw survival; while addition of methyl-β-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.

  13. The role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in comparison with whole egg yolk for sperm cryopreservation in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Qiao-Xiang Dong; Sarah E Rodenburg; Dana Hill; Catherine A VandeVoort

    2011-01-01

    Low-density lipoprotein (LDL) extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein (HDL) in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant (glycerol) on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL-sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL-sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in post-thaw survival; while addition of methyl-β-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.

  14. Low-Density Lipoprotein (LDL-Antioxidant Biflavonoids from Garcinia madruno

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    Jaume Bastida

    2013-05-01

    Full Text Available Six biflavonoids were isolated from G. madruno, one of which, 7''-O-(6''''-acetyl-glucoside of morelloflavone, is a new compound identified on the basis of 1D, 2D NMR (HMQC and HMBC spectroscopic methods and chemical evidence. The antioxidant activity of the biflavonoids against low-density lipoprotein (LDL peroxidation induced with Cu2+, was studied by means of a TBARS assay. The antioxidant potential of a biflavonoid fraction (BF was also evaluated and correlated with its biflavonoid content. The flavanone-(3→8''-flavone biflavonoids displayed antioxidant activity, particularly morelloflavone, which was significantly more potent than quercetin, with a CE50 of 12.36 μg/mL. Lipid peroxidation, was also significantly reduced in the presence of the BF (EC50 = 11.85 μg/mL. These results suggest that the BF is an excellent antioxidant.

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

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    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.

  16. Influence of Honey on the Suppression of Human Low Density Lipoprotein (LDL Peroxidation (In Vitro

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    Ahmed G. Hegazi

    2009-01-01

    Full Text Available The antioxidant activity of four honey samples from different floral sources (Acacia, Coriander, Sider and Palm were evaluated with three different assays; DPPH free radical scavenging assay, superoxide anion generated in xanthine–xanthine oxidase (XOD system and low density lipoprotein (LDL peroxidation assay. The dark Palm and Sider honeys had the highest antioxidant activity in the DPPH assay. But all the honey samples exhibited more or less the same highly significant antioxidant activity within the concentration of 1mg honey/1 ml in XOD system and LDL peroxidation assays. The chemical composition of these samples was investigated by GC/MS and HPLC analysis, 11 compounds being new to honey. The GC/MS revealed the presence of 90 compounds, mainly aliphatic acids (37 compounds, which represent 54.73, 8.72, 22.87 and 64.10% and phenolic acids (15 compound 2.3, 1.02, 2.07 and 11.68% for Acacia, Coriander, Sider and Palm honeys. In HPLC analysis, 19 flavonoids were identified. Coriander and Sider honeys were characterized by the presence of large amounts of flavonoids.

  17. Unique cellular events occurring during the initial interaction of macrophages with matrix-retained or methylated aggregated low density lipoprotein (LDL). Prolonged cell-surface contact during which ldl-cholesteryl ester hydrolysis exceeds ldl protein degradation.

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    Buton, X; Mamdouh, Z; Ghosh, R; Du, H; Kuriakose, G; Beatini, N; Grabowski, G A; Maxfield, F R; Tabas, I

    1999-11-05

    A critical event in atherogenesis is the interaction of arterial wall macrophages with subendothelial lipoproteins. Although most studies have investigated this interaction by incubating cultured macrophages with monomeric lipoproteins dissolved in media, arterial wall macrophages encounter lipoproteins that are mostly bound to subendothelial extracellular matrix, and these lipoproteins are often aggregated or fused. Herein, we utilize a specialized cell-culture system to study the initial interaction of macrophages with aggregated low density lipoprotein (LDL) bound to extracellular matrix. The aggregated LDL remains extracellular for a relatively prolonged period of time and becomes lodged in invaginations in the surface of the macrophages. As expected, the degradation of the protein moiety of the LDL was very slow. Remarkably, however, hydrolysis of the cholesteryl ester (CE) moiety of the LDL was 3-7-fold higher than that of the protein moiety, in stark contrast to the situation with receptor-mediated endocytosis of acetyl-LDL. Similar results were obtained using another experimental system in which the degradation of aggregated LDL protein was delayed by LDL methylation rather than by retention on matrix. Additional experiments indicated the following properties of this interaction: (a) LDL-CE hydrolysis is catalyzed by lysosomal acid lipase; (b) neither scavenger receptors nor the LDL receptor appear necessary for the excess LDL-CE hydrolysis; and (c) LDL-CE hydrolysis in this system is resistant to cellular potassium depletion, which further distinguishes this process from receptor-mediated endocytosis. In summary, experimental systems specifically designed to mimic the in vivo interaction of arterial wall macrophages with subendothelial lipoproteins have demonstrated an initial period of prolonged cell-surface contact in which CE hydrolysis exceeds protein degradation.

  18. Novel mechanism by which probucol lowers low density lipoprotein levels demonstrated in the LDL receptor-deficient rabbit

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    Naruszewicz, M.; Carew, T.E.; Pittman, R.C.; Witztum, J.L.; Steinberg, D.

    1984-11-01

    Treatment of low density lipoprotein (LDL) receptor-deficient rabbits (WHHL rabbits) with probucol (1% w/w in a chow diet) lowered their LDL-cholesterol levels by 36%, consonant with the reported effectiveness of the drug in patients deficient in the LDL receptor. Initial studies of LDL fractional catabolic rate (FCR) using /sup 125/I-labeled LDL prepared from the serum of untreated WHHL rabbits showed no difference between probucol-treated WHHL rabbits and untreated WHHL rabbits. When, however, /sup 125/I-labeled LDL was prepared from donor WHHL rabbits under treatment with probucol and injected back into them, the FCR was found to be increased by about 50% above that measured simultaneously using /sup 131/I-labeled LDL prepared from untreated WHHL donors. The labeled LDL from probucol-treated donors was also metabolized more rapidly than that from untreated donors when injected into untreated WHHL rabbits or into untreated wild-type New Zealand White rabbits. Finally, it was shown that rabbit skin fibroblasts in culture degraded labeled LDL prepared from probucol-treated WHHL rabbits more rapidly than that prepared from untreated WHHL donors. This was true both for normal rabbit fibroblasts and also for WHHL skin fibroblasts, although the absolute degradation rates in the latter were, of course, much lower for both forms of LDL. The data indicate that a major mechanism by which probucol lowers LDL levels relates not to changes in the cellular mechanisms for LDL uptake or to changes in LDL production but rather to intrinsic changes in the structure and metabolism of the plasma LDL of the probucol-treated animal.

  19. Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

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    Pires, L.A. [Laboratório de Metabolismo de Lípides, Instituto do Coração, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Departamento de Ginecologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Hegg, R. [Departamento de Ginecologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Freitas, F.R.; Tavares, E.R.; Almeida, C.P. [Laboratório de Metabolismo de Lípides, Instituto do Coração, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Baracat, E.C. [Departamento de Ginecologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Maranhão, R.C. [Laboratório de Metabolismo de Lípides, Instituto do Coração, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP (Brazil)

    2012-05-04

    Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy.

  20. Rapid characterization of disease-causing mutations in the low density lipoprotein receptor (LDL-R) gene by overexpression in COS cells

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    Jensen, T G; Andresen, B S; Jensen, H K;

    1996-01-01

    To characterize disease-causing mutations in the low density lipoprotein receptor (LDL-R) gene, COS cells are transfected with the mutant gene in an EBV-based expression vector and characterized by flow cytometry. Using antibodies against the LDL-receptor the amount of receptor protein on the cell...

  1. Lectin-like Oxidized Low-Density Lipoprotein (LDL) Receptor (LOX-1): A Chameleon Receptor for Oxidized LDL.

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    Zeya, Bushra; Arjuman, Albina; Chandra, Nimai Chand

    2016-08-16

    LOX-1, one of the main receptors for oxLDL, is found mainly on the surface of endothelial cells. It is a multifacet 52 kDa type II transmembrane protein that structurally belongs to the C-type lectin family. It exists with short intracellular N-terminal and long extracellular C-terminal hydrophilic domains separated by a hydrophobic domain of 26 amino acids. LOX-1 acts like a bifunctional receptor either showing pro-atherogenicity by activating the NFκB-mediated down signaling cascade for gene activation of pro-inflammatory molecules or playing an atheroprotective agent by receptor-mediated uptake of oxLDL in the presence of an anti-inflammatory molecule like IL-10. Mildly, moderately, and highly oxidized LDL show their characteristic features upon LOX-1 activation and its ligand binding indenture. The polymorphic LOX-1 genes are intensively associated with increased susceptibility to myocardial diseases. The splicing variant LOX IN dimerizes with the native form of LOX-1 and protects cells from damage by oxidized LDL. In the developing field of regenerating medicine, LOX-1 is a potential target for therapeutic intervention.

  2. Oxidized Low-Density Lipoprotein-β2-Glycoprotein I Complex But Not Free Oxidized LDL Is Associated With the Presence and Severity of Coronary Artery Disease.

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    Bliden, Kevin P; Chaudhary, Rahul; Lopez, Luis R; Damrongwatanasuk, Rongras; Guyer, Kirk; Gesheff, Martin G; Franzese, Christopher J; Kaza, Himabindu; Tantry, Udaya S; Gurbel, Paul A

    2016-09-01

    Oxidized low-density lipoprotein (oxLDL) and β2-glycoprotein I (β2GPI) have been identified in human atherosclerotic lesions and when complexed have been implicated as a pro-atherothrombotic antigen. We examined the association of free oxLDL and oxLDL-β2GPI complex in patients with coronary artery disease who underwent elective cardiac catheterization. Serum was collected from patients with suspected coronary artery disease immediately before elective cardiac catheterization who were either treated (n = 385) or not treated (n = 150) with statins and from healthy volunteers (n = 134). OxLDL and oxLDL-β2GPI complex levels were determined by enzyme-linked immunosorbent assay. Disease severity was defined angiographically as none-minimal (75%) luminal diameter obstruction of any major coronary vessel. Both oxLDL and oxLDL-β2GPI complex were lower in patients on statins (p LDL4 and triglycerides increased with oxLDL-β2GPI complex quartiles (p = 0.001). OxLDL-β2GPI complex (>0.32 U/ml) was predictive of severe atherosclerosis by receiver-operating characteristic curve analysis in statin-naive patients (area under the curve 0.66, p = 0.002). In conclusion, oxLDL-β2GPI appears more predictive of coronary artery disease severity than oxLDL alone in statin-naive patients.

  3. Resolving Low-Density Lipoprotein (LDL) on the Human Aortic Surface Using Large Eddy Simulation

    Science.gov (United States)

    Lantz, Jonas; Karlsson, Matts

    2011-11-01

    The prediction and understanding of the genesis of vascular diseases is one of the grand challenges in biofluid engineering. The progression of atherosclerosis is correlated to the build- up of LDL on the arterial surface, which is affected by the blood flow. A multi-physics simulation of LDL mass transport in the blood and through the arterial wall of a subject specific human aorta was performed, employing a LES turbulence model to resolve the turbulent flow. Geometry and velocity measurements from magnetic resonance imaging (MRI) were incorporated to assure physiological relevance of the simulation. Due to the turbulent nature of the flow, consecutive cardiac cycles are not identical, neither in vivo nor in the simulations. A phase average based on a large number of cardiac cycles is therefore computed, which is the proper way to get reliable statistical results from a LES simulation. In total, 50 cardiac cycles were simulated, yielding over 2.5 Billion data points to be post-processed. An inverse relation between LDL and WSS was found; LDL accumulated on locations where WSS was low and vice-versa. Large temporal differences were present, with the concentration level decreasing during systolic acceleration and increasing during the deceleration phase. This method makes it possible to resolve the localization of LDL accumulation in the normal human aorta with its complex transitional flow.

  4. High-density lipoprotein inhibits ox-LDL-induced adipokine secretion by upregulating SR-BI expression and suppressing ER Stress pathway.

    Science.gov (United States)

    Song, Guohua; Wu, Xia; Zhang, Pu; Yu, Yang; Yang, Mingfeng; Jiao, Peng; Wang, Ni; Song, Haiming; Wu, You; Zhang, Xiangjian; Liu, Huaxia; Qin, Shucun

    2016-07-29

    Endoplasmic reticulum stress (ERS) in adipocytes can modulate adipokines secretion. The aim of this study was to explore the protective effect of high-density lipoprotein (HDL) on oxidized low-density lipoprotein (ox-LDL)-induced ERS-C/EBP homologous protein (CHOP) pathway-mediated adipokine secretion. Our results showed that serum adipokines, including visfatin, resistin and TNF-α, correlated inversely with serum HDL cholesterol level in patients with abdominal obesity. In vitro, like ERS inhibitor 4-phenylbutyric acid (PBA), HDL inhibited ox-LDL- or tunicamycin (TM, an ERS inducer)-induced increase in visfatin and resistin secretion. Moreover, HDL inhibited ox-LDL-induced free cholesterol (FC) accumulation in whole cell lysate and in the endoplasmic reticulum. Additionally, like PBA, HDL inhibited ox-LDL- or TM-induced activation of ERS response as assessed by the decreased phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2α and reduced nuclear translocation of activating transcription factor 6 as well as the downregulation of Bip and CHOP. Furthermore, HDL increased scavenger receptor class B type I (SR-BI) expression and SR-BI siRNA treatment abolished the inhibitory effects of HDL on ox-LDL-induced FC accumulation and CHOP upregulation. These data indicate that HDL may suppress ox-LDL-induced FC accumulation in adipocytes through upregulation of SR-BI, subsequently preventing ox-LDL-induced ER stress-CHOP pathway-mediated adipocyte inflammation.

  5. A bovine papillomavirus-1 based vector restores the function of the low-density lipoprotein receptor in the receptor-deficient CHO-ldlA7 cell line

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    Ustav Mart

    2002-04-01

    Full Text Available Abstract Background The rationale of using bovine papillomavirus-1 (BPV-1 derived vectors in gene therapy protocols lies in their episomal maintenance at intermediate to high copy number, and stable, high-level expression of the gene products. We constructed the BPV-1 based vector harbouring the human low-density lipoprotein receptor (LDLR gene cDNA and tested its ability to restore the function of the LDLR in the receptor-deficient cell line CHO-ldlA7. Results The introduced vector p3.7LDL produced functionally active LDL receptors in the receptor-deficient cell line CHO-ldlA7 during the 32-week period of observation as determined by the internalisation assay with the labelled LDL particles. Conclusion Bovine papillomavirus type-1 (BPV-1-derived vectors could be suitable for gene therapy due to their episomal maintenance at intermediate to high copy number and stable, high-level expression of the gene products. The constructed BPV-1 based vector p3.7LDL produced functionally active LDL receptors in the LDLR-deficient cell line CHO-ldlA7 during the 32-week period of observation. In vivo experiments should reveal, whether 1–5% transfection efficiency obtained in the current work is sufficient to bring about detectable and clinically significant lowering of the amount of circulating LDL cholesterol particles.

  6. Investigation of MDA-LDL (malondialdehyde-modified low-density lipoprotein) as a prognostic marker for coronary artery disease in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Kotani, Kazuo; Tashiro, Jun; Yamazaki, Kenya; Nakamura, Yoshitake; Miyazaki, Akira; Bujo, Hideaki; Saito, Yasushi; Kanno, Takashi; Maekawa, Masato

    2015-10-23

    Although increased circulating levels of malondialdehyde-modified low-density lipoprotein (MDA-LDL) are associated with coronary artery disease (CAD), there is no direct evidence that increased MDA-LDL is a prognostic factor for CAD. Forty-two patients (20 diabetic and 22 non-diabetic patients) who underwent percutaneous coronary intervention (PCI) were enrolled, and their baseline MDA-LDL levels were determined by immunoassay. Follow-up coronary angiography was performed at 2 to 7 months post-PCI. The patients were then divided into 2 groups, with in-stent restenosis (ISR) (n=13) and without ISR (n=29), and the baseline MDA-LDL levels were compared. We also studied 34 diabetics with CAD for up to 57 months until the onset of the next coronary event. In the diabetic patients, the mean MDA-LDL level was significantly higher in those with ISR than in those without ISR (151+/-61 vs. 90+/-26 U/l, p=0.010). A baseline MDA-LDL value of 110 U/l for differentiating between diabetics with and without ISR was defined as the cut-off value. Kaplan-Meier analysis demonstrated that a circulating MDA-LDL of ≥ 110 U/l correlated significantly with a higher prevalence of cardiac events than MDA-LDL diabetic patients with CAD. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Phenolic-extract from argan oil (Argania spinosa L.) inhibits human low-density lipoprotein (LDL) oxidation and enhances cholesterol efflux from human THP-1 macrophages.

    Science.gov (United States)

    Berrougui, Hicham; Cloutier, Martin; Isabelle, Maxim; Khalil, Abdelouahed

    2006-02-01

    Argan oil is rich in unsaturated fatty acids, tocopherol and phenolic compounds. These protective molecules make further study of its cardiovascular diseases (CVDs) action interesting. Furthermore, no previous study has explored the antioxidant activity of argan oil in comparison with olive oil. The present study was conducted to evaluate the beneficial properties of Virgin argan oil phenolic extracts (VAO-PE) towards CVD by: (A) protecting human (low-density lipoprotein, LDL) against lipid peroxidation and (B) promoting high-density lipoprotein (HDL)-mediated cholesterol efflux. Human LDLs were oxidized by incubation with CuSO(4) in the presence of different concentrations of VAO-PE (0-320mug/ml). LDL lipid peroxidation was evaluated by conjugated diene and MDA formation as well as Vitamin E disappearance. Incubation of LDL with VAO-PE significantly prolonged the lag-phase and lowered the progression rate of lipid peroxidation (Pargan oil provides a source of dietary phenolic antioxidants, which prevent cardiovascular diseases by inhibiting LDL-oxidation and enhancing reverse cholesterol transport. These properties increase the anti-atherogenic potential of HDL.

  8. Microarray analysis of ox-LDL (oxidized low-density lipoprotein)-regulated genes in human coronary artery smooth muscle cells.

    Science.gov (United States)

    Minta, Joe; Jungwon Yun, James; St Bernard, Rosanne

    2010-01-01

    Recent studies suggest that circulating LDL (low-density lipoproteins) play a central role in the pathogenesis of atherosclerosis, and the oxidized form (ox-LDL) is highly atherogenic. Deposits of ox-LDL have been found in atherosclerotic plaques, and ox-LDL has been shown to promote monocyte recruitment, foam cell formation and the transition of quiescent and contractile vascular SMCs (smooth muscle cells) to the migratory and proliferative phenotype. SMC phenotype transition and hyperplasia are the pivotal events in the pathogenesis of atherosclerosis. To comprehend the complex molecular mechanisms involved in ox-LDL-mediated SMC phenotype transition, we have compared the differential gene expression profiles of cultured quiescent human coronary artery SMCs with cells induced with ox-LDL for 3 and 21 h using Affymetrix HG-133UA cDNA microarray chips. Assignment of the regulated genes into functional groups indicated that several genes involved in metabolism, membrane transport, cell-cell interactions, signal transduction, transcription, translation, cell migration, proliferation and apoptosis were differentially expressed. Our data suggests that the interaction of ox-LDL with its cognate receptors on SMCs modulates the induction of several growth factors and cytokines, which activate a variety of intracellular signalling mechanisms (including PI3K, MAPK, Jak/STAT, sphingosine, Rho kinase pathways) that contribute to SMC transition from the quiescent and contractile phenotype to the proliferative and migratory phenotype. Our study has also identified several genes (including CDC27, cyclin A1, cyclin G2, glypican 1, MINOR, p15 and apolipoprotein) not previously implicated in ox-LDL-induced SMC phenotype transition and substantially extends the list of potential candidate genes involved in atherogenesis.

  9. Protective effect of the silkworm protein 30Kc6 on human vascular endothelial cells damaged by oxidized low density lipoprotein (Ox-LDL).

    Science.gov (United States)

    Yu, Wei; Ying, Huihui; Tong, Fudan; Zhang, Chen; Quan, Yanping; Zhang, Yaozhou

    2013-01-01

    Although the 30K family proteins are important anti-apoptotic molecules in silkworm hemolymph, the underlying mechanism remains to be investigated. This is especially the case in human vascular endothelial cells (HUVECs). In this study, a 30K protein, 30Kc6, was successfully expressed and purified using the Bac-to-Bac baculovirus expression system in silkworm cells. Furthermore, the 30Kc6 expressed in Escherichia coli was used to generate a polyclonal antibody. Western blot analysis revealed that the antibody could react specifically with the purified 30Kc6 expressed in silkworm cells. The In vitro cell apoptosis model of HUVEC that was induced by oxidized low density lipoprotein (Ox-LDL) and in vivo atherosclerosis rabbit model were constructed and were employed to analyze the protective effects of the silkworm protein 30Kc6 on these models. The results demonstrated that the silkworm protein 30Kc6 significantly enhanced the cell viability in HUVEC cells treated with Ox-LDL, decreased the degree of DNA fragmentation and markedly reduced the level of 8-isoprostane. This could be indicative of the silkworm protein 30Kc6 antagonizing the Ox-LDL-induced cell apoptosis by inhibiting the intracellular reactive oxygen species (ROS) generation. Furthermore, Ox-LDL activated the cell mitogen activated protein kinases (MAPK), especially JNK and p38. As demonstrated with Western analysis, 30Kc6 inhibited Ox-LDL-induced cell apoptosis in HUVEC cells by preventing the MAPK signaling pathways. In vivo data have demonstrated that oral feeding of the silkworm protein 30Kc6 dramatically improved the conditions of the atherosclerotic rabbits by decreasing serum levels of total triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Furthermore, 30Kc6 alleviated the extent of lesions in aorta and liver in the atherosclerotic rabbits. These data are not only helpful in understanding the anti

  10. Protective effect of the silkworm protein 30Kc6 on human vascular endothelial cells damaged by oxidized low density lipoprotein (Ox-LDL.

    Directory of Open Access Journals (Sweden)

    Wei Yu

    Full Text Available Although the 30K family proteins are important anti-apoptotic molecules in silkworm hemolymph, the underlying mechanism remains to be investigated. This is especially the case in human vascular endothelial cells (HUVECs. In this study, a 30K protein, 30Kc6, was successfully expressed and purified using the Bac-to-Bac baculovirus expression system in silkworm cells. Furthermore, the 30Kc6 expressed in Escherichia coli was used to generate a polyclonal antibody. Western blot analysis revealed that the antibody could react specifically with the purified 30Kc6 expressed in silkworm cells. The In vitro cell apoptosis model of HUVEC that was induced by oxidized low density lipoprotein (Ox-LDL and in vivo atherosclerosis rabbit model were constructed and were employed to analyze the protective effects of the silkworm protein 30Kc6 on these models. The results demonstrated that the silkworm protein 30Kc6 significantly enhanced the cell viability in HUVEC cells treated with Ox-LDL, decreased the degree of DNA fragmentation and markedly reduced the level of 8-isoprostane. This could be indicative of the silkworm protein 30Kc6 antagonizing the Ox-LDL-induced cell apoptosis by inhibiting the intracellular reactive oxygen species (ROS generation. Furthermore, Ox-LDL activated the cell mitogen activated protein kinases (MAPK, especially JNK and p38. As demonstrated with Western analysis, 30Kc6 inhibited Ox-LDL-induced cell apoptosis in HUVEC cells by preventing the MAPK signaling pathways. In vivo data have demonstrated that oral feeding of the silkworm protein 30Kc6 dramatically improved the conditions of the atherosclerotic rabbits by decreasing serum levels of total triglyceride (TG, high density lipoprotein cholesterol (HDL-C, low density lipoprotein cholesterol (LDL-C and total cholesterol (TC. Furthermore, 30Kc6 alleviated the extent of lesions in aorta and liver in the atherosclerotic rabbits. These data are not only helpful in understanding the anti

  11. 收缩压和LDL-C对颈动脉斑块的影响%Effects of systolic blood pressure and low density lipoprotein on carotid plaques

    Institute of Scientific and Technical Information of China (English)

    姚涛; 李雯; 张晓辉; 孙静; 王德胜; 赵永猛; 王张锋; 赵性泉; 吴寿岭

    2012-01-01

    Objective To explore the different effects of systolic blood pressure(SBP) and low density lipoprotein on carotid plaques(LDL-C).Methods A total of 101 510 serving and retired workers of a company who participated in the health examination in 2006-2009,5852 participants were selected as study subjects by stratified random sampling according to the age and sex ratio.These subjects took their health examination in 2010-2011 including the carotid ultrasound.Finally,5361 eligible participants with complete data were included in the analysis.The detection and weighted rates of carotid plaques were calculated for four groups:normal SBP and LDL-C group (3524 subjects),normal SBP and high LDL-C group (356 subjects),elevated SBP and normal LDL-C group (1308 subjects) and elevated SBP and high LDL-C group (173 subjects).The effects of different baseline SBP and LDL-C on detection rates of the carotid artery plaques were analyzed by logistic regression.Results The detection rate of carotid plaques in normal SBP and LDL-C group,normal SBP and high LDL-C group,elevated SBP and normal LDL-C group,elevated SBP and high LDL-C group was 33.7% (1186/3524),41.3% (147/356),64.8% (847/1308),68.8% (119/173) (x2 =425.75,P < 0.05) and the weighted detection rate was 36.0%,42.0%,64.5%and 68.3 % respectively.For men,the detection rate was 44.2% (877/1985),51.1% (97/190),70.6%(657/930),71.3% (82/1 15) (x2 =194.02,P < 0.05) and the weighted detection rate was 31.2%,36.1%,49.8% and 50.3% respectively.For women,the detection rate was 20.1% (309/1539),30.1%(50/166),50.3% (190/378),63.8% (37/58) (x2 =180.17,P < 0.05) and the weighted detection rate was 30.9%,46.3%,70.3%,and 88.1% respectively.After adjusted for other risk factors,the OR (95 % CI) value was 1.37 (1.05-1.78),2.05 (1.74-2.43) and 2.12 (1.45-3.12) for normal SBP and high LDL-C group,elevated SBP and normal LDL-C group and elevated SBP and high LDL-C group respectively compared

  12. Plasma kinetics of an LDL-like non-protein nanoemulsion and transfer of lipids to high-density lipoprotein (HDL) in patients with rheumatoid arthritis.

    Science.gov (United States)

    Pozzi, Fernanda S; Maranhão, Raul C; Guedes, Lissiane K; Borba, Eduardo F; Laurindo, Ieda M M; Bonfa, Eloisa; Vinagre, Carmen G

    2015-01-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with cardiovascular risk, but with normal plasma lipids. The aim was to investigate low-density lipoprotein (LDL) and high-density lipoprotein (HDL) metabolism in RA patients using radioactive nanoemulsions resembling an LDL lipid structure (LDE) as metabolic probes. Thirty patients with RA, 16 in remission and 14 in high activity, and 30 healthy controls were studied. LDE labeled with (14)C-cholesteryl ester ((14)C-CE) and (3)H-unesterified cholesterol ((3)H-UC) was intravenously injected followed by 24-hour plasma sampling. Fractional clearance rates (FCR, h(-1)) were calculated by compartmental analysis. Lipid transfers to HDL were assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids; % lipids transferred to HDL were quantified after chemical precipitation. LDL cholesterol, triglycerides, unesterified cholesterol, and oxidized LDL were equal in RA and controls, and HDL cholesterol was even higher in RA. Compared with controls, apolipoprotein B was lower, apolipoprotein A1 was equal, and apolipoprotein E was higher in RA. Decay curves of LDE labels were faster in RA patients than in controls ((14)C-CE: 0.072 ± 0.066 and 0.038 ± 0.027, P = .0115; (3)H-UC: 0.066 ± 0.042 and 0.035 ± 0.039; P < .0044). FCRs were equal in 2 RA subgroups. Transfer of UC, triglycerides, and phospholipids to HDL was equal between RA and controls, but CE transfer was lower in RA. HDL size was smaller in RA patients than in controls (8.5 ± 0.5 nm; 9.2 ± 0.8 nm, P < .0001). RA patients were more efficient in removing atherogenic LDL from plasma, as indicated by higher CE and UC FCR, with in lower apolipoprotein B. This was unexpected because of the higher cardiovascular risk in RA. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  13. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation

    Science.gov (United States)

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-08-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease.

  14. Chemical structures of 4-oxo-flavonoids in relation to inhibition of oxidized low-density lipoprotein (LDL)-induced vascular endothelial dysfunction.

    Science.gov (United States)

    Yi, Long; Jin, Xin; Chen, Chun-Ye; Fu, Yu-Jie; Zhang, Ting; Chang, Hui; Zhou, Yong; Zhu, Jun-Dong; Zhang, Qian-Yong; Mi, Man-Tian

    2011-01-01

    Vascular endothelial dysfunction induced by oxidative stress has been demonstrated to be the initiation step of atherosclerosis (AS), and flavonoids may play an important role in AS prevention and therapy. Twenty-three flavonoids categorized into flavones, flavonols, isoflavones, and flavanones, all with 4-oxo-pyronenucleus, were examined for what structural characteristics are required for the inhibitory effects on endothelial dysfunction induced by oxidized low-density lipoprotein (oxLDL). Human vascular endothelial cells EA.hy926 were pretreated with different 4-oxo-flavonoids for 2 hs, and then exposed to oxLDL for another 24 hs. Cell viability and the level of malondialdehyde (MDA), nitric oxide (NO) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured, respectively. Then, correlation analysis and paired comparison were used to analyze the structure-activity relationships. Significant correlations were observed between the number of -OH moieties in total or in B-ring and the inhibitory effectson endothelial dysfunction. Furthermore, 3',4'-ortho-dihydroxyl on B-ring, 3-hydroxyl on C-ring and 2,3-double bondwere correlated closely to the inhibitory effects of flavonolson cell viability decrease and lipid peroxidation. 5,7-meta-dihydroxyl group on A-ring was crucial for the anti-inflammatory effects of flavones and isoflavones in endothelial cells. Moreover, the substituted position of B-ring on C3 rather than C2 was important for NO release. Additionally, hydroxylation at C6 position significantly attenuated the inhibitory effects of 4-oxo-flavonoids on endothelial dysfunction. Our findings indicated that the effective agents in inhibiting endothelial dysfunction include myricetin, quercetin, luteolin, apigenin, genistein and daidzein. Our work might provide some evidence for AS prevention and a strategy for the design of novel AS preventive agents.

  15. Chemical Structures of 4-Oxo-Flavonoids in Relation to Inhibition of Oxidized Low-Density Lipoprotein (LDL-Induced Vascular Endothelial Dysfunction

    Directory of Open Access Journals (Sweden)

    Man-Tian Mi

    2011-08-01

    Full Text Available Vascular endothelial dysfunction induced by oxidative stress has been demonstrated to be the initiation step of atherosclerosis (AS, and flavonoids may play an important role in AS prevention and therapy. Twenty-three flavonoids categorized into flavones, flavonols, isoflavones, and flavanones, all with 4-oxo-pyronenucleus, were examined for what structural characteristics are required for the inhibitory effects on endothelial dysfunction induced by oxidized low-density lipoprotein (oxLDL. Human vascular endothelial cells EA.hy926 were pretreated with different 4-oxo-flavonoids for 2 hs, and then exposed to oxLDL for another 24 hs. Cell viability and the level of malondialdehyde (MDA, nitric oxide (NO and soluble intercellular adhesion molecule-1 (sICAM-1 were measured, respectively. Then, correlation analysis and paired comparison were used to analyze the structure–activity relationships. Significant correlations were observed between the number of –OH moieties in total or in B-ring and the inhibitory effectson endothelial dysfunction. Furthermore, 3',4'-ortho-dihydroxyl on B-ring, 3-hydroxyl on C-ring and 2,3-double bondwere correlated closely to the inhibitory effects of flavonolson cell viability decrease and lipid peroxidation. 5,7-meta-dihydroxyl group on A-ring was crucial for the anti-inflammatory effects of flavones and isoflavones in endothelial cells. Moreover, the substituted position of B-ring on C3 rather than C2 was important for NO release. Additionally, hydroxylation at C6 position significantly attenuated the inhibitory effects of 4-oxo-flavonoids on endothelial dysfunction. Our findings indicated that the effective agents in inhibiting endothelial dysfunction include myricetin, quercetin, luteolin, apigenin, genistein and daidzein. Our work might provide some evidence for AS prevention and a strategy for the design of novel AS preventive agents.

  16. Effects of High Fat Feeding and Diabetes on Regression of Atherosclerosis Induced by Low-Density Lipoprotein Receptor Gene Therapy in LDL Receptor-Deficient Mice.

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    Florian Willecke

    Full Text Available We tested whether a high fat diet (HFD containing the inflammatory dietary fatty acid palmitate or insulin deficient diabetes altered the remodeling of atherosclerotic plaques in LDL receptor knockout (Ldlr-/- mice. Cholesterol reduction was achieved by using a helper-dependent adenovirus (HDAd carrying the gene for the low-density lipoprotein receptor (Ldlr; HDAd-LDLR. After injection of the HDAd-LDLR, mice consuming either HFD, which led to insulin resistance but not hyperglycemia, or low fat diet (LFD, showed regression compared to baseline. However there was no difference between the two groups in terms of atherosclerotic lesion size, or CD68+ cell and lipid content. Because of the lack of effects of these two diets, we then tested whether viral-mediated cholesterol reduction would lead to defective regression in mice with greater hyperglycemia. In both normoglycemic and streptozotocin (STZ-treated hyperglycemic mice, HDAd-LDLR significantly reduced plasma cholesterol levels, decreased atherosclerotic lesion size, reduced macrophage area and lipid content, and increased collagen content of plaque in the aortic sinus. However, reductions in anti-inflammatory and ER stress-related genes were less pronounced in STZ-diabetic mice compared to non-diabetic mice. In conclusion, HDAd-mediated Ldlr gene therapy is an effective and simple method to induce atherosclerosis regression in Ldlr-/- mice in different metabolic states.

  17. Goal attainments and their discrepancies for low density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) in over 2,000 Chinese patients with known coronary artery disease or type 2 diabetes.

    Science.gov (United States)

    He, Yong-Ming; Yang, Xiang-Jun; Zhao, Xin; Xu, Hai-Feng

    2015-04-01

    Low density lipoprotein cholesterol (LDL-C) is primary treatment target for patients with dislipidemia. The apolipoprotein B (apo B), an emerging biomarker for cardiovascular risk prediction, appears to be superior to the LDL-C. However, little is known about goal attainments and their discrepancies for LDL-C and apo B in Chinese patients with known CAD or DM. A total of 2,172 hospitalized patients with known coronary artery disease (CAD) or DM, aged >27 years of old, were enrolled. The success rates for apo B and LDL-C goal attainments were evaluated and compared by categorization and by sex. When the success rates for apo B were compared with the ones for LDL-C, the former was higher than the latter across all categorizations, with the statistically significant differences seen in all patients, CAD alone and DM alone (P<0.0001), but not in coexistence of CAD and DM (P=0.190). The trend toward to higher success rates for LDL-C and apo B goal attainments in men than in women were noteworthy across all categorizations although only in all patients and in DM alone patients were the statistically significant differences found (P<0.01). The LDL-C lags behind the apo B in goal attainments in Chinese patients. Whether these discrepancies are associated with the occurrence differences for CAD and for stroke between the East Asia and the Western countries warrants further study.

  18. PENGHAMBATAN OKSIDASI LDL DAN AKUMULASI KOLESTEROL PADA MAKROFAG OLEH EKSTRAK TEMULAWAK (Curcuma xanthorriza Roxb [The Inhibition of Low Density Lipoprotein Oxidation and Cholesterol Accumulation on the Macrophage by Temulawak Extract

    Directory of Open Access Journals (Sweden)

    Aisyah Tri Septiana1

    2006-12-01

    Full Text Available Coronary heart disease is caused among others by atherosclerosis, which is the result of oxidized low density lipoprotein (LDL and cholesterol accumulation on macrophage, and which is inhibited by temulawak (Curcuma xanthorriza Roxb extract. The objective of this study was to find out the kinds and consentration of temulawak extract which could inhibit LDL oxidation, and to find out the effect of temulawak extract on the accumulation of cholesterol on macrophage. Temulawak was extracted by water, ethanol, aceton and dichlorometane. Inhibition of LDL oxidation was found out by measuring the level of malonaldehyde content of oxidized LDL-CuSO4 which was supplemented with water extract, ethanol extract, aceton extract and dichlorometane extract. of temulawak at concentrations of 43 g, 430 g, and 4300 g per ml of LDL. The percentage of malonaldehyde reduction due to supplementation with water extract, ethanol extract, acetone extract and dichloromethane extract was 44.27; 47.68; 51.83 and 61.2 respectively. The inhibition of LDL oxidation by temulawak extract depends on its concentration. The percentage of malonaldehyde reduction due to supplementation with temulawak extract of 43 µg, 430 µg, and 4300 µg per ml of LDL was 43.63; 56.72; and 53.89.. Concentration of temulawak extract resulting in the highest inhibition of LDL oxidation was 430 µg/ml LDL. Temulawak extract tends to inhibit cholesterol accumulation on macrophage. There is a relationship between the inhibition of cholesterol accumulation on the macrophage and the inhibition of LDL oxidation by temulawak extract

  19. Cyclic tensile stretch load and oxidized low density lipoprotein synergistically induce lectin-like oxidized ldl receptor-1 in cultured bovine chondrocytes, resulting in decreased cell viability and proteoglycan synthesis.

    Science.gov (United States)

    Akagi, Masao; Nishimura, Shunji; Yoshida, Kohji; Kakinuma, Takumi; Sawamura, Tatsuya; Munakata, Hiroshi; Hamanishi, Chiaki

    2006-08-01

    Mechanical stimulation is known to be an essential factor in the regulation of cartilage metabolism. We tested the hypothesis that expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) can be modulated by cyclic tensile stretch load in chondrocytes. Cyclic loading of repeated stretch stress at 10 cycles per minute with 10 kPa of stress for 6 h induced expression of LOX-1 to 2.6 times control in cultured bovine articular chondrocytes, equivalent to the addition of 10 microg/mL oxidized low density lipoprotein (ox-LDL) (2.4 times control). Application of the cyclic load to the chondrocytes along with 10 microg/mL ox-LDL resulted in synergistically increased LOX-1 expression to 6.3 times control. Individual application of cyclic loading and 10 microg/mL ox-LDL significantly suppressed chondrocytes viability (84.6% +/- 3.4% and 80.9% +/- 3.2% of control at 24 h, respectively; n = 3; p LDL (n = 3)]. Cyclic loading and 10 microg/mL ox-LDL synergistically affected cell viability and proteoglycan synthesis, which were significantly suppressed to 45.6% +/- 4.9% and 48.7% +/- 6.7% of control at 24 h, respectively (n = 3; p LDL). In this study, we demonstrated synergistic effects of cyclic tensile stretch load and ox-LDL on cell viability and proteoglycan synthesis in chondrocytes, which may be mediated through enhanced expression of LOX-1 and which has important implications in the progression of cartilage degeneration in osteoarthritis.

  20. Low-density lipoprotein analysis in microchip capillary electrophoresis systems

    NARCIS (Netherlands)

    Ceriotti, Laura; Shibata, Takayuki; Folmer, Britta; Weiller, Bruce H.; Roberts, Matthew A.; De Rooij, Nico F.; Verpoorte, Elisabeth

    2002-01-01

    Due to the mounting evidence for altered lipoprotein and cholesterol-lipoprotein content in several disease states, there has been an increasing interest in analytical methods for lipoprotein profiling for diagnosis. The separation of low- and high-density lipoproteins (LDL and HDL, respectively)

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

    NARCIS (Netherlands)

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

    1991-01-01

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

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

    NARCIS (Netherlands)

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

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

  3. Hydrogen sulfide suppresses oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 generation from macrophages via the nuclear factor κB (NF-κB) pathway.

    Science.gov (United States)

    Du, Junbao; Huang, Yaqian; Yan, Hui; Zhang, Qiaoli; Zhao, Manman; Zhu, Mingzhu; Liu, Jia; Chen, Stella X; Bu, Dingfang; Tang, Chaoshu; Jin, Hongfang

    2014-04-01

    This study was designed to examine the role of hydrogen sulfide (H2S) in the generation of oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 (MCP-1) from macrophages and possible mechanisms. THP-1 cells and RAW macrophages were pretreated with sodium hydrosulfide (NaHS) and hexyl acrylate and then treated with ox-LDL. The results showed that ox-LDL treatment down-regulated the H2S/cystathionine-β-synthase pathway, with increased MCP-1 protein and mRNA expression in both THP-1 cells and RAW macrophages. Hexyl acrylate promoted ox-LDL-induced inflammation, whereas the H2S donor NaHS inhibited it. NaHS markedly suppressed NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter in ox-LDL-treated macrophages. Furthermore, NaHS decreased the ratio of free thiol groups in p65, whereas the thiol reductant DTT reversed the inhibiting effect of H2S on the p65 DNA binding activity. Most importantly, site-specific mutation of cysteine 38 to serine in p65 abolished the effect of H2S on the sulfhydration of NF-κB and ox-LDL-induced NF-κB activation. These results suggested that endogenous H2S inhibited ox-LDL-induced macrophage inflammation by suppressing NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter. The sulfhydration of free thiol group on cysteine 38 in p65 served as a molecular mechanism by which H2S inhibited NF-κB pathway activation in ox-LDL-induced macrophage inflammation.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  5. Oxidized low-density lipoprotein in postmenopausal women

    DEFF Research Database (Denmark)

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

    2014-01-01

    of this study was to determine the prevalence of serum oxLDL in postmenopausal women and to identify possible associations of clinical and laboratory features with oxLDL in these patients. METHOD: After clinical examination and completing a clinical questionnaire, an ultrasound examination of both carotid.......10-0.43). Although intima-media thickness did not differ, postmenopausal women with serous oxLDL had more often atherosclerotic plaques compared to women without oxLDL (6/66 vs. 0/467; P high-density lipoprotein, impaired glucose intolerance, and DBP were independently associated...... with the occurrence of oxLDL. If oxLDL was present, higher high-density lipoprotein and glucose intolerance were associated with higher concentrations of oxLDL. In contrast, higher blood urea concentrations were associated with lower concentrations of oxLDL. CONCLUSION: This study presents the prevalence...

  6. 枸杞子糖缀合物及其糖链对LDL氧化修饰的抑制作用%STUDIES ON THE GLYCOCONJUGATES AND GLYCANS FROM LYCIUM BARBARUM L IN INHIBITING LOW DENSITY LIPOPROTEIN (LDL) PEROXIDATION

    Institute of Scientific and Technical Information of China (English)

    黄琳娟; 田庚元; 王仲孚; 董继斌; 吴满平

    2001-01-01

    的 研究枸杞子糖缀合物及其糖链对LDL氧化修饰的抑制作用。方法 在Cu2+诱导的LDL氧化模型中测定了脂质过氧化产物硫代巴比妥酸反应物质(TBARS)的含量及LDL在琼脂糖凝胶电泳上的迁移率以反映从枸杞子中分离、纯化得到的糖缀合物及糖链对LDL氧化修饰的抑制作用。结果 枸杞子糖缀合物及糖链抗LDL氧化的能力是不同的,其中LbGp5可明显的抑制LDL的氧化。结论 枸杞子糖缀合物具有抗LDL氧化作用,而糖链不具有抗LDL氧化的作用。%AIM To determine the effects of glycoconjugates and their glycans from Lycium barbarum L. on inhibiting low density lipoprotein (LDL) peroxidation. METHODS Using Cu2+-induced oxidation as a model, the oxidative production of thiobarbituric acid-reactive substances (TBARS) and the LDL electrophoresis migration on agarose gel were measured. RESULTS The effects of glycoconjugates and their glycans from Lycium barbarum L. on inhibiting LDL peroxidation were different, among them, glycoconjugate LbGp5 showed the best effect on inhibiting LDLperoxidation. CONCLUSION The glycoconjugates can inhibit LDL peroxidatin while their glycans showed no effects on inhibiting LDL peroxidation.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    John S. Parks

    2013-07-01

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

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

    Science.gov (United States)

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

    2013-07-12

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

  11. Apolipoprotein E LDL receptor-binding domain-containing high-density lipoprotein: a nanovehicle to transport curcumin, an antioxidant and anti-amyloid bioflavonoid.

    Science.gov (United States)

    Khumsupan, Panupon; Ramirez, Ricardo; Khumsupan, Darin; Narayanaswami, Vasanthy

    2011-01-01

    Curcumin is an antioxidant and anti-inflammatory bioflavonoid that has been recently identified as an anti-amyloid agent as well. To make it more available in its potent form as a potential amyloid disaggregation agent, we employed high-density lipoproteins (HDL), which are lipid-protein complexes that transport plasma cholesterol, to transport curcumin. The objective of this study was to employ reconstituted HDL containing human apoE3 N-terminal (NT) domain, as a vehicle to transport curcumin. The NT domain serves as a ligand to mediate binding and uptake of lipoprotein complexes via the low-density lipoprotein receptor (LDLr) family of proteins located at the cell surface. Reconstituted HDL was prepared with phospholipids and recombinant apoE3-NT domain in the absence or presence of curcumin. Non-denaturing polyacrylamide gel electrophoresis indicated that the molecular mass and Stokes' diameter of HDL bearing curcumin were ~670kDa and ~17nm, respectively, while electron microscopy revealed the presence of discoidal particles. Fluorescence emission spectra of HDL bearing (the intrinsically fluorescent) curcumin indicated that the wavelength of maximal fluorescence emission (λ(max)) of curcumin was ~495nm, which is highly blue-shifted compared to λ(max) of curcumin in solvents of varying polarity (λ(max) ranging from 515-575nm) or in aqueous buffers. In addition, an enormous enhancement in fluorescence emission intensity was noted in curcumin-containing HDL compared to curcumin in aqueous buffers. Curcumin fluorescence emission was quenched to a significant extent by lipid-based quenchers but not by aqueous quenchers. These observations indicate that curcumin has partitioned efficiently into the hydrophobic milieu of the phospholipid bilayer of HDL. Functional assays indicated that the LDLr-binding ability of curcumin-containing HDL with apoE3-NT is similar to that of HDL without curcumin. Taken together, we report that apoE-containing HDL has a tremendous

  12. MCP-1 binds to oxidized LDL and is carried by lipoprotein(a) in human plasma

    Science.gov (United States)

    Wiesner, Philipp; Tafelmeier, Maria; Chittka, Dominik; Choi, Soo-Ho; Zhang, Li; Byun, Young Sup; Almazan, Felicidad; Yang, Xiaohong; Iqbal, Navaid; Chowdhury, Punam; Maisel, Alan; Witztum, Joseph L.; Handel, Tracy M.; Tsimikas, Sotirios; Miller, Yury I.

    2013-01-01

    Lipoprotein oxidation plays an important role in pathogenesis of atherosclerosis. Oxidized low density lipoprotein (OxLDL) induces profound inflammatory responses in vascular cells, such as production of monocyte chemoattractant protein-1 (MCP-1) [chemokine (C-C motif) ligand 2], a key chemokine in the initiation and progression of vascular inflammation. Here we demonstrate that OxLDL also binds MCP-1 and that the OxLDL-bound MCP-1 retains its ability to recruit monocytes. A human MCP-1 mutant in which basic amino acids Arg-18 and Lys-19 were replaced with Ala did not bind to OxLDL. The MCP-1 binding to OxLDL was inhibited by the monoclonal antibody E06, which binds oxidized phospholipids (OxPLs) in OxLDL. Because OxPLs are carried by lipoprotein(a) [Lp(a)] in human plasma, we tested to determine whether Lp(a) binds MCP-1. Recombinant wild-type but not mutant MCP-1 added to human plasma bound to Lp(a), and its binding was inhibited by E06. Lp(a) captured from human plasma contained MCP-1 and the Lp(a)-associated endogenous MCP-1 induced monocyte migration. These results demonstrate that OxLDL and Lp(a) bind MCP-1 in vitro and in vivo and that OxPLs are major determinants of the MCP-1 binding. The association of MCP-1 with OxLDL and Lp(a) may play a role in modulating monocyte trafficking during atherogenesis. PMID:23667177

  13. Epidemiological reference ranges for low-density lipoprotein ...

    African Journals Online (AJOL)

    1991-04-06

    Apr 6, 1991 ... (LDL-C) and high-density lipoprotein cholesterol (HDL-C) is recommended for subjects .... with this differential precipitation method for LDL-C in non- fasting subjects did not ..... Henderson LO er al. Phase V Preliminary Repor!

  14. Interaction of low density lipoproteins with rat liver cells

    NARCIS (Netherlands)

    L. Harkes (Leendert)

    1985-01-01

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

  15. LDL-C边缘升高患者血清ONOO-、脂联素及TNF-α的变化%Adiponectin and tumor necrosis factor α in patients with borderline high low density lipoprotein cholesterol

    Institute of Scientific and Technical Information of China (English)

    丁铭格; 李榕; 王晓明

    2012-01-01

    目的:观察LDL-C边缘升高患者血清过氧亚硝酸阴离子(ONOO-)、脂联素、肿瘤坏死因子-α(TNF-α)水平的变化及意义.方法:选取LDL-C边缘升高患者50例和健康对照者40例,分别采用酶联免疫吸附法和放射免疫法测定血清ONOO-生成的标记物硝基酪氨酸(NT)、脂联素及TNF-α水平.结果:①与对照组比较,LDL-C边缘升高组血浆NT水平[(14.63±4.93)μmol/L∶(24.78±2.21)μmol/L,P<0.01]与脂联素水平[(5.17±2.36)μg/L∶(7.25±3.19)μg/L,P<0.01]增高,而TNF-α水平降低[(101.8±15.66) μg/L∶(50.37±16.31)μg/L,P<0.01].②LDL-C边缘升高组血清LDL-C水平与脂联素水平(r=0.848 5,P<0.01)及NT水平(r=0.908 7,P<0.05)呈正相关,但与TNF-α无统计学相关性(P>0.05).血清脂联素水平与TNF-α呈负相关(r=-0.539 4,P<0.01).结论:LDL-C边缘升高患者血清ONOO-和脂联素增多,TNF-α的分泌下降.%Objective:To explore plasma peroxynitrite, adiponectin (APN) and tumor necrosis factor a (TNF-α) level and their correlation in patients with borderline high low density lipoprotein cholesterol (LDL-C) level. Method:Fifty patients with borderline high LDL-C level and forty normal controls were enrolled in this study. Plasma levels of nitrotyrosine (NT), APN and TNF-α were detected by ELISA and RIA respectively. Result:① Compared with control group, NT ([14. 63 ± 4. 93]μmol/L vs. [24. 78 + 2. 21]μmol/L, P<0.01) and APN ([5. 17±2. 36]μg/L vs. [7. 25±3. 19]μg/L, P<0. 01) were significantly increased in patients with borderline high LDL-C level, and TNF-α concentrations ([101. 8±15. 66]μg/L vs. [50. 37 + 16. 3l]μg/L, P<0. 01) were decreased. ②LDL-C was correlated positively with APN (r=0. 848 5, P<0. 01) and NT (r=0. 908 7, P< 0.05). APN was correlated negatively with TNF-α(r= -0.539 4, P<0. 01). Conclusion: Increased NT and APN, decreased TNF-o levels were represented during the early stage of hypercholesterolemia.

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

    Science.gov (United States)

    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 lipoproteins, large very low-density lipoprotein (P lipoprotein to smaller high-density lipoprotein particles was increased (P lipoprotein (a) (P 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.

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

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2011-01-01

    To evaluate whether new and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), triglyceride-rich lipoproteins, and HDL cholesterol associate with the risk of cardiovascular disease expected from the effect on lipoprotein levels. Concordance or discordance...... of such genetic determinants with cardiovascular disease risk will either favor or disfavor that these lipoproteins are causally related to cardiovascular disease....

  18. Salvianolic acid B inhibits macrophage uptake of modified low density lipoprotein (mLDL) in a scavenger receptor CD36-dependent manner

    Science.gov (United States)

    Bao, Yi; Wang, Li; Xu, Yanni; Yang, Yuan; Wang, Lifei; Si, Shuyi; Cho, Sunghee; Hong, Bin

    2012-01-01

    CD36, a class B scavenger receptor, has been implicated in the pathogenesis of a host of vascular inflammatory diseases. Through a high-throughput screening (HTS) assay for CD36 antagonist, we previously identified salvianolic acid B (SAB), a hydrophilic component derived from the herb Danshen, as a potential candidate. Danshen, the dried roots of Salvia miltiorrhiza, has been widely used in China for the prevention and treatment of atherosclerosis-related disorders. Previous studies showed that SAB acted as an anti-oxidant by preventing lipid peroxidation and oxidized LDL (oxLDL) formation. The present study was to investigate the specificity and efficacy of SAB in the inhibition of CD36-mediated lipid uptake. SAB reduced modified LDL (mLDL) uptake in a dose-dependent manner in phorbol-12-myristate-13-acetate (PMA)-stimulated THP-1 and RAW 264.7 cells. In the CD36 silenced THP-1 cells, SAB had no effect in reducing mLDL uptake, whereas its over-expression in CHO cells reinstates the effect, indicating a specific involvement of SAB in antagonizing the CD36's function. Surface plasmon resonance (SPR) analysis revealed a direct binding of SAB to CD36 with a high affinity (KD =3.74 μM), confirming physical interactions of SAB with the receptor. Additionally, SAB reduced oxLDL-induced CD36 gene expression in the cultured cell lines and primary macrophages. In ApoE KO mice fed a high fat diet, SAB reduced CD36 gene expression and lipid uptake in macrophages, showing its ability to antagonize CD36 pathways in vivo. These results demonstrate that SAB is an effective CD36 antagonist and suggest SAB as a potential anti-atherosclerotic agent. PMID:22658257

  19. Lipoprotein lipase S447X variant associated with VLDL, LDL and HDL diameter clustering in the MetS

    Science.gov (United States)

    Previous analysis clustered 1,238 individuals from the general population Genetics of Lipid Lowering Drugs Network (GOLDN) study by the size of their fasting very low-density, low-density and high-density lipoproteins (VLDL, LDL, HDL) using latent class analysis. From two of the eight identified gro...

  20. Lipid oxidation in human low-density lipoprotein induced by metmyoglobin/H2O2

    DEFF Research Database (Denmark)

    Witting, P K; Willhite, C A; Davies, Michael Jonathan

    1999-01-01

    Metmyoglobin (metMb) and H(2)O(2) can oxidize low-density lipoprotein (LDL) in vitro, and oxidized LDL may be atherogenic. The role of alpha-tocopherol (alpha-TOH) in LDL oxidation by peroxidases such as metMb is unclear. Herein, we show that during metMb/H(2)O(2)-induced oxidation of native LDL...

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

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

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2011-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  4. Low density lipoproteins mediated nanoplatforms for cancer targeting

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-09-15

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

  5. Development of an integrated model for analysis of the kinetics of apolipoprotein B in plasma very low density lipoproteins, intermediate density lipoproteins, and low density lipoproteins.

    Science.gov (United States)

    Beltz, W F; Kesäniemi, Y A; Howard, B V; Grundy, S M

    1985-01-01

    To quantify more precisely the metabolism of apolipoprotein B (apo B) in human beings, an integrated model was developed for the analysis of the isotope kinetics of apo B in very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL). The experimental basis for model development was a series of 30 triple-isotope studies in which patients received autologous 131I-VLDL, 125I-IDL, and [3H]glycerol as a precursor of VLDL triglycerides. The currently proposed model contains the following components: (a) a VLDL delipidation cascade that has a variable number of subcompartments, (b) a slowly catabolized pool of VLDL, (c) an IDL compartment consisting of two closely connected subcompartments, one of which is outside the immediate circulation, and (d) a two-compartment subsystem for LDL. Because mass data indicate that not all VLDL were converted to LDL, the model allows for irreversible removal of apo B from VLDL (or IDL) subsystems. It accounts for apparent "direct" input of LDL by postulating an early, rapidly metabolized compartment of VLDL that is converted directly to IDL. The model appears to be consistent with specific activity curves from the current triple-isotope studies and with present concepts of lipoprotein physiology; it also can be used to quantify pathways of lipoprotein apo B transport in normal and abnormal states. PMID:4031063

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Lipid droplets play a central role in energy storage and metabolism on a cellular scale. Their core is comprised of hydrophobic lipids covered by a surface region consisting of amphiphilic lipids and proteins. For example, high and low density lipoproteins (HDL and LDL, respectively) are essentia...... of interfacial tension becomes significant for particles with a radius of similar to 5 nm, when the area per molecule in the surface region is...

  7. Correlation of Friedewald's calculated low-density lipoprotein cholesterol levels with direct low-density lipoprotein cholesterol levels in a tertiary care hospital.

    Science.gov (United States)

    Nanda, Sunil Kumar; Bharathy, M; Dinakaran, Asha; Ray, Lopamudra; Ravichandran, K

    2017-01-01

    One of the risk factors for the development of coronary heart disease is high low-density lipoprotein (LDL) cholesterol levels. National Cholesterol Education Program ATP III guidelines suggest drug therapy to be considered at LDL-cholesterol levels >130 mg/dl. This makes accurate reporting of LDL cholesterol crucial in the management of Coronary heart disease. Estimation of LDL cholesterol by direct LDL method is accurate, but it is expensive. Hence, We compared Friedewald's calculated LDL values with direct LDL values. To evaluate the correlation of Friedewalds calculated LDL with direct LDL method. We compared LDL cholesterol measured by Friedewald's formula with direct LDL method in 248 samples between the age group of 20-70 years. Paired t-test was used to test the difference in LDL concentration obtained by a direct method and Friedewald's formula. The level of significance was taken as P correlation formula was used to test the correlation between direct LDL values with Friedewald's formula. There was no significant difference between the direct LDL values when compared to calculated LDL by Friedewalds formula (P = 0.140). Pearson correlation showed there exists good correlation between direct LDL versus Friedewalds formula (correlation coefficient = 0.98). The correlation between direct LDL versus Friedewalds calculated LDL was best at triglycerides values between 101 and 200 mg/dl. This study indicates calculated LDL by Friedewalds equation can be used instead of direct LDL in patients who cannot afford direct LDL method.

  8. Correlation of Friedewald's calculated low-density lipoprotein cholesterol levels with direct low-density lipoprotein cholesterol levels in a tertiary care hospital

    Science.gov (United States)

    Nanda, Sunil Kumar; Bharathy, M; Dinakaran, Asha; Ray, Lopamudra; Ravichandran, K

    2017-01-01

    Background: One of the risk factors for the development of coronary heart disease is high low-density lipoprotein (LDL) cholesterol levels. National Cholesterol Education Program ATP III guidelines suggest drug therapy to be considered at LDL-cholesterol levels >130 mg/dl. This makes accurate reporting of LDL cholesterol crucial in the management of Coronary heart disease. Estimation of LDL cholesterol by direct LDL method is accurate, but it is expensive. Hence, We compared Friedewald's calculated LDL values with direct LDL values. Aim: To evaluate the correlation of Friedewalds calculated LDL with direct LDL method. Materials and Methods: We compared LDL cholesterol measured by Friedewald's formula with direct LDL method in 248 samples between the age group of 20–70 years. Paired t-test was used to test the difference in LDL concentration obtained by a direct method and Friedewald's formula. The level of significance was taken as P values with Friedewald's formula. Results: There was no significant difference between the direct LDL values when compared to calculated LDL by Friedewalds formula (P = 0.140). Pearson correlation showed there exists good correlation between direct LDL versus Friedewalds formula (correlation coefficient = 0.98). The correlation between direct LDL versus Friedewalds calculated LDL was best at triglycerides values between 101 and 200 mg/dl. Conclusion: This study indicates calculated LDL by Friedewalds equation can be used instead of direct LDL in patients who cannot afford direct LDL method.

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

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

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

  10. Eicosapentanoic acid reduces plasma levels of remnant lipoproteins and prevents in vivo peroxidation of LDL in dialysis patients

    National Research Council Canada - National Science Library

    Ando, M; Sanaka, T; Nihei, H

    1999-01-01

    .... Remnant lipoproteins are atherogenic and are frequently observed in uremic plasma. LDL from uremic patients has been shown to be susceptible to in vitro peroxidation, suggesting that oxidized LDL (ox-LDL...

  11. Low-density lipoprotein-lowering strategies: target versus maximalist versus population percentile.

    NARCIS (Netherlands)

    Sniderman, A.D.; Graaf, J. de; Couture, P.

    2012-01-01

    PURPOSE OF REVIEW: Maximalist low-density lipoprotein (LDL)-lowering strategies such as lowering LDL as much as possible or, alternatively, using the most potent LDL-lowering regimens have become increasingly popular. Almost all attention has focused on the potential advantages of these approaches w

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

    NARCIS (Netherlands)

    Murtola, Teemu; Vuorela, Timo A.; Hyvonen, Marja T.; Marrink, Siewert-Jan; Karttunen, Mikko; Vattulainen, Ilpo

    2011-01-01

    Low-density lipoprotein (LDL) transports cholesterol in the bloodstream and plays an important role in the development of cardiovascular diseases, in particular atherosclerosis. Despite its importance to health, the structure of LDL is not known in detail. This is worrying since the lack of LDL's st

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

    Science.gov (United States)

    Tellis, Constantinos C; Tselepis, Alexandros D

    2014-01-01

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

  14. Aggregation and fusion of modified low density lipoprotein.

    Science.gov (United States)

    Pentikäinen, M O; Lehtonen, E M; Kovanen, P T

    1996-12-01

    In atherogenesis, low density lipoprotein (LDL, diameter 22 nm) accumulates in the extracellular space of the arterial intima in the form of aggregates of lipid droplets (droplet diameter up to 400 nm). Here we studied the effects of various established in vitro LDL modifications on LDL aggregation and fusion. LDL was subjected to vortexing, oxidation by copper ions, proteolysis by alpha-chymotrypsin, lipolysis by sphingomyelinase, and nonenzymatic glycosylation, and was induced to form adducts with malondialdehyde or complexes with anti-apoB-100 antibodies. To assess the amount of enlarged LDL-derived structures formed (due to aggregation or fusion), we measured the turbidity of solutions containing modified LDL, and quantified the proportion of modified LDL that 1) sedimented at low-speed centrifugation (14,000 g), 2) floated at an increased rate at high-speed centrifugation (rate zonal flotation at 285,000 gmax), 3) were excluded in size-exclusion column chromatography (exclusion limit 40 MDa), or 4) failed to enter into 0.5%. Fast Lane agarose gel during electrophoresis. To detect whether particle fusion had contributed to the formation of the enlarged LDL-derived structures, particle morphology was examined using negative staining and thin-section transmission electron microscopy. We found that 1) aggregation was induced by the formation of LDL-antibody complexes, malondialdehyde treatment, and glycosylation of LDL; 2) fusion of LDL was induced by proteolysis of LDL by alpha-chymotrypsin; and 3) aggregation and fusion of LDL were induced by vortexing, oxidation by copper ions, and lipolysis by sphingomyclinase of LDL. The various modifications of LDL differed in their ability to induce aggregation and fusion.

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

    OpenAIRE

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-06-14

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

  17. Low-Density Lipoprotein Cholesterol, Non-High-Density Lipoprotein Cholesterol, Triglycerides, and Apolipoprotein B and Cardiovascular Risk in Patients With Manifest Arterial Disease

    NARCIS (Netherlands)

    van den Berg, M Johanneke; van der Graaf, Yolanda; de Borst, Gert Jan; Kappelle, L Jaap; Nathoe, Hendrik M; Visseren, Frank L J

    2016-01-01

    Low-density lipoprotein cholesterol (LDL-C) only partly represents the atherogenic lipid burden, and a growing body of evidence suggests that non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and apolipoprotein B (apoB) are more accurate in estimating lipid-related cardiovascular

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

    Directory of Open Access Journals (Sweden)

    Simon C Mathews

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

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

    Science.gov (United States)

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

    2007-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Katrin Hübner

    2008-05-01

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

  1. In LDL receptor-deficient mice, catabolism of remnant lipoproteins requires a high level of apoE but is inhibited by excess apoE

    NARCIS (Netherlands)

    Dijk, K.W. van; Vlijmen, B.J.M. van; Hof, H.B. van 't; Zee, A. van der; Santamarina-Fojo, S.; Berkel, T.J.C. van; Havekes, L.M.; Hofker, M.H.

    1999-01-01

    To investigate the quantitative requirement for apolipoprotein (apo) E in the clearance of lipoproteins via the non-low density lipoprotein (LDL) receptor mediated pathway, human APOE was overexpressed at various levels in the livers of mice deficient for both the endogenous Apoe and Ldlr genes

  2. Abnormal high density lipoproteins in cerebrotendinous xanthomatosis

    Energy Technology Data Exchange (ETDEWEB)

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

    1981-11-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

  4. Low density lipoproteins as circulating fast temperature sensors.

    Directory of Open Access Journals (Sweden)

    Ruth Prassl

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    1996-06-01

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

  7. 血清 LDL-C 水平与老年射血分数降低性心衰患者预后的关系%Prognostic significance of serum low - density lipoprotein cholesterol levels in elderly patients hospitalized for heart failure with reduced ejection fraction

    Institute of Scientific and Technical Information of China (English)

    田甜; 徐予; 夏长伟; 张新雨

    2016-01-01

    Objective To observe the long - term relationship between levels of low - density lipoprotein cholesterol and post - discharge mortality among elderly patients hospitalized for heart failure with reduced ejection fraction(HFrEF). Methods This study was a single - center retrospective study. A total of 340 elderly HFrEF patients were included from August of 2007 to February of 2012. The cohort was divided into tertiles according to LDL - C levels:the low LDL - C level group(LDL - C≤2. 2667 mmol/ L),the moderate LDL - C level group( LDL - C 2. 873 3 mmol/ L ≤ )and the high LDL - C level group(LDL - C ﹥2. 873 3 mmol/ L). All - cause mortalities were compared. The impact of the different levels of LDL - C on all - cause mortality was analyzed by using multiariable Cox proportional hazards regression model. Results There were 116 all - cause deaths. All - cause mortality in the high LDL - C level group(23. 89%) was significantly lower than the moderate LDL - C level group( 36. 09%)and the low LDL - C level group( 43. 36%). Kaplan - Meier curves showed the all - cause mortality was lower in the high LDL - C level group than in the other two groups. According to the Cox proportional hazards regression model,the patients in the low LDL - C level group had a hazard ratio of all - cause death of 2. 135(95%CI:1. 311 ~3. 477,P = 0. 002)compared to those with high LDL - C level. Conclusion The high LDL - C levels were associated with a reduced post - discharge mortality among elderly patients hospitalized for HFrEF.%目的:研究血清低密度脂蛋白胆固醇(LDL - C)水平对老年住院射血分数降低性心力衰竭(HFrEF)患者长期预后的影响。方法本研究为单中心回顾性研究。选取2007年8月至2012年2月于郑州大学人民医院住院治疗的不同病因的340例老年 HFrEF 患者,依据血清 LDL - C 水平分为3组:低水平 LDL - C 组(LDL - C≤2.2667 mmol/ L),中等水平 LDL - C 组(LDL - C≤2.8733 mmol/ L

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

    Science.gov (United States)

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

    2014-03-03

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  10. Effects of Oxidized Low Density Lipoprotein and Native LDL on Low Shear-Induced Platelet Aggregation(Special Issue in Hornor of the Retirement of Professor Makoto Iwata at the Department of Neurology, Tokyo Women's Medical University)

    OpenAIRE

    矢野, 知佐子; 山崎, 昌子; 内山, 真一郎; 岩田, 誠; YANO, Chisako; YAMAZAKI, Masako; UCHIYAMA, Shinichiro; IWATA, Makoto

    2008-01-01

    Oxidized LDL (ox-LDL) is known to be closely associated with atherosclerosis, and it is one of the sources of oxidized cellular injury. Previous studies show that ox-LDL affects platelet aggregation. We studied the effects of ox-LDL on shear-induced platelet aggregation (SIPA) and compared it with native LDL. Methods: We incubated ox-LDL with LDL and CuSO_4 for 16 hours at 37℃. We incubated platelet-rich plasma (PRP) with ox-LDL or native LDL, and measured SIP A. And we compared the effect of...

  11. Enzymatic Modification of Plasma Low Density Lipoproteins in Rabbits: A Potential Treatment for Hypercholesterolemia

    Science.gov (United States)

    Labeque, Regine; Mullon, Claudy J. P.; Ferreira, Joao Paulo M.; Lees, Robert S.; Langer, Robert

    1993-04-01

    Phospholipase A_2 (EC 3.1.1.4) hydrolyzes certain phospholipids of low density lipoprotein (LDL). Plasma clearance of phospholipase A_2-modified human LDL is up to 17 times faster than that of native human LDL in hypercholesterolemic rabbits. Modification of blood lipoproteins of hypercholesterolemic rabbits was performed by using an extracorporeal circuit containing immobilized phospholipase A_2. After 90-min treatments, nearly 30% decreases in plasma cholesterol concentrations were observed. Erythrocyte, leukocyte, and platelet counts showed no net change after treatment. This technique does not require any fluid replacement or sorbent regeneration and offers a potential approach for lowering serum cholesterol and LDL levels.

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

    Science.gov (United States)

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

    2012-07-01

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

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

    Science.gov (United States)

    Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2011-04-01

    To evaluate whether new and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), triglyceride-rich lipoproteins, and HDL cholesterol associate with the risk of cardiovascular disease expected from the effect on lipoprotein levels. Concordance or discordance of such genetic determinants with cardiovascular disease risk will either favor or disfavor that these lipoproteins are causally related to cardiovascular disease. Evidence for concordance or discordance with cardiovascular disease risk has come from Mendelian randomization studies, whereas indirect evidence also has emerged from genome-wide and candidate gene association studies. The major limitations of studies of genetic variation and concordance or discordance with cardiovascular disease are pleiotropic effects of the variants studied, and/or lack of sufficient statistical power of the majority of studies to firmly demonstrate a positive association, or even more difficult, to exclude an association. New and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), and triglyceride-rich lipoproteins are concordant with both the magnitude and direction of the expected risk of cardiovascular disease, whereas this is unclear for HDL cholesterol. The data are compatible with cardiovascular disease causality for the three former lipoprotein classes, but not for HDL cholesterol.

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  15. Phenotype of heterozygotes for low-density lipoprotein receptor mutations identified in different background populations

    DEFF Research Database (Denmark)

    Tybjaerg-Hansen, Anne; Jensen, Henrik Kjaerulf; Benn, Marianne

    2005-01-01

    The effect of mutations on phenotype is often overestimated because of ascertainment bias. We determined the effect of background population on cholesterol phenotype associated with specific mutations in the low-density lipoprotein (LDL) receptor and the relative importance of background population...... and type of mutation (LDL receptor [LDLR] or APOB R3500Q) for cholesterol phenotype....

  16. Remnant lipoproteins induced proliferation of human prostate cancer cell, PC-3 but not LNCaP, via low density lipoprotein receptor.

    Science.gov (United States)

    Sekine, Yoshitaka; Koike, Hidekazu; Nakano, Takamitsu; Nakajima, Katsuyuki; Takahashi, Sadao; Suzuki, Kazuhiro

    2009-07-01

    Hypertriglyceridemia has been shown to be one of the risk factors for prostate cancer. In this study, we investigated the effect of remnant lipoproteins on cell growth in prostate cancer cell lines. Remnant lipoproteins were isolated as remnant like particles (RLP) from human plasma. We used RLP for TG-rich lipoproteins and low density lipoproteins (LDL) for cholesterol-rich lipoproteins respectively and examined the effect of lipoproteins on proliferation of PC-3 and LNCaP cells using MTS assays. Moreover, we studied the effect of RLP and LDL treatment on the regulation of lipoprotein receptors in prostate cancer cells to investigate the relationship between lipoprotein-induced cell proliferation and lipoprotein receptor expression using real-time PCR, Western blotting assays and siRNA. RLP effectively induced PC-3 cell proliferation more than LDL, whereas both RLP and LDL could not induce LNCaP cell proliferation except at a higher concentration of RLP. LDL receptor (LDLr) was expressed in both prostate cancer cells but there was a sharp difference of sterol regulation between two cells. In PC-3 cells, LDL decreased the LDLr expression in some degree, but RLP did not. Meanwhile LDLr expression in LNCaP was easily downregulated by RLP and LDL. Blocking LDLr function significantly inhibited both RLP- and LDL-induced PC-3 cell proliferation. This study demonstrated that RLP-induced PC-3 cell proliferation more than LDL; however, both RLP and LDL hardly induced LNCaP cell proliferation. The differences of proliferation by lipoproteins might be involved in the regulation of LDLr expression.

  17. EFFECT OF HERB-MEDICINE-CAKE-SEPARATED MOXIBUSTION ON SERUM LIPOPROTEIN CONTENTS AND RATIO OF HDL-Ch AND LDL-Ch IN HYPERLIPEMIA RABBITS

    Institute of Scientific and Technical Information of China (English)

    常小荣; 严洁; 岳增辉; 易受乡; 林亚平; 曹湘平; 沈菁

    2004-01-01

    Objective: To observe the effect of herb-medicine-cake-separated moxibustion on serum lipoprotein in hyperlipemia rabbits. Methods: 55 New-Zealand rabbits were randomly divided into control group (n=13), model group (n=14), direct moxibustion group (n=14) and herb-medicine-cake-separated moxibustion (indirect moxibustion) group (n=14). Hyperlipemia model was established by feeding the animals with specialized forage (15% vitellus powder, 5% lard, 0.5% cholesterol and common forage) for 6 weeks. Moxibustion was applied to "Juque"(CV 14), "Tianshu"(ST 25), "Fenglong"(ST 40), etc., 4 moxa-cones for every acupoint, once daily and continuously for 40 days. Serum high density lipoprotein-cholesterol (HDL-Ch), low density lipoprotein-cholesterol (LDL-Ch) and total cholesterol (TCh) contents were assayed with colorimetric method. Results: Compared with control group, serum LDL-Ch content, HDL-Ch/LDL-Ch and HDL-Ch/TCh of model group were significantly higher (P<0.05~0.01), while compared with model group, LDL-Ch contents of two moxibustion groups were strikingly lower (P<0.01). No significant differences were found between two moxibustion groups in all the 4 indexes. Conclusion: Both direct and indirect moxibustion can effectively lower serum LDL-Ch, raise HDL-Ch, HDL-Ch/LDL-Ch and HDL-Ch/TCh, and regulate lipoprotein metabolism in hyperlipemia rabbits.

  18. Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

    DEFF Research Database (Denmark)

    Varbo, Anette; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2013-01-01

    Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown....

  19. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

    DEFF Research Database (Denmark)

    Chapman, M John; Ginsberg, Henry N; Amarenco, Pierre

    2011-01-01

    Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipop...

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

    Science.gov (United States)

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

    2014-12-01

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

  1. Circulating Lipoproteins: A Trojan Horse Guiding Squalenoylated Drugs to LDL-Accumulating Cancer Cells.

    Science.gov (United States)

    Sobot, Dunja; Mura, Simona; Rouquette, Marie; Vukosavljevic, Branko; Cayre, Fanny; Buchy, Eric; Pieters, Grégory; Garcia-Argote, Sébastien; Windbergs, Maike; Desmaële, Didier; Couvreur, Patrick

    2017-07-05

    Selective delivery of anticancer drugs to rapidly growing cancer cells can be achieved by taking advantage of their high receptor-mediated uptake of low-density lipoproteins (LDLs). Indeed, we have recently discovered that nanoparticles made of the squalene derivative of the anticancer agent gemcitabine (SQGem) strongly interacted with the LDLs in the human blood. In the present study, we showed both in vitro and in vivo that such interaction led to the preferential accumulation of SQGem in cancer cells (MDA-MB-231) with high LDL receptor expression. As a result, an improved pharmacological activity has been observed in MDA-MB-231 tumor-bearing mice, an experimental model with a low sensitivity to gemcitabine. Accordingly, we proved that the use of squalene moieties not only induced the gemcitabine insertion into lipoproteins, but that it could also be exploited to indirectly target cancer cells in vivo. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  2. Reliability of Calculated Low-Density Lipoprotein Cholesterol.

    Science.gov (United States)

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

    2015-08-15

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Cédric Delporte

    2013-01-01

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

  5. [Elevated Lipoprotein(a) Cncentration and Presence of Subfractions of Small Dense Low Density Lipoproteins as Independent Factors of Risk of Ischemic Heart Disease].

    Science.gov (United States)

    Afanasieva, O I; Utkina, E A; Artemieva, N V; Ezhov, M V; Adamova, I Yu; Pokrovsky, S N

    2016-06-01

    To study relation of lipoproteina - Lp(a) and subfractional composition of apoB containing lipoproteins to the presence of ischemic heart disease (IHD). Manerial and methods. Parameters of lipid spectrum, Lp(a), and subfractions of apoB containing lipoproteins were determined in blood serum of 187 patients with known data of instrumental examination. Lp(a) concentration was not linked to any of risk factors, levels total cholesterol (TC), low and high density lipoprotein CH, and subfractions of lipoproteins. In total group triglyceride (TGG) level correlated with content of small dense LDL (sdLDL) (r=0.445, 2 mg/dl in blood plasma (atherogenic profile B), as well as lowering of concentration of large LDL subfractions significantly increased probability of IHD presence in patients with elevated Lp(a) concentration Lp(a) concentration. Lp(a) is an independent factor of risk of coronary atherosclerosis more significant than shifts in subfractional composition of apoB containing lipoproteins. In patients with Lp(a) concentration less or equal 30 mg/dl subfractions of sdLDL were directly related to TG. Level of sdLDL and large lipoproteins of intermediate density are directly related to the presence of IHD. Large LDL correlates with concentration of HDL DL C and probably is cardioprotective. sdLDL content>2 mg/l or hypertriglyceridemia (TG>1.7 mmol/l) significantly increase chances of detection of confirmed IHD in patients with elevated Lp(a).

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

    Directory of Open Access Journals (Sweden)

    Hanson Mary E

    2010-11-01

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

  7. Transvascular low-density lipoprotein transport in patients with diabetes mellitus (type 2)

    DEFF Research Database (Denmark)

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

    2002-01-01

    accumulation and, thus, atherosclerosis. METHODS AND RESULTS: We developed an in vivo method for measurement of transvascular transport of low density lipoprotein (LDL) and applied it in 16 patients with maturity-onset diabetes (type 2) and 29 healthy control subjects. Autologous 131I-labeled LDL...... plasma insulin levels in diabetic patients. CONCLUSIONS: Transvascular LDL transport may be increased in patients with type 2 diabetes. This suggests that lipoprotein flux into the arterial wall is increased in people with diabetes, possibly explaining the accelerated development of atherosclerosis....... in patients with diabetes and control subjects, respectively (P2.5%/h and 5.3+/-1.6%/h (P

  8. Association of triglyceride-rich lipoproteins-related markers and low-density lipoprotein heterogeneity with cardiovascular risk: effectiveness of polyacrylamide-gel electrophoresis as a method of determining low-density lipoprotein particle size.

    Science.gov (United States)

    Tani, Shigemasa; Matsumoto, Michiaki; Nagao, Ken; Hirayama, Atsushi

    2014-01-01

    Despite well-controlled low-density lipoprotein cholesterol (LDL-C), hypertriglyceridemia is an independent predictor of coronary events. We investigated the risk of atherosclerotic cardiovascular disease through examining the relation between triglyceride (TG) metabolism and LDL-heterogeneity as assessed by polyacrylamide-gel electrophoresis (PAGE). Estimated LDL-particle size [relative LDL migration (LDL-Rm value)] measured by PAGE with the LipoPhor system (Joko, Tokyo, Japan) was evaluated in 645 consecutive patients with one additional risk factor for atherosclerotic cardiovascular disease.Multivariate regression analysis after adjustments for traditional risk factors revealed an elevated triglyceride-rich lipoproteins (TRLs)-related markers [TG, remnant-like particle cholesterol (RLP-C), very LDL (VLDL) fraction, apolipoprotein (apo) C-II, and apo C-III] level to be an independent predictor of smaller-size LDL-particle size, both in the overall population, and in a subset of patients with serum LDL-C cardiovascular disease, it may be of particular importance to pay attention not only to the quantitative change in the serum LDL-C, but also TG-metabolism associated with LDL-heterogeneity. Combined evaluation of TRLs-related markers and LDL-Rm value may be useful for assessing the risk of atherosclerotic cardiovascular disease. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  9. PCSK9 R46L Loss-of-Function Mutation Reduces Lipoprotein(a), LDL Cholesterol, and Risk of Aortic Valve Stenosis

    DEFF Research Database (Denmark)

    Langsted, Anne; Nordestgaard, Børge; Benn, Marianne

    2016-01-01

    CONTEXT: Novel, low-density lipoprotein (LDL) cholesterol-lowering proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors also lower lipoprotein(a) levels, but the effect on aortic valve stenosis and myocardial infarction is unknown. OBJECTIVE: We tested the hypothesis that the PCSK9 R46L...... loss-of-function mutation is associated with lower levels of lipoprotein(a) and with reduced risk of aortic valve stenosis and myocardial infarction. DESIGN: We used two prospective cohort studies of the general population and one patient-based cohort. SETTING: Cohort studies selected at random...... individuals of Danish descent. PARTICIPANTS: We studied 103 083 individuals from the Copenhagen General Population Study, the Copenhagen City Heart Study, and the Copenhagen Ischemic Heart Disease Study. MAIN OUTCOME MEASURES: Lipoprotein(a), LDL cholesterol, and PCSK9 R46L genotype and diagnoses of aortic...

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

    Science.gov (United States)

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

    2016-01-01

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

  11. Effects of atorvastatin and simvastatin on low-density lipoprotein subfraction profile, low-density lipoprotein oxidizability, and antibodies to oxidized low-density lipoprotein in relation to carotid intima media thickness in familial hypercholesterolemia.

    NARCIS (Netherlands)

    Tits, L.J.H. van; Smilde, T.J.; Wissen, S. van; Graaf, J. de; Kastelein, J.J.P.; Stalenhoef, A.F.H.

    2004-01-01

    BACKGROUND: Little is known about the effects of statins on the quality of circulating low-density lipoprotein (LDL) in relation to atherosclerosis progression. METHODS: In a double-blind, randomized trial of 325 patients with familial hypercholesterolemia (FH), we assessed the effects of high-dose

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

    Directory of Open Access Journals (Sweden)

    Rivasi Paolo

    2009-12-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2011-05-01

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

  15. Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels

    Science.gov (United States)

    Maximal doses of atorvastatin and rosuvastatin are highly effective in lowering low-density lipoprotein (LDL) cholesterol and triglyceride levels; however, rosuvastatin has been shown to be significantly more effective than atorvastatin in lowering LDL cholesterol and in increasing high-density lipo...

  16. Nonpharmacological approaches for reducing serum low-density lipoprotein cholesterol.

    Science.gov (United States)

    Griffin, Bruce A

    2014-07-01

    To reinforce the key role of diet and lifestyle modification as the first-line treatment for the reduction of raised serum low-density lipoprotein cholesterol (LDL-C) and prevention of cardiovascular disease. Also, to counter recent claims that the current dietary guidelines for the treatment of cardiovascular disease have misplaced emphasis on the importance of removing dietary saturated fat instead of sugar. This review provides new insight into the effects of diet and lifestyle factors with established efficacy in lowering serum LDL-C. This includes energy-restricted weight loss and new findings on the effects of alternative day fasting; novel metabolic and molecular effects of replacing palmitic acid with oleic acid; evidence for a dose-response relationship between the intake of dietary stanols and LDL-C; and identification of a unique metabolic pathway for the excretion of cholesterol. The review reports new evidence for the efficacy of alternate day fasting, reassurance that the current dietary guidelines are not misguided by recommending removal of saturated fat, that a high intake of dietary stanols can achieve a reduction in LDL-C of up to 18%, and describes a pathway of cholesterol excretion that may help to explain variation in the response of serum LDL-C to dietary fat and cholesterol.

  17. Low density lipoprotein levels linkage with the periodontal status patients of coronary heart disease

    Science.gov (United States)

    Ahmad, Nafisah Ibrahim; Masulili, Sri Lelyati C.; Lessang, Robert; Radi, Basuni

    2017-02-01

    Studies found an association between periodontitis and coronary heart disease (CHD), but relationship between periodontal status CHD patients with LDL (Low Density Lipoprotein) levels, as risk factors for atherosclerosis, has not been studied. Objective: To analyze relationship between LDL and periodontal status CHD. Methods: Periodontal status of 60 CHD, 40 controls were examined (PBI, PPD, CAL) and their blood was taken to assess levels of LDL. Result: Found significant differences LDL (p=0.005), correlation between LDL with PPD (p=0.003) and CAL CHD (p=0.013), and PPD (p=0.001), CAL (p=0.008) non-CHD, but no significant correlation between LDL with PBI CAD (p=0.689) and PBI non-CHD (p=0.320). Conclusion: There is a correlation between the LDL levels with periodontal status.

  18. Fatty liver in men is associated with high serum levels of small, dense low-density lipoprotein cholesterol

    Directory of Open Access Journals (Sweden)

    Hosoyamada Kaori

    2012-07-01

    Full Text Available Abstract Aims Our study addressed potential associations between fatty liver and small, dense low-density lipoprotein cholesterol (sd-LDL-C levels using a cross-sectional analysis. Methods We enrolled 476 male subjects. Serum sd-LDL-C concentrations were determined using precipitation assays. Results Subjects were divided into four groups based on triglyceride (TG and LDL-C levels: A, TG  Conclusions Fatty liver is a significant determinant of serum sd-LDL-C levels independent of the presence of obesity or hyperglycemia. Fatty liver may alter hepatic metabolism of TG and LDL-C, resulting in increased sd-LDL-C levels.

  19. Effect of monounsaturated fatty acids on high-density and low-density lipoprotein cholesterol levels and blood pressure in healthy men and women.

    NARCIS (Netherlands)

    Mensink, R.P.

    1990-01-01

    The purpose of the studies described in this thesis was to examine the effect of monounsaturated fatty acids on the distribution of serum cholesterol over high-density and low-density lipoproteins (HDL and LDL) and on blood pressure in healthy men and women. High levels of LDL cholesterol and bl

  20. Effect of monounsaturated fatty acids on high-density and low-density lipoprotein cholesterol levels and blood pressure in healthy men and women

    NARCIS (Netherlands)

    Mensink, R.P.

    1990-01-01

    The purpose of the studies described in this thesis was to examine the effect of monounsaturated fatty acids on the distribution of serum cholesterol over high-density and low-density lipoproteins (HDL and LDL) and on blood pressure in healthy men and women. High levels of LDL cholesterol

  1. Functional analysis of low-density lipoprotein receptor in homozygous familial hypercholesterolemia patients with novel 1439 C→T mutation of low-density lipoprotein receptor gene

    Institute of Scientific and Technical Information of China (English)

    LIN Jie; JIANG Zhi-sheng; WANG Lu-ya; LIU Shu; XIA Jun-hui; YONG Qiang; DU Lan-ping; PAN Xiao-dong; XUE Hong; CHEN Bao-sheng

    2008-01-01

    Background Familial hypercholesterolemia (FH), caused by low density lipoprotein (LDL) receptor (LDL-R) gene mutations, is associated with increased risk of premature coronary heart disease. Until now, limited molecular data concerning FH are available in China. The present study described the clinical profiles and cell biological defects of a Chinese FH kindred with novel LDL-R gene mutation.Methods The patient's LDL-R gene coding region was sequenced. The patient's lymphocytes were isolated and the LDL-R expression, binding and up-take functions were observed by immunohistochemistry staining and flow cytometry detection. The patient's heart and the major large vessels were detected by vessel ultrasound examination and myocardial perfusion imaging (MPI).Results The patient's LDL-R expression, LDL binding and up-take functions were significantly lower than normal control (39%, 63% and 76% respectively). A novel homozygous 1439 C→T mutation of the LDL-R gene was detected in the patient and his family. ECG showed atypical angina pectoris. Echocardiogram showed stenosis of the coronary artery and calcification of the aortic valve and its root. Blood vessel ultrasound examination showed the thickness of large vessel intima, and the vessel lumen was narrowed by 71%. MPI showed ischemic changes.Conclusions The LDL-R synthesis dysfunction of FH patients leads to arterial stenosis and calcification, which are the major phenotype of the clinical disorder. The mutation of the LDL-R gene is determined. These data increase the mutational spectrum of FH in China.

  2. Low-Density Lipoprotein Uptake Demonstrates a Hepatocyte Phenotype in the Dog, but Is Nonspecific.

    Science.gov (United States)

    Gow, Adam G; Muirhead, Rhona; Hay, David C; Argyle, David J

    2016-01-01

    Low-density lipoprotein (LDL) uptake is one of a number of tests used to demonstrate hepatocyte-like function after stem cell differentiation. Use of two compounds, LDL and acetylated LDL (AcLDL), has been described despite each having different mechanisms of uptake. Three primary hepatocyte cultures and three sets of mesenchymal stromal cell (MSC) cultures, derived from both adipose tissue and bone marrow, were harvested from dogs. Those cells were compared to commercially available human and mouse bone marrow-derived MSCs. LDL receptor expression was demonstrated by gene expression and immunofluorescence in all primary hepatocyte cultures, undifferentiated canine bone marrow MSCs and canine adipose MSCs. Undifferentiated human and mouse bone marrow MSCs also expressed the LDL receptor. In vitro, canine hepatocytes took up labeled LDL, but not AcLDL. All undifferentiated MSCs took up LDL, but not AcLDL. In conclusion, LDL and not AcLDL is a test of canine hepatocyte-like phenotype, but this is not tissue or species specific and, therefore, is not informative assay when testing proof of MSC to hepatocyte differentiation.

  3. Triglyceride-rich lipoprotein metabolism in unique VLDL receptor, LDL receptor, and LRP triple-deficient mice

    NARCIS (Netherlands)

    Espirito Santo, S.M.S.; Rensen, P.C.N.; Goudriaan, J.R.; Bensadoun, A.; Bovenschen, N.; Voshol, P.J.; Havekes, L.M.; Vlijmen, B.J.M. van

    2005-01-01

    The very low density lipoprotein receptor (VLDLR), low density lipoprotein receptor (LDLR), and low density lipoprotein receptor-related protein (LRP) are the three main apolipoprotein E-recognizing endocytic receptors involved in the clearance of triglyceride (TG)-rich lipoproteins from plasma.

  4. High density lipoprotein as a source of cholesterol for adrenal steroidogenesis : A study in individuals with low plasma HDL-C

    NARCIS (Netherlands)

    Bochem, Andrea E.; Holleboom, Adriaan G.; Romijn, Johannes A.; Hoekstra, Menno; Dallinga-Thie, Geesje M.; Motazacker, Mahdi M.; Hovingh, G. Kees; Kuivenhoven, Jan A.; Stroes, Erik S. G.

    2013-01-01

    Few studies have addressed the delivery of lipoprotein-derived cholesterol to the adrenals for steroid production in humans. While there is evidence against a role for low-density lipoprotein (LDL), it is unresolved whether high density lipoprotein (HDL) contributes to adrenal steroidogenesis. To st

  5. Clinic application of serum low-density lipoprotein cholesterol level in predicting expansion hematoma in elderly male patients with acute hypertensive intracerebral hemorrhage%血清LDL-C水平对老年男性高血压性脑出血血肿扩大的预测作用

    Institute of Scientific and Technical Information of China (English)

    周红霞; 刘首峰; 李玉旺; 王欣; 徐小林

    2015-01-01

    Objective To investigate whether serum level of low-density lipoprotein cholesterol can predict the expan⁃sion of hemorrhage growth in elderly male patients with acute hypertensive intracerebral hemorrhage. Methods Patients (n=108) who visited our hospital with from June 2012 until May 2014 spontaneous hypertensive intracerebral hemorrhage with⁃in 6 hours of onset which is confirmed by initial computed tomography (CT) were sent to repeated CT within 24 hours of on⁃set. All selected patients were divided into the LDL-C≥2.49 mmol/L group and LDL-C<2.49 mmol/L group. Clinical data of these 2 groups were compared and the relationships of hematoma growth and its risk factors were analyzed. Results Baseline blood pressure, the level of blood glucose, PT, APTT, FIB, PLT and hemorrhage volume did not differ significantly between the LDL-C≥2.49 mmol/L group and LDL-C<2.49 mmol/L group. The ratio of hemorrhage growth in LDL-C<2.49 mmol/L group was significantly higher than that in LDL-C≥2.49 mmol/L group (34.21%vs 11.43%). Multiple logistic regres⁃sion analysis showed that LDL-C<2.49 mmol/L was the only risk factor contribute to hemorrhage growth. Conclusion Pa⁃tients with LDL-C<2.49 mmol/L in acute intracerebral hemorrhage are of high risk of hemorrhage growth so early attention and appropriate procedure are needed to prevent or slow its growth.%目的:探讨血清低密度脂蛋白胆固醇(LDL-C)水平对老年男性高血压性脑出血急性期血肿扩大有无预测作用。方法收集我院2012年6月—2014年5月发病6 h以内的老年男性高血压性脑出血患者108例,按发病时LDL-C水平分为LDL-C<2.49 mmol/L组和LDL-C≥2.49 mmol/L组,对2组患者入院时的收缩压(SBP)、舒张压(DBP)、血糖水平、凝血酶原时间(PT)、部分活化凝血酶时间(APTT)、纤维蛋白原(FIB)、血小板计数、血肿体积进行对比分析,并于发病24 h复查头CT了解2组血肿扩大情况并进

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

    Science.gov (United States)

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

    2007-01-01

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

  7. Transendothelial exchange of low-density lipoprotein is unaffected by the presence of severe atherosclerosis

    DEFF Research Database (Denmark)

    Kornerup, Karen; Nordestgaard, Børge Grønne; Jensen, Trine Krogsgaard

    2004-01-01

    OBJECTIVE: We tested the hypothesis that transendothelial exchange of low-density lipoprotein (LDL) is influenced by the presence of severe atherosclerosis; we previously found this exchange elevated in diabetes patients. METHODS: By an in vivo isotope method, we compared transendothelial LDL...... exchange in 24 patients with angiographically verified coronary atherosclerosis, 11 patients with angiographically verified peripheral atherosclerosis, 60 patients with diabetes, and in 42 controls. Autologous 131-iodinated LDL ((131)I-LDL) and 125-iodinated albumin ((125)I-albumin) were injected...... intravenously (i.v.), and the 1-h fractional escape rates (FER(LDL) and FER(alb)) were taken as indices of transendothelial exchange. RESULTS: Patients with coronary or peripheral atherosclerosis had FER(LDL) similar to that of controls [4.3 (3.5-5.1) and 3.2 (2.3-4.1) versus 4.2 (3.7-4.7)%/h; P>0.05], even...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  9. Inhibition of human low-density lipoprotein oxidation in vitro by ginger extracts.

    Science.gov (United States)

    Gunathilake, K D Prasanna P; Rupasinghe, H P Vasantha

    2014-04-01

    Oxidative modification of low-density lipoprotein (LDL) is thought to play a key role in atherosclerotic plaque formation. Currently, there is a renewed interest in ginger because of its antioxidants and cardioprotective properties. The effects of ethanol, methanol, ethyl acetate, and hexane solvent extracts of ginger and pure major ginger constituents on Cu(2+)-induced oxidation of human LDL in vitro were examined. The LDL oxidation inhibition by ethanol, methanol, ethyl acetate, and hexane extracts of ginger was 71%, 76%, 67%, and 67%, respectively, at their optimum extraction conditions. Inhibition of LDL oxidation by water extracts of ginger, which was prepared by ultrasonic-assisted extraction conditions of 52°C for 15 min, was about 43%. Phenolic bioactives of ginger-6-gingerols, 8-gingerols, 10-gingerols, and 6-shogaol-seem to be strong inhibitors of Cu(+2)-induced LDL oxidation. Overall, ginger extracts, including the water extract possess the antioxidant activities to inhibit human LDL oxidation in vitro.

  10. Enhanced susceptibility of low-density lipoproteins to oxidation in coronary bypass patients with progression of atherosclerosis

    NARCIS (Netherlands)

    Rijke, Y.B. de; Verwey, H.F.; Vogelezang, C.J.M.; Velde, E.A. van der; Princen, H.M.G.; Laarse, A. van der; Bruschke, A.V.G.; Berkel, T.J.C. van

    1995-01-01

    Oxidation of low-density lipoprotein (LDL) may play a causal role in atherosclerosis. In this study we analyzed whether the severity of progression of coronary atherosclerosis is related to the susceptibility of LDL to oxidative modification. On the basis of repeated coronary angiography, 28 coronar

  11. Antioxidant properties of modified rutin esters by DPPH, reducing power, iron chelation and human low density lipoprotein assays

    DEFF Research Database (Denmark)

    Lue, Bena-Marie; Nielsen, Nina Skall; Jacobsen, Charlotte;

    2010-01-01

    rutin compounds exhibited decreased reducing power and metal chelating abilities as compared to rutin. Conversely, investigations on the oxidation of human low density lipoprotein (LDL) revealed that rutin laurate was most effective in inhibiting oxidation by prolonging LDL lag time for an in vitro...

  12. Enhanced susceptibility of low-density lipoproteins to oxidation in coronary bypass patients with progression of atherosclerosis

    NARCIS (Netherlands)

    Rijke, Y.B. de; Verwey, H.F.; Vogelezang, C.J.M.; Velde, E.A. van der; Princen, H.M.G.; Laarse, A. van der; Bruschke, A.V.G.; Berkel, T.J.C. van

    1995-01-01

    Oxidation of low-density lipoprotein (LDL) may play a causal role in atherosclerosis. In this study we analyzed whether the severity of progression of coronary atherosclerosis is related to the susceptibility of LDL to oxidative modification. On the basis of repeated coronary angiography, 28 coronar

  13. Enhanced susceptibility of low-density lipoproteins to oxidation in coronary bypass patients with progression of atherosclerosis

    NARCIS (Netherlands)

    Rijke, Y.B. de; Verwey, H.F.; Vogelezang, C.J.M.; Velde, E.A. van der; Princen, H.M.G.; Laarse, A. van der; Bruschke, A.V.G.; Berkel, T.J.C. van

    1995-01-01

    Oxidation of low-density lipoprotein (LDL) may play a causal role in atherosclerosis. In this study we analyzed whether the severity of progression of coronary atherosclerosis is related to the susceptibility of LDL to oxidative modification. On the basis of repeated coronary angiography, 28

  14. Carbamylated low-density lipoprotein induces oxidative stress and accelerated senescence in human endothelial progenitor cells.

    Science.gov (United States)

    Carracedo, Julia; Merino, Ana; Briceño, Carolina; Soriano, Sagrario; Buendía, Paula; Calleros, Laura; Rodriguez, Mariano; Martín-Malo, Alejandro; Aljama, Pedro; Ramírez, Rafael

    2011-04-01

    Carbamylated low-density lipoprotein (cLDL) plays a role in atherosclerosis. In this study we evaluate the effect of uremia on LDL carbamylation and the effect of cLDL and oxidized LDL (oxLDL; 200 μg/ml) on number, function, and genomic stability of endothelial progenitor cells (EPCs) obtained from healthy volunteers. cLDL was generated after incubation of native LDL (nLDL) with uremic serum from patients with chronic kidney disease (CKD) stages 2-4. Oxidative stress was measured by flow cytometry and fluorescent microscopy, mitochondrial depolarization by flow cytometry, senescence by β-galactosidase activity and telomere length, and DNA damage by phosphorylated histone H2AX (γH2AX). The percentage of cLDL by uremic serum was related to the severity of CKD. Compared with nLDL, cLDL induced an increase in oxidative stress (62±5 vs. 8±3%, P<0.001) and cells with mitochondrial depolarization (73±7 vs. 9±5%, P<0.001), and a decrease in EPC proliferation and angiogenesis. cLDL also induced accelerated senescence (73±16 vs. 12±9%, P<0.001), which was associated with a decrease in the expression of γH2AX (62±9 vs. 5±3%, P<0.001). The degree of injury induced by cLDL was comparable to that observed with oxLDL. This study supports the hypothesis that cLDL triggers genomic damage in EPCs, resulting in premature senescence. We can, therefore, hypothesize that EPCs injury by cLDL contributes to an increase in atherosclerotic disease in CKD.

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

    Science.gov (United States)

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

    1984-08-15

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

  16. Antioxidative activity of high-density lipoprotein (HDL): Mechanistic insights into potential clinical benefit.

    Science.gov (United States)

    Brites, Fernando; Martin, Maximiliano; Guillas, Isabelle; Kontush, Anatol

    2017-12-01

    Uptake of low-density lipoprotein (LDL) particles by macrophages represents a key step in the development of atherosclerotic plaques, leading to the foam cell formation. Chemical modification of LDL is however necessary to induce this process. Proatherogenic LDL modifications include aggregation, enzymatic digestion and oxidation. LDL oxidation by one-electron (free radicals) and two-electron oxidants dramatically increases LDL affinity to macrophage scavenger receptors, leading to rapid LDL uptake and fatty streak formation. Circulating high-density lipoprotein (HDL) particles, primarily small, dense, protein-rich HDL3, provide potent protection of LDL from oxidative damage by free radicals, resulting in the inhibition of the generation of pro-inflammatory oxidized lipids. HDL-mediated inactivation of lipid hydroperoxides involves their initial transfer from LDL to HDL and subsequent reduction to inactive hydroxides by redox-active Met residues of apolipoprotein A-I. Several HDL-associated enzymes are present at elevated concentrations in HDL3 relative to large, light HDL2 and can be involved in the inactivation of short-chain oxidized phospholipids. Therefore, HDL represents a multimolecular complex capable of acquiring and inactivating proatherogenic lipids. Antioxidative function of HDL can be impaired in several metabolic and inflammatory diseases. Structural and compositional anomalies in the HDL proteome and lipidome underlie such functional deficiency. Concomitant normalization of the metabolism, circulating levels, composition and biological activities of HDL particles, primarily those of small, dense HDL3, can constitute future therapeutic target.

  17. Predictive value of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio on the cardiovascular events in patients undergoing percutaneous coronary intervention%LDL-C/HDL-C比值对经皮冠脉介入术后患者心血管事件的预测价值

    Institute of Scientific and Technical Information of China (English)

    师姗姗; 刘幼文; 金光临; 潘楚梅; 王涓; 曾繁芳

    2013-01-01

    目的 评估低密度脂蛋白胆固醇(LDL-C)/高密度脂蛋白胆固醇(HDL-C)比值对经皮冠脉介入(PCI)术后患者心血管事件的预测价值.方法 选择急性冠脉综合征(ACS)并予前降支置入支架的患者119例,依据血浆LDL-C/HDL-C比值将患者分为3组,随访1年,评估三组患者心血管事件发生率,以及各危险因素与心血管事件发生率的关系.结果 ①与LDL-C/HDL-C比值较低的两组相比,比值较高组患者体重指数、女性患者百分率、吸烟人数及糖化血红蛋白、高敏C反应蛋(hs-CRP)、总胆固醇和LDL-C水平均明显升高,而HDL-C水平和他汀类药物使用率则较低(P<0.05).②第1组风险比(HR)1.04,95%可信区间(CI)0.98~1.08,第2组HR 1.16,95%CI 1.08~1.20,第3组HR 1.27,95%CI 1.19~1.36(P<0.05).随着LDL-C/HDL-C比值的升高,PCI术后1年患者心血管事件发生率也逐渐升高(P<0.05).③Cox比例风险回归模型提示,LDL-C/HDL-C比值对PCI术后心血管事件风险的预测价值优于其他危险因素.结论 LDL-C/HDL-C比值对PCI术后患者1年内心血管事件再发具有一定的预测价值.%Objective To investigate the predictive value of LDL-C/HDL-C ratio on the cardiovascular events in patients with PCI treatment. Methods One hundred and nineteen patients defined as acute coronary syndrome treating with stent implantation in anterior descending artery were enrolled. According to the category of LDL-C/HDL-C ratio, patients were assigned into 3 groups and were followed up for one year to evaluate the occurrence of cardiovascular events and the relationship of cardiovascular events with risk factors. Results (1)Compared to the two low categories of LDL-C/HDL-C ratio groups, body mass index, percentage of female, number of smoker, levels of GHBA1C, hs-CRP, total cholesterol and LDL-C were higher, while level of HDL-C and usage of statin were lower (P<0.05). (2)In line with the escalation of LDL-C/HDL-C ratio, the rate of

  18. Strategies for vascular disease prevention: the role of lipids and related markers including apolipoproteins, low-density lipoproteins (LDL)-particle size, high sensitivity C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2 (Lp-PLA₂) and lipoprotein(a) (Lp(a)).

    Science.gov (United States)

    Dallmeier, Dhayana; Koenig, Wolfgang

    2014-06-01

    Considerable progress has been achieved in the treatment of dyslipidemias. However, half of cardiovascular events occur in individuals with average or low cholesterol levels and there is still a considerable residual risk with 70% of patients having an event despite statin treatment. In the era of personalized medicine there is increased interest in the incorporation of individual biomarkers in risk score algorithms in order to improve cardiovascular risk stratification followed by the prompt initiation of preventive measures. Since the 2001 third report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment on High Blood Cholesterol in Adults (ATP III) several studies have evaluated the prognostic value of lipid related biomarkers such as non-HDL-cholesterol, apolipoprotein B, apolipoprotein B/apolipoprotein A1 ratio, lipoprotein(a), lipoprotein-associated phospholipase A2, and C-reactive protein. This article tries to summarize the most recent results in this area. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells.

    OpenAIRE

    Cushing, S D; Berliner, J A; Valente, A. J.; Territo, M C; Navab, M; Parhami, F; Gerrity, R; Schwartz, C J; Fogelman, A M

    1990-01-01

    After exposure to low density lipoprotein (LDL) that had been minimally modified by oxidation (MM-LDL), human endothelial cells (EC) and smooth muscle cells (SMC) cultured separately or together produced 2- to 3-fold more monocyte chemotactic activity than did control cells or cells exposed to freshly isolated LDL. This increase in monocyte chemotactic activity was paralleled by increases in mRNA levels for a monocyte chemotactic protein 1 (MCP-1) that is constitutively produced by the human ...

  20. 微粒化非诺贝特和洛代他汀对老年人低高密度脂蛋白胆固醇(HDL-ch)和高低密度脂蛋白(LDL-ch)的疗效比较%A Comparison of the Therapeutic Effects of Comicromised Fenofibrate with Lovastatin in the Treatment of Eldly with Low High-density Lipoprotein(HDL) Cholesterol and Elevated Low-density Lipoprotein(LDL) Cholesterol

    Institute of Scientific and Technical Information of China (English)

    施行舟; 叶志荣

    2002-01-01

    为了比较微粒化非诺贝特和洛伐他汀对低HDL-ch和高LDL -ch的疗效,将80例低HDL伴高LDL的老年唤者随机分为非诺贝特组和洛代他汀组,每组各40例,分别予服用微粒化非诺贝特和洛代他汀,疗程为12周.结果发现非诺贝特组于治疗后8周即可有显著的升高HDL-ch,且疗效随疗程的增加而增加,而洛伐他汀组仅有轻度升高HDL-ch作用,尚未达到显著性水平,二组疗效相比,具有显著性意义(P=0.0271).非洛贝特组和洛伐他汀组于治疗后4周都可以显著降低LDL(P<0.05),且疗效都随着疗程的增加而增加,二组疗效相比,尚未达到显著性水平(P=0.0785).因此,微粒化非诺贝特可升高老年患者的HDL-ch,降低LDL-ch水平,而洛伐他门仅能够显著降低患者的LDL-ch水平,对于同时伴有低HDL-ch和高LDL-ch老年患者,应首先考虑选择非诺贝特进行降脂治疗.

  1. A randomized trial and novel SPR technique identifies altered lipoprotein-LDL receptor binding as a mechanism underlying elevated LDL-cholesterol in APOE4s

    Science.gov (United States)

    Calabuig-Navarro, M. V.; Jackson, K. G.; Kemp, C. F.; Leake, D. S.; Walden, C. M.; Lovegrove, J. A.; Minihane, A. M.

    2017-01-01

    At a population level APOE4 carriers (~25% Caucasians) are at higher risk of cardiovascular diseases. The penetrance of genotype is however variable and influenced by dietary fat composition, with the APOE4 allele associated with greater LDL-cholesterol elevation in response to saturated fatty acids (SFA). The etiology of this greater responsiveness is unknown. Here a novel surface plasmon resonance technique (SPR) is developed and used, along with hepatocyte (with the liver being the main organ modulating lipoprotein metabolism and plasma lipid levels) uptake studies to establish the impact of dietary fatty acid composition on, lipoprotein-LDL receptor (LDLR) binding, and hepatocyte uptake, according to APOE genotype status. In men prospectively recruited according to APOE genotype (APOE3/3 common genotype, or APOE3/E4), triglyceride-rich lipoproteins (TRLs) were isolated at fasting and 4–6 h following test meals rich in SFA, unsaturated fat and SFA with fish oil. In APOE4s a greater LDLR binding affinity of postprandial TRL after SFA, and lower LDL binding and hepatocyte internalization, provide mechanisms for the greater LDL-cholesterol raising effect. The SPR technique developed may be used for the future study of the impact of genotype, and physiological and behavioral variables on lipoprotein metabolism. Trial registration number NCT01522482. PMID:28276521

  2. Effect of methylglyoxal on the physico-chemical and biological properties of low-density lipoprotein

    NARCIS (Netherlands)

    Schalkwijk, C.G.; Vermeer, M.A.; Stehouwer, C.D.A.; Koppele, J. te; Princen, H.M.G.; Hinsbergh, V.W.M. van

    1998-01-01

    In patients with diabetes, non-enzymatic glycation of low-density lipoprotein (LDL) has been suggested to be involved in the development of atherosclerosis. α-Dicarbonyl compounds were identified as intermediates in the non-enzymatic glycation and increased levels were reported in patients with diab

  3. Phenotype of heterozygotes for low-density lipoprotein receptor mutations identified in different background populations

    DEFF Research Database (Denmark)

    Tybjaerg-Hansen, Anne; Jensen, Henrik Kjaerulf; Benn, Marianne;

    2005-01-01

    The effect of mutations on phenotype is often overestimated because of ascertainment bias. We determined the effect of background population on cholesterol phenotype associated with specific mutations in the low-density lipoprotein (LDL) receptor and the relative importance of background population...

  4. Direct Low Density Lipoprotein Cholesterol and Glycated Albumin Levels in Type 2 Diabetes Mellitus

    Science.gov (United States)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) have been associated with a decreased risk of these complications. The aim in this st...

  5. Glycated albumin and direct low density lipoprotein cholesterol levels in type 2 diabetes mellitus

    Science.gov (United States)

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

  6. Low density lipoprotein induces upregulation of vasoconstrictive endothelin type B receptor expression

    DEFF Research Database (Denmark)

    Xu, Cang-Bao; Zheng, Jian-Pu; Zhang, Wei

    2014-01-01

    Vasoconstrictive endothelin type B (ET(B)) receptors promote vasospasm and ischemic cerebro- and cardiovascular diseases. The present study was designed to examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive ET(B) receptor expression and if extracellular signal...

  7. Effect of methylglyoxal on the physico-chemical and biological properties of low-density lipoprotein

    NARCIS (Netherlands)

    Schalkwijk, C.G.; Vermeer, M.A.; Stehouwer, C.D.A.; Koppele, J. te; Princen, H.M.G.; Hinsbergh, V.W.M. van

    1998-01-01

    In patients with diabetes, non-enzymatic glycation of low-density lipoprotein (LDL) has been suggested to be involved in the development of atherosclerosis. α-Dicarbonyl compounds were identified as intermediates in the non-enzymatic glycation and increased levels were reported in patients with

  8. Low-Density Lipoprotein Receptor-Dependent and Low-Density Lipoprotein Receptor-Independent Mechanisms of Cyclosporin A-Induced Dyslipidemia.

    Science.gov (United States)

    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

  9. Cellular uptake of a dexamethasone palmitate-low density lipoprotein complex by macrophages and foam cells.

    Science.gov (United States)

    Tauchi, Yoshihiko; Chono, Sumio; Morimoto, Kazuhiro

    2003-04-01

    To evaluate the utility of a dexamethasone palmitate (DP)-low density lipoprotein (LDL) complex to transport drug into foam cells, the cellular uptake of DP-LDL complex by macrophages and foam cells was examined. The DP-LDL complex was prepared by incubation with DP and LDL, and the DP-LDL complex and murine macrophages were incubated. No cellular uptake of the DP-LDL complex by macrophages was found until 6 h after the start of incubation, but this gradually increased from 12 to 48 h. On the other hand, the cellular uptake of the oxidized DP-LDL complex was already apparent at 3 h after the start incubation, and then markedly increased until 48 h incubation along with that of the lipid emulsion (LE) containing DP (DP-LE). The cellular uptake of DP-LE by foam cells was significantly lower than that by macrophages. However, the cellular uptake of DP-LDL complex by foam cells was similar to that by macrophages. These findings suggest that the DP-LDL complex is oxidatively modified, and then incorporated into macrophages and foam cells through the scavenger receptor pathway. Since selective delivery of drugs into foam cells in the early stage of atherosclerosis is a useful protocol for antiatherosclerosis treatment, the DP-LDL complex appears to be a potentially useful drug-carrier complex for future antiatherosclerotic therapy.

  10. Effects of flow on LOX-1 and oxidized low-density lipoprotein interactions in brain endothelial cell cultures.

    Science.gov (United States)

    Mao, Xiaoou; Xie, Lin; Greenberg, David A

    2015-12-01

    Fluid shear stress and uptake of oxidized low-density lipoprotein (ox-LDL) into the vessel wall both contribute to atherosclerosis, but the relationship between shear stress and ox-LDL uptake is unclear. We examined the effects of flow, induced by orbital rotation of bEnd.3 brain endothelial cell cultures for 1 wk, on ox-LDL receptor (LOX-1) protein expression, ox-LDL uptake and ox-LDL toxicity. Orbitally rotated cultures showed no changes in LOX-1 protein expression, ox-LDL uptake or ox-LDL toxicity, compared to stationary cultures. Flow alone does not modify ox-LDL/LOX-1 signaling in bEnd.3 brain endothelial cells in vitro, suggesting that susceptibility of atheroprone vascular sites to lipid accumulation is not due solely to effects of altered flow on endothelium.

  11. Lipoprotein associated phospholipase A2 activity & its correlation with oxidized LDL & glycaemic status in early stages of type-2 diabetes mellitus.

    Science.gov (United States)

    Garg, Seema; Madhu, S V; Suneja, Shilpa

    2015-01-01

    Lipoprotein associated phospholipase A 2 (Lp-PLA 2 ) is an important risk predictor of coronary artery disease (CAD). This study was aimed to evaluate Lp-PLA 2 activity and oxidized low density lipoprotein (oxLDL) in newly diagnosed patients of type 2 diabetes mellitus and to determine the correlation of Lp-PLA 2 activity with oxLDL and plasma glucose levels. Blood samples were collected in patients with newly diagnosed type 2 diabetes (n=40) before any treatment was started and healthy controls (n=40). These were processed for estimating plasma glucose: fasting and post prandial, ox LDL, and Lp-PLA2 activity. The parameters in the two groups were compared. Correlation between different parameters was calculated by Pearson correlation analysis in both groups. Lp-PLA 2 activity (24.48 ± 4.91 vs 18.63 ± 5.29 nmol/min/ml, Pdiabetes may be due to increase in Lp-PLA 2 activity during the early course of the disease. A positive correlation between enzyme activity and fasting plasma glucose indicates an association between hyperglycaemia and increased activity of Lp-PLA2. This may explain a higher occurrence of CAD in patients with diabetes. A positive correlation between oxLDL and Lp-PLA2 activity suggests that Lp-PLA2 activity may be affected by oxLDL also.

  12. Practical technique to quantify small, dense low-density lipoprotein cholesterol using dynamic light scattering

    Science.gov (United States)

    Trirongjitmoah, Suchin; Iinaga, Kazuya; Sakurai, Toshihiro; Chiba, Hitoshi; Sriyudthsak, Mana; Shimizu, Koichi

    2016-04-01

    Quantification of small, dense low-density lipoprotein (sdLDL) cholesterol is clinically significant. We propose a practical technique to estimate the amount of sdLDL cholesterol using dynamic light scattering (DLS). An analytical solution in a closed form has newly been obtained to estimate the weight fraction of one species of scatterers in the DLS measurement of two species of scatterers. Using this solution, we can quantify the sdLDL cholesterol amount from the amounts of the low-density lipoprotein cholesterol and the high-density lipoprotein (HDL) cholesterol, which are commonly obtained through clinical tests. The accuracy of the proposed technique was confirmed experimentally using latex spheres with known size distributions. The applicability of the proposed technique was examined using samples of human blood serum. The possibility of estimating the sdLDL amount using the HDL data was demonstrated. These results suggest that the quantitative estimation of sdLDL amounts using DLS is feasible for point-of-care testing in clinical practice.

  13. Expression of scavenger receptor-BI and low-density lipoprotein receptor and differential use of lipoproteins to support early steroidogenesis in luteinizing macaque granulosa cells.

    Science.gov (United States)

    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) (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.

  14. Cholesteryl Ester Hydroperoxides Are Biologically Active Components of Minimally Oxidized Low Density Lipoprotein*S⃞

    Science.gov (United States)

    Harkewicz, Richard; Hartvigsen, Karsten; Almazan, Felicidad; Dennis, Edward A.; Witztum, Joseph L.; Miller, Yury I.

    2008-01-01

    Oxidation of low density lipoprotein (LDL) occurs in vivo and significantly contributes to the development of atherosclerosis. An important mechanism of LDL oxidation in vivo is its modification with 12/15-lipoxygenase (LO). We have developed a model of minimally oxidized LDL (mmLDL) in which native LDL is modified by cells expressing 12/15LO. This mmLDL activates macrophages inducing membrane ruffling and cell spreading, activation of ERK1/2 and Akt signaling, and secretion of proinflammatory cytokines. In this study, we found that many of the biological activities of mmLDL were associated with cholesteryl ester (CE) hydroperoxides and were diminished by ebselen, a reducing agent. Liquid chromatography coupled with mass spectroscopy demonstrated the presence of many mono- and polyoxygenated CE species in mmLDL but not in native LDL. Nonpolar lipid extracts of mmLDL activated macrophages, although to a lesser degree than intact mmLDL. The macrophage responses were also induced by LDL directly modified with immobilized 12/15LO, and the nonpolar lipids extracted from 12/15LO-modified LDL contained a similar set of oxidized CE. Cholesteryl arachidonate modified with 12/15LO also activated macrophages and contained a similar collection of oxidized CE molecules. Remarkably, many of these oxidized CE were found in the extracts of atherosclerotic lesions isolated from hyperlipidemic apoE–/– mice. These results suggest that CE hydroperoxides constitute a class of biologically active components of mmLDL that may be relevant to proinflammatory activation of macrophages in atherosclerotic lesions. PMID:18263582

  15. A green tea catechin extract upregulates the hepatic low-density lipoprotein receptor in rats.

    Science.gov (United States)

    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 extract was able to increase the efflux of cholesterol from liver cells.

  16. 5-Lipoxygenase is not essential in macrophage-mediated oxidation of low-density lipoprotein.

    Science.gov (United States)

    Jessup, W; Darley-Usmar, V; O'Leary, V; Bedwell, S

    1991-08-15

    The concentration-dependent effects of a series of lipoxygenase inhibitors and antioxidants on the macrophage-mediated oxidative modification of low-density lipoprotein (LDL) were measured. Their influence on macrophage 5-lipoxygenase pathway activity was also studied over the same concentration range. No correlation between inhibition of 5-lipoxygenase and of macrophage-mediated oxidation of LDL was observed. The capacity of the compounds to prevent cell-mediated modification of LDL could be explained in terms of their activity as either aqueous- or lipid-peroxyl radical scavengers. Two potent 5-lipoxygenase inhibitors (MK 886 and Revlon 5901), which had no radical-scavenging properties, were unable to block LDL modification. It is concluded that 5-lipoxygenase is not essential for LDL oxidation by macrophages.

  17. Effect of Curcumin on the Gene Expression of Low Density Lipoprotein Receptors

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective: To investigate the molecular mechanisms and effective target ponits of lipid-lowering drug, Rhizoma Curcumae Longae, and study the effect of curcumin on the expression of low density lipoprotein (LDL) receptors in macrophages in mice. Methods: Macrophages in mice were treated with curcumin, which was purified from the ethanolly extraction of Rhizoma Curcumae Longae for 24 h. The LDL receptors expressed in the macrophages were determined by enzyme-linked immunosorbent assay (ELISA) and assay of Dil labeled LDL uptake by flow cytometer. Results: It was found for the first time that 10 μmol/L-50μmol/L curcumin could obviously up-regulate the expression of LDL receptor in macrophages in mice, and a dose-effect relationship was demonstrated. Conclusion: One of the lipid-lowering mechanisms of traditional Chinese medicine, Rhizoma Curcumae Longae, was completed by the effect of curcumin through the up-regulation of the expression of LDL receptor.

  18. Safety profile of subjects treated to very low low-density lipoprotein cholesterol levels (JUPITER).

    Science.gov (United States)

    Everett, Brendan M; Mora, Samia; Glynn, Robert J; MacFadyen, Jean; Ridker, Paul M

    2014-12-01

    Recent US guidelines expand the indications for high-intensity statin therapy, yet data on the safety of attaining very low-density lipoprotein cholesterol (LDL-C) levels are scarce. Among 16,304 participants in the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) with on-treatment LDL-C levels, we identified 767 who did and 7,387 who did not achieve LDL-C JUPITER, achieving LDL-C levels <30 mg/dl with high-intensity statin therapy appeared to be generally well tolerated but associated with certain adverse events, including more physician-reported diabetes, hematuria, hepatobiliary disorders, and insomnia. These data may guide the monitoring of patients on intensive statin therapy and adverse events in trials of therapies that lead to very low LDL-C levels.

  19. Comparison of low-density lipoprotein obtained from the Friedewald formula and new formulae in a heterogeneous population

    Directory of Open Access Journals (Sweden)

    César Augusto Guevara-Cuéllar

    2010-12-01

    Full Text Available Introduction: Although the levels of low-density lipoprotein (LDL-C should ideally be determined by beta quantification or enzymatic methods, there are limitations in developing countries. The goal of this study is to compare LDL-C obtained through three formulae (LDL-Cnf with LDL-C obtained through the Friedewald formula (LDL-Cf using LDL-C through enzymatic methods as the most-accepted reference method in clinical practice (LDL-Cr.Methods: A concordance study was carried out in a reference laboratory in Cali, Colombia. The three formulae were (mg/dl: Men with triglycerides under 400 mg/dl: LDL-C = Total Cholesterol (TC - triglycerides (TG /6.5 - 45; men with triglycerides equal to or greater than 400 mg/dl: LDL-C = (TC - (TG / 7 -50 and women: LDL-C = (TC-(TG /6.5 - 70.Results: Three-hundred fifteen values were obtained of which 53% were for women. The mean age and LDL-Cr were 54 years (±15.8 and 112.1 mg/dl (±32.5, respectively. The median (interquartile range, mg/dl of TC, high-density lipoprotein (HDL-C and TG were 204 mg/dl (171-229, 51 mg/dl (41-61, and 156 mg/dl (99-237, respectively. There were no differences between mean values of LDL-Cr and LDL-Cnf (113.48 vs. 112.67 mg/dl; p=0.45. The intraclass correlation coefficient among LDL-Cr and LDL-Cf and LDL-Cnf were high (R=0.93 and 0.92, respectively. The correlation between LDL-Cf and LDL-Cnf was 0.95. There is no difference between the areas under the receiver operating characteristic (ROC curve with the level of LDL-Cr at 160 mg/dl for LDL-Cnf and LDL-Cf. (0.94 vs. 0.93; p=0.27.Conclusion: There is high concordance between LDL-Cf and LDL-Cnf. These formulae could be an alternative when there are limitations to determine LDL-C because of the lack of enzymatic methods or through Friedewald formula due to the absence of HDL-C.

  20. Comparison of low-density lipoprotein obtained from the Friedewald formula and new formulae in a heterogeneous population

    Directory of Open Access Journals (Sweden)

    César Augusto Guevara-Amador

    2011-01-01

    Full Text Available Introduction: Although the levels of low-density lipoprotein (LDL-C should ideally be determined by beta quantification or enzymatic methods, there are limitations in developing countries. The goal of this study is to compare LDL-C obtained through three formulae (LDL-Cnf with LDL-C obtained through the Friedewald formula (LDL-Cf using LDL-C through enzymatic methods as the most-accepted reference method in clinical practice (LDL-Cr. Methods: A concordance study was carried out in a reference laboratory in Cali, Colombia. The three formulae were (mg/dl: Men with triglycerides under 400 mg/dl: LDL-C = Total Cholesterol (TC - triglycerides (TG /6.5 - 45; men with triglycerides equal to or greater than 400 mg/dl: LDL-C = (TC - (TG / 7 -50 and women: LDL-C = (TC-(TG /6.5 - 70. Results: Three-hundred fifteen values were obtained of which 53% were for women. The mean age and LDL-Cr were 54 years (±15.8 and 112.1 mg/dl (±32.5, respectively. The median (interquartile range, mg/dl of TC, high-density lipoprotein (HDL-C and TG were 204 mg/dl (171-229, 51 mg/dl (41-61, and 156 mg/dl (99-237, respectively. There were no differences between mean values of LDL-Cr and LDL-Cnf (113.48 vs. 112.67 mg/dl; p=0.45. The intraclass correlation coefficient among LDL-Cr and LDL-Cf and LDL-Cnf were high (R=0.93 and 0.92, respectively. The correlation between LDL-Cf and LDL-Cnf was 0.95. There is no difference between the areas under the receiver operating characteristic (ROC curve with the level of LDL-Cr at 160 mg/dl for LDL-Cnf and LDL-Cf. (0.94 vs. 0.93; p=0.27. Conclusion: There is high concordance between LDL-Cf and LDL-Cnf. These formulae could be an alternative when there are limitations to determine LDL-C because of the lack of enzymatic methods or through Friedewald formula due to the absence of HDL-C.

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

    Science.gov (United States)

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

    2001-02-13

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

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

    African Journals Online (AJOL)

    Human Low Density Lipoprotein as a Vehicle of Atherosclerosis. ... Low-density lipoproteins have been sufficiently established as an important precursor of atherosclerosis. The actual mechanism is still ... Article Metrics. Metrics Loading .

  3. Low density lipoprotein for oxidation and metabolic studies. Isolation from small volumes of plasma using a tabletop ultracentrifuge.

    Science.gov (United States)

    Himber, J; Bühler, E; Moll, D; Moser, U K

    1995-01-01

    A rapid method is described for the isolation of small volumes of plasma low density lipoprotein (LDL) free of plasma protein contaminants using the TL-100 Tabletop Ultracentrifuge (Beckman). The isolation of LDL was achieved by a 25 min discontinuous gradient density centrifugation between the density range of 1.006 and 1.21 g/ml, recovery of LDL by tube slicing followed by a 90 min flotation step (d = 1.12 g/ml). The purity of LDL and apolipoprotein B100 (apo B100) were monitored by agarose electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), radial immunodiffusion and micropreparative fast protein liquid chromatography (FPLC). The ability of LDL oxidation was assessed by following absorbance at 234 nm after addition of copper ions. The functional integrity of the isolated LDL was checked by clearance kinetics after injection of [125I]-labelled LDL in estrogen-treated rats. The additional purification step led to LDL fractions free of protein contamination and left apo B100, alpha-tocopherol and beta-carotene intact. The LDL prepared in this way was free of albumin, as evident from analytic tests and from its enhanced oxidative modification by copper ions. Used for analytical purposes, this method allows LDL preparations from plasma volumes up to 570 microliters. This method is also convenient for metabolic studies in small animals, especially those relating to the determination of kinetic parameters of LDL in which LDL-apo B100 has to be specifically radiolabelled.

  4. The advantages of combining low-density lipoproteins with glutamine for cryopreservation of canine semen.

    Science.gov (United States)

    Bencharif, D; Amirat, L; Pascal, O; Anton, M; Schmitt, E; Desherces, S; Delhomme, G; Langlois, M-L; Barrière, P; Larrat, M; Tainturier, D

    2010-04-01

    Twenty sperm samples from five dogs were frozen in liquid nitrogen at -196 degrees C in 16 different media, two control media containing 20% egg yolk and 6% low-density lipoproteins (LDL); 10 test media containing 6% LDL (the active cryoprotective ingredient of chicken egg yolk) combined with 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100 mmol of glutamine respectively at 4%, 5%, 7%, and 8% LDL. Following thawing, sperm mobility was assessed using an image analyser, HAMILTON THORN CERROS 12. The percentage of mobile spermatozoa was 62.05% in the 6% LDL + 20 mmol glutamine medium compared with 48.90% in the egg yolk-based medium (p < 0.05) or 57.55% for the 6% LDL medium (p < 0.05). Furthermore, in most cases, the motility parameters (average path velocity, curvilinear velocity, straight line velocity) in the 6% LDL + 20 mmol glutamine medium, were superior, to a statistically significant extent, to those in the control media. Finally, the 6% LDL + 20 mmol glutamine combination provides spermatozoa with better protection during freezing than egg yolk or the 6% LDL medium alone in terms of acrosome integrity (fluorescein isothiocyanate--Pisum sativum agglutinin test: p < 0.05), the flagellar plasma membrane (hypo-osmotic test: p < 0.05 for 6% LDL), the DNA (acridine orange test; no significant difference) and the integrity of the acrosome (Spermac test: no significant difference).

  5. Effects of oxidized low density lipoprotein on the growth of human artery smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    ZHAO Gao-feng; SENG Jing-jing; ZHANG Hua; SHE Ming-peng

    2005-01-01

    Background Studies have shown that oxidized low density lipoprotein (ox-LDL) promotes the pathogenesis and development of atherosclerosis (AS), and that the proliferation, migration and phenotype alteration of vascular smooth muscle cells (vSMCs) into foam cells are critical changes in AS. It is proposed that ox-LDL might play a novel role in the pathologic process of vSMCs. The present study was performed ex vivo to investigate the effects of ox-LDL on the growth of cultured human vSMCs.Methods Using NaBr density gradient centrifugation, LDL from human plasma was isolated and purified. ox-LDL was produced from LDL after being incubated with CuSO4. ox-LDL was then added to the culture medium at different concentrations (25 μg/ml, 50 μg/ml, 75 μg/ml, 100 μg/ml, 125 μg/ml, and 150 μg/ml) for 7 days. The influence of ox-LDL on vSMC growth was observed from several aspects as growth curve, mitosis index, lipid staining, and in situ determination of apoptosis. The digital results were analyzed with SPSS 10.0.Results The ox-LDL produced ex vivo had a good purity and optimal oxidative degree, which was similar to the intrinsic ox-LDL in atherosclerotic plaque. ox-LDL at a concentration of 25 μg/ml demonstrated the strongest proliferation. At the concentration of 125 μg/ml, ox-LDL suppressed the growth of vSMCs. At concentrations of 25 μg/ml and 50 μg/ml, ox-LDL presented powerful mitotic trigger. When the concentration of ox-LDL increased, the mitotic index of vSMCs decreased gradually. ox-LDL induced more foam cells from vSMCs with rich intracellular lipid accumulation at concentrations of 25 μg/ml and 50 μg/ml. ox-LDL at higher concentrations induced more apoptotic vSMCs.Conclusions ox-LDL at lower concentrations may trigger proliferation and phenotype alteration into foam cells of vSMCs, and at higher concentrations it may induce apoptosis in vSMCs. ox-LDL plays an important role in the pathogenesis and development of atherosclerosis by its effect on v

  6. Targeting PCSK9 as a promising new mechanism for lowering low-density lipoprotein cholesterol.

    Science.gov (United States)

    Della Badia, Laura A; Elshourbagy, Nabil A; Mousa, Shaker A

    2016-08-01

    Statins and other lipid-lowering drugs have dominated the market for many years for achievement of recommended levels of low-density lipoprotein cholesterol (LDL-C). However, a substantial number of high-risk patients are unable to achieve the LDL-C goal. Proprotein convertase subtilisin/kexin 9 (PCSK9) has recently emerged as a new, promising key therapeutic target for hypercholesterolemia. PCSK9 is a protease involved in chaperoning the low-density lipoprotein receptor to the process of degradation. PCSK9 inhibitors and statins effectively lower LDL-C. The PCSK9 inhibitors decrease the degradation of the LDL receptors, whereas statins mainly interfere with the synthetic machinery of cholesterol by inhibiting the key rate limiting enzyme, the HMG CoA reductase. PCSK9 inhibitors are currently being developed as monoclonal antibodies for their primary use in lowering LDL-C. They may be especially useful for patients with homozygous familial hypercholesterolemia, who at present receive minimal benefit from traditional statin therapy. The monoclonal antibody PCSK9 inhibitors, recently granted FDA approval, show the most promising safety and efficacy profile compared to other, newer LDL-C lowering therapies. This review will primarily focus on the safety and efficacy of monoclonal antibody PCSK9 inhibitors in comparison to statins. The review will also address new, alternative PCSK9 targeting drug classes such as small molecules, gene silencing agents, apolipoprotein B antisense oligonucleotides, and microsomal triglyceride transfer protein inhibitors.

  7. Protective effects of endomorphins, endogenous opioid peptides in the brain, on human low density lipoprotein oxidation.

    Science.gov (United States)

    Lin, Xin; Xue, Li-Ying; Wang, Rui; Zhao, Qian-Yu; Chen, Qiang

    2006-03-01

    Neurodegenerative disorders are associated with oxidative stress. Low density lipoprotein (LDL) exists in the brain and is especially sensitive to oxidative damage. Oxidative modification of LDL has been implicated in the pathogenesis of neurodegenerative diseases. Therefore, protecting LDL from oxidation may be essential in the brain. The antioxidative effects of endomorphin 1 (EM1) and endomorphin 2 (EM2), endogenous opioid peptides in the brain, on LDL oxidation has been investigated in vitro. The peroxidation was initiated by either copper ions or a water-soluble initiator 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH). Oxidation of the LDL lipid moiety was monitored by measuring conjugated dienes, thiobarbituric acid reactive substances, and the relative electrophoretic mobility. Low density lipoprotein oxidative modifications were assessed by evaluating apoB carbonylation and fragmentation. Endomorphins markedly and in a concentration-dependent manner inhibited Cu2+ and AAPH induced the oxidation of LDL, due to the free radical scavenging effects of endomorphins. In all assay systems, EM1 was more potent than EM2 and l-glutathione, a major intracellular water-soluble antioxidant. We propose that endomorphins provide protection against free radical-induced neurodegenerative disorders.

  8. Association of low density lipoprotein levels and glycaemic control in type-2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Yathish TR.

    2010-01-01

    Full Text Available Earlier diabetes mellitus (DM was thought to be a disease of carbohydrate metabolism. Looking at the effects of insulin deficiency on carbohydrate and lipid metabolism, diabetes mellitus is now being called more a disease of lipid metabolism than carbohydrate metabolism. A cross-sectional study was conducted during March 2005 to March 2006 to study the low-density lipoproteins (LDL levels in diabetes mellitus and its relation to glycaemic control. LDL levels were estimated. Comparison of lipid levels were made between group of diabetic patients with glycated hemoglobin less than 8.0% and a group of diabetic patients with glycated hemoglobin more than 8.0% and the controls. The lipid fractions i.e. total cholesterol (TC, triglycerides (TG, and low-density lipoprotein (LDL levels were higher in the poorly controlled diabetes patients as compared to well controlled diabetic patients and nondiabetic patients. Increased levels of low-density lipoprotein may be a contributory factor to the high risk of atherosclerosis induced coronary artery disease observed in diabetes mellitus patients. Reduction of blood glucose levels is likely to reduce low density lipoprotein levels and the risk of complication, with the lowest risk being in those with glycosylated hemoglobin values in the normal range ie. Less than 8.0%

  9. The interaction between human low density lipoproteins and bovine aortic endothelial cells. Measurements of membrane fluidity.

    Science.gov (United States)

    Badea, M G; Sima, A; Jinga, V V; Hörer, O

    1989-01-01

    Bovine aortic endothelial cells in culture have been incubated with human low density lipoproteins (LDL) characterized in their cholesterol content. The incubation was done at different time intervals up to 72 h and various LDL concentrations. It began after endothelial cells had been starved for 24 h in lipoprotein deficient serum. The transfer of some LDL-components to endothelial cells plasmalemma was monitored by measurements of membrane fluidity. Namely, the fluorescent probe trimethylamonio-diphenyl hexatriene was inserted in the cell membrane and fluorescence anisotropy was determined; a higher fluorescence anisotropy means a higher rigidity of the plasmalemma. The results show that the rigidity of the endothelial cell plasmalemma increased progressively with the time of incubation (+11% to +19.5% after 24 h and 72 h, respectively for the concentration of 200 micrograms. LDL-cholesterol/dish) and with the greater amount of cholesterol in LDL (+10.9%) for 200 micrograms LDL-cholesterol/dish to +15% for 800 micrograms LDL-cholesterol/dish after 24 h incubation). In order to see if the LDL material transfer proceeded by receptor-mediated endocytosis of LDL and/or directly through aqueous solution a lysosomal inhibitor, chloroquine, was used at the concentration of 20 microM for preventing the lysosomal hydrolase activity. In the presence of this inhibitor the fluorescence anisotropy in treated endothelial cells increased by a lesser amount, suggesting an approx. 30% participation of intracellular route. Therefore, the transfer of material (probably cholesterol) from LDL to endothelial plasmalemma could take place both by receptor-mediated endocytosis and directly through the aqueous solution.

  10. [Cholesterol in serum high density lipoprotein fraction (author's transl)].

    Science.gov (United States)

    Schatz, C; Jeanblanc, B; Offner, M

    1980-11-22

    The risk of atheroma can be assessed and valid epidemiological surveys can be carried out by measuring cholesterol in serum high density lipoprotein fraction (HDL) and calculating the HDL cholesterol: VLDL + LDL ratio. This was done in 39 patients free from surgically confirmed atheromatous lesions and in 51 patients presenting with such lesions. Of the four different techniques used for separation in these patients (ultracentrifugation, precipitation with heparin-Mn2+, precipitation with phosphotungstate-Mg2+ and electrophoresis), precipitation with phosphotungstate-Mg/2+ seems to be the most suitable, since there is no degradation of the HDL fraction as during electrophoresis on polyacrylamide gel, and less floculation of the supernatant after separation. Contrary to ultracentrifugation, which requires sophisticated equipment and good technical skill, the technique is easily carried out.

  11. PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischemic heart disease: 3 independent studies and meta-analyses

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Grande, Peer

    2010-01-01

    The aim of this study was to examine the effect of PCSK9 R46L on low-density lipoprotein cholesterol (LDL-C), risk of ischemic heart disease (IHD), and mortality.......The aim of this study was to examine the effect of PCSK9 R46L on low-density lipoprotein cholesterol (LDL-C), risk of ischemic heart disease (IHD), and mortality....

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  13. Determination of the alpha-tocopherol inhibition rate constant for peroxidation in low-density lipoprotein.

    Science.gov (United States)

    Culbertson, Sean M; Antunes, Fernando; Havrilla, Christine M; Milne, Ginger L; Porter, Ned A

    2002-06-01

    This work reports an estimate of the inhibition rate constant (k(inh)) for alpha-tocopherol (alpha-TOH) in low-density lipoproteins (LDL) based on cholesteryl linoleate hydroperoxide products formed during autoxidation of intact lipoproteins. The ratio of cis,trans/trans,trans product hydroperoxides was determined during the consumption of the antioxidant. For a reasonable determination of k(inh) in LDL, the pro-oxidant behavior of alpha-TOH was minimized by oxidizing LDL with an unsymmetrical amphiphilic azo initiator which significantly reduces phase-transfer mediated pro-oxidant effects of alpha-TOH. This initiator delivers a more constant flux of initiator radicals into LDL lipid regions and permits determination of alpha-TOH k(inh) in LDL. Development of a tocopherol-mediated peroxidation (TMP) model and analysis of cholesteryl linoleate hydroperoxide cis,trans/trans,trans product ratios provided an estimated value for the inhibition rate constant of alpha-TOH in a lipoprotein of k(inh) = 5.9 +/- 0.5 x 10(5) M(-)(1) s(-)(1)

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

    Science.gov (United States)

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

    2016-04-18

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

  15. [Study on the selective removal of plasma low-density lipoprotein and fibrinogen by degraded carrageenan].

    Science.gov (United States)

    Cong, Haixia; Yin, Liang; Fang, Bo; Du, Longbing; Zhao, Hui; Chen, Jingling; You, Chao

    2010-08-01

    The selective removal of low density lipoprotein (LDL) and fibrinogen (Fib) by degraded carrageenan was studied by the present authors. Degraded carrageenan was prepared by acid with carrageenan as the main material. The effects of acid conditions on the molecular weight were investigated, and the proper reaction conditions were ascertained. The results of infrared spectrometry indicated that the degraded carrageenan is a heparin-like polysaccharide. Then the selective removal of LDL/Fibrinogen by degraded carrageenan was studied. When molecular weight was about 10,000, pH was 5.10 and the concentration of degraded carrageenan was 800 mg/L, the average reduction percentages were 60.0% for total cholesterol(TC), 79.4% for LDL and very low-density lipoprotein (VLDL), and 93.8% for fibrinogen. There were no significant changes with relation to the level of high-density lipoprotein (HDL) and total protein (TP). So, degraded carrageenan was shown to be of good selectivity on plasma LDL/Fibrinogen apheresis.

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

    DEFF Research Database (Denmark)

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

    1994-01-01

    The fusion of separate lines of research has greatly helped in elucidating the function of the giant members of the low density lipoprotein (LDL) receptor (LDLR) supergene family. The cDNA encoding a large protein structurally closely related to LDLR, and hence named LDLR-related protein (LRP......), was cloned by Herz et al. in 1988.'Evidence was provided demonstrating that LRP can function as a receptor for chylomicron remnants@-migrating very low density lipoproteins (P-VLDL) rich in apolipoprotein E (apoE)?' The a2-macroglobulin (a2M) receptor (a2MR) was purified from rat livep and human p l a~e n t...

  17. Social Inclusion Predicts Lower Blood Glucose and Low-Density Lipoproteins in Healthy Adults.

    Science.gov (United States)

    Floyd, Kory; Veksler, Alice E; McEwan, Bree; Hesse, Colin; Boren, Justin P; Dinsmore, Dana R; Pavlich, Corey A

    2016-07-27

    Loneliness has been shown to have direct effects on one's personal well-being. Specifically, a greater feeling of loneliness is associated with negative mental health outcomes, negative health behaviors, and an increased likelihood of premature mortality. Using the neuroendocrine hypothesis, we expected social inclusion to predict decreases in both blood glucose levels and low-density lipoproteins (LDLs) and increases in high-density lipoproteins (HDLs). Fifty-two healthy adults provided self-report data for social inclusion and blood samples for hematological tests. Results indicated that higher social inclusion predicted lower levels of blood glucose and LDL, but had no effect on HDL. Implications for theory and practice are discussed.

  18. [Effect of metal cations on the copper induced peroxidation of the low density lipoproteins].

    Science.gov (United States)

    Dremina, E S; Vlasova, I I; Vakhrusheva, T V; Sharov, V S; Azizova, O A

    1997-01-01

    The effect of metal cations on copper-catalyzed lipid peroxidation (LPO) of low density lipoproteins (LDL) was examined. The presence of metal cations in the incubation media containing LDL (0.8 mg protein/ml) and CuSO4 (0-80 microM) influenced on LPO of LDL as evident by the measurement of TBARS. With the concentrations of CuSO4 less than 10 microM, the metal cations caused an increase in LDL peroxidation. Zn2+ appeared to be the most effective inductor, Mn2+ was less effective, and the influence of Ca2+ and Mg2+ was insignificant. With greater CuSO4 concentrations Mg2+ showed no effect on TBARS formation in LDL while the addition of other nontransition metal cations to the incubation mixture led to the inhibition of LDL peroxidation. The capacity for inhibition decreased in the row Mn2+ > Zn2+ > Ca2+ > Mg2+. The possible mechanism explaining these results may be in the competition of metal ions for copper binding sites on LDL. Our results allow to suggest the existence of two types of copper binding sites on LDL, tight-binding sites which are non-effective in LPO and effective weak-binding sites.

  19. Low-density Lipoprotein Improves Motility and Plasma Membrane Integrity of Cryopreserved Canine Epididymal Spermatozoa

    Directory of Open Access Journals (Sweden)

    N. Prapaiwan

    2016-05-01

    Full Text Available Cryopreservation of caudal epididymal spermatozoa is an effective technique to conserve genetic potentials of superior dogs when it is not possible to collect ejaculated spermatozoa. Although hen egg yolk is commonly supplemented into the semen extender, active substances within the egg yolk which protect sperm against cryoinjury remain to be discovered. Among its compositions, low-density lipoprotein (LDL has been reported to have a cryoprotective property for sperm cryopreservation. However, the effects of LDL on dog epididymal spermatozoa during cryopreservation have not yet been investigated. This study aimed to investigate the effects of LDL on epididymal spermatozoa quality following cryopreservation and thawing. After routine castration of 12 dogs, caudal epididymides from individuals were separated from the testes and cut into a few pieces in a Tris-buffer. Spermatozoa recovered from each sample were examined at once for sperm quality and divided into six groups of extender: no LDL, 20% egg yolk, 4%, 8%, 16%, and 24% LDL, before cryopreservation. The sperm aliquots were then equilibrated and conventionally frozen. After thawing, sperm motility, morphology, plasma membrane integrity, and acrosome integrity were evaluated. The results revealed that 4% LDL and 20% egg yolk yielded significantly higher sperm motility (57.69% and 52.69%, respectively, p<0.05 than other LDLs. In addition, 4% LDL yielded the significantly highest plasma membrane integrity (70.54%, p<0.05. In conclusion, the supplementation of 4% LDL in Tris-glucose extender could be applied for cryopreservation of canine epididymal spermatozoa.

  20. Antioxidative effect of schisanhenol on human low density lipoprotein and its quantum chemical calculation

    Institute of Scientific and Technical Information of China (English)

    Ling-hong YU; Geng-tao LIU; You-min SUN; Hong-yu ZHANG

    2004-01-01

    AIM: To investigate the effect of schisanhenol (Sal) on copper ion-induced oxidative modulation of human low density lipoprotein (LDL). METHODS: The antioxidative activity of eight schisandrins (DCL) on microsome lipid peroxidation induced by Vit C/NADPH system was first observed, and then, the effect of Sal on Cu2+-induced human LDL oxidation was studied. The generation of malondialdehyde (MDA), lipofuscin, reactive oxygen species (ROS), consumption of α-tocopherol as well as electrophoretic mobility of LDL were determined as criteria of LDL oxidation. Finally, the quantum chemical method was used to calculate the theoretical parameters of eight DCL for elucidating the difference of their antioxidant ability. RESULTS: Sal was shown to be the most active one among eight schizandrins in inhibiting microsome lipid oxidation induced by Vit C/NADPH. Sal 100, 50, and 10 μrnol/L inhibited production of MDA, lipofuscin and ROS as well as the consumption of α-tocopherol in Cu2+-induced oxidation of human LDL in a dose-dependent manner. Sal also reduced electrophoretic mobility of the oxidized human LDL. Further study of quantum chemistry found that Sal was the strongest one among eight DCL to scavenge O-2, R·, RO·, and ROO· radicals. CONCLUSION: Sal has antioxidative effect on human LDL oxidation.The mechanism of Sal against LDL oxidation may be through scavenging free radicals.

  1. Lower low-density lipoprotein cholesterol levels are associated with Parkinson's disease.

    Science.gov (United States)

    Huang, Xuemei; Chen, Honglei; Miller, William C; Mailman, Richard B; Woodard, Jennifer L; Chen, Peter C; Xiang, Dong; Murrow, Richard W; Wang, Yi-Zhe; Poole, Charles

    2007-02-15

    The apolipoprotein E (APOE) epsilon2 allele has been associated with both Parkinson's disease (PD) and lower low-density lipoprotein cholesterol (LDL-C). We tested the hypothesis that lower LDL-C may be associated with PD. This case-control study used fasting lipid profiles obtained from 124 PD cases and 112 controls. The PD cases were recruited from consecutive cases presenting at our tertiary Movement Disorder Clinic, and the controls were recruited from the spouse populations of the same clinic. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from unconditional logistic regressions, adjusting for age, gender, smoking status, and use of cholesterol-lowering agents. Lower LDL-C concentrations were associated with a higher occurrence of PD. Compared with participants with the highest LDL-C (> or =138 mg/dL), the OR was 2.2 (95% CI = 0.9-5.1) for participants with LDL-C of 115 to 137, 3.5 (95% CI = 1.6-8.1) for LDL-C of 93 to 114, and 2.6 (95% CI = 1.1-5.9) for LDL-C of < or = 92. Interestingly, use of either cholesterol-lowering drugs, or statins alone, was related to lower PD occurrence. Thus, our data provide preliminary evidence that low LDL-C may be associated with higher occurrence of PD, and/or that statin use may lower PD occurrence, either of which finding warrants further investigation.

  2. Adsorption/Desorption of Low-density Lipoprotein on a Heparinized Surface of Gold Sensors

    Institute of Scientific and Technical Information of China (English)

    LAN Ping; JI Jing; HUANG Xiao-Jun; GUDURU Deepak; GROTH Thomas; VIENKEN J(o)rg; DING Hui

    2012-01-01

    Heparin has been considered to be a potentially useful ligand for low-density lipoprotein(LDL)detection and analysis in a clinical context.In order to construct an affinity surface for preferential adsorption of LDL,heparin-modified gold surface(GS-Hep)was fabricated by a self-assembling method and hydrophobic-modified gold surfaces(GS-Hydro)was used as a control.The morphologies of the modified gold surfaces were investigated by atomic force microscopy(AFM)and the quantity of heparin bound to gold surface was assayed by the toluidine blue(TB)colorimetric method.Water contact angles were determined to investigate wettability on GS-Hep and GS-Hydro.Surface plasmon resonance(SPR)technique was used subsequently to detect the selective binding of LDL with heparin.And the investigation on the effect of pH on LDL adsorption suggests that lower pH lead to higher quantities of LDL adsorption on GS-Hep.Compared with GS-Hydro,GS-Hep is selective for LDL from both single and binary protein solutions.Moreover,adsorbed LDL on GS-Hep could be washed off by injecting elution solution,such as NaCl solution,for the purpose of the regeneration of GS-Hep for further LDL adsorption.

  3. Phospholipase A2-modified low-density lipoprotein activates macrophage peroxisome proliferator-activated receptors.

    Science.gov (United States)

    Namgaladze, Dmitry; Morbitzer, Daniel; von Knethen, Andreas; Brüne, Bernhard

    2010-02-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors modulating metabolic and inflammatory responses of phagocytes to stimuli such as fatty acids and their metabolites. We studied the role of PPARs in macrophages exposed to low-density lipoprotein (LDL) modified by secretory phospholipase A(2) (PLA). By analyzing PPAR ligand-binding domain luciferase reporter activation, we observed that PLA-LDL transactivates PPARalpha and PPARdelta, but not PPARgamma. We confirmed that PLA-LDL induced PPAR response element reporter activation by endogenous PPARalpha and PPARdelta in human THP-1 macrophages. By using THP-1 cells with a stable knockdown of PPARalpha and PPARdelta, we showed that PLA-LDL-activated PPARdelta altered macrophage gene expression related to lipid metabolism and lipid droplet formation. Although PPARalpha/delta silencing did not affect cholesterol and triglyceride accumulation in PLA-LDL-treated macrophages, PPARdelta activation by PLA-LDL attenuated macrophage inflammatory gene expression induced by interferon gamma and lipopolysaccharide. PPARdelta activation by PLA-LDL does not influence lipid accumulation in PLA-LDL-treated macrophages. However, it attenuates macrophage inflammatory responses, thus contributing to an anti-inflammatory cell phenotype.

  4. High hydrostatic pressure specifically affects molecular dynamics and shape of low-density lipoprotein particles

    Science.gov (United States)

    Golub, M.; Lehofer, B.; Martinez, N.; Ollivier, J.; Kohlbrecher, J.; Prassl, R.; Peters, J.

    2017-04-01

    Lipid composition of human low-density lipoprotein (LDL) and its physicochemical characteristics are relevant for proper functioning of lipid transport in the blood circulation. To explore dynamical and structural features of LDL particles with either a normal or a triglyceride-rich lipid composition we combined coherent and incoherent neutron scattering methods. The investigations were carried out under high hydrostatic pressure (HHP), which is a versatile tool to study the physicochemical behavior of biomolecules in solution at a molecular level. Within both neutron techniques we applied HHP to probe the shape and degree of freedom of the possible motions (within the time windows of 15 and 100 ps) and consequently the flexibility of LDL particles. We found that HHP does not change the types of motion in LDL, but influences the portion of motions participating. Contrary to our assumption that lipoprotein particles, like membranes, are highly sensitive to pressure we determined that LDL copes surprisingly well with high pressure conditions, although the lipid composition, particularly the triglyceride content of the particles, impacts the molecular dynamics and shape arrangement of LDL under pressure.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-04-01

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

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

    African Journals Online (AJOL)

    The usefulness of total cholesterol and high density lipoprotein - cholesterol ratio in ... cholesterol and/or highdensity lipoprotein cholesterol/total cholesterol ratios in the interpretation of lipid profile result in clinical practice. ... Article Metrics.

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

    Directory of Open Access Journals (Sweden)

    Simonetta Geninatti Crich

    2007-12-01

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

  8. Electronegative LDL: A Circulating Modified LDL with a Role in Inflammation

    Directory of Open Access Journals (Sweden)

    Montserrat Estruch

    2013-01-01

    Full Text Available Electronegative low density lipoprotein (LDL(− is a minor modified fraction of LDL found in blood. It comprises a heterogeneous population of LDL particles modified by various mechanisms sharing as a common feature increased electronegativity. Modification by oxidation is one of these mechanisms. LDL(− has inflammatory properties similar to those of oxidized LDL (oxLDL, such as inflammatory cytokine release in leukocytes and endothelial cells. However, in contrast with oxLDL, LDL(− also has some anti-inflammatory effects on cultured cells. The inflammatory and anti-inflammatory properties ascribed to LDL(− suggest that it could have a dual biological effect.

  9. Discordance of Low-Density Lipoprotein and High-Density Lipoprotein Cholesterol Particle Versus Cholesterol Concentration for the Prediction of Cardiovascular Disease in Patients With Metabolic Syndrome and Diabetes Mellitus (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

    Science.gov (United States)

    Tehrani, David M; Zhao, Yanglu; Blaha, Michael J; Mora, Samia; Mackey, Rachel H; Michos, Erin D; Budoff, Matthew J; Cromwell, William; Otvos, James D; Rosenblit, Paul D; Wong, Nathan D

    2016-06-15

    A stronger association for low-density lipoprotein particle (LDL-P) and high-density lipoprotein particle (HDL-P) versus cholesterol concentrations (LDL-C and HDL-C) in predicting coronary heart disease (CHD) has been noted. We evaluate the role of these factors and extent of particle-cholesterol discordance in those with diabetes mellitus (DM) and metabolic syndrome (MetS) for event prediction. In the Multi-Ethnic Study of Atherosclerosis, we examined discordance of LDL and HDL (defined as a subject's difference between baseline particle and cholesterol percentiles), LDL-C, LDL-P, HDL-C, and HDL-P in relation to incident CHD and cardiovascular disease (CVD) events in subjects with DM, MetS (without DM), or neither condition using Cox regression. Of the 6,417 subjects with 10-year follow-up, those with MetS (n = 1,596) and DM (n = 838) had significantly greater LDL and HDL discordance compared with those without these conditions. In discordance models, only LDL discordance (per SD) within the MetS group was positively associated with CHD events (adjusted hazard ratio [HR] = 1.22, 95% confidence interval [CI] 1.01 to 1.48, p lipoprotein particles and discordances in those with MetS and DM. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. High density lipoprotein 3 inhibits oxidized low density lipoprotein-induced apoptosis via promoting cholesterol efflux in RAW264.7 cells

    Institute of Scientific and Technical Information of China (English)

    Pei JIANG; Peng-ke YAN; Jian-xiong CHEN; Bing-yang ZHU; Xiao-yong LEI; Wei-dong YIN; Duan-fang LIAO

    2006-01-01

    Aim: To investigate the protective effect of high density lipoprotein 3 (HDL3) on oxidized low density lipoprotein (ox-LDL)-induced apoptosis in RAW264.7 cells.Methods: RAW264.7 cells were exposed to 50 mg/L ox-LDL for various durations up to 48 h, and apoptosis was detected using Hoechst 33258 staining and flow cytometric analysis. Total cholesterol levels were detected by high performance liquid chromatography, cholesterol efflux was determined by Tritium labeling, and the cellular lipid droplets were assayed by oil red O staining. Results: Treatment with 50 mg/L ox-LDL for 12, 24, and 48 h increased the apoptotic rate of RAW264.7 cells in a time-dependent manner. The peak apoptotic rate (47.7%) was observed after 48 h incubation. HDL3 at various concentrations (50 mg/L, 100 mg/L, and 200mg/L) inhibited the ox-LDL (50 mg/L for 48 h)-mediated apoptosis that was accompanied by an increased rate of intracellular cholesterol efflux, and decreased total cholesterol levels in cells in a concentration-dependent manner. Blockage of cholesterol efflux by brefeldin decreased the protective effect of HDL3 on ox-LDL-induced apoptosis. Increase of the cholesterol efflux effected by another cholesterol acceptor, β-cyclodextrin, led to a dramatic decrease in the apoptotic rate of cells. Conclusion: HDL3 antagonizes ox-LDL-induced apoptosis in RAW264.7cells, through reducing the accumulation of toxic cholesterol.

  11. Overexpression of LOXIN Protects Endothelial Progenitor Cells From Apoptosis Induced by Oxidized Low Density Lipoprotein.

    Science.gov (United States)

    Veas, Carlos; Jara, Casandra; Willis, Naomi D; Pérez-Contreras, Karen; Gutierrez, Nicolas; Toledo, Jorge; Fernandez, Paulina; Radojkovic, Claudia; Zuñiga, Felipe A; Escudero, Carlos; Aguayo, Claudio

    2016-04-01

    Human endothelial progenitor cells (hEPC) are adult stem cells located in the bone marrow and peripheral blood. Studies have indicated that hEPC play an important role in the recovery and repair of injured endothelium, however, their quantity and functional capacity is reduced in several diseases including hypercholesterolemia. Recently, it has been demonstrated that hEPC express lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and its activation by oxidized low-density lipoprotein (ox-LDL) induces cellular dysfunction and apoptosis. This study aimed to investigate whether overexpression of LOXIN, a truncated isoform of LOX-1 that acts as a dominant negative, plays a protective role against ox-LDL-induced apoptosis in hEPC. Human endothelial progenitor cells exposed to ox-LDL showed a significant increase in LOX-1 expression, and apoptosis began at ox-LDL concentrations above 50 μg/mL. All hEPC apoptosed at 200 μg/mL ox-LDL. High LOXIN expression was generated using adenoviral systems in hEPC and SiHa cells transduced with 100 colony-forming units per cell. Transduced LOXIN localized to the plasma membrane and blocked ox-LDL uptake mediated by LOX-1. Overexpression of LOXIN protected hEPC from ox-LDL-induced apoptosis, and therefore maybe a novel way of improving hEPC function and quantity. These results suggest that adenoviral vectors of LOXIN may provide a possible treatment for diseases related to ox-LDL and vascular endothelium dysfunction, including atherosclerosis.

  12. Apolipoprotein C-III and the Metabolic Basis for Hypertriglyceridemia and the Dense Low-Density Lipoprotein Phenotype

    Science.gov (United States)

    Zheng, Chunyu; Khoo, Christina; Furtado, Jeremy; Sacks, Frank M.

    2011-01-01

    Background Here, we aim to identify defects of apolipoprotein (apo) B lipoprotein metabolism that characterize hypertriglyceridemia, focusing on apoC-III and apoE. Methods and Results We studied the transport of plasma apoB within 21 distinct subfractions as separated by anti–apoC-III and anti–apoE immunoaffinity chromatography and ultracentrifugation in 9 patients with moderate hypertriglyceridemia and 12 normotriglyceridemic control subjects. Hypertriglyceridemia was characterized by a 3-fold higher liver secretion of very low-density lipoprotein (VLDL) that had apoC-III but not apoE and a 50% lower secretion of VLDL with both apoC-III and apoE (both Phypertriglyceridemia, associated with increased apoC-III contents of these particles. LDL distribution shifted from light and medium LDL to dense LDL in hypertriglyceridemia through a quartet of kinetic perturbations: increased flux from apoC-III–containing triglyceride-rich lipoproteins, a shift in liver LDL secretion pattern from light to dense LDL, an increased conversion rate from light and medium LDL to dense LDL, and retarded catabolism of dense LDL. Conclusions These results support a central role for apoC-III in metabolic defects leading to hypertriglyceridemia. Triglyceride-rich lipoprotein metabolism shifts from an apoE-dominated system in normotriglyceridemic participants characterized by rapid clearance from circulation of VLDL to an apoC-III–dominated system in hypertriglyceridemic patients characterized by reduced clearance of triglyceride-rich lipoproteins and the formation of the dense LDL phenotype. PMID:20368524

  13. Rspo2 suppresses CD36-mediated apoptosis in oxidized low density lipoprotein-induced macrophages

    OpenAIRE

    2016-01-01

    Oxidized low density lipoprotein (oxLDL)-induced apoptosis of macrophages contributes to the formation of atherosclerotic plaques. R-spondin 2 (Rspo2), a member of the cysteine-rich secreted proteins, has been shown to be involved in the oncogenesis of several types of cancer. It has also been found to be abundantly expressed among the four R-spondin members in macrophages. The present study was performed to determine whether Rspo2 is involved in the ox-LDL-induced apoptosis of macrophages. I...

  14. Drugs targeting high-density lipoprotein cholesterol for coronary artery disease management.

    Science.gov (United States)

    Katz, Pamela M; Leiter, Lawrence A

    2012-01-01

    Many patients remain at high risk for future cardiovascular events despite levels of low-density lipoprotein cholesterol (LDL-C) at, or below, target while taking statin therapy. Much effort is therefore being focused on strategies to reduce this residual risk. High-density lipoprotein cholesterol (HDL-C) is a strong, independent, inverse predictor of coronary heart disease risk and is therefore an attractive therapeutic target. Currently available agents that raise HDL-C have only modest effects and there is limited evidence of additional cardiovascular risk reduction on top of background statin therapy associated with their use. It was hoped that the use of cholesteryl ester transfer protein (CETP) inhibitors would provide additional benefit, but the results of clinical outcome studies to date have been disappointing. The results of ongoing trials with other CETP inhibitors that raise HDL-C to a greater degree and also lower LDL-C, as well as with other emerging therapies are awaited.

  15. Association of Plasma Adiponectin and Oxidized Low-Density Lipoprotein with Carotid Intima-Media Thickness in Diabetic Nephropathy

    OpenAIRE

    Anna Tavridou; Anastasia Georgoulidou; Athanasios Roumeliotis; Stefanos Roumeliotis; Efstathia Giannakopoulou; Nikolaos Papanas; Ploumis Passadakis; Manolopoulos, Vangelis G; Vassilis Vargemezis

    2015-01-01

    Aims. We sought to determine the association between levels of adiponectin and oxidized low-density lipoprotein (ox-LDL) in patients with diabetic nephropathy as well as their effect on carotid intima-media thickness (cIMT). Methods. Adiponectin and ox-LDL were determined in 25 diabetic patients without nephropathy and 94 patients at different stages of diabetic nephropathy including subjects on hemodialysis. cIMT was measured using real-time B-mode ultrasonography. Results. Plasma adiponecti...

  16. Characterization of a disease-causing Glu119-Lys mutation in the low-density lipoprotein receptor gene in two Danish families with heterozygous familial hypercholesterolemia

    DEFF Research Database (Denmark)

    Jensen, H K; Jensen, T G; Jensen, L G

    1994-01-01

    Mutations in the gene for the low-density lipoprotein receptor (LDL receptor) cause the autosomal dominant inherited disease familial hypercholesterolemia (FH). In 15 Danish patients with heterozygous FH we have screened exon 4 of the LDL receptor gene for point mutations and small rearrangements...

  17. Silent exonic mutations in the low-density lipoprotein receptor gene that cause familial hypercholesterolemia by affecting mRNA splicing.

    NARCIS (Netherlands)

    Defesche, J.C.; Schuurman, E.J.M.; Klaaijsen, L.N.; Khoo, K.L.; Wiegman, A.; Stalenhoef, A.F.H.

    2008-01-01

    In a large group of patients with the clinical phenotype of familial hypercholesterolemia, such as elevated low-density lipoprotein (LDL) cholesterol and premature atherosclerosis, but without functional mutations in the genes coding for the LDL receptor and apolipoprotein B, we examined the effect

  18. C-reactive protein and annexin A5 bind to distinct sites of negatively charged phospholipids present in oxidized low-density lipoprotein.

    NARCIS (Netherlands)

    Tits, L.J.H. van; Graaf, J. de; Toenhake, H.; Heerde, W.L. van; Stalenhoef, A.F.H.

    2005-01-01

    OBJECTIVE: To investigate binding of C-reactive protein (CRP) and annexin A5, 2 proteins with high affinity for negatively charged phospholipids, to oxidized low-density lipoprotein (LDL) and the consequences of these interactions for subsequent binding of oxidized LDL to monocyte/macrophage-like

  19. Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy

    OpenAIRE

    Zabirnyk, Olga; Liu, Wei; Khalil, Shadi; Sharma, Anit; Phang, James M.

    2009-01-01

    Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible ...

  20. Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy

    OpenAIRE

    2009-01-01

    Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible ...

  1. Influence of Oxidized Low Density Lipoprotein on the Proliferation of Human Artery Smooth Muscle Cells in vitro

    Institute of Scientific and Technical Information of China (English)

    QIAO Chenhui; ZHANG Kailun; XIA Jiahong

    2007-01-01

    The effects of oxidized low density lipoprotein (ox-LDL) on the proliferation of culturedhuman vascular smooth muscle cells (vSMC) were investigated in vitro. By using NaBr density gradient centrifugation, LDL was isolated and purified from human plasma. Ox-LDL was produced from LDL by being incubated with CuSO4. ox-LDL was then added to the culture medium at different concentrations (35, 60, 85, 110, 135 and 160 μg/mL) for 7 days. The influence of ox-LDL on vSMC proliferation was observed in growth curve, mitosis index, and in situ determination of apoptosis. The data were analyzed with SPSS 10.0 software. The results showed that the ox-LDL produced in vitro had a good purity and optimal oxidative degree, which was similar to the intrinsic ox-LDL in atherosclerotic plaque. ox-LDL at a concentration of 35 μg/mL demonstrated the strongest proliferation inducement, and at a concentration of 135 μg/mL, ox-LDL could inhibit the growth of vSMC. ox-LDL at concentrations of 35 and 50 μg/mL presented powerful mitotic trigger, and with the increase of ox-LDL concentration, the mitotic index of vSMC was decreased gradually. ox-LDL at higher concentrations promoted more apoptotic vSMCs. ox-LDL at lower concentrations triggered proliferation of vSMCs, and at higher concentrations induced apoptosis in vSMCs. ox-LDL played a promotional role in the pathogenesis and development of atherosclerosis by affecting vSMC proliferation and apoptosis.

  2. Metabolism of high density lipoproteins in liver cancer

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2010-11-01

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

  4. Structure-based Design Targeted at LOX-1, a Receptor for Oxidized Low-Density Lipoprotein

    Science.gov (United States)

    Thakkar, Shraddha; Wang, Xianwei; Khaidakov, Magomed; Dai, Yao; Gokulan, Kuppan; Mehta, Jawahar L.; Varughese, Kottayil I.

    2015-11-01

    Atherosclerosis related cardiovascular diseases continue to be the primary cause of mortality in developed countries. The elevated level of low density lipoprotein (LDL) is generally considered to be the driver of atherosclerosis, but recent years have seen a shift in this perception in that the vascular plaque buildup is mainly caused by oxidized LDL (ox-LDL) rather than native-LDL. The scavenger receptor LOX-1 found in endothelial cells binds and internalizes ox-LDL which leads to the initiation of plaque formation in arteries. Using virtual screening techniques, we identified a few potential small molecule inhibitors of LOX-1 and tested their inhibitory potential using differential scanning fluorimetry and various cellular assays. Two of these molecules significantly reduced the uptake of ox-LDL by human endothelial cells, LOX-1 transcription and the activation of ERK1/2 and p38 MAPKs in human endothelial cells. In addition, these molecules suppressed ox-LDL-induced VCAM-1 expression and monocyte adhesion onto human endothelial cells demonstrating their therapeutic potential.

  5. Patients with Rheumatoid Arthritis Show Altered Lipoprotein Profiles with Dysfunctional High-Density Lipoproteins that Can Exacerbate Inflammatory and Atherogenic Process.

    Science.gov (United States)

    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.

  6. INHIBITION OF HUMAN LOW-DENSITY LIPOPROTEINS OXIDATION BY Hibiscus radiatus CUV. CALYCES EXTRACT

    Directory of Open Access Journals (Sweden)

    Hernawan Hernawan

    2010-06-01

    Full Text Available Hibiscus radiatus Cuv calyces extracts rich in polyphenols was screened for their potential to inhibit oxidation of human low-density lipoproteins-cholesterol (LDL-C in vitro. The inhibition of LDL-C oxidation (antioxidant activity was determined by measuring the formation of conjugated dienes and thiobarbituric acid reagent substances (TBARS. LDL-C oxidation was carried out in the presence of H. radiatus Cuv calyces extract (20 and 50 μM. CuSO4 (10 μM was used as the oxidation initiator and  butylated hydroxytoluene (BHT at 50 μM was used as standard antioxidant. The protective effect of H. radiatus Cuv. calyces extract toward human low-density lipoproteins, complex lipid system was  demonstrated by significant increase lag time (> 103 min, diminished of the propagation rate (44 %, and diminution of conjugated dienes formation 59.42 % (50 μM compared to control.   Keywords: antioxidant, conjugated dienes, Hibiscus radiatus Cuv, low-density lipoproteins-cholesterol

  7. Oxidized low-density lipoprotein is associated with advanced-stage prostate cancer.

    Science.gov (United States)

    Wan, Fangning; Qin, Xiaojian; Zhang, Guiming; Lu, Xiaolin; Zhu, Yao; Zhang, Hailiang; Dai, Bo; Shi, Guohai; Ye, Dingwei

    2015-05-01

    Clinical and epidemiological data suggest coronary artery disease shares etiology with prostate cancer (PCa). The aim of this work was to assess the effects of several serum markers reported in cardiovascular disease on PCa. Serum markers (oxidized low-density lipoprotein [ox-LDL], apolipoprotein [apo] B100, and apoB48) in peripheral blood samples from 50 patients from Fudan University Shanghai Cancer Center (FUSCC) with localized or lymph node metastatic PCa were investigated in this study. Twenty-five samples from normal individuals were set as controls. We first conducted enzyme-linked immunosorbent assay analysis to select candidate markers that were significantly different between these patients and controls. Then, the clinical relevance between OLR1 (the ox-LDL receptor) expression and PCa was analyzed in The Cancer Genome Atlas (TCGA) cohort. We also investigated the function of ox-LDL in PCa cell lines in vitro. Phosphorylation protein chips were used to analyze cell signaling pathways in ox-LDL-treated PC-3 cells. The ox-LDL level was found to be significantly correlated with N stage of prostate cancer. OLR1 expression was correlated with lymph node metastasis in the TCGA cohort. In vitro, ox-LDL stimulated the proliferation, migration, and invasion of LNCaP and PC-3 in a dose-dependent manner. The results of phosphoprotein microarray illustrated that ox-LDL could influence multiple signaling pathways of PC-3. Activation of proliferation promoting signaling pathways (including β-catenin, cMyc, NF-κB, STAT1, STAT3) as well as apoptosis-associating signaling pathways (including p27, caspase-3) demonstrated that ox-LDL had complicated effects on prostate cancer. Increased serum ox-LDL level and OLR1 expression may indicate advanced-stage PCa and lymph node metastasis. Moreover, ox-LDL could stimulate PCa proliferation, migration, and invasion in vitro.

  8. Low-density lipoprotein electronegativity is a novel cardiometabolic risk factor.

    Directory of Open Access Journals (Sweden)

    Jing-Fang Hsu

    Full Text Available BACKGROUND: Low-density lipoprotein (LDL plays a central role in cardiovascular disease (CVD development. In LDL chromatographically resolved according to charge, the most electronegative subfraction-L5-is the only subfraction that induces atherogenic responses in cultured vascular cells. Furthermore, increasing evidence has shown that plasma L5 levels are elevated in individuals with high cardiovascular risk. We hypothesized that LDL electronegativity is a novel index for predicting CVD. METHODS: In 30 asymptomatic individuals with metabolic syndrome (MetS and 27 healthy control subjects, we examined correlations between plasma L5 levels and the number of MetS criteria fulfilled, CVD risk factors, and CVD risk according to the Framingham risk score. RESULTS: L5 levels were significantly higher in MetS subjects than in control subjects (21.9±18.7 mg/dL vs. 11.2±10.7 mg/dL, P:0.01. The Jonckheere trend test revealed that the percent L5 of total LDL (L5% and L5 concentration increased with the number of MetS criteria (P<0.001. L5% correlated with classic CVD risk factors, including waist circumference, body mass index, waist-to-height ratio, smoking status, blood pressure, and levels of fasting plasma glucose, triglyceride, and high-density lipoprotein. Stepwise regression analysis revealed that fasting plasma glucose level and body mass index contributed to 28% of L5% variance. The L5 concentration was associated with CVD risk and contributed to 11% of 30-year general CVD risk variance when controlling the variance of waist circumference. CONCLUSION: Our findings show that LDL electronegativity was associated with multiple CVD risk factors and CVD risk, suggesting that the LDL electronegativity index may have the potential to be a novel index for predicting CVD. Large-scale clinical trials are warranted to test the reliability of this hypothesis and the clinical importance of the LDL electronegativity index.

  9. Characterization of the structure of polydisperse human low-density lipoprotein by neutron scattering.

    Science.gov (United States)

    Meyer, D F; Nealis, A S; Bruckdorfer, K R; Perkins, S J

    1995-09-01

    Low-density lipoproteins (LDL) in plasma are constructed from a single molecule of apolipoprotein B-100 (M(r) 512000) in association with lipid (approximate M(r) 2-3 x 10(6)). The gross structure was studied using an updated pulsed-neutron camera LOQ with an area detector to establish the basis for the interpretation of structural changes seen during dynamic studies of LDL oxidation. Neutron-scattering data for LDL in 100% 2H2O buffers emphasize their external appearance. Guinier analysis on a continuous-flux neutron camera D17 revealed pronounced concentration-dependences in the radius of gyration, RG, and the intensity of forward scattering, I(0) (equivalent to the M(r) of LDL) between 0.5 and 11 mg of LDL protein/ml. LDL preparations from different donors gave different RG values. When extrapolated to zero concentration, RG values ranged between 8.3 and 10.6 nm and were linearly correlated with M(r), which is consistent with a spherical structure. The distance-distribution function P(r) in real space showed a single maximum at 9.1-10.9 nm, which is just under half the observed maximum dimension of 23.1 +/- 1.2 nm expected for a spherical structure. The neutron radial-density function p(r) exhibited a plateau of high and featureless density at the centre of LDL. LDL can be modelled by a polydisperse assembly of spheres with two internal densities and a mean radius close to 10.0 nm in a normal distribution of radii with a standard deviation of 2.0 nm. The data are consistent with recent electron-microscopy and ultracentrifugation data.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Evaluation of biodistribution and imaging of atherosclerotic lesions using [sup 111]In-labeled low-density lipoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Yamashina, Hisayo (Toho Univ., Tokyo (Japan). School of Medicine)

    1993-07-01

    [sup 111]In-labeled low-density lipoprotein (LDL) was administered to Watanabe heritable hyperlipidemic rabbits (WHHL group) and control rabbits (control group) to evaluate its biodistribution and scintigraphic images by [gamma]-camera and radioactivity of each organ. With external imaging, the heart, liver, kidney, bone and spleen of each rabbit were observed. By setting the region of interest, the liver/heart ratio of the WHHL group was significantly lower than that of the control group (p<0.05), the plasma half life of LDL was longer and radioactivity in blood, heart and aorta was higher in the WHHL group. Each aorta was autoradiographed and significant accumulation of [sup 111]In-labeled-LDL was recognized in the aortic arch, bifurcation of intercostal and celiac artery in the WHHL group. By the use of labeled LDL with the combination of [gamma]-camera, it is capable of detecting the regulation of lipoprotein metabolism and imaging atherosclerotic lesions externally. (author).

  11. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

    DEFF Research Database (Denmark)

    Chapman, M John; Ginsberg, Henry N; Amarenco, Pierre;

    2011-01-01

    Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipop......Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high......-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic...... studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated...

  12. Nanotechnology for Synthetic High Density Lipoproteins

    Science.gov (United States)

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

    2014-01-01

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

  13. Partial characterization of low density lipoprotein preparations isolated from fresh and frozen plasma after radiolabeling by seven different methods

    Energy Technology Data Exchange (ETDEWEB)

    Atsma, D.E.; Kempen, H.J.; Nieuwenhuizen, W.; van ' t Hooft, F.M.; Pauwels, E.K. (Gaubius Institute TNO, Leiden (Netherlands))

    1991-01-01

    Four {sup 99m}Tc and three {sup 123}I labeling methods were evaluated for their suitability to label low density lipoproteins (LDL) for the purpose of scintigraphic biodistribution studies. For {sup 99m}Tc these methods were: direct incorporation in LDL of {sup 99m}TcO4- using sodium dithionite (dithionite method); a method using first N,N-dimethylformamide to prepare a {sup 99m}Tc-complex reacting with LDL in a subsequent step (DMF method); a technique in which {sup 99m}TcO4- is first coupled to a diamide dithiolate derivative of pentanoic acid by reduction with dithionite, followed by coupling of this ligand to LDL (N2S2 method); and a method using sodium borohydride and stannous chloride as reducing agents (borohydride method). The iodination techniques were based on oxidation of I(-)----I+, using iodine monochloride (ICl method), 1,3,4,6-tetrachloro-3,6-diphenylglycoluril (Iodogen method), and N-bromosuccinimide (NBS method) as oxidants. We studied labeling yields, modification of LDL caused by the labeling procedures using agarose-gel electrophoresis, and radiochemical stability of the labeled LDL complex upon incubation in plasma at 37 degrees C for 15 h. We used Sepharose CL6B chromatography to separate LDL from other plasma proteins. We also examined whether LDL isolated from frozen plasma (Pool-LDL) gave results similar to LDL obtained from freshly prepared plasma (Fresh-LDL). Pool-LDL radiolabeled by the dithionite, DMF, NBS, and Iodogen methods lost its label upon incubation with plasma. This also happened with Fresh-LDL when the DMF, NBS and Iodogen methods were used. Upon agarose-gel electrophoresis, no modification of LDL was observed with all methods when the radionuclide/LDL ratio was kept low.

  14. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage

    Energy Technology Data Exchange (ETDEWEB)

    Frei, B. (Department of Nutrition, Harvard School of Public Health, Boston, MA (Unites States))

    1991-12-01

    The authors exposed human blood plasma and low-density lipoprotein (LDL) to many different oxidative challenges and followed the temporal consumption of endogenous antioxidants in relation to the initiation of oxidative damage. Under all types of oxidizing conditions, ascorbic acid completely protects lipids in plasma and LDL against detectable peroxidative damage as assessed by a specific and highly sensitive assay for lipid peroxidation. Ascorbic acid proved to be superior to the other water-soluble plasma antioxidants bilirubin, uric acid, and protein thiols as well as to the lipoprotein-associated antioxidants alpha-tocopherol, ubiquinol-10, lycopene, and beta-carotene. Although these antioxidants can lower the rate of detectable lipid peroxidation, they are not able to prevent its initiation. Only ascorbic acid is reactive enough to effectively intercept oxidants in the aqueous phase before they can attack and cause detectable oxidative damage to lipids.

  15. Persistent high levels of plasma oxidized low-density lipoprotein after acute myocardial infarction predict stent restenosis

    NARCIS (Netherlands)

    T. Naruko; M. Ueda; S. Ehara; A. Itoh; K. Haze; N. Shirai; Y. Ikura; M. Ohsawa; H. Itabe; Y. Kobayashi; H. Yamagishi; M. Yoshiyama; J. Yoshikawa; A.E. Becker

    2006-01-01

    Objective-Recently, elevated levels of plasma oxidized low-density lipoprotein (LDL) have been shown to relate to plaque instability in human atherosclerotic lesions. We investigated prospectively patients admitted with acute myocardial infarction (AMI) who underwent primary coronary stenting to eva

  16. Identification of Toxic 2,4-Decadienal in Oxidized, Low-Density Lipoprotein by Solid-Phase Microextraction.

    Science.gov (United States)

    Spiteller; Spiteller

    2000-02-01

    The oxidation of low-density lipoprotein (LDL) in vitro was studied by a combination of solid-phase microextraction and GC/MS. 2-trans,4-cis-2,4-Decadienal, which is strongly toxic in vitro, was detected as the early oxidation product. This compound is degraded further to hexanal and (by cyclization of 4-hydroxy-2-nonenal) to 2-pentylfuran.

  17. Association Between Low-Density Lipoprotein Cholesterol-Lowering Genetic Variants and Risk of Type 2 Diabetes

    DEFF Research Database (Denmark)

    Lotta, Luca A; Sharp, Stephen J; Burgess, Stephen;

    2016-01-01

    Importance: Low-density lipoprotein cholesterol (LDL-C)-lowering alleles in or near NPC1L1 or HMGCR, encoding the respective molecular targets of ezetimibe and statins, have previously been used as proxies to study the efficacy of these lipid-lowering drugs. Alleles near HMGCR are associated with...

  18. Identification of the Best Anthropometric Predictors of Serum High- and Low-Density Lipoproteins Using Machine Learning.

    Science.gov (United States)

    Lee, Bum Ju; Kim, Jong Yeol

    2015-09-01

    Serum high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels are associated with risk factors for various diseases and are related to anthropometric measures. However, controversy remains regarding the best anthropometric indicators of the HDL and LDL cholesterol levels. The objectives of this study were to identify the best predictors of HDL and LDL cholesterol using statistical analyses and two machine learning algorithms and to compare the predictive power of combined anthropometric measures in Korean adults. A total of 13,014 subjects participated in this study. The anthropometric measures were assessed with binary logistic regression (LR) to evaluate statistically significant differences between the subjects with normal and high LDL cholesterol levels and between the subjects with normal and low HDL cholesterol levels. LR and the naive Bayes algorithm (NB), which provides more reasonable and reliable results, were used in the analyses of the predictive power of individual and combined measures. The best predictor of HDL was the rib to hip ratio (p =anthropometric measures, the body mass index (BMI), WHR, forehead to waist ratio, forehead to rib ratio, and forehead to chest ratio were the strongest predictors of LDL; these measures had similar predictive powers. The strongest predictor in men was BMI (p =anthropometric measures was higher for HDL than for LDL, and the predictive power for both HDL and LDL in women was higher than for men. A combination of anthropometric measures slightly improved the predictive power for both HDL and LDL cholesterol. The best indicator for HDL and LDL might differ according to the type of cholesterol and the gender. In women, but not men, age was the variable that strongly predicted HDL and LDL cholesterol levels. Our findings provide new information for the development of better initial screening tools for HDL and LDL cholesterol.

  19. Allele-specific expression of the low density lipoprotein receptor gene

    Energy Technology Data Exchange (ETDEWEB)

    Minnich, A.; Lussier-Cacan, S.; Roy, M. [Clincial Research Institute of Montreal, Quebec (Canada)

    1994-09-01

    Approximately 60% of familial hypercholesterolemia (FH) in French Canadians is due to a > 10 kb deletion of the promoter region of the gene encoding the low density lipoprotein (LDL) receptor (LDL-R), allowing determination of the influence of a single LDL-R allele on phenotypic expression of FH. Normal allele haplotypes of approximately 250 heterozygotes were determined with 7 RFLPs. In vitro maximal LDL-R activity of blood lymphocytes from a subset of approximately 150 heterozygotes, measured by immunocytofluorometry, was significantly higher (20 to 30%) in subjects with LDL-R normal allele haplotype G (n=11), and O (n=7) compared to the most frequent haplotype F (n=43), while no differences were observed among F, E (n=11), and the 2 other most prevalent haplotypes (n=43). LDL-R mRNA in these lymphocytes was significantly elevated 2.3-, 1.7-, and 1.8- fold, in G, O, and E, respectively, compared to F, while no significant differences were apparent between F and the other two most frequent haplotyes. Large interindividual variability in lymphocyte LDL-R mRNA levels and activity was observed even among subjects with the same LDL-R normal allele haplotype. However, maximally induced lymphocyte LDL-R mRNA levels correlated poorly with levels measured in freshly isolated cells (n=14). Relative to haplotype F (n=47 women (W), 39 men (M)), mean plasma LDL cholesterol levels adjusted for age and apolipoprotein E genotype were 5-10% lower in men and women with haplotypes G (n=16 W, 12 M) and O (n=8 W, 6 M), and 20% lower in 7 W with haplotype E. These results suggest that (1) normal LDL-R allele haplotype G and O may contain sequence variations which confer relatively high gene expression and (2) environmental and genetic influences other than the LDL-R gene contribute substantially to variability in LDL-R expression and plasma LDL cholesterol levels in French Canadian FH heterozygotes.

  20. Alpha slow-moving high-density-lipoprotein subfraction in serum of a patient with radiation enteritis and peritoneal carcinosis

    Energy Technology Data Exchange (ETDEWEB)

    Peynet, J.; Legrand, A.; Messing, B.; Thuillier, F.; Rousselet, F.

    1989-04-01

    An alpha slow-moving high-density-lipoprotein (HDL) subfraction was seen in a patient presenting with radiation enteritis and peritoneal carcinosis, who was given long-term cyclic parenteral nutrition. This subfraction, observed in addition to normal HDL, was precipitated with low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) by sodium phosphotungstate-magnesium chloride. The patient's serum lipoproteins were analyzed after fractionation by density gradient ultracentrifugation. The alpha slow-moving HDL floated in the ultracentrifugation subfractions with densities ranging from 1.028 to 1.084 kg/L, and their main apolipoproteins included apolipoprotein E in addition to apolipoprotein A-I. These HDL were larger than HDL2. The pathogenesis of this unusual HDL subfraction is hypothesized.

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

    Science.gov (United States)

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

    2011-08-01

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

  2. Systematic review: association of low-density lipoprotein subfractions with cardiovascular outcomes.

    Science.gov (United States)

    Ip, Stanley; Lichtenstein, Alice H; Chung, Mei; Lau, Joseph; Balk, Ethan M

    2009-04-07

    Measures of low-density lipoprotein (LDL) subfractions have been proposed as an independent risk factor for cardiovascular disease. To review published studies that reported relationships between LDL subfractions and cardiovascular outcomes. MEDLINE (1950 to 5 January 2009), CAB Abstracts (1973 to 30 June 2008), and Cochrane Central Register of Controlled Trials (2nd quarter of 2008), limited to English-language studies. 3 reviewers selected longitudinal studies with 10 or more participants that reported an association between LDL subfractions and incidence or severity of cardiovascular disease and in which plasma samples were collected before outcome determination. Data were extracted from 24 studies. The 10 studies that used analytical methods available for clinical use (all of which used nuclear magnetic resonance) had full data extraction, including quality assessment (good, fair, or poor). All studies were extracted by 1 researcher and verified by another. All 24 studies, and the subset of 10 nuclear magnetic resonance studies, were heterogeneous in terms of the specific tests analyzed, analytical methods used, participants investigated, and outcomes measured. Higher LDL particle number was consistently associated with increased risk for cardiovascular disease, independent of other lipid measurements. Other LDL subfractions were generally not associated with cardiovascular disease after adjustment for cholesterol concentrations. No study evaluated the incremental value of LDL subfractions beyond traditional cardiovascular risk factors or their test performance. Publication bias was a possibility. Higher LDL particle number has been associated with cardiovascular disease incidence, but studies have not determined whether any measures of LDL subfractions add incremental benefit to traditional risk factor assessment. Routine use of clinically available LDL subfraction tests to estimate cardiovascular disease risk is premature.

  3. The Relationship of Plasma miR-29a and Oxidized Low Density Lipoprotein with Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Yu-Qing Huang

    2016-12-01

    Full Text Available Background/Aims: Atherosclerosis is a chronic inflammatory condition associated with a variety of vascular diseases. Previous studies showed that both miR-29a and oxidized low density lipoprotein (ox-LDL were vital in the development of atherosclerosis. However, the relationship between miR-29a and ox-LDL remains unknown. This study was designed to investigate the association of miR-29a and ox-LDL and to test whether circulating miR-29a and ox-LDL levels could predict atherosclerosis. Methods: In 170 participants, plasma levels of miR-29a were assessed by quantitative real-time polymerase chain reaction (qRT-PCR while plasma ox-LDL levels were determined using enzyme-linked immunosorbent assay (ELISA kits. The relationship between miR-29a level and ox-LDL and carotid intima-media thickness (cIMT was assessed using the Spearman correlation coefficient and multiple liner regression. Results: Compared with the normal cIMT group, the increased cIMT group had higher levels of ox-LDL (0.47 ± 0.08 vs 0.29 ± 0.06 ng/ml, p = 0.003 and miR-29a (32.93 ± 4.26 vs 26.37 ± 1.04, p p p Conclusion: Increased miR-29a and ox-LDL levels were associated with an early stage of atherosclerosis, and the combination of miR-29a and ox-LDL offered better predictive values for atherosclerosis than either alone.

  4. Activation of sonic hedgehog signaling attenuates oxidized low-density lipoprotein-stimulated brain microvascular endothelial cells dysfunction in vitro.

    Science.gov (United States)

    Jiang, Xiu-Long; Chen, Ting; Zhang, Xu

    2015-01-01

    The study was performed to investigate the role of sonic hedgehog (SHH) in the oxidized low-density lipoprotein (oxLDL)-induced blood-brain barrier (BBB) disruption. The primary mouse brain microvascular endothelial cells (MBMECs) were exposed to oxLDL. The results indicated that treatment of MBMECs with oxLDL decreased the cell viability, and oxidative stress was involved in oxLDL-induce MBMECs dysfunction with increasing intracellular ROS and MDA formation as well as decreasing NO release and eNOS mRNA expression. In addition, SHH signaling components, such as SHH, Smo and Gli1, mRNA and protein levels were significantly decreased after incubation with increasing concentrations of oxLDL. Treatment with oxLDL alone or SHH loss-of-function significantly increased the permeability of MBMECs, and overexpression of SHH attenuated oxLDL-induced elevation of permeability in MBMECs. Furthermore, SHH gain-of-function could reverse oxLDL-induced apoptosis through inhibition caspase3 and caspase8 levels in MBMECs. Taken together, these results demonstrated that the suppression of SHH in MBMECs might contribute to the oxLDL-induced disruption of endothelial barrier. However, the overexpression of SHH could reverse oxLDL-induced endothelial cells dysfunction in vitro.

  5. Counterpoint: Low-Density Lipoprotein Cholesterol Targets Are Not Needed in Lipid Treatment Guidelines.

    Science.gov (United States)

    Robinson, Jennifer G; Ray, Kausik

    2016-04-01

    On the basis of accumulating evidence, low-density lipoprotein cholesterol (LDL-C) treat-to-goal approaches no longer seem to be the best way to optimize lipid-modifying therapy to prevent atherosclerotic cardiovascular disease (ASCVD). The potential for a net ASCVD risk reduction benefit is a more individualized approach to clinical decision making and may better inform patient preferences. However, risk estimation tools will need to be developed to facilitate more personalized CVD risk estimation in statin-treated patients. In the meantime, LDL-C thresholds rather than targets may aid in determining which patients might benefit from additional LDL-C-lowering therapy beyond statins. © 2016 American Heart Association, Inc.

  6. Pregnancy in a Woman with Homozygous Familial Hypercholesterolemia Not on Low-Density Lipoprotein Apheresis

    Directory of Open Access Journals (Sweden)

    Akl C. Fahed

    2012-11-01

    Full Text Available Pregnancy in women with homozygous familial hypercholesterolemia (FH has been rarely reported and might pose risks on the mother and her fetus. Although most reported cases remained on low-density lipoprotein (LDL apheresis, there are no clear guidelines regarding the management of this entity. We report the first case of an uncomplicated pregnancy in a 24-year-old homozygous FH woman who was not maintained on LDL apheresis. FH expresses a wide variability in the phenotype, and management of homozygous FH cases who desire to become pregnant should be individualized based on preconceptional assessment with frequent antenatal follow-up. Decisions on management should be made after weighing the risks versus benefits of LDL apheresis.

  7. The association of the Clock 3111 T/C SNP with lipids and lipoproteins including small dense low-density lipoprotein: results from the Mima study.

    Science.gov (United States)

    Tsuzaki, Kokoro; Kotani, Kazuhiko; Sano, Yoshiko; Fujiwara, Shinji; Takahashi, Kaoru; Sakane, Naoki

    2010-10-21

    The clock molecule plays major roles in circadian rhythmicity and regulating lipid and glucose metabolism in peripheral organs. Disruption of the circadian rhythm can lead to cardiometabolic disorders. The existence of small dense low-density lipoprotein (sdLDL) in the circulation, an abnormality of lipid metabolism, in part associated with lifestyle, is also one of risk parameters for cardiometabolic disorders. The 3111 T/C single nucleotide polymorphism (SNP) of the Clock gene has been reported to be associated with lifestyle including morning/evening preference. We investigated whether the Clock 3111 T/C SNP may affect lipids and lipoproteins including sdLDL. In 365 community-dwelling subjects (170 men and 195 women, mean age 63 ± 14 years), the 3111 T/C SNP was genotyped using a fluorescent allele-specific DNA primer assay system. The levels of sdLDL were measured with the electrophoretic separation of lipoproteins employing the Lipoprint system. The frequency of the Clock 3111 C allele was 0.14. The area of sdLDL did not differ between the subjects with obesity and those without. In carriers of T/T homozygotes, the area of sdLDL was significantly higher compared with carriers of the C allele (T/C or C/C) (1.7 ± 3.4 vs. 0.8 ± 1.9%; p < 0.05). A multiple regression analysis showed that the area of sdLDL was significantly and negatively correlated with the Clock 3111 T/C SNP (β = -0.114, p < 0.05), independently of age, sex, body mass index, and exercise habits. Our findings indicated that the Clock 3111 T/C SNP might be associated with the existence of sdLDL.

  8. l-Cystathionine Inhibits the Mitochondria-Mediated Macrophage Apoptosis Induced by Oxidized Low Density Lipoprotein

    Science.gov (United States)

    Zhu, Mingzhu; Du, Junbao; Chen, Siyao; Liu, Angie Dong; Holmberg, Lukas; Chen, Yonghong; Zhang, Chunyu; Tang, Chaoshu; Jin, Hongfang

    2014-01-01

    This study was designed to investigate the regulatory role of l-cystathionine in human macrophage apoptosis induced by oxidized low density lipoprotein (ox-LDL) and its possible mechanisms. THP-1 cells were induced with phorbol 12-myristate 13-acetate (PMA) and differentiated into macrophages. Macrophages were incubated with ox-LDL after pretreatment with l-cystathionine. Superoxide anion, apoptosis, mitochondrial membrane potential, and mitochondrial permeability transition pore (MPTP) opening were examined. Caspase-9 activities and expression of cleaved caspase-3 were measured. The results showed that compared with control group, ox-LDL treatment significantly promoted superoxide anion generation, release of cytochrome c (cytc) from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and cell apoptosis, in addition to reduced mitochondrial membrane potential as well as increased MPTP opening. However, 0.3 and 1.0 mmol/L l-cystathionine significantly reduced superoxide anion generation, increased mitochondrial membrane potential, and markedly decreased MPTP opening in ox-LDL + l-cystathionine macrophages. Moreover, compared to ox-LDL treated-cells, release of cytc from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and apoptosis levels in l-cystathionine pretreated cells were profoundly attenuated. Taken together, our results suggested that l-cystathionine could antagonize mitochondria-mediated human macrophage apoptosis induced by ox-LDL via inhibition of cytc release and caspase activation. PMID:25514411

  9. Edaravone attenuates monocyte adhesion to endothelial cells induced by oxidized low-density lipoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhijuan, E-mail: zjlee038@163.com; Cheng, Jianxin; Wang, Liping

    2015-10-30

    Oxidized low-density lipoprotein (oxLDL) plays a vital role in recruitment of monocytes to endothelial cells, which is important during early stages of atherosclerosis development. Edaravone, a potent and novel scavenger of free radicals inhibiting hydroxyl radicals, has been clinically used to reduce the neuronal damage following ischemic stroke. In the present study, Edaravone was revealed to markedly reduce oxLDL-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). The inhibitory mechanism of Edaravone was associated with suppression of the chemokine MCP-1 and adhesion molecule VCAM-1 and ICAM-1 expression. In addition, luciferase reporter assay results revealed that administration of Edaravone attenuated the increase in NF-κB transcriptional activity induced by oxLDL. Notably, it's also shown that Edaravone treatment blocked oxLDL induced p65 nuclear translocation in HUVECs. Results indicate that Edaravone negatively regulates endothelial inflammation. - Highlights: • Edaravone reduces oxLDL-induced monocyte adhesion to HUVECs. • Edaravone attenuates oxLDL-induced expression of MCP-1, VCAM-1, and ICAM-1. • Edaravone reduces NF-κB transcriptional activity and p65 nuclear translocation.

  10. Clinical efficacy and safety of evolocumab for low-density lipoprotein cholesterol reduction.

    Science.gov (United States)

    Henry, Courtney A; Lyon, Ronald A; Ling, Hua

    2016-01-01

    Multiple categories of medications have been developed to manage lipid profiles and reduce the risk of cardiovascular events in patients with heart disease. However, currently marketed medications have not solved the problems associated with preventing and treating cardiovascular diseases completely. A substantial population of patients cannot take advantage of statin therapy due to statin intolerance, heart failure, or kidney hemodialysis, suggesting a need for additional effective agents to reduce low-density lipoprotein cholesterol (LDL-C) levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was discovered in 2003 and subsequently emerged as a novel target for LDL-C-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2) directed against human PCSK9. By inactivating PCSK9, evolocumab upregulates LDL receptors causing increased catabolism of LDL-C and the consequent reduction of LDL-C levels in blood. Overall, evolocumab has had notable efficacy, with LDL-C reduction ranging from 53% to 75% in monotherapy and combination therapies, and is associated with minor adverse effects. However, studies regarding the ability of evolocumab to reduce mortality as well as long-term safety concerns are limited. The fact that the drug was introduced at a cost much higher than the existing medications and shows a low incremental mortality benefit suggests that many payers will consider evolocumab to have an unfavorable cost-benefit ratio.

  11. How Do PCSK9 Inhibitors Stack Up to Statins for Low-Density Lipoprotein Cholesterol Control?

    Science.gov (United States)

    Zimmerman, Marj P.

    2015-01-01

    Despite advances in the approach toward treating hypercholesterolemia and widespread access to statin medications, not all people are able to reach target low-density lipoprotein cholesterol (LDL-C) levels to reduce their cardiovascular risk. Some of the reasons include the inability to tolerate statin therapy, LDL-C levels that remain high even in the presence of statin therapy, and a familial disorder that is characterized by extremely high levels of LDL-C. A new therapeutic class, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, represents a novel and promising approach to reducing LDL-C levels using a mechanism at the LDL receptor level. The recent approval of the first 2 PCSK9 inhibitors and the anticipated approval of the third agent in this class within approximately 1 year may provide clinicians powerful new weapons to lower LDL-C levels in patients who are not satisfactorily managed with statins. However, the results of long-term studies of the ability of these new medications to influence cardiovascular outcomes will not be known for several years. PMID:26702335

  12. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD

    Science.gov (United States)

    Funamoto, Masafumi; Sunagawa, Yoichi; Katanasaka, Yasufumi; Miyazaki, Yusuke; Imaizumi, Atsushi; Kakeya, Hideaki; Yamakage, Hajime; Satoh-Asahara, Noriko; Komiyama, Maki; Wada, Hiromichi; Hasegawa, Koji; Morimoto, Tatsuya

    2016-01-01

    Purpose COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin–low-density lipoprotein (AT-LDL) complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin®, a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD. Patients and methods This is a randomized, double-blind, parallel-group study. Subjects with stages I–II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin® or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated. Results There were no differences between the Theracurmin® and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure and hemoglobin A1c and LDL-cholesterol, triglyceride, or high-density lipoprotein-cholesterol levels after treatment were similar for the two groups. However, the percent change in the AT-LDL level was significantly (P=0.020) lower in the Theracurmin® group compared with the placebo group. Conclusion Theracurmin® reduced levels of atherosclerotic AT-LDL, which may lead to the prevention of future cardiovascular events in mild COPD subjects. PMID:27616885

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

    Science.gov (United States)

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

    1997-01-01

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

  14. Association of lipase lipoprotein polymorphisms with high-density lipoprotein and triglycerides in elderly men

    OpenAIRE

    Araujo,Lara Miguel Quirino; Cendoroglo, Maysa Seabra [UNIFESP; Gigek, Carolina de Oliveira; Chen, Elizabeth Suchi; Smith, Maria de Arruda Cardoso [UNIFESP

    2010-01-01

    Lipoprotein lipase is essential for triglyceride hydrolysis. the polymorphisms S447X in exon 9 and HindIII in intron 8 have been associated with lower triglyceride levels and lower cardiovascular risk in adult men. We examined the association of these lipoprotein lipase polymorphisms with high-density lipoprotein (HDL) and triglyceride levels in elderly men. Blood samples were obtained from 87 elderly men, 48 of whom had cardiovascular disease and 39 (controls) had no history of cardiovascula...

  15. Effect of alirocumab on specific lipoprotein non-high-density lipoprotein cholesterol and subfractions as measured by the vertical auto profile method: analysis of 3 randomized trials versus placebo.

    Science.gov (United States)

    Toth, Peter P; Hamon, Sara C; Jones, Steven R; Martin, Seth S; Joshi, Parag H; Kulkarni, Krishnaji R; Banerjee, Poulabi; Hanotin, Corinne; Roth, Eli M; McKenney, James M

    2016-02-13

    The effect of alirocumab on potentially atherogenic lipoprotein subfractions was assessed in a post hoc analysis using the vertical auto profile (VAP) method. Patients from three Phase II studies with low-density lipoprotein cholesterol (LDL-C) ≥ 2.59 mmol/L (100 mg/dL) at baseline on stable statin therapy were randomised to receive subcutaneous alirocumab 50-150 mg every 2 weeks (Q2W) or 150-300 mg every 4 weeks (according to study) or placebo for 8-12 weeks. Samples from patients treated with alirocumab 150 mg Q2W (n = 74; dose common to all three trials) or placebo (n = 71) were analysed by VAP. Percent change in lipoprotein subfractions with alirocumab vs. placebo was analysed at Weeks 6, 8 or 12 using analysis of covariance. Alirocumab significantly reduced LDL-C and the cholesterol content of subfractions LDL1, LDL2 and LDL3+4. Significant reductions were also observed in triglycerides, apolipoproteins CII and CIII and the cholesterol content of very low-density, intermediate-density, and remnant lipoproteins. Alirocumab achieved reductions across a spectrum of atherogenic lipoproteins in patients receiving background statin therapy. Clinicaltrials.gov identifiers: NCT01288443, NCT01288469, NCT01266876.

  16. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Low-density lipoprotein immunological test system....5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein... the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein in...

  17. In vitro studies of PBT Nonwoven Fabrics adsorbent for the removal of low density lipoprotein from hyperlipemia plasma

    Energy Technology Data Exchange (ETDEWEB)

    Cao Ye; Wang Hong [Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052 (China); Yang Chao [State Key Lab of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240 (China); Zhong Rui [Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052 (China); Lei Yu [Chengdu Blood Center, Chengdu 610041 (China); Sun Kang [State Key Lab of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240 (China); Liu Jiaxin, E-mail: jxliu8122@vip.sina.com [Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052 (China)

    2011-06-15

    Polyanion ligands such as acrylic acid (AA) and heparin were grafted on PBT Nonwoven Fabrics (PBTNF) to study their effect on the adsorption of low density lipoprotein (LDL). These modified PBTNFs were characterized by Horizontal Attenuated Total Reflectance Fourier Transform Infrared spectroscopy and X-ray Photoelectron spectroscopy. The blood compatibilities of the modified PBTNFs were examined using in vitro hemolysis rate (HR), platelet adhesion, total protein (TP) and activated partial thromboplastin time. The results showed that direct immobilized heparin could improve PBTNF-PAA's blood compatibility and decrease the adsorption capability of useful high density lipoprotein, but would possess so low bioactivity that could not further improve the absorption of LDL and TC. Since the PBTNF-PAA55-Heparin adsorbent had quite good adsorption selectivity for these proteins, it can be an excellent candidate for depletion of LDL with good blood compatibility.

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

    Science.gov (United States)

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

    2004-04-01

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

  19. Phosphoethanolamine-complexed C-reactive protein: A pharmacological-like macromolecule that binds to native low-density lipoprotein in human serum

    Science.gov (United States)

    Singh, Sanjay K.; Suresh, Madathilparambil V.; Prayther, Deborah C.; Moorman, Jonathan P.; Rusiñol, Antonio E.; Agrawal, Alok

    2008-01-01

    Background C-reactive protein (CRP) is an acute phase plasma protein. An important binding specificity of CRP is for the modified forms of low-density lipoprotein (LDL) in which the phosphocholine-binding sites of CRP participate. CRP, however, does not bind to native LDL. Methods We investigated the interaction of CRP with native LDL using sucrose density gradient ultracentrifugation. Results We found that the blocking of the phosphocholine-binding sites of CRP with phosphoethanolamine (PEt) converted CRP into a potent molecule for binding to native LDL. In the presence of PEt, CRP acquired the ability to bind to fluid-phase purified native LDL. Because purified native LDL may undergo subtle modifications, we also used whole human serum as the source of native LDL. In the presence of PEt, CRP bound to native LDL in serum also. The effect of PEt on CRP was selective for LDL because PEt-complexed CRP did not bind to high-density lipoprotein in the serum. Conclusions The pharmacologic intervention of endogenous CRP by PEt-based compounds, or the use of exogenously prepared CRP-PEt complexes, may turn out to be an effective approach to capture native LDL cholesterol in vivo to prevent the development of atherosclerosis. PMID:18486609

  20. Low density lipoprotein development and evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Kahl, S.B. [Univ. of California, San Francisco, CA (United States)

    1995-11-01

    Although significant progress toward the application of boronated LDL for site selective boron drug delivery has been made during the past year, the loss of our animal and cell culture testing site at WSU has seriously hampered progress on this project. Results are reported of one in vivo biodistribution study in B16BL6-bearing mice and a series of in vitro studies that demonstrate very substantial uptake of boronated LDL in certain cell lines. The influence of 17{alpha}-ethinyl estradiol (EE) on cellular uptake has also been probed. Most significantly LDL loaded with HC was demonstrated to be taken up with exceptional aridity in several lines. Significant progress has also been made in the development of a rapid infrared analysis of boron in boronated LDL solution, which may be useful for clinical BNCT studies in Finland.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  3. Nanobiotechnology applications of reconstituted high density lipoprotein.

    Science.gov (United States)

    Ryan, Robert O

    2010-12-01

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

  4. High-density lipoprotein cholesterol: How High

    Directory of Open Access Journals (Sweden)

    G Rajagopal

    2012-01-01

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

  5. Hepatitis C virus G1b infection decreases the number of small low-density lipoprotein particles.

    Science.gov (United States)

    Kinoshita, Chika; Nagano, Tomohisa; Seki, Nobuyoshi; Tomita, Yoichi; Sugita, Tomonori; Aida, Yuta; Itagaki, Munenori; Satoh, Kenichi; Sutoh, Satoshi; Abe, Hiroshi; Tsubota, Akihito; Aizawa, Yoshio

    2016-08-07

    To investigate how hepatitis C virus (HCV) G1b infection influences the particle number of lipoproteins. The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1b infection (active HCV group) and 91 with cleared HCV infection (SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using LipoSEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1b infection and the lipoprotein particle number was determined by multiple linear regression analysis. The median number of low-density lipoprotein (LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range (IQR): 444 nmol/L] than in the SVR group (1363 nmol/L, IQR: 472 nmol/L, P lipoprotein (HDL) particles (14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein (VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium (median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P < 0.001), small (median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P < 0.001), and very small LDL particles (median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P < 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL particles or any sub-fractions of VLDL and HDL particles. HCV

  6. Low high-density lipoprotein cholesterol is a residual risk factor associated with long-term clinical outcomes in diabetic patients with stable coronary artery disease who achieve optimal control of low-density lipoprotein cholesterol.

    Science.gov (United States)

    Ogita, Manabu; Miyauchi, Katsumi; Miyazaki, Tadashi; Naito, Ryo; Konishi, Hirokazu; Tsuboi, Shuta; Dohi, Tomotaka; Kasai, Takatoshi; Yokoyama, Takayuki; Okazaki, Shinya; Kurata, Takeshi; Daida, Hiroyuki

    2014-01-01

    Diabetes mellitus is recognized an independent risk factor for coronary artery disease (CAD) and mortality. Clinical trials have shown that statins significantly reduce cardiovascular events in diabetic patients. However, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein cholesterol (LDL-C) levels with statin. High-density lipoprotein cholesterol (HDL-C) is an established coronary risk factor that is independent of LDL-C levels. We evaluated the impact of HDL-C on long-term mortality in diabetic patients with stable CAD who achieved optimal LDL-C. We enrolled 438 consecutive diabetic patients who were scheduled for percutaneous coronary intervention between 2004 and 2007 at our institution. We identified 165 patients who achieved target LDL-C diabetic patients with low-HDL-C who achieved optimal LDL-C (6.9 vs 17.9 %, log-rank P = 0.030). Multivariate Cox regression analysis showed that HDL-C is significantly associated with clinical outcomes (adjusted hazard ratio for MACE 1.33, 95 % confidence interval 1.01-1.75, P = 0.042). Low HDL-C is a residual risk factor that is significantly associated with long-term clinical outcomes among diabetic patients with stable CAD who achieve optimal LDL-C levels.

  7. Screening, expression, and characterization of an anti-human oxidized low-density lipoprotein single-chain variable fragment.

    Science.gov (United States)

    Kumano-Kuramochi, Miyuki; Fujimura, Takashi; Komba, Shiro; Maeda-Yamamoto, Mari; Machida, Sachiko

    2016-09-01

    Increased levels of oxidized low-density lipoprotein (OxLDL) in the blood circulation are correlated with atherosclerosis. Monoclonal antibody-based detection systems have been reported for OxLDL. We identified novel single-chain variable fragments (scFvs) having affinity for human OxLDL and related ligands. We constructed an scFv library from nonimmunized human spleen mRNA. Two types (γ+κ and μ+λ) of scFv phage libraries were enriched by biopanning, and five scFv clones with affinity for OxLDL were identified. The γκ5 scFv, which showed the highest affinity for OxLDL, was cloned into pET-22b(+) and expressed in Escherichia coli BL21(DE3). γκ5, expressed as an inclusion body in BL21(DE3), was refolded and purified. The specificity and sensitivity of γκ5 were analyzed using enzyme-linked immunosorbent assays (ELISAs). The γκ5 scFv showed affinity for OxLDL and acetylated LDL. The sensitivity of γκ5 to low concentrations (1-2 μg/mL) of OxLDL was higher than that to AcLDL and LDL. Finally, we developed a sandwich ELISA using γκ5 and CTLD14 (a lectin-like OxLDL receptor-1 ligand recognition region), which allowed specific detection of OxLDL at a level below 0.1 μg/mL. Our results indicated that the γκ5 scFv was a promising molecule for the detection of modified LDL at very low concentrations.

  8. The effect of a spatially heterogeneous transmural water flux on concentration polarization of low density lipoprotein in arteries.

    Science.gov (United States)

    Vincent, Peter E; Sherwin, Spencer J; Weinberg, Peter D

    2009-04-22

    Uptake of low density lipoprotein (LDL) by the arterial wall is likely to play a key role in atherogenesis. A particular process that may cause vascular scale heterogeneity in the rate of transendothelial LDL transport is the formation of a flow-dependent LDL concentration polarization layer on the luminal surface of the arterial endothelium. In this study, the effect of a spatially heterogeneous transmural water flux (that traverses the endothelium only via interendothelial cell clefts) on such concentration polarization is investigated numerically. Unlike in previous investigations, realistic intercellular cleft dimensions are used here and several values of LDL diffusivity are considered. Particular attention is paid to the spatially averaged LDL concentration adjacent to different regions of the endothelial surface, as such measures may be relevant to the rate of transendothelial LDL transport. It is demonstrated in principle that a heterogeneous transmural water flux can act to enhance such measures, and cause them to develop a shear dependence (in addition to that caused by vascular scale flow features, affecting the overall degree of LDL concentration polarization). However, it is shown that this enhancement and additional shear dependence are likely to be negligible for a physiologically realistic transmural flux velocity of 0.0439 mum s(-1) and an LDL diffusivity (in blood plasma) of 28.67 mum(2) s(-1). Hence, the results imply that vascular scale studies of LDL concentration polarization are justified in ignoring the effect of a spatially heterogeneous transmural water flux.

  9. Altered activation of endothelial anti- and proapoptotic pathways by high-density lipoprotein from patients with coronary artery disease: role of high-density lipoprotein-proteome remodeling

    National Research Council Canada - National Science Library

    Riwanto, Meliana; Rohrer, Lucia; Roschitzki, Bernd; Besler, Christian; Mocharla, Pavani; Mueller, Maja; Perisa, Damir; Heinrich, Kathrin; Altwegg, Lukas; von Eckardstein, Arnold; Lüscher, Thomas F; Landmesser, Ulf

    2013-01-01

    ...). High-density lipoprotein from healthy subjects (HDL(Healthy)) has been proposed to exert endothelial antiapoptotic effects that may represent an important antiatherogenic property of the lipoprotein...

  10. Low-density lipoprotein concentration in the normal left coronary artery tree

    Directory of Open Access Journals (Sweden)

    Louridas George E

    2008-10-01

    Full Text Available Abstract Background The blood flow and transportation of molecules in the cardiovascular system plays a crucial role in the genesis and progression of atherosclerosis. This computational study elucidates the Low Density Lipoprotein (LDL site concentration in the entire normal human 3D tree of the LCA. Methods A 3D geometry model of the normal human LCA tree is constructed. Angiographic data used for geometry construction correspond to end-diastole. The resulted model includes the LMCA, LAD, LCxA and their main branches. The numerical simulation couples the flow equations with the transport equation applying realistic boundary conditions at the wall. Results High concentration of LDL values appears at bifurcation opposite to the flow dividers in the proximal regions of the Left Coronary Artery (LCA tree, where atherosclerosis frequently occurs. The area-averaged normalized luminal surface LDL concentrations over the entire LCA tree are, 1.0348, 1.054 and 1.23, for the low, median and high water infiltration velocities, respectively. For the high, median and low molecular diffusivities, the peak values of the normalized LDL luminal surface concentration at the LMCA bifurcation reach 1.065, 1.080 and 1.205, respectively. LCA tree walls are exposed to a cholesterolemic environment although the applied mass and flow conditions refer to normal human geometry and normal mass-flow conditions. Conclusion The relationship between WSS and luminal surface concentration of LDL indicates that LDL is elevated at locations where WSS is low. Concave sides of the LCA tree exhibit higher concentration of LDL than the convex sides. Decreased molecular diffusivity increases the LDL concentration. Increased water infiltration velocity increases the LDL concentration. The regional area of high luminal surface concentration is increased with increasing water infiltration velocity. Regions of high LDL luminal surface concentration do not necessarily co-locate to the

  11. 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

    Science.gov (United States)

    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

  12. Mendelian Disorders of High-Density Lipoprotein Metabolism

    NARCIS (Netherlands)

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

    2014-01-01

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

  13. The association of the Clock 3111 T/C SNP with lipids and lipoproteins including small dense low-density lipoprotein: results from the Mima study

    Directory of Open Access Journals (Sweden)

    Takahashi Kaoru

    2010-10-01

    Full Text Available Abstract Background The clock molecule plays major roles in circadian rhythmicity and regulating lipid and glucose metabolism in peripheral organs. Disruption of the circadian rhythm can lead to cardiometabolic disorders. The existence of small dense low-density lipoprotein (sdLDL in the circulation, an abnormality of lipid metabolism, in part associated with lifestyle, is also one of risk parameters for cardiometabolic disorders. The 3111 T/C single nucleotide polymorphism (SNP of the Clock gene has been reported to be associated with lifestyle including morning/evening preference. We investigated whether the Clock 3111 T/C SNP may affect lipids and lipoproteins including sdLDL. Methods In 365 community-dwelling subjects (170 men and 195 women, mean age 63 ± 14 years, the 3111 T/C SNP was genotyped using a fluorescent allele-specific DNA primer assay system. The levels of sdLDL were measured with the electrophoretic separation of lipoproteins employing the Lipoprint system. Results The frequency of the Clock 3111 C allele was 0.14. The area of sdLDL did not differ between the subjects with obesity and those without. In carriers of T/T homozygotes, the area of sdLDL was significantly higher compared with carriers of the C allele (T/C or C/C (1.7 ± 3.4 vs. 0.8 ± 1.9%; p Clock 3111 T/C SNP (β = -0.114, p Conclusion Our findings indicated that the Clock 3111 T/C SNP might be associated with the existence of sdLDL.

  14. Plasma fasting and nonfasting triglycerides and high-density lipoprotein cholesterol in atherosclerotic stroke: different profiles according to low-density lipoprotein cholesterol.

    Science.gov (United States)

    Kim, Suk Jae; Park, Yun Gyoung; Kim, Ji Hyun; Han, Yun Kyung; Cho, Hong Keun; Bang, Oh Young

    2012-08-01

    Although low-density lipoprotein cholesterol (LDL-C) is the main lipid target for cardiovascular risk reduction, recent studies suggest that other lipid indicies are also associated with vascular events. We hypothesized that the association of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) with atherosclerotic stroke (AS) differs depending on LDL-C levels. Data prospectively collected on subjects admitted with acute ischemic stroke to a university medical center were analyzed. We divided the patients into AS and non-atherosclerotic stroke (NAS) groups and independent association of lipid parameters and genetic influences of apolipoprotein A5 (ApoA5) polymorphisms with AS were evaluated. Of 268 patients, 160 (59.7%) were classified with AS and 108 (40.3%) were classified with NAS. Vascular risk factors were more prevalent in AS patients than in those with NAS; additionally, AS patients' anthropometric indexes and laboratory findings showed that they were prone to atherosclerosis. AS was independently associated with fasting TG (OR per 10 mg/dL increase, 1.38; 95% CI, 1.16-1.64; OR for highest vs. lowest tertile, 12.85; 95% CI, 3.31-49.85), HDL-C (OR per 10 mg/dL increase, 0.61; 95% CI, 0.42-0.88; OR for lowest vs. highest tertile, 4.28; 95% CI, 1.16-15.86), and nonfasting TG (OR per 10 10 mg/dL increase, 1.25; 95% CI, 1.11-1.42; OR for highest vs. lowest tertile, 8.20; 95% CI, 1.98-33.88) only among patients with LDL <100 mg/dL. No interaction was observed between fasting and nonfasting TG and ApoA5 polymorphisms. In conclusion, fasting and nonfasting TG and HDL-C were associated with AS only when patients had low levels of LDL-C. Non-LDL-C may have an additional role in addition to the LDL-C levels in AS development. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy.

    Science.gov (United States)

    Zabirnyk, Olga; Liu, Wei; Khalil, Shadi; Sharma, Anit; Phang, James M

    2010-03-01

    Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible for the latter. To elucidate the role of POX in oxLDL-mediated cytotoxicity, we knocked down POX via small interfering RNA and found that this (i) further reduced viability of cancer cells treated with oxLDL; (ii) decreased oxLDL-associated reactive oxygen species generation; (iii) decreased autophagy measured via beclin-1 protein level and light-chain 3 protein (LC3)-I into LC3-II conversion. Using POX-expressing cell model, we established that single POX overexpression was sufficient to activate autophagy. Thus, it led to autophagosomes accumulation and increased conversion of LC3-I into LC3-II. Moreover, beclin-1 gene expression was directly dependent on POX catalytic activity, namely the generation of POX-dependent superoxide. We conclude that POX is critical in the cellular response to the noxious effects of oxLDL by activating protective autophagy.

  16. Pomegranate wine has greater protection capacity than red wine on low-density lipoprotein oxidation.

    Science.gov (United States)

    Sezer, Ebru Demirel; Akçay, Yasemin Delen; Ilanbey, Bilal; Yildirim, Hatice Kalkan; Sözmen, Eser Yildirim

    2007-06-01

    Although there is a large body of evidence on the main role of red wine in protection of low-density lipoprotein (LDL) against oxidation, there are few data on the role of pomegranate juice, which has high phenolic content. We conducted this study considering the possible importance of pomegranate wine as an antioxidant and in order to make a comparison between red and pomegranate wines. The phenol levels of pomegranate and red wines (4,850 mg/L gallic acid equivalents and 815 mg/L gallic acid equivalents, respectively) were in accordance with their total antioxidant activity (39.5% and 33.7%, respectively). Both wines decreased LDL-diene levels following a 30-minute incubation period compared with controls (145 +/- 3.2 micromol/mg of LDL protein). However, pure pomegranate wine demonstrated a greater antioxidant effect (P wine (124 +/- 3.2 micromol/mg of LDL protein). In conclusion, we suggest that pomegranate wine has potential protective effects toward LDL oxidation, and it may be a dietary choice for people who prefer fruit wines.

  17. Fe3O4@ZnO core-shell nanocomposites for efficient and repetitive removal of low density lipoprotein in plasma and on blood vessel

    Science.gov (United States)

    Huang, Xiao; Lu, Juan; Yue, Danyang; Fan, Yijuan; Yi, Caixia; Wang, Xiaoying; Zhang, Mengxue; Pan, Jun

    2015-03-01

    Low density lipoprotein (LDL)-apheresis therapy, which directly removes LDL from plasma by LDL-adsorbents in vitro is found to be clinically effective and safe to lower the LDL content in blood to prevent cardiovascular disease. Thus, developing excellent LDL adsorbents are becoming more and more attractive. Herein, functional Fe3O4@ZnO core-shell nanocomposites have been synthesized by a facile and eco-friendly two-step method. Not only do they possess high LDL adsorption (in PBS/plasma as well as on blood vessels) and favorable magnetic targeting ability but they can also be reused conveniently, which offer the Fe3O4@ZnO core-shell nanocomposites significant potential in the removal of LDL in vitro and in vivo.

  18. High payload delivery of optical imaging and photodynamic therapy agents to tumors using phthalocyanine-reconstituted low-density lipoprotein nanoparticles.

    Science.gov (United States)

    Li, Hui; Marotta, Diane E; Kim, Soungkyoo; Busch, Theresa M; Wileyto, E Paul; Zheng, Gang

    2005-01-01

    To improve the labeling efficiency of a low-density lipoprotein (LDL)-based photosensitizer (PS) for achieving high probe to protein payload, a tetra-t-butyl silicon phthalocyanine bearing two oleate moieties at its axial positions, SiPcBOA, is designed and synthesized. Using this novel strategy, SiPcBOA reconstituted LDL (r-SiPcBOA-LDL) with a very high payload (SiPcBOA to LDL molar ratio >3000 to 35001:1) is obtained. Using electron microscopy, we find reconstituted LDL (rLDL) with such a high payload essentially retains the mean particle size of native LDL. Since acetylated LDL binds to scavenger receptors of endothelial and microglial cells instead of LDLR, SiPcBOA reconstituted acetylated LDL (r-SiPcBOA-AcLDL) is also prepared to serve as a negative control to validate the LDL receptor (LDLR) targeting specificity. Confocal microscopy studies demonstrate that the internalization of r-SiPcBOA-LDL by human hepatoblastoma G2 (HepG2) tumor cells is mediated by LDLR pathway. The in vitro photodynamic therapy (PDT) response of HepG2 cells to r-SiPcBOA-LDL is compared to SiPcBOA (free drug control) using a clonogenic assay. The slopes of the linear regression fit to the logarithmic data for these two plots are significantly different from each other (p=0.0007), indicating greatly enhanced efficacy of LDLR-targeted PDT.

  19. Macroporous poly(vinyl alcohol) microspheres bearing phosphate groups as a new adsorbent for low-density lipoprotein apheresis

    Energy Technology Data Exchange (ETDEWEB)

    Wang Weichao; Xie Hui; Ou Lailiang; Wang Lianyong; Yu Yaoting; Kong Deling [Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin 300071 (China); Sun Lisha, E-mail: wly@nankai.edu.c, E-mail: kongdeling@nankai.edu.c [General Hospital, Tianjin Medical University, Tianjin 300052 (China)

    2009-12-15

    A new low-density lipoprotein (LDL) adsorbent with phosphate groups as the ligand was prepared in this study. Macroporous poly(vinyl acetate-co-triallyl isocyanurate) microspheres were prepared using a free-radical suspension polymerization method. A hydrolysis reaction in sodium hydroxide/methanol changed the materials into poly(vinyl alcohol) (PVA) microspheres. Further reaction with phosphorus oxychloride in anhydrous DMF led to the LDL adsorbent PVA-phosphate microspheres. The preparation conditions such as reaction time, temperature and the amount of phosphorus oxychloride were optimized. The adsorption of plasma lipoproteins was examined by in vitro adsorption assays. The influence of adsorption time, plasma volume and ionic strength on the adsorption capacity was investigated. The circulation adsorption showed that the pathogenic lipoproteins in the plasma such as total cholesterol (TC), LDL and triglyceride (TG) could be removed markedly, in which the removal percentages were 42.9%, 45.0% and 44.74%, respectively. However, the reduction of high-density lipoprotein (HDL) and other normal plasma components was very slight. For in vivo experiment, rabbits were fed with high-cholesterol food to develop a hyperlipidemia model and treated by extracorporeal blood perfusion using the PVA-phosphate columns. Eight hyperlipidemia rabbits were treated with the PVA-phosphate adsorbent, and the removal of TC, LDL and TG was 45.03 +- 6.64%, 48.97 +- 9.92% and 35.42 +- 14.17%, respectively. The sterilization and storage tests showed that the adsorbent was chemically and functionally stable. It could be easily sterilized by a common method and stored for months without loss of adsorption capacity. Therefore, this new PVA-phosphate-based LDL adsorbent may have potential for application in LDL apheresis.

  20. Prevalence and characteristics of patients with low levels of low-density lipoprotein cholesterol in northern Denmark: a descriptive study

    Directory of Open Access Journals (Sweden)

    Schmidt SA

    2015-02-01

    Full Text Available Sigrun Alba Johannesdottir Schmidt,1 Uffe Heide-Jørgensen,1 Angelika D Manthripragada,2 Vera Ehrenstein1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA Background: With the emergence of new lipid-lowering therapies, more patients are expected to achieve substantial lowering of low-density lipoprotein cholesterol (LDL-C. However, there are limited data examining the clinical experience of patients with low (<1.3 mmol/L or very low (<0.65 mmol/L levels of LDL-C. To provide information on patients with low LDL-C, we identified and characterized persons with low LDL-C using data from Danish medical databases. Methods: Using a population-based clinical laboratory database, we identified adults with at least one LDL-C measurement in northern Denmark between 1998 and 2011 (population approximately 1.5 million persons. Based on the lowest measurement during the study period, we divided patients into groups with low (<1.3 mmol/L, moderate (1.3–3.3 mmol/L, or high (>3.3 mmol/L LDL-C. We described their demographic characteristics, entire comorbidity history, and 90-day prescription history prior to the lowest LDL-C value measured. Finally, we further restricted the analysis to individuals with very low LDL-C (<0.65 mmol/L. Results: Among 765,503 persons with an LDL-C measurement, 23% had high LDL-C, 73% had moderate LDL-C, and 4.8% had low LDL-C. In the latter group, 9.6% (0.46% of total had very low LDL-C. Compared with the moderate and high LDL-C categories, the low LDL-C group included more males and older persons with a higher prevalence of cardiovascular disease, diabetes, chronic pulmonary disease, ulcer disease, and obesity, as measured by hospital diagnoses or relevant prescription drugs for these diseases. Cancer and use of psychotropic drugs were also more prevalent. These patterns of distribution became even more pronounced when

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

    Science.gov (United States)

    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

  2. Clinical efficacy and safety of evolocumab for low-density lipoprotein cholesterol reduction

    Directory of Open Access Journals (Sweden)

    Henry CA

    2016-04-01

    Full Text Available Courtney A Henry, Ronald A Lyon, Hua Ling Department of Pharmacy Practice, School of Pharmacy, Hampton University, Hampton, VA, USA Abstract: Multiple categories of medications have been developed to manage lipid profiles and reduce the risk of cardiovascular events in patients with heart disease. However, currently marketed medications have not solved the problems associated with preventing and treating cardiovascular diseases completely. A substantial population of patients cannot take advantage of statin therapy due to statin intolerance, heart failure, or kidney hemodialysis, suggesting a need for additional effective agents to reduce low-density lipoprotein cholesterol (LDL-C levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9 was discovered in 2003 and subsequently emerged as a novel target for LDL-C-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2 directed against human PCSK9. By inactivating PCSK9, evolocumab upregulates LDL receptors causing increased catabolism of LDL-C and the consequent reduction of LDL-C levels in blood. Overall, evolocumab has had notable efficacy, with LDL-C reduction ranging from 53% to 75% in monotherapy and combination therapies, and is associated with minor adverse effects. However, studies regarding the ability of evolocumab to reduce mortality as well as long-term safety concerns are limited. The fact that the drug was introduced at a cost much higher than the existing medications and shows a low incremental mortality benefit suggests that many payers will consider evolocumab to have an unfavorable cost–benefit ratio. Keywords: PCSK9, hyperlipidemia, evolocumab, LDL-C, familial hypercholesterolemia

  3. α-Tocopherol modulates the low density lipoprotein receptor of human HepG2 cells

    Directory of Open Access Journals (Sweden)

    Bottema Cynthia DK

    2003-05-01

    Full Text Available Abstract The aim of this study was to determine the effects of vitamin E (α-tocopherol on the low density lipoprotein (LDL receptor, a cell surface protein which plays an important role in controlling blood cholesterol. Human HepG2 hepatoma cells were incubated for 24 hours with increasing amounts of α, δ, or γ-tocopherol. The LDL receptor binding activity, protein and mRNA, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase mRNA, cell cholesterol and cell lathosterol were measured. The effect of α-tocopherol was biphasic. Up to a concentration of 50 μM, α-tocopherol progressively increased LDL receptor binding activity, protein and mRNA to maximum levels 2, 4 and 6-fold higher than control, respectively. The HMG-CoA reductase mRNA and the cell lathosterol concentration, indices of cholesterol synthesis, were also increased by 40% over control by treatment with 50 μM α-tocopherol. The cell cholesterol concentration was decreased by 20% compared to control at 50 μM α-tocopherol. However, at α-tocopherol concentrations higher than 50 μM, the LDL receptor binding activity, protein and mRNA, the HMG-CoA reductase mRNA and the cell lathosterol and cholesterol concentrations all returned to control levels. The biphasic effect on the LDL receptor was specific for α-tocopherol in that δ and γ-tocopherol suppressed LDL receptor binding activity, protein and mRNA at all concentrations tested despite the cells incorporating similar amounts of the three homologues. In conclusion, α-tocopherol, exhibits a specific, concentration-dependent and biphasic "up then down" effect on the LDL receptor of HepG2 cells which appears to be at the level of gene transcription. Cholesterol synthesis appears to be similarly affected and the cell cholesterol concentration may mediate these effects.

  4. High Density Lipoprotein Metabolism in Man

    Science.gov (United States)

    Blum, Conrad B.; Levy, Robert I.; Eisenberg, Shlomo; Hall, Marshall; Goebel, Robert H.; Berman, Mones

    1977-01-01

    The turnover of 125I-high density lipoprotein (HDL) was examined in a total of 14 studies in eight normal volunteers in an attempt to determine the metabolic relationship between apolipoproteins A-I (apoA-I) and A-II (apoA-II) of HDL and to define further some of the determinants of HDL metabolism. All subjects were first studied under conditions of an isocaloric balanced diet (40% fat, 40% carbohydrate). Four were then studied with an 80% carbohydrate diet, and two were studied while receiving nicotinic acid (1 g three times daily) and ingesting the same isocaloric balanced diet. The decay of autologous 125I-HDL and the appearance of urinary radioactivity were followed for at least 2 wk in each study. ApoA-I and apoA-II were isolated by Sephadex G-200 chromatography from serial plasma samples in each study. The specific activities of these peptides were then measured directly. It was found that the decay of specific activity of apoA-I and apoA-II were parallel to one another in all studies. The mean half-life of the terminal portion of decay was 5.8 days during the studies with a balanced diet. Mathematical modeling of the decay of plasma radioactivity and appearance of urinary radioactivity was most consistent with a two-compartment model. One compartment is within the plasma and exchanges with a nonplasma component. Catabolism occurs from both of these compartments. With a balanced isocaloric diet, the mean synthetic rate for HDL protein was 8.51 mg/kg per day. HDL synthesis was not altered by the high carbohydrate diet and was only slightly decreased by nicotinic acid treatment. These perturbations had effects on HDL catabolic pathways that were reciprocal in many respects. With an 80% carbohydrate diet, the rate of catabolism from the plasma compartment rose by a mean of 39.1%; with nicotinic acid treatment, it fell by 42.2%. Changes in the rate of catabolism from the second compartment were generally opposite those in the rate of catabolism from the plasma

  5. Extract of mangosteen increases high density lipoprotein levels in rats fed high lipid

    Directory of Open Access Journals (Sweden)

    Dwi Laksono Adiputro

    2015-12-01

    Full Text Available BACKGROUND In cardiovascular medicine, Garcinia mangostana has been used as an antioxidant to inhibit oxidation of low density lipoproteins and as an antiobesity agent. The effect of Garcinia mangostana on hyperlipidemia is unknown. The aim of this study was to evaluate the effect of an ethanolic extract of Garcinia mangostana pericarp on lipid profile in rats fed a high lipid diet. METHODS A total of 40 rats were divided into five groups control, high lipid diet, and high lipid diet + ethanolic extract of Garcinia mangostana pericarp at dosages of 200, 400, and 800 mg/kg body weight. The control group received a standard diet for 60 days. The high lipid diet group received standard diet plus egg yolk, goat fat, cholic acid, and pig fat for 60 days with or without ethanolic extract of Garcinia mangostana pericarp by the oral route. After 60 days, rats were anesthesized with ether for collection of blood by cardiac puncture. Analysis of blood lipid profile comprised colorimetric determination of cholesterol, triglyceride, low density lipoprotein (LDL, and high density lipoprotein (HDL. RESULTS From the results of one-way ANOVA it was concluded that there were significant between-group differences in cholesterol, trygliceride, LDL, and HDL levels (p=0.000. Ethanolic extract of Garcinia mangostana pericarp significantly decreased cholesterol, trygliceride, and LDL levels, starting at 400 mg/kg body weight (p=0.000. Ethanolic extract of Garcinia mangostana pericarp significantly increased HDL level starting at 200 mg/kg body weight (p=0.000. CONCLUSION Ethanolic extract of Garcinia mangostana pericarp has a beneficial effect on lipid profile in rats on a high lipid diet.

  6. Investigation of Serum Oxidized Low-Density Lipoprotein IgG Levels in Patients with Angiographically Defined Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Mohsen Moohebati

    2014-01-01

    Full Text Available It has been suggested that antioxidized low-density lipoprotein (anti-oxLDL antibodies play a role in the pathogenesis of atherosclerosis. The aim of this study was to measure serum ox-LDL IgG levels in 31 patients with angiographically defined coronary artery disease (CAD (≥50% stenosis in at least one major coronary artery; CAD+ group and compare these levels with those of 32 subjects with <50% coronary stenosis (CAD− group and 24 healthy age- and sex-matched controls using ELISA. We did not find any significant difference between CAD+, CAD−, and control groups in regard to oxLDL IgG levels (P=0.83. Serum oxLDL IgG levels did not differ between 1VD (one vessel disease, 2VD (2 vessels disease, and 3VD (3 vessels disease subgroups of CAD+ patients (P=0.20. Serum anti-oxLDL titers were only significantly correlated with LDL-C in the CAD+ group (P<0.05 and waist and hip circumference (P<0.05 and P<0.01, resp. in the CAD− group. In stepwise regression analysis, none of the conventional cardiovascular risk factors was associated with serum ox-LDL IgG levels. The present results suggest that serum levels of ox-LDL IgG are neither associated with the presence and severity of CAD nor with the conventional cardiovascular risk factors.

  7. Pneumococcal vaccination may induce anti-oxidized low-density lipoprotein antibodies that have potentially protective effects against cardiovascular disease.

    Science.gov (United States)

    Suthers, B; Hansbro, P; Thambar, S; McEvoy, M; Peel, R; Attia, J

    2012-06-08

    Many animal and human studies have found an inverse association between anti-oxidized low-density lipoprotein (oxLDL) antibodies (anti-oxLDL) and atherosclerotic burden. Furthermore, anti-oxLDL antibodies have been shown to cause regression of atherosclerotic plaque in mice. Animal studies indicate that the 23-valent pneumococcal vaccine may induce the production of these potentially protective anti-oxLDL antibodies, and human epidemiological studies support their potentially beneficial effect in reducing cardiovascular events. Here we describe the association between self-reported pneumococcal vaccination, vaccination verified by linkage to health records, and anti-pneumococcal antibody titers, and anti-ox-LDL titers in a group of 116 older people. We found a bimodal distribution of anti-oxLDL antibodies, and a significant association between pneumococcal IgG and anti-oxLDL antibody titers that remained after multivariate adjustment for potential confounders (p=0.04). There was no significant association between self-reported vaccination or vaccination verified by health record linkage and ox-LDL titers, which may be due to reporting error or variability in response to the vaccine. These results support a mechanistic link between pneumococcal vaccination and a potential protective effect on cardiovascular disease, and indicate that self-reported or verified vaccine status may not be sufficient to detect this association. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Ethanol extract of propolis protects endothelial cells from oxidized low density lipoprotein-induced injury by inhibiting lectin-like oxidized low density lipoprotein receptor-1-mediated oxidative stress.

    Science.gov (United States)

    Fang, Yongqi; Li, Jinguo; Ding, Mingde; Xu, Xiaoyan; Zhang, Jiajun; Jiao, Peng; Han, Ping; Wang, Jiafu; Yao, Shutong

    2014-12-01

    Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), as the primary oxidized low-density lipoprotein (ox-LDL) receptor on endothelial cells, plays a crucial role in endothelial injury, which is a driving force in the initiation and development of atherosclerosis. Our previous studies have shown that ethanol extract of propolis (EEP) promotes reverse cholesterol transport and inhibits atherosclerotic lesion development. However, the protective effects of EEP against ox-LDL-induced injury in endothelial cells and the underlying mechanisms are still unknown. This study was designed to test the hypothesis that EEP attenuates ox-LDL-induced endothelial oxidative injury via modulation of LOX-1-mediated oxidative stress. Our results showed that exposure of human umbilical vein endothelial cells (HUVECs) to ox-LDL (100 mg/L) led to the decrease in cell viability and increase in lactate dehydrogenase (LDH) release, caspase-3 activation, and apoptosis, whereas pretreatment with EEP (7.5, 15 and 30 mg/L) protected against such damages in a dose-dependent manner. In addition, EEP mitigated ox-LDL uptake by HUVECs and attenuated ox-LDL-upregulated LOX-1 expression both at the mRNA and protein levels. Moreover, EEP suppressed the ox-LDL-induced oxidative stress as assessed by decreased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, reactive oxygen species (ROS), and malondialdehyde (MDA) generation as well as increased antioxidant enzyme activities. Similar results were observed in the anti-LOX-1 antibody or diphenyleneiodonium (DPI)-pretreated HUVECs. These data indicate that EEP may protect HUVECs from ox-LDL-induced injury and that the mechanism at least partially involves its ability to inhibit endothelial LOX-1 upregulation and subsequent oxidative stress. © 2014 by the Society for Experimental Biology and Medicine.

  9. Beyond high-density lipoprotein cholesterol levels evaluating high-density lipoprotein function as influenced by novel therapeutic approaches

    National Research Council Canada - National Science Library

    deGoma, Emil M; deGoma, Rolando L; Rader, Daniel J

    2008-01-01

    A number of therapeutic strategies targeting high-density lipoprotein (HDL) cholesterol and reverse cholesterol transport are being developed to halt the progression of atherosclerosis or even induce regression...

  10. Relations Between Atherogenic Index of Plasma, Ratio of Small Dense Low Density Lipoprotein/Lecithin Cholesterol Acyl Transferase and Ratio of Small Dense Low Density Lipoprotein/Cholesteryl Ester Transfer Protein of Controlled and Uncontrolled Type 2 DM

    Directory of Open Access Journals (Sweden)

    Ellis Susanti

    2009-08-01

    Full Text Available BACKGROUND: Patients with Diabetes Melitus are proven to be prone to atherosclerosis and coronary heart disease, especially type 2 Diabetes Melitus (T2DM patient who have higher risk and mortality for cardiovascular risk factor. The Dyslipidemia condition is very common in T2DM as one of the risk factors. Diabetic dyslipidemia is marked by the increased triglyceride (TG, low HDL cholesterol (HDL-C, and increased small dense LDL and apolipoprotein B. Therefore the aim of this study is to assess the differential and correlation between Atherogenic Index of Plasma (AIP, ratio of small dense low density lipoprotein (sdLDL/lecithin cholesterol acyl transferase (LCAT and ratio of sdLDL/cholesteryl ester transfer protein (CETP of controlled and uncontrolled T2DM. METHODS: This study was observational with cross sectional design. In total of 72 patients with T2DM consist of 36 controlled and 36 uncontrolled, participated in this study. The serum TG, HDL-C, sdLDL, LCAT and CETP were examined in their relationship with to T2DM risk. RESULTS: The results of the study indicate that the AIP (p<0.001 increase controlled and uncontrolled T2DM and the ratio of sdLDL/CETP (p=0.004, odds ratio of AIP was 4 (95% CI: 1.501-10.658 and odds ratio of sdLDL/CETP ratio was 4 (95% CI: 1.501-10.658 in uncontrolled T2DM. CONCLUSIONS: This study showed that the AIP and ratio of small dense LDL/CETP had a significant correlation with the uncontrolled T2DM. The AIP and ratio of small dense LDL/CETP increase was found at the uncontrolled T2DM to be 4 times greater than the controlled T2DM. KEYWORDS: T2DM, atherosclerosis, atherogenic index of plasma, small dense LDL, LCAT, CETP, ratio of sdLDL/LCAT, ratio of sdLDL/CETP.

  11. Mechanisms of dysregulation of low-density lipoprotein receptor expression in HepG2 cells induced by inflammatory cytokines

    Institute of Scientific and Technical Information of China (English)

    CHEN Ya-xi; RUAN Xiong-zhong; HUANG Ai-long; LI Qiu; John F. Moorhead; Zac Varghese

    2007-01-01

    Background Low-density lipoprotein(LDL)receptor is normally regulated via a feedback system that is dependent on intracellular cholesterol levels.We have demonstrated that cytokines disrupt cholesterol-mediated LDL receptor feedback regulation causing intracellular accumulation of unmodified LDL in peripheral cells.Liver is the centraI organ for lipid homeostasis.The aim of this study was to investigate the regulation of cholesterol exogenous uptake via LDL receptor and its underlying mechanisms in human hepatic cell line(HepG2)cells under physiological and inflammatory conditions.Methods Intracellular total cholesterol(TC),free cholesterol(FC)and cholesterol ester(CE)were measured by an enzymic assay.Oil Red O staining was used to visualize lipid droplet accumulation in cells.Total cellular RNA was isolated from cells for detecting LDL receptor,sterol regulatory element binding protein (SREBP)-2 and SREBP cleavage-activating protein(SCAP)mRNA levels using real-time quantitative PCR.LDL receptor and SREBP-2 protein expression were examined by Western blotting.Confocal microscopy was used to investigate the translocation of SCAP-SREBP complex from the endoplasmic reticulum(ER)to the Golgi by dual staining with anti-human SCAP and anti-Golgin antibodies.Results LDL loading increased intracellular cholesterol level,thereby reduced LDL receptor mRNA and protein expression in HepG2 cells under physiological conditions.However,interleukin 1β(IL-1β)further increased intracellular cholesterol level in the presence of LDL by increasing both LDL receptor mRNA and protein expression in HepG2.LDL also reduced the SREBP and SCAP mRNA level under physiological conditions.Exposure to IL-1β caused Over-expression of SREBP-2 and also disrupted normal distribution of SCAP-SREBP complex in HepG2 by enhancing translocation of SCAP-SREBP from the ER to the Golgi despite a high concentration of LDL in the culture medium.Conclusions IL-1β disrupts cholesterol-mediated LDL receptor

  12. Low-Density Lipoprotein Cholesterol, Non-High-Density Lipoprotein Cholesterol, Triglycerides, and Apolipoprotein B and Cardiovascular Risk in Patients With Manifest Arterial Disease.

    Science.gov (United States)

    van den Berg, M Johanneke; van der Graaf, Yolanda; de Borst, Gert Jan; Kappelle, L Jaap; Nathoe, Hendrik M; Visseren, Frank L J

    2016-09-15

    Low-density lipoprotein cholesterol (LDL-C) only partly represents the atherogenic lipid burden, and a growing body of evidence suggests that non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and apolipoprotein B (apoB) are more accurate in estimating lipid-related cardiovascular disease risk. Our objective was to compare the relation among LDL-C, non-HDL-C, triglycerides, and apoB and the occurrence of future vascular events and mortality in patients with manifest arterial disease. This is a prospective cohort study of 7,216 patients with clinically manifest arterial disease in the Secondary Manifestations of Arterial Disease Study. Cox proportional hazard models were used to quantify the risk of major cardiovascular events (MACE; i.e., stroke, myocardial infarction, and vascular mortality) and all-cause mortality. Interaction was tested for type of vascular disease at inclusion. MACE occurred in 1,185 subjects during a median follow-up of 6.5 years (interquartile range 3.4 to 9.9 years). Adjusted hazard ratios (HRs) of MACE per 1 SD higher were for LDL-C (HR 1.15, 95% confidence interval [CI] 1.09 to 1.22), for non-HDL-C (HR 1.17, 95% CI 1.11 to 1.23), for log(triglycerides) (HR 1.12, 95% CI 1.06 to 1.19), and for apoB HR (1.12, 95% CI 0.99 to 1.28). The relation among LDL-C, non-HDL-C, and cardiovascular events was comparable in patients with cerebrovascular disease, coronary artery disease, or polyvascular disease and absent in those with aneurysm of abdominal aorta or peripheral artery disease. In conclusion, in patients with a history of cerebrovascular, coronary artery, or polyvascular disease, but not aneurysm of abdominal aorta or peripheral artery disease, higher levels of LDL-C and non-HDL-C are related to increased risk of future MACE and of comparable magnitude. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. DETECTING LOW DENSITY LIPOPROTEIN RECEPTOR MUTANT GENE OF RABBIT BY PCR

    Institute of Scientific and Technical Information of China (English)

    Liu Enqi; Zhao Sihai; Chen Zhenglan; Yang Penghui

    2006-01-01

    Objective Watanabe Heritable Hyperlipidaemic (WHHL) rabbits with low density lipoprotein receptor (LDLr) gene mutation have provided unprecedented opportunities for the study of human atherosclerosis, in order to confirm LDL receptor gene status in rabbits, we developed a simple PCR technique to detect LDL mutations in rabbits. Methods Rabbits genomic DNA were extracted from ear biopsy, and amplified by PCR to detect 12 bp deletion mutation in WHHL rabbits. PCR products were directly digested with BglⅠ, and then applied to polyacrylamide gel electrophoresis. Results PCR products from homozygous LDLr +/+ rabbits generated 2 bands of 212 and 94 bp after BglⅠ digestion, LDLr +/- rabbits generated 3 bands (294, 212, and 94 bp), LDLr -/- animals, however, generated only 1 product (294 bp). Conclusion This modified PCR method is simple and reliable.

  14. Low-density lipoprotein cholesterol and survival in pulmonary arterial hypertension

    Science.gov (United States)

    Kopeć, Grzegorz; Waligóra, Marcin; Tyrka, Anna; Jonas, Kamil; Pencina, Michael J.; Zdrojewski, Tomasz; Moertl, Deddo; Stokwiszewski, Jakub; Zagożdżon, Paweł; Podolec, Piotr

    2017-01-01

    Low-density lipoprotein cholesterol(LDL-C) is a well established metabolic marker of cardiovascular risk, however, its role in pulmonary arterial hypertension (PAH) has not been determined. Therefore we assessed whether LDL-C levels are altered in PAH patients, if they are associated with survival in this group and whether pulmonary hypertension (PH) reversal can influence LDL-C levels. Consecutive 46 PAH males and 94 females were age matched with a representative sample of 1168 males and 1245 females, respectively. Cox regression models were used to assess the association between LDL-C and mortality. The effect of PH reversal on LDL-C levels was assessed in 34 patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing invasive treatment. LDL-C was lower in both PAH (2.6 ± 0.8 mmol/l) and CTEPH (2.7 ± 0.7 mmol/l) patients when compared to controls (3.2 ± 1.1 mmol/l, p < 0.001). In PAH patients lower LDL-C significantly predicted death (HR:0.44/1 mmol/l, 95%CI:0.26–0.74, p = 0.002) after a median follow-up time of 33(21–36) months. In the CTEPH group, LDL-C increased (from 2.6[2.1–3.2] to 4.0[2.8–4.9]mmol/l, p = 0.01) in patients with PH reversal but remained unchanged in other patients (2.4[2.2–2.7] vs 2.3[2.1–2.5]mmol/l, p = 0.51). We concluded that LDL-C level is low in patients with PAH and is associated with an increased risk of death. Reversal of PH increases LDL-C levels. PMID:28198422

  15. Effect of dietary fat saturation and cholesterol on low density lipoprotein degradation by mononuclear cells of Cebus monkeys.

    Science.gov (United States)

    Kuo, P C; Rudd, M A; Nicolosi, R; Loscalzo, J

    1989-01-01

    The mechanism by which dietary unsaturated fatty acids lower low density lipoprotein (LDL) cholesterol is unknown. Unsaturated fatty acids incorporated into the cell membrane can increase membrane fluidity and, as a result, dramatically alter membrane-dependent cell functions. Therefore, we examined the effect of long-term dietary consumption of corn oil and coconut oil with and without cholesterol in amounts equivalent to those of a typical Western diet on the degradation of human LDL by peripheral blood mononuclear cells in Cebus albifrons monkeys. Cellular LDL degradation was dramatically enhanced in the mononuclear cells isolated from animals fed corn oil in comparison with those from animals fed coconut oil. The addition of cholesterol to the diets resulted in a slight attenuation of LDL degradation in the corn oil group while no effect was noted in the coconut oil group. Crossover LDL binding and degradation experiments with LDL isolated from animals fed corn oil diets and coconut oil diets demonstrated increased binding and degradation of LDL in mononuclear cells from animals fed corn oil diets. Enhanced mononuclear cell LDL degradation was accompanied by increased cellular cis-unsaturated fatty acyl content, increased membrane fluidity, and decreased plasma cholesterol. Increased cellular cis-unsaturated fatty acyl content with its concomitant increase in membrane fluidity mirrored the dietary lipid profile of the host animal. A linear relationship was observed between cellular LDL degradation and both cellular cis-unsaturated fatty acyl content and membrane fluidity. These observations parallel results noted in whole-animal LDL catabolic studies with these same animals described elsewhere. These data suggest a novel mechanism by which dietary unsaturated fatty acids exert their LDL-lowering effect.

  16. Time-resolved luminescence and singlet oxygen formation after illumination of the hypericin-low-density lipoprotein complex.

    Science.gov (United States)

    Gbur, Peter; Dedic, Roman; Chorvat, Dusan; Miskovsky, Pavol; Hala, Jan; Jancura, Daniel

    2009-01-01

    Time-resolved fluorescence and phosphorescence study of hypericin (Hyp) in complex with low-density lipoproteins (LDL) as well as the evolution of singlet oxygen formation and annihilation after illumination of Hyp/LDL complexes at room temperature are presented in this work. The observed shortening of the fluorescence lifetime of Hyp at high Hyp/LDL molar ratios (>25:1) proves the self-quenching of the excited singlet state of monomeric Hyp at these concentration ratios. The very short lifetime ( approximately 0.5 ns) of Hyp fluorescence at very high Hyp/LDL ratios (>150:1) suggests that at high local Hyp concentration inside LDL molecules fast and ultrafast nonradiative decay processes from excited singlet state of Hyp become more important. Contrary to the lifetime of the singlet excited state, the lifetime (its shorter component) of Hyp phosphorescence is not dependent on Hyp/LDL ratio in the studied concentration range. The amount of singlet oxygen produced as well as the integral intensity of Hyp phosphorescence after illumination of Hyp/LDL complexes resemble the dependence of the concentration of molecules of Hyp in monomeric state on Hyp/LDL until a concentration ratio of 60:1. This fact confirms that only monomeric Hyp is able to produce the excited triplet state of Hyp, which in aerobic conditions leads to singlet oxygen production. The value of singlet oxygen lifetime ( approximately 8 micros) after its formation from the excited triplet state of Hyp in LDL proves that molecules of singlet oxygen remain for a certain period of time inside LDL particles and are not immediately released to the aqueous surrounding. That Hyp exists in the complex with LDL in the monodeprotonated state is also demonstrated.

  17. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD

    Directory of Open Access Journals (Sweden)

    Funamoto M

    2016-08-01

    Full Text Available Masafumi Funamoto,1,2 Yoichi Sunagawa,1–3 Yasufumi Katanasaka,1–3 Yusuke Miyazaki,1,2 Atsushi Imaizumi,4 Hideaki Kakeya,5 Hajime Yamakage,2 Noriko Satoh-Asahara,2 Maki Komiyama,2 Hiromichi Wada,2 Koji Hasegawa,2 Tatsuya Morimoto1–3 1Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 2Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, 3Shizuoka General Hospital, Shizuoka, 4Theravalues Corporation, Kioicho, Tokyo, 5Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan Purpose: COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin–low-density lipoprotein (AT-LDL complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin®, a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD.Patients and methods: This is a randomized, double-blind, parallel-group study. Subjects with stages I–II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin® or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated.Results: There were no differences between the Theracurmin® and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure

  18. Both poor cardiorespiratory and weak muscle fitness are related to a high concentration of oxidized low-density lipoprotein lipids.

    Science.gov (United States)

    Kosola, J; Ahotupa, M; Kyröläinen, H; Santtila, M; Vasankari, T

    2012-12-01

    Good physical fitness is associated with favorable serum lipids. Oxidized low-density lipoprotein (ox-LDL) could be even more atherogenic than serum lipids. We studied the association of ox-LDL and serum lipids with physical fitness. Healthy young (mean age 25 years) men (n=846) underwent maximal oxygen uptake (VO(2max)) and muscle fitness index (MFI) tests and completed a leisure-time physical activity (LTPA) questionnaire. Age (ANCOVA1), age+waist circumference+systolic blood pressure+fasting blood glucose+smoking (ANCOVA3) were used as covariates. The groups with the lowest VO(2max), MFI and LTPA had 23%, 16% and 8% higher concentrations of ox-LDL than the groups with the highest VO(2max) (PLDL/high-density lipoprotein (HDL)-cholesterol, total cholesterol, LDL-cholesterol, triglycerides and a low level of HDL-cholesterol (ANCOVA1, in all, PLDL/HDL-cholesterol and triglycerides, and with a low level of HDL-cholesterol (ANCOVA3, in all, PLDL/HDL-cholesterol (ANCOVA1, P=0.001). In conclusion, both poor fitness (both low VO(2max) and low MFI) and low LTPA are associated with a higher concentration of ox-LDL lipids and serum lipids, which may indicate a higher risk for atherosclerosis.

  19. Effect of hypertension on low-density lipoprotein transport within a multi-layered arterial wall: modelling consistent with experiments

    CERN Document Server

    Jesionek, Katarzyna; Kostur, Marcin

    2016-01-01

    The influence of hypertension on low-density lipoproteins intake into the arterial wall is an important factor for understanding mechanisms of atherosclerosis. It has been experimentally observed that the increased pressure leads to the higher level of the LDL inside the wall. In this paper we attempt to construct a model of the LDL transport which reproduces quantitatively experimental outcomes. We supplement the well known four-layer arterial wall model to include two pressure induced effects: the compression of the intima tissue and the increase of the fraction of leaky junctions. We demonstrate that such model can reach the very good agreement with experimental data.

  20. The effect of oxidized low-density lipoprotein combined with adriamycin on the proliferation of Eca-109 cell line

    OpenAIRE

    2011-01-01

    Abstract Background The purpose of this study was to identify the affect on the proliferation Eca-109 cells treated with oxidized low-density lipoprotein (ox-LDL) combined with adriamycin (ADM). Methods Eca-109 cell were cultured in the presence of oxLDL/ADM, and cell proliferation tested by MTT and cell apoptosis was monitored by the proportion of apoptosis and cell cycle by flow cytomester. We simultaneously evaluated the level of associated- apoptosis Bcl-2, Bax, and Caspase-3 gene mRNA an...

  1. Low-density lipoprotein cholesterol is associated with fracture risk in diabetes patients - a nested case-control study

    DEFF Research Database (Denmark)

    Starup-Linde, Jakob; Gregersen, Søren; Vestergaard, Peter

    2014-01-01

    available for an analysis of patient characteristics, co-morbidities, biochemical parameters and drug usage. Results: Patient age at the time of diabetes diagnosis, a diagnosis of previous fracture, an alcohol related diagnosis, total cholesterol level, and the usage of antidepressants, antiepileptics...... and insulin all increased the odds of fracture. Low-density lipoprotein cholesterol (LDL) levels decreased the odds of fracture, where the level of 3.04-5.96 mmol/l was optimal with regard to fracture risk. Conclusion: LDL may add to the understanding of fractures in diabetes patients and it may be added...

  2. Effect of cocoa bran on low-density lipoprotein oxidation and fecal bulking.

    Science.gov (United States)

    Jenkins, D J; Kendall, C W; Vuksan, V; Vidgen, E; Wong, E; Augustin, L S; Fulgoni, V

    Legumes have reported benefits in terms of reduced risk for coronary heart disease and of colonic health. A novel legume fiber, cocoa bran, also may have favorable health effects on serum lipid levels, low-density lipoprotein (LDL) cholesterol oxidation, and fecal bulk. Twenty-five healthy normolipidemic subjects (13 men and 12 women) (mean +/- SEM age, 37 +/- 2 years; mean +/- SEM body mass index [calculated as weight in kilograms divided by the square of height in meters], 24.6 +/- 0.7) ate cocoa-bran and chocolate-flavored low-fiber breakfast cereals for 2-week periods, with 2-week washout, in a double-blind crossover study. The cocoa-bran cereal provided 25.0 g/d of total dietary fiber (TDF). The low-fiber cereal (5.6 g/d TDF) was of similar appearance and energy value. Fasting blood samples were obtained at the start and end of each period, and 4-day fecal collections were made from days 11 through 14. High-density lipoprotein (HDL) cholesterol level was higher (7.6% +/- 2.9%; P =.02) and the LDL/HDL cholesterol ratio was lower (6.7% +/- 2.3%; P =.007) for cocoa-bran compared with low-fiber cereal at 2 weeks. No effect was seen on LDL cholesterol oxidation. Mean fecal output was significantly higher for cocoa-bran than for low-fiber cereal (56 +/- 14 g/d; Pchocolate-flavored cocoa-bran cereal increased fecal bulk similarly to wheat bran and was associated with a reduction in the LDL/HDL cholesterol ratio. In view of the low-fat, high-fiber nature of the material, these results suggest a possible role for this novel fiber source in the diets of normal, hyperlipidemic, and constipated subjects.

  3. A 90 minute soccer match decreases triglyceride and low density lipoprotein but not high-density lipoprotein and cholesterol levels

    Directory of Open Access Journals (Sweden)

    Nader - Rahnama

    2009-11-01

    Full Text Available

    • BACKGROUND: The association between the lipid profiles level and the incidence and severity of coronary heart disease (CHD is very pronounced in epidemiological studies, and an inverse relation between physical fitness and the incidence of coronary heart disease has been observed in many studies. The aim of this study was to investigate the impact of a soccer match on lipid parameters of professional soccer players.
    • METHODS: Twenty two professional soccer players participated in the study. Blood (10ml for determination of lipid profiles was obtained at rest and immediately after a 90 minute soccer match. Lipid parameters were measured using Boehringer Mannheim kits and Clinilab and BioMerieux analyser.
    • RESULTS: The results of this study showed that the triglyceride was significantly higher before the match than afterwards (159.09 ± 58.2 vs. 88.63 ± 34.1 mg/dl, p < 0.001, whereas the low-density lipoprotein (LDL was lower before the match than after it (98.04 ± 28.9 vs. 112.31 ± 30.5 mg/dl. Moreover, there were no significant differences in cholesterol concentration (171.4 ± 30.28 mg/dl vs. 173.18 ± 32.75 mg/dl and high-density lipoprotein (HDL concentration (34.04 ± 5.58 mg/dl vs. 34.4 ± 4.6 mg/dl between before and after the match.
    • CONCLUSIONS: Although the soccer competitive match has no favourable acute effect on lipid

    • Cubilin, the endocytic receptor for intrinsic factor-vitamin B(12) complex, mediates high-density lipoprotein holoparticle endocytosis.

      Science.gov (United States)

      Hammad, S M; Stefansson, S; Twal, W O; Drake, C J; Fleming, P; Remaley, A; Brewer, H B; Argraves, W S

      1999-08-31

      Receptors that endocytose high-density lipoproteins (HDL) have been elusive. Here yolk-sac endoderm-like cells were used to identify an endocytic receptor for HDL. The receptor was isolated by HDL affinity chromatography and identified as cubilin, the recently described endocytic receptor for intrinsic factor-vitamin B(12). Cubilin antibodies inhibit HDL endocytosis by the endoderm-like cells and in mouse embryo yolk-sac endoderm, a prominent site of cubilin expression. Cubilin-mediated HDL endocytosis is inhibitable by HDL(2), HDL(3), apolipoprotein (apo)A-I, apoA-II, apoE, and RAP, but not by low-density lipoprotein (LDL), oxidized LDL, VLDL, apoC-I, apoC-III, or heparin. These findings, coupled with the fact that cubilin is expressed in kidney proximal tubules, suggest a role for this receptor in embryonic acquisition of maternal HDL and renal catabolism of filterable forms of HDL.

    • The effects of weight gain after smoking cessation on atherogenic α1-antitrypsin-low-density lipoprotein.

      Science.gov (United States)

      Komiyama, Maki; Wada, Hiromichi; Ura, Shuichi; Yamakage, Hajime; Satoh-Asahara, Noriko; Shimada, Sayaka; Akao, Masaharu; Koyama, Hiroshi; Kono, Koichi; Shimatsu, Akira; Takahashi, Yuko; Hasegawa, Koji

      2015-11-01

      Although cardiovascular risks decrease after quitting smoking, body weight often increases in the early period after smoking cessation. We have previously reported that the serum level of the α1-antitrypsin-low-density lipoprotein complex (AT-LDL)-an oxidatively modified low-density lipoprotein that accelerates atherosclerosis-is high in current smokers, and that the level rapidly decreases after smoking cessation. However, the effects of weight gain after smoking cessation on this cardiovascular marker are unknown. In 183 outpatients (134 males, 49 females) who had successfully quit smoking, serum AT-LDL levels were measured using an enzyme-linked immunosorbent assay. For all persons who had successfully quit smoking, body mass index (BMI) significantly increased 12 weeks after the first examination (p smoking is influenced by weight gain after smoking cessation.

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

      Science.gov (United States)

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

      2017-07-01

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

    • Analysis of non-Newtonian effects on Low-Density Lipoprotein accumulation in an artery.

      Science.gov (United States)

      Iasiello, Marcello; Vafai, Kambiz; Andreozzi, Assunta; Bianco, Nicola

      2016-06-14

      In this work, non-Newtonian effects on Low-Density Lipoprotein (LDL) transport across an artery are analyzed with a multi-layer model. Four rheological models (Carreau, Carreau-Yasuda, power-law and Newtonian) are used for the blood flow through the lumen. For the non-Newtonian cases, the arterial wall is modeled with a generalized momentum equation. Convection-diffusion equation is used for the LDL transport through the lumen, while Staverman-Kedem-Katchalsky, combined with porous media equations, are used for the LDL transport through the wall. Results are presented in terms of filtration velocity, Wall Shear Stresses (WSS) and concentration profiles. It is shown that non-Newtonian effects on mass transport are negligible for a healthy intramural pressure value. Non-Newtonian effects increase slightly with intramural pressure, but Newtonian assumption can still be considered reliable. Effects of arterial size are also analyzed, showing that Newtonian assumption can be considered valid for both medium and large arteries, in predicting LDL deposition. Finally, non-Newtonian effects are also analyzed for an aorta-common iliac bifurcation, showing that Newtonian assumption is valid for mass transport at low Reynolds numbers. At a high Reynolds number, it has been shown that a non-Newtonian fluid model can have more impact due to the presence of flow recirculation.

    • Adrenal imaging with technetium-99m-labelled low density lipoproteins

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      Isaacsohn, J.L.; Lees, A.M.; Lees, R.S.; Strauss, H.W.; Barlai-Kovach, M.; Moore, T.J.

      1986-04-01

      Evaluation of adrenal cortical function by external imaging is currently accomplished by injection of radiolabelled analogs of cholesterol. Although the adrenals do utilized exogenous cholesterol for steroid hormone synthesis, the cholesterol is delivered to the glands not as free cholesterol but through the uptake of low density lipoproteins (LDL), which are subsequently degraded within the adrenal cortical cells to provide cholesterol. Thus, we sought to assess the use of /sup 99m/Tc-labelled LDL injected into rabbits to obtain external images of the adrenal glands. Adrenal images of all nine rabbits tested were obtained within 18 to 21 hours after injection of /sup 99m/Tc-LDL. Seven of the rabbits were subjected to adrenal cortical suppression with dexamethasone and then all nine rabbits were imaged a second time. In the untreated animals, visualization of the adrenal glands was accompanied by normal serum cortisol concentrations and accumulation of radiolabel in the adrenals, whereas in the dexamethasone-treated animals, lack of visualization of the adrenal glands was correlated with low serum cortisols, and greatly decreased accumulation of the radionuclide in the adrenals. These findings demonstrate for the first time that LDL, when labelled with /sup 99m/Tc, can be used to evaluate adrenal cortical function by external imaging.

    • Comparison of two low-density lipoprotein apheresis systems in patients with homozygous familial hypercholesterolemia.

      Science.gov (United States)

      Drouin-Chartier, Jean-Philippe; Tremblay, André J; Bergeron, Jean; Pelletier, Maude; Laflamme, Nathalie; Lamarche, Benoît; Couture, Patrick

      2016-08-01

      Low-density lipoprotein (LDL) apheresis (LA) is a reliable method to decrease LDL-C concentrations and remains the gold standard therapy in homozygous familial hypercholesterolemia (HoFH). The objective of this study was to compare the efficacy of two LA systems [heparin-induced extracorporeal LDL precipitation (HELP) vs. dextran sulfate adsorption (DS) on the reduction of lipids, inflammatory markers, and adhesion molecules in a sample of genetically defined HoFH subjects (n = 9)]. Fasting blood samples were collected before and after LA. All subjects served as their own control and were first treated with the HELP system then with DS in this single sequence study. Compared with HELP, DS led to significantly greater reductions in total cholesterol (-63.3% vs. -59.9%; P = 0.05), LDL-C (-70.5% vs. -63.0%; P = 0.02), CRP (-75.3% vs. -48.8%; P Apheresis 31:359-367, 2016. © 2015 Wiley Periodicals, Inc.

    • Uptake and accumulation of oxidized low-density lipoprotein during Mycobacterium tuberculosis infection in guinea pigs.

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      Gopinath S Palanisamy

      Full Text Available The typical host response to infection of humans and some animals by M. tuberculosis is the accumulation of reactive oxygen species generating inflammatory cells into discrete granulomas, which frequently develop central caseous necrosis. In previous studies we showed that infection of immunologically naïve guinea pigs with M. tuberculosis leads to localized and systemic oxidative stress that results in a significant depletion of serum total antioxidant capacity and the accumulation of malondialdehyde, a bi-product of lipid peroxidation. Here we show that in addition, the generation of excessive reactive oxygen species in vivo resulted in the accumulation of oxidized low density lipoproteins (OxLDL in pulmonary and extrapulmonary granulomas, serum and lung macrophages collected by bronchoalveolar lavage. Macrophages from immunologically naïve guinea pigs infected with M. tuberculosis also had increased surface expression of the type 1 scavenger receptors CD36 and LOX1, which facilitate the uptake of oxidized host macromolecules including OxLDL. Vaccination of guinea pigs with Bacillus Calmette Guerin (BCG prior to aerosol challenge reduced the bacterial burden as well as the intracellular accumulation of OxLDL and the expression of macrophage CD36 and LOX1. In vitro loading of guinea pig lung macrophages with OxLDL resulted in enhanced replication of bacilli compared to macrophages loaded with non-oxidized LDL. Overall, this study provides additional evidence of oxidative stress in M. tuberculosis infected guinea pigs and the potential role OxLDL laden macrophages have in supporting intracellular bacilli survival and persistence.

    • Oxidized low density lipoproteins--do we know enough about them?

      Science.gov (United States)

      Jiang, Xueting; Yang, Zhaohui; Chandrakala, Aluganti Narasimhulu; Pressley, Dawn; Parthasarathy, Sampath

      2011-10-01

      Since the discovery of oxidized low density lipoprotein (Ox-LDL), over 5,000 articles have appeared on the topic with over 400 articles appearing every year during the past decade. LDL contains esterified polyunsaturated fatty acid containing lipids, such as, phosphatidylcholine (PtdCho) and cholesterol esters (CE). Peroxidation of polyunsaturated fatty acid (PUFA) containing lipids has been known for a long time. Numerous studies have documented that peroxidized lipids as well as products derived from their decomposition, particularly aldehydes, have deleterious biological properties. This concept has been exemplified in the study of atherosclerosis. A plethora of in vitro and animal studies, as well as human epidemiological and correlatory studies, have supported the notion that oxidative processes and the formation of Ox-LDL might contribute to atherosclerosis. Yet the negative outcomes of human clinical trials with α-tocopherol and other antioxidants have convinced even staunch supporters of the hypothesis to take a step backwards and reconsider reasons of their failure and suggest alternative approaches. Ox-LDL is a complex mixture of numerous chemical entities, many of them are yet uncharacterized. Why and how it is formed or its nature in vivo is poorly understood. It is recognized by numerous cell surface receptors, which are ubiquitously expressed in many different cell types. These receptors might perform a variety of functions. In addition, components of Ox-LDL might also have favorable effects that are difficult to dissociate from its pathological effects. In this review, the nature of Ox-LDL and potential problems in inhibiting its formation are discussed.

    • Uptake of (/sup 3/H)vitamin D/sub 3/ from low and high density lipoproteins by cultured human fibroblasts

      Energy Technology Data Exchange (ETDEWEB)

      Shireman, R.B.; Williams, D.; Remsen, J.F.

      1986-03-01

      The plasma distribution and cellular uptake of (/sup 3/H)vitamin D/sub 3/ was studied in vitro using cultured human fibroblasts. Incubation of (/sup 3/H)vitamin D/sub 3/ (cholecalciferol) with plasma followed by sequential ultracentrifugal fractionation of the lipoproteins indicated that 2-4% of the radioactivity associated with the very low density lipoprotein (VLDL), 12% with low density lipoprotein (LDL), and approximately 60% with the high density lipoprotein (HDL). The remaining radioactivity, 25%, was associated with the sedimented plasma fractions. By comparison, an average of 86% of the radioactivity from (/sup 3/H) 1,25-dihydroxycholecalciferol associated with the sedimented plasma fractions. The uptake of (/sup 3/H)vitamin D/sub 3/ from plasma, LDL, or HDL was studied in cultured human cells; uptake by normal fibroblasts was greatest from LDL and least from plasma. The cellular association of vitamin D/sub 3/ was time, concentration, and temperature dependent. At a concentration of 50 ..mu..g LDL/ml of medium, the uptake of (/sup 3/H)vitamin D/sub 3/ from LDL at 37/sup 0/C was rapid and reached a maximum at approximately 4 hr; it was slower from HDL but continued to increase slowly up to 24 hr. The significance of these in vitro findings is uncertain since much of the vitamin D/sub 3/ absorbed from the intestine reportedly associates with chylomicrons and is rapidly taken up by the liver.

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

      Science.gov (United States)

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

      1992-01-01

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

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

      Science.gov (United States)

      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.

    • Validation of the Martin Method for Estimating Low-Density Lipoprotein Cholesterol Levels in Korean Adults: Findings from the Korea National Health and Nutrition Examination Survey, 2009-2011.

      Directory of Open Access Journals (Sweden)

      Jongseok Lee

      Full Text Available Despite the importance of accurate assessment for low-density lipoprotein cholesterol (LDL-C, the Friedewald formula has primarily been used as a cost-effective method to estimate LDL-C when triglycerides are less than 400 mg/dL. In a recent study, an alternative to the formula was proposed to improve estimation of LDL-C. We evaluated the performance of the novel method versus the Friedewald formula using a sample of 5,642 Korean adults with LDL-C measured by an enzymatic homogeneous assay (LDL-CD. Friedewald LDL-C (LDL-CF was estimated using a fixed factor of 5 for the ratio of triglycerides to very-low-density lipoprotein cholesterol (TG:VLDL-C ratio. However, the novel LDL-C (LDL-CN estimates were calculated using the N-strata-specific median TG:VLDL-C ratios, LDL-C5 and LDL-C25 from respective ratios derived from our data set, and LDL-C180 from the 180-cell table reported by the original study. Compared with LDL-CF, each LDL-CN estimate exhibited a significantly higher overall concordance in the NCEP-ATP III guideline classification with LDL-CD (p< 0.001 for each comparison. Overall concordance was 78.2% for LDL-CF, 81.6% for LDL-C5, 82.3% for LDL-C25, and 82.0% for LDL-C180. Compared to LDL-C5, LDL-C25 significantly but slightly improved overall concordance (p = 0.008. LDL-C25 and LDL-C180 provided almost the same overall concordance; however, LDL-C180 achieved superior improvement in classifying LDL-C < 70 mg/dL compared to the other estimates. In subjects with triglycerides of 200 to 399 mg/dL, each LDL-CN estimate showed a significantly higher concordance than that of LDL-CF (p< 0.001 for each comparison. The novel method offers a significant improvement in LDL-C estimation when compared with the Friedewald formula. However, it requires further modification and validation considering the racial differences as well as the specific character of the applied measuring method.

    • Olmesartan Attenuates the Impairment of Endothelial Cells Induced by Oxidized Low Density Lipoprotein through Downregulating Expression of LOX-1

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      Ruolong Zheng

      2012-02-01

      Full Text Available Oxidized low density lipoprotein (ox-LDL and its receptor, lectin-Like ox-LDL receptor-1 (LOX-1, play important roles in the development of endothelial injuries. Olmesartan can protect endothelial cells from the impairment caused by various pathological stimulations. In the present study we investigated whether olmesartan decreased the impairment of endothelial cells induced by ox-LDL by exerting its effects on LOX-1 both in vitro and in vivo. Incubation of cultured endothelial cells of neonatal rats with ox-LDL for 24 h or infusion of ox-LDL in mice for 3 weeks led to the remarkable impairment of endothelial cells, including increased lactate dehydrogenase synthesis, phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK and expression of apoptotic genes such as B-cell leukemia/lymphoma 2 (Bcl-2-associated X protein (Bax and caspase-3. Simultaneously, the cell vitality and expression of Bcl-2 gene were greatly reduced. All these effects, however, were significantly suppressed by the treatment with olmesartan. Furthermore, ox-LDL promoted up-regulation of LOX-1 expression either in cultured endothelial cells or in the aortas of mice, which was reversed with the administration of olmesartan. Our data indicated that olmesartan may attenuate the impairment of endothelial cell via down-regulation of the increased LOX-1 expression induced by ox-LDL.

    • Olmesartan Attenuates the Impairment of Endothelial Cells Induced by Oxidized Low Density Lipoprotein through Downregulating Expression of LOX-1

      Science.gov (United States)

      Zhang, Hua; Ma, Genshan; Yao, Yuyu; Qian, Huidong; Li, Weizhang; Chen, Xinjun; Jiang, Wenlong; Zheng, Ruolong

      2012-01-01

      Oxidized low density lipoprotein (ox-LDL) and its receptor, lectin-Like ox-LDL receptor-1 (LOX-1), play important roles in the development of endothelial injuries. Olmesartan can protect endothelial cells from the impairment caused by various pathological stimulations. In the present study we investigated whether olmesartan decreased the impairment of endothelial cells induced by ox-LDL by exerting its effects on LOX-1 both in vitro and in vivo. Incubation of cultured endothelial cells of neonatal rats with ox-LDL for 24 h or infusion of ox-LDL in mice for 3 weeks led to the remarkable impairment of endothelial cells, including increased lactate dehydrogenase synthesis, phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK) and expression of apoptotic genes such as B-cell leukemia/lymphoma 2 (Bcl-2)-associated X protein (Bax) and caspase-3. Simultaneously, the cell vitality and expression of Bcl-2 gene were greatly reduced. All these effects, however, were significantly suppressed by the treatment with olmesartan. Furthermore, ox-LDL promoted up-regulation of LOX-1 expression either in cultured endothelial cells or in the aortas of mice, which was reversed with the administration of olmesartan. Our data indicated that olmesartan may attenuate the impairment of endothelial cell via down-regulation of the increased LOX-1 expression induced by ox-LDL. PMID:22408405

    • Effects of low-density lipoproteins extracted from different avian yolks on boar spermatozoa quality following freezing-thawing.

      Science.gov (United States)

      Wang, Peng; Wang, Yan-Feng; Wang, Chun-Wei; Bu, Shu-Hai; Hu, Jian-Hong; Li, Qing-Wang; Pang, Wei-Jun; Yang, Gong-She

      2014-05-01

      Low-density lipoproteins (LDL) is known to protect boar sperm during freezing-thawing, but little information is known about the effects of LDL extracted from different avian egg yolks on post-thaw boar semen quality. The purpose of this study was to compare and analyze the effects of LDL at various concentrations and different species on boar sperm quality after freezing-thawing. LDL extracted from the yolk of hen egg, duck egg, quail egg, pigeon egg or ostrich egg was added to the extender at the concentrations of 0.06, 0.07, 0.08, 0.09 and 0.1 g/ml, respectively, and their effects on frozen-thawed boar sperm quality were assessed. According to all measured parameters, the results showed that sperm motility, acrosome integrity and plasma membrane integrity were 43.20%, 52.57% and 48.13%, respectively, after being frozen-thawed with 0.09 g/ml LDL extracted from pigeon egg yolk. All these quality parameters were higher than that of other groups (P boar sperm among all of the groups supplemented with LDL from five kinds of avian egg in extender. The optimum concentration of LDL extracted from pigeon egg in boar semen freezing extender was 0.09 g/ml.

    • Recognition of Porphyromonas gingivalis gingipain epitopes by natural IgM binding to malondialdehyde modified low-density lipoprotein.

      Directory of Open Access Journals (Sweden)

      S Pauliina Turunen

      Full Text Available OBJECTIVE: Increased risk for atherosclerosis is associated with infectious diseases including periodontitis. Natural IgM antibodies recognize pathogen-associated molecular patterns on bacteria, and oxidized lipid and protein epitopes on low-density lipoprotein (LDL and apoptotic cells. We aimed to identify epitopes on periodontal pathogen Porphyromonas gingivalis recognized by natural IgM binding to malondialdehyde (MDA modified LDL. METHODS AND RESULTS: Mouse monoclonal IgM (MDmAb specific for MDA-LDL recognized epitopes on P. gingivalis on flow cytometry and chemiluminescence immunoassays. Immunization of C57BL/6 mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and apoptotic cells. Immunization of LDLR(-/- mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and diminished aortic lipid deposition. On Western blot MDmAb bound to P. gingivalis fragments identified as arginine-specific gingipain (Rgp by mass spectrometry. Recombinant domains of Rgp produced in E. coli were devoid of phosphocholine epitopes but contained epitopes recognized by MDmAb and human serum IgM. Serum IgM levels to P. gingivalis were associated with anti-MDA-LDL levels in humans. CONCLUSION: Gingipain of P. gingivalis is recognized by natural IgM and shares molecular identity with epitopes on MDA-LDL. These findings suggest a role for natural antibodies in the pathogenesis of two related inflammatory diseases, atherosclerosis and periodontitis.

    • The effect of oxidized low-density lipoprotein combined with adriamycin on the proliferation of Eca-109 cell line

      Directory of Open Access Journals (Sweden)

      Cui Jia

      2011-06-01

      Full Text Available Abstract Background The purpose of this study was to identify the affect on the proliferation Eca-109 cells treated with oxidized low-density lipoprotein (ox-LDL combined with adriamycin (ADM. Methods Eca-109 cell were cultured in the presence of oxLDL/ADM, and cell proliferation tested by MTT and cell apoptosis was monitored by the proportion of apoptosis and cell cycle by flow cytomester. We simultaneously evaluated the level of associated- apoptosis Bcl-2, Bax, and Caspase-3 gene mRNA and protein. Results OxLDL were cytotoxic and activate apoptosis. OxLDL combined with ADM significant enhanced the proportion rate of apoptosis on a time and dose dependency. The expressions of the inhibiting apoptosis Bcl-2 gene mRNA and protein were down regulated, whereas, the expressions of the promoting apoptosis Bax, and Caspase-3 genes mRNA and protein were up regulation. Conclusion These results suggested that oxLDL have cytotoxicity and activate apoptosis on the Eca-109 cells. OxLDL combined with ADM have a synergistic effect on the apoptosis induced Eca-109 cells. Furthermore, oxLDL may contribute to the improvement of clinical chemotherapy of cancer need to make further investigation.

  1. Association of Plasma Adiponectin and Oxidized Low-Density Lipoprotein with Carotid Intima-Media Thickness in Diabetic Nephropathy

    Science.gov (United States)

    Georgoulidou, Anastasia; Roumeliotis, Athanasios; Roumeliotis, Stefanos; Giannakopoulou, Efstathia; Papanas, Nikolaos; Passadakis, Ploumis; Manolopoulos, Vangelis G.; Vargemezis, Vassilis

    2015-01-01

    Aims. We sought to determine the association between levels of adiponectin and oxidized low-density lipoprotein (ox-LDL) in patients with diabetic nephropathy as well as their effect on carotid intima-media thickness (cIMT). Methods. Adiponectin and ox-LDL were determined in 25 diabetic patients without nephropathy and 94 patients at different stages of diabetic nephropathy including subjects on hemodialysis. cIMT was measured using real-time B-mode ultrasonography. Results. Plasma adiponectin levels increased significantly with severity of diabetic nephropathy (P = 0.002), on the contrary to ox-LDL which decreased with disease severity (P < 0.001). cIMT was significantly higher at late stages of diabetic nephropathy compared with early stages (P = 0.022). Adiponectin was a significant negative predictor of ox-LDL levels (β = −5.45, P = 0.023), independently of confounding factors. There was no significant correlation between cIMT and adiponectin or ox-LDL either in the total sample population or according to disease staging. Cluster analysis showed that patients with the highest cIMT values, highest levels of adiponectin, and lowest levels of ox-LDL were included in one cluster and all assigned to stage 5 of diabetic nephropathy. Conclusions. There was no significant association between adiponectin or ox-LDL and cIMT and, therefore, other factors affecting this surrogate marker of cardiovascular disease in diabetic nephropathy should be sought. PMID:26064982

  2. Association of Plasma Adiponectin and Oxidized Low-Density Lipoprotein with Carotid Intima-Media Thickness in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Anna Tavridou

    2015-01-01

    Full Text Available Aims. We sought to determine the association between levels of adiponectin and oxidized low-density lipoprotein (ox-LDL in patients with diabetic nephropathy as well as their effect on carotid intima-media thickness (cIMT. Methods. Adiponectin and ox-LDL were determined in 25 diabetic patients without nephropathy and 94 patients at different stages of diabetic nephropathy including subjects on hemodialysis. cIMT was measured using real-time B-mode ultrasonography. Results. Plasma adiponectin levels increased significantly with severity of diabetic nephropathy (P=0.002, on the contrary to ox-LDL which decreased with disease severity (P<0.001. cIMT was significantly higher at late stages of diabetic nephropathy compared with early stages (P=0.022. Adiponectin was a significant negative predictor of ox-LDL levels (β=-5.45, P=0.023, independently of confounding factors. There was no significant correlation between cIMT and adiponectin or ox-LDL either in the total sample population or according to disease staging. Cluster analysis showed that patients with the highest cIMT values, highest levels of adiponectin, and lowest levels of ox-LDL were included in one cluster and all assigned to stage 5 of diabetic nephropathy. Conclusions. There was no significant association between adiponectin or ox-LDL and cIMT and, therefore, other factors affecting this surrogate marker of cardiovascular disease in diabetic nephropathy should be sought.

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

    Science.gov (United States)

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

    2008-12-01

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

  4. Predominance of small dense low-density lipoproteins and abnormal glucose regulation in patients with acute coronary syndrome.

    Science.gov (United States)

    Ban, Yoshihisa; Koba, Shinji; Tsunoda, Fumiyoshi; Yokota, Yuuya; Ezumi, Hitoshi; Kondo, Takeshi; Suzuki, Hiroshi; Katagiri, Takashi

    2006-04-01

    Although small dense low-density lipoprotein (sd-LDL) has an established association with diabetic dyslipidemia, previous studies have failed to show an association between sd-LDL and diabetes among coronary heart disease patients. This study investigated the prevalence of sd-LDL and abnormal glucose regulation in acute coronary syndrome (ACS). LDL size at the onset of ACS was measured by nondenatured gradient gel electrophoresis in 314 of 429 consecutive patients. Sd-LDL was prevalent in 54% of the patients, irrespective of the presence of previously known diabetes (50% vs 60% in nondiabetes and diabetes, respectively). Diabetes was present in 122 (28%) of the patients, and 110 patients without diabetes underwent an oral glucose tolerance test. Impaired glucose tolerance (IGT) and newly detected diabetes were found in as many as 44% and 22% of the patients tested, even though their hemoglobinA1c levels were in the normal range (5.3+/-0.5%). The prevalence of sd-LDL was significantly higher in patients with glucose intolerance than in those with normal glucose tolerance (61% vs 42%). IGT and diabetes were far more common than normal glucose regulation in ACS patients, and the abnormal glycometabolism was closely associated with highly atherogenic sd-LDL.

  5. Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Cushing, S.D.; Berliner, J.A.; Valente, A.J.; Territo, M.C.; Navab, M.; Parhami, F.; Gerrity, R.; Schwartz, C.J.; Fogelman, A.M.

    1990-07-01

    After exposure to low density lipoprotein (LDL) that had been minimally modified by oxidation (MM-LDL), human endothelial cells (EC) and smooth muscle cells (SMC) cultured separately or together produced 2- to 3-fold more monocyte chemotactic activity than did control cells or cells exposed to freshly isolated LDL. This increase in monocyte chemotactic activity was paralleled by increases in mRNA levels for a monocyte chemotactic protein 1 (MCP-1) that is constitutively produced by the human glioma U-105MG cell line. Antibody that had been prepared against cultured baboon smooth muscle cell chemotactic factor (anti-SMCF) did not inhibit monocyte migration induced by the potent bacterial chemotactic factor f-Met-Leu-Phe. However, anti-SMCF completely inhibited the monocyte chemotactic activity found in the media of U-105MG cells, EC, and SMC before and after exposure to MM-LDL. Moreover, monocyte migration into the subendothelial space of a coculture of EC and SMC that had been exposed to MM-LDL was completely inhibited by anti-SMCF. Anti-SMCF specifically immunoprecipitated 10-kDa and 12.5-kDa proteins from EC. Incorporation of (35S)methionine into the immunoprecipitated proteins paralleled the monocyte chemotactic activity found in the medium of MM-LDL stimulated EC and the levels of MCP-1 mRNA found in the EC. We conclude that SMCF is in fact MCP-1 and MCP-1 is induced by MM-LDL.

  6. Relationship between Icodextrin use and decreased level of small low-density lipoprotein cholesterol fractioned by high-performance gel permeation chromatography.

    Science.gov (United States)

    Kanda, Eiichiro; Ai, Masumi; Iwamoto, Asami; Okazaki, Mitsuyo; Maeda, Yoshitaka; Sasaki, Sei; Yoshida, Masayuki

    2013-10-26

    Because of the absorption of glucose in peritoneal dialysis (PD) solution, PD patients show an atherogenic lipid profile, which is predictive of poor survival in PD patients. Lipoprotein subclasses consist of a continuous spectrum of particles of different sizes and densities (fraction). In this study, we investigated the lipoprotein fractions in PD patients with controlled serum low-density lipoprotein (LDL) cholesterol level, and evaluated the effects of icodextrin on lipid metabolism. Forty-nine PD patients were enrolled in this cross-sectional study in Japan. The proportions of cholesterol levels to total cholesterol level (cholesterol proportion) in 20 lipoprotein fractions were measured using an improved method of high-performance gel permeation chromatography (HPGPC). Twenty-six patients used icodextrin. Although no significant differences in cholesterol levels in LDL and high-density lipoprotein (HDL) were observed between the patients using icodextrin (icodextrin group) and control groups, HPGPC showed that the icodextrin group had significantly lower cholesterol proportions in the small LDL (t-test, p=0.053) and very small LDL (p=0.019), and significantly higher cholesterol proportions in the very large HDL and large HDL than the control group (p=0.037; p=0.066, respectively). Multivariate analysis adjusted for patient characteristics and statin use showed that icodextrin use was negatively associated with the cholesterol proportions in the small LDL (p=0.037) and very small LDL (p=0.026), and positively with those in the very large HDL (p=0.040), large HDL (p=0.047), and medium HDL (p=0.009). HPGPC showed the relationship between icodextrin use and the cholesterol proportions in lipoprotein fractions in PD patients. These results suggest that icodextrin may improve atherogenic lipid profiles in a manner different from statin.

  7. The Potential Protective Effects of Phenolic Compounds against Low-density Lipoprotein Oxidation.

    Science.gov (United States)

    Amarowicz, Ryszard; Pegg, Ronald B

    2017-01-01

    The exact mechanism(s) of atherosclerosis in humans remains elusive, but one theory hypothesizes that this deleterious process results from the oxidative modification of low-density lipoprotein (LDL). Research suggests that foods rich in dietary phenolic compounds with antioxidant activity can mitigate the extent of LDL oxidation in vivo. With regard to the different classes of flavonoids, there appears to be a structurefunction relationship between the various moieties/constituents attached to the flavonoids' three ring system and their impact at retarding LDL oxidation. This article summarizes the findings to date of both in vitro and in vivo studies using foods or phenolic extracts isolated from foodstuffs at inhibiting the incidence of LDL oxidation. Three bases: SCOPUS, Web Science, and PubMed were used for search. An often used method for the determination of antioxidant properties of natural phenolic compounds is the LDL oxidation assay. LDLs are isolated from human plasma and their oxidation is induced by Cu2+ ions or 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH). The sample is incubated with a phenolic extract or individual/isolated phenolic compounds. LDL oxidation is then monitored by various chemical methods (e.g., measurement of the generation of conjugated dienes and trienes). This technique confirmed the antioxidant properties of several extracts as obtained from plant material (e.g., grapes, berries, orange, grapefruit, coffee, tea, chocolate, olives, nuts) as well as the individual phenolic compounds (e.g., luteolinidin, apigenidin, caffeic acid, chlorogenic acid, catechin, quercetin, rutin). Several studies in vivo confirmed protective effects of phenolic compounds against LDL oxidation. They covered the healthy subjects with hyperlipidaemia, overweight, obesity, metabolic syndrome, heavy smokers, patients receiving haemodialysis, patients with peripheral vascular disease, and subjects at high cardiovascular risk. The studies comprise

  8. [Study on the selective removal of plasma low-density lipoprotein and fibrinogen by degraded guar sulfate].

    Science.gov (United States)

    Zhu, Ye; Fang, Bo; Huang, Li; Guan, Chen; Yang, Guang

    2008-10-01

    Degraded guar was prepared by acid with guar as the main material, which was then brought into reaction with chlorosulfonic acid under proper conditions, the sulfonated degraded guar was obtained successfully. The effects of sulfonation conditions on the SO4(2-) content were investigated, and the proper reaction conditions were determined. The results of infrared spectrometry showed that this sulfated derivative is a novel heparin-like polysaccharide. At the same time, the selective removal of low density lipoprotein (LDL) and fibrinogen (Fib) by degraded guar gum sulfate was studied. The experimental results showed that degraded guar gum sulfate is a novel LDL/ Fib purifying agent. When pH= 5.15 and the initial concentration of the degraded guar gum sulfate is 2500 mg/L, the reduction percentages were about 60%-66% for total cholesterol, about 76%-89% for LDL and very low-density lipoproteins (VLDL), and almost 100% for fibrinogen. There were no significant changes regarding the level of high-density lipoproteins and total proteins.

  9. Enzymatically Modified Low-Density Lipoprotein Promotes Foam Cell Formation in Smooth Muscle Cells via Macropinocytosis and Enhances Receptor-Mediated Uptake of Oxidized Low-Density Lipoprotein.

    Science.gov (United States)

    Chellan, Bijoy; Reardon, Catherine A; Getz, Godfrey S; Hofmann Bowman, Marion A

    2016-06-01

    Enzyme-modified nonoxidized low-density lipoprotein (ELDL) is present in human atherosclerotic lesions. Our objective is to understand the mechanisms of ELDL uptake and its effects on vascular smooth muscle cells (SMC). Transformation of murine aortic SMCs into foam cells in response to ELDL was analyzed. ELDL, but not acetylated or oxidized LDL, was potent in inducing SMC foam cell formation. Inhibitors of macropinocytosis (LY294002, wortmannin, amiloride) attenuated ELDL uptake. In contrast, inhibitors of receptor-mediated endocytosis (dynasore, sucrose) and inhibitor of caveolae-/lipid raft-mediated endocytosis (filipin) had no effect on ELDL uptake in SMC, suggesting that macropinocytosis is the main mechanism of ELDL uptake by SMC. Receptor for advanced glycation end products (RAGE) is not obligatory for ELDL-induced SMC foam cell formation, but primes SMC for the uptake of oxidized LDL in a RAGE-dependent manner. ELDL increased intracellular reactive oxygen species, cytosolic calcium, and expression of lectin-like oxidized LDL receptor-1 in wild-type SMC but not in RAGE(-/-) SMC. The macropinocytotic uptake of ELDL is regulated predominantly by intracellular calcium because ELDL uptake was completely inhibited by pretreatment with the calcium channel inhibitor lacidipine in wild-type and RAGE(-/-) SMC. This is in contrast to pretreatment with PI3 kinase inhibitors which completely prevented ELDL uptake in RAGE(-/-) SMC, but only partially in wild-type SMC. ELDL is highly potent in inducing foam cells in murine SMC. ELDL endocytosis is mediated by calcium-dependent macropinocytosis. Priming SMC with ELDL enhances the uptake of oxidized LDL. © 2016 American Heart Association, Inc.

  10. α5β1 integrin signaling mediates oxidized low-density lipoprotein-induced inflammation and early atherosclerosis.

    Science.gov (United States)

    Yurdagul, Arif; Green, Jonette; Albert, Patrick; McInnis, Marshall C; Mazar, Andrew P; Orr, A Wayne

    2014-07-01

    Endothelial cell activation drives early atherosclerotic plaque formation. Both fibronectin deposition and accumulation of oxidized low-density lipoprotein (oxLDL) occur early during atherogenesis, and both are implicated in enhanced endothelial cell activation. However, interplay between these responses has not been established. The objective of our study was to determine whether endothelial matrix composition modulates the inflammatory properties of oxLDL. We now show that oxLDL-induced nuclear factor-κB activation, proinflammatory gene expression, and monocyte binding are significantly enhanced when endothelial cells are attached to fibronectin compared with basement membrane proteins. This enhanced response does not result from altered oxLDL receptor expression, oxLDL uptake, or reactive oxygen species production, but results from oxLDL-induced activation of the fibronectin-binding integrin α5β1. Preventing α5β1 signaling (blocking antibodies, knockout cells) inhibits oxLDL-induced nuclear factor-κB activation and vascular cell adhesion molecule-1 expression. Furthermore, oxLDL drives α5β1-dependent integrin signaling through the focal adhesion kinase pathway, and focal adhesion kinase inhibition (PF-573228, small interfering RNA) blunts oxLDL-induced nuclear factor-κB activation, vascular cell adhesion molecule-1 expression, and monocyte adhesion. Last, treatment with the α5β1 signaling inhibitor, ATN-161, significantly blunts atherosclerotic plaque development in apolipoprotein E-deficient mice, characterized by reduced vascular cell adhesion molecule-1 expression and macrophage accumulation without affecting fibrous cap size. Our data suggest that α5β1-mediated cross-talk between fibronectin and oxLDL regulates inflammation in early atherogenesis and that therapeutics that inhibit α5 integrins may reduce inflammation without adversely affecting plaque structure. © 2014 American Heart Association, Inc.

  11. Intracellular transport of low density lipoprotein-derived cholesterol is defective in Niemann-Pick type C fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Liscum, L.; Ruggiero, R.M.; Faust, J.R.

    1989-05-01

    Niemann-Pick disease type C (NPC) is characterized by substantial intracellular accumulation of unesterified cholesterol. The accumulation of unesterified cholesterol in NPC fibroblasts cultured with low density lipoprotein (LDL) appears to result from the inability of LDL to stimulate cholesterol esterification in addition to impaired LDL-mediated downregulation of LDL receptor activity and cellular cholesterol synthesis. Although a defect in cholesterol transport in NPC cells has been inferred from previous studies, no experiments have been reported that measure the intracellular movement of LDL-cholesterol specifically. We have used four approaches to assess intracellular cholesterol transport in normal and NPC cells and have determined the following: (a) mevinolin-inhibited NPC cells are defective in using LDL-cholesterol for growth. However, exogenously added mevalonate restores cell growth equally in normal and NPC cells; (b) the transport of LDL-derived (3H)cholesterol to the plasma membrane is slower in NPC cells, while the rate of appearance of (3H)acetate-derived, endogenously synthesized (3H)cholesterol at the plasma membrane is the same for normal and NPC cells; (c) in NPC cells, LDL-derived (3H)cholesterol accumulates in lysosomes to higher levels than normal, resulting in defective movement to other cell membranes; and (d) incubation of cells with LDL causes an increase in cholesterol content of NPC lysosomes that is threefold greater than that observed in normal lysosomes. Our results indicate that a cholesterol transport defect exists in NPC that is specific for LDL-derived cholesterol.

  12. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management.

    Science.gov (United States)

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

    2011-06-01

    Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥ 1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal.

  13. Preliminary analysis of modified low density lipoproteins in the serum of healthy and obese dogs and cats

    Directory of Open Access Journals (Sweden)

    Nobuko eMori

    2015-09-01

    Full Text Available Oxidized low-density lipoprotein (LDL is thought to play an important role in the inflammatory response associated with human obesity. The purpose of this preliminary study was to determine oxidized LDL concentrations in healthy dogs and cats, and to evaluate whether obesity affects oxidized LDL concentration, using 39 cats and 19 dogs that had visited 2 different veterinary clinics in Japan. We hypothesized that oxidized LDL concentrations measured against body condition score (BCS may have a potential value in evaluating the qualities of accumulated or circulating lipids in obese dogs and cats that do not show signs of metabolic diseases. The mean oxidized LDL value in BCS3 dogs (2.4 ± 0.9 μg/dl was very similar to that of BCS5 dogs (2.2 ± 0.3 μg/dl. The mean oxidized LDL value of BCS4 dogs was 7.2 ± 10.3 μg/dl and the highest among three groups. BCS4 dogs included two dogs whose oxidized LDL values were higher than the mean oxidized LDL value of healthy humans (11.2 ± 0.3 μg/dl. On the other hand, the mean oxidized LDL value of BCS3 cats was 2.5 ± 0.9 μg/dl, and those of BCS4 and 5 cats were higher than that of BCS3, but there was no significant difference. The BCS4 cat group included one cat with a higher oxidized LDL value, and the BCS5 group also included two cats with oxidized LDL values higher than the mean oxidized LDL value of healthy humans. Interestingly, the oxidized LDL values in 2 obese dogs and 3 obese cats were indeed higher than the mean oxidized LDL value of humans with coronary artery disease (20.1 ± 1.1 μg/dl. In conclusion, this preliminary study showed reference ranges of oxidized dogs and cats against BCS. Obesity alone does not appear to have any direct effect on serum oxidized LDL values in healthy dogs and cats.

  14. Chromatofocusing of human high density lipoproteins and isolation of lipoproteins A and A-I.

    Science.gov (United States)

    Nestruck, A C; Niedmann, P D; Wieland, H; Seidel, D

    1983-08-29

    Using chromatofocusing, a column chromatography method with an internally generated pH gradient and focusing effects, human plasma high density lipoproteins (HDL) were fractionated into six subclasses within an interval of less than 1 pH unit (pH 5.1-4.2). All fractions floated in the ultracentrifuge at density = 1.21 g X ml-1, retained a typical HDL electron micrographic morphology and as a single band, alpha-migration on agarose electrophoresis. Compositional analysis of the subclasses revealed an inverse relationship between cholesterol ester and cholesterol on a molar basis. Distinct differences in the distribution of the apolipoproteins between the fractions were found. Two of the subclasses contained only apolipoprotein A-I and were therefore considered to be two forms of the lipid-combined form of apolipoprotein A-I, i.e., lipoprotein A-I. One subclass contained only apolipoproteins A-I + A-II and was, therefore, lipoprotein A. One subclass contained apolipoproteins A-I + A-II + D, and the two remaining contained additionally apolipoproteins C and E. Lipoprotein A-I was also demonstrated after immunoabsorption of apolipoprotein A-II-containing lipoproteins from whole serum. It is suggested that this method, which allows the fractionation of HDL into subclasses with distinct differences in apolipoprotein composition, offers new avenues for the study of the structural and metabolic heterogeneity of HDL.

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

    NARCIS (Netherlands)

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

    1998-01-01

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

  16. DETECTING LOW DENSITY LIPOPROTEIN RECEPTOR MUTANT GENE OF RABBIT BY PCR

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Many factors playi mportant roles inthe devel-opment of human atherosclerotic lesions,the lead-ing risk factor for atherosclerosis is familial hyper-cholesterolaemia(FH)[1-2].FHis a genetic diseasecharacterized by a deficiency of receptors for lowdensity lipoprotein(LDL)on the plas malemma ofendothelial cells,a high level of serum LDL,andearly development of atherosclerosis[3].WatanabeHeritable Hyperlipidaemic(WHHL)rabbits withunprovoked hypercholesterolaemia,increased bloodlevel of LDL,pronounced atheroscl...

  17. Genetic variation at the SLCO1B1 gene locus and low density lipoprotein cholesterol lowering response to pravastatin in the elderly

    Science.gov (United States)

    Our goal was to determine whether genetic variation at genes affecting statin metabolism or targets of statin therapy would influence low density lipoprotein (LDL) cholesterol lowering with pravastatin, baseline heart disease, or cardiac endpoints on trial. We examined associations of single nucleot...

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

    Science.gov (United States)

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

    2010-02-01

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

  19. Association of lecithin-cholesterol acyltransferase activity measured as a serum cholesterol esterification rate and low-density lipoprotein heterogeneity with cardiovascular risk: a cross-sectional study.

    Science.gov (United States)

    Tani, Shigemasa; Takahashi, Atsuhiko; Nagao, Ken; Hirayama, Atsushi

    2016-06-01

    The cholesterol-esterifying enzyme, lecithin-cholesterol acyltransferase (LCAT), is believed to play a key role in reverse cholesterol transport. However, recent investigations have demonstrated that higher LCAT activity levels increase the formation of triglyceride (TG)-rich lipoproteins (TRLs) and atherogenesis. We hypothesized that higher LCAT activity measured as a serum cholesterol esterification rate by the endogenous substrate method might increase the formation of TRLs and thereby alter low-density lipoprotein (LDL) heterogeneity. The estimated LDL particle size [relative LDL migration (LDL-Rm)] was measured by polyacrylamide gel electrophoresis with the LipoPhor system (Joko, Tokyo, Japan) in 538 consecutive patients with at least risk factor for atherosclerosis. Multivariate regression analysis after adjustments for traditional risk factors identified elevated TRL-related marker (TG, remnant-like particle cholesterol, apolipoprotein C-II, and apolipoprotein C-III) levels as independent predictors of smaller-sized LDL particle size, both in the overall subject population and in the subset of patients with serum LDL cholesterol levels of cardiovascular disease, it may be of importance to pay attention not only to a quantitative change in the serum LDL-C, but also to the LCAT activity which is possibly associated with LDL heterogeneity.

  20. Low-Density Lipoprotein and Intracerebral Hematoma Expansion in Daily Alcohol Users

    Directory of Open Access Journals (Sweden)

    Gayle R. Pletsch

    2014-01-01

    Full Text Available Background: Epidemiological studies suggest that the intracerebral hemorrhage (ICH rate correlates with alcohol consumption. Alcohol leads to elevated blood pressure (BP and inhibition of platelet aggregation. These factors could promote excessive bleeding. To our knowledge, in the setting of normal liver function tests, there are no studies that have systematically evaluated the relationship between daily alcohol use and hematoma expansion. The aim of this study is to compare the baseline ICH characteristics, frequency of hematoma expansion, and outcomes in patients with ICH who are daily alcohol users with those who are not daily alcohol users. Methods: A retrospective chart review was performed on consecutive patients who presented from July 2008 to July 2013 to the Tulane University Hospital in New Orleans, La., USA, with a spontaneous ICH. Ninety-nine patients who met these criteria were admitted. Patients who underwent hematoma evacuation were excluded. Hemorrhage volumes were calculated based on the ABC/2 method. Low-density lipoprotein (LDL was dichotomized into low (2 and nonparametric equivalents where appropriate. ICH growth in 24 h and LDL were evaluated using linear regression. Results: Of the 226 patients who met inclusion criteria, 20.4% had a history of daily alcohol use. The average age was 61 years (range 19-94, 55.6% of the patients were males, and 67.1% were of African American origin. Daily alcohol use was associated with male gender, lower rate of home antihypertensive, higher presenting BP, and lower platelet counts, but there was no difference in ICH characteristics, ICH growth, or clinical outcome. Daily alcohol use in patients with a low LDL level was associated with supratentorial location and trends for lower baseline Glasgow Coma Scale score, higher ICH score, and follow-up ICH volume, but no significant difference in significant hematoma expansion or clinical outcome except for a trend for higher mortality was found

  1. Oxidized Low Density Lipoprotein Among the Elderly in Qinghai-Tibet Plateau.

    Science.gov (United States)

    Sakamoto, Ryota; Okumiya, Kiyohito; Wang, Hongxin; Dai, Qingxiang; Fujisawa, Michiko; Wada, Taizo; Imai, Hissei; Kimura, Yumi; Ishimoto, Yasuko; Fukutomi, Eriko; Chen, Wingling; Sasiwongsaroj, Kwanchit; Kato, Emiko; Ge, Ri-Li; Matsubayashi, Kozo

    2015-09-01

    Several environmental factors including hypoxia have been reported to contribute to oxidative stress in individuals living in the highlands. However, little is known about the role of oxidized low-density lipoprotein (ox-LDL) among community-dwelling elderly in the Qinghai-Tibet plateau. The study population comprised 168 community-dwelling elderly subjects aged 60 years or older (male to female ratio, 70:98; mean age, 65.8 years) living in Haiyan County, located 3000 to 3200 m above sea level, 30 km northwest of Xining, Qinghai. The subjects were volunteers who joined a Comprehensive Geriatric Assessment. Plasma ox-LDL was measured in 168 community-dwelling elderly subjects aged 60 years or older (23 Tibetans and 145 Hans) with a monoclonal antibody-based enzyme-linked immunosorbent assay. Mean ox-LDL level was higher among Tibetan elderly than Han elderly (Tibetan, 79.0 ± 29.6 U/L; Han, 62.8 ± 23.5 U/L; P = .003). Tibetan ethnicity was significantly associated with ox-LDL levels after adjusting for LDL cholesterol levels. In addition, high ox-LDL levels (≥70 U/L) were significantly associated with a homeostasis model assessment insulin resistance index of at least 1.6 (odds ratio [OR], 2.82; 95% confidence interval [95% CI], 1.11 to 7.15; P = .029) and ankle brachial pressure index of less than 1.0 (OR, 4.85; 95% CI, 1.14 to 10.00; P = .028), after adjusting for age, sex, and ethnicity. Our findings support the hypothesis that ox-LDL levels are higher among Tibetan elderly highlanders compared with those among Han elderly. As ox-LDL levels can affect insulin resistance and arteriosclerosis, further research is needed to determine how oxidative stress influences the health situation among elderly individuals at high altitudes. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  2. Blood pressure, low-density lipoprotein cholesterol, and incidences of coronary artery disease and ischemic stroke in Japanese: the Suita study.

    Science.gov (United States)

    Tsukinoki, Rumi; Okamura, Tomonori; Watanabe, Makoto; Kokubo, Yoshihiro; Higashiyama, Aya; Nishimura, Kunihiro; Takegami, Misa; Murakami, Yoshitaka; Okayama, Akira; Miyamoto, Yoshihiro

    2014-11-01

    Blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) are risk factors for coronary artery disease (CAD) and ischemic stroke. However, the hazards of their coexistence are not fully understood in Asian populations. We investigated whether the relationship between BP and cardiovascular disease (CVD) outcomes are modified by LDL-C level in a Japanese population. Individuals aged 30-79 years (n = 5,151) were classified into 6 groups according to LDL-C levels (low LDL-C and optimal BP). Hazard ratios (HRs) were calculated after adjusting for age, high-density lipoprotein cholesterol, diabetes, smoking status, and alcohol consumption. The effect modification of LDL-C on BP-CVD association was assessed using likelihood ratio tests. There were 264 CAD and 215 ischemic stroke events during 13 years of follow-up. With low LDL-C, the HRs of prehypertension and hypertension for CAD were 2.01 and 4.71, respectively. Similar trends of HRs were observed with high LDL-C (optimal BP = 2.09, prehypertension = 3.45, hypertension = 5.94). However, the HRs for ischemic stroke did not differ between normal and high LDL-C levels at the same BP level. The apparent effect modification of LDL-C was not observed in the BP-CVD association in either CAD (P = 0.48) or ischemic stroke (P = 0.39). The HRs for CAD in prehypertensive and hypertensive groups were higher than those in the optimal BP group at the same LDL-C levels in a Japanese population; however, there was no statistical effect modification of LDL-C on the BP-CAD association. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    Fen Gao

    2016-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Scott J Cameron

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

  5. Ceruloplasmin enhances smooth muscle cell- and endothelial cell-mediated low density lipoprotein oxidation by a superoxide-dependent mechanism

    Science.gov (United States)

    Mukhopadhyay, C. K.; Ehrenwald, E.; Fox, P. L.

    1996-01-01

    Cultured vascular smooth muscle cells (SMC) and endothelial cells (EC) stimulate low density lipoprotein (LDL) oxidation by free radical-mediated, transition metal-dependent mechanisms. The physiological source(s) of metal ions is not known; however, purified ceruloplasmin, a plasma protein containing 7 coppers, oxidizes LDL in vitro. We now show that ceruloplasmin also increases LDL oxidation by vascular cells. In metal ion-free medium, human ceruloplasmin increased bovine aortic SMC- and EC-mediated LDL oxidation by up to 30- and 15-fold, respectively. The maximal response was at 100-300 microg ceruloplasmin/ml, a level at or below the unevoked physiological plasma concentration. Oxidant activity was dependent on protein structure as a specific proteolytic cleavage or removal of one of the seven ceruloplasmin copper atoms inhibited activity. Three lines of evidence indicated a critical role for cellular superoxide (O2.) in ceruloplasmin-stimulated oxidation. First, the rate of production of O2. by cells correlated with their rates of LDL oxidation. Second, superoxide dismutase effectively blocked ceruloplasmin-stimulated oxidation by both cell types. Finally, O2. production by SMC quantitatively accounted for the observed rate of LDL oxidation. To show this, the course of O2. production by SMC was simulated by repeated addition of xanthine and xanthine oxidase to culture medium under cell-free conditions. Neither ceruloplasmin nor O2. alone increased LDL oxidation, but together they completely reconstituted the oxidation rate of ceruloplasmin-stimulated SMC. These results are the first to show that ceruloplasmin stimulates EC- and SMC-mediated oxidation of LDL and that cell-derived O2. accounts quantitatively for metal-dependent, free radical-initiated oxidation of LDL by these cells.

  6. Antiapoptotic effects of propolis extract and propol on human macrophages exposed to minimally modified low density lipoprotein.

    Science.gov (United States)

    Claus, R; Kinscherf, R; Gehrke, C; Bonaterra, G; Basnet, P; Metz, J; Deigner, H P

    2000-04-01

    An aqueous extract of propolis and the phenolic component of propolis, propol, were assayed for antioxidative and antiapoptotic properties. Both additions inhibited Cu(2+)-initiated low density lipoprotein (LDL) oxidation as characterized by a reduction of the lag time, reduced the increase of relative electrophoretic mobility during oxidation and markedly diminished apoptosis of human macrophages exposed to minimally modified (mmLDL). Moreover, aqueous propolis extract and propol blocked the mmLDL-induced decrease of glutathione (GSH) and the activation of the transcription factor NF-kappa B in these cells. The potent phenolic antioxidant propol thus expands the capability of cells to neutralize oxidative stress and to prevent apoptosis and is therefore suggested to significantly contribute to the antiinflammatory and antioxidative effects of propolis.

  7. The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol

    Directory of Open Access Journals (Sweden)

    Poirier S

    2013-10-01

    Full Text Available Steve Poirier,1,2 Gaétan Mayer1–31Laboratory of Molecular Cell Biology, Montreal Heart Institute, Montréal, QC, Canada; 2Départements de Pharmacologie, 3Médecine, Faculté de Médecine, Université de Montréal, Montréal, QC, CanadaAbstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9 directly binds to the epidermal growth factor-like repeat A domain of low-density lipoprotein receptor and induces its degradation, thereby controlling circulating low-density lipoprotein cholesterol (LDL-C concentration. Heterozygous loss-of-function mutations in PCSK9 can decrease the incidence of coronary heart disease by up to 88%, owing to lifelong reduction of LDL-C. Moreover, two subjects with PCSK9 loss-of-function mutations on both alleles, resulting in a total absence of functional PCSK9, were found to have extremely low circulating LDL-C levels without other apparent abnormalities. Accordingly, PCSK9 could represent a safe and effective pharmacological target to increase clearance of LDL-C and to reduce the risk of coronary heart disease. Recent clinical trials using anti-PCSK9 monoclonal antibodies that block the PCSK9:low-density lipoprotein receptor interaction were shown to considerably reduce LDL-C levels by up to 65% when given alone and by up to 72% in patients already receiving statin therapy. In this review, we will discuss how major scientific breakthroughs in PCSK9 cell biology have led to the development of new and forthcoming LDL-C-lowering pharmacological agents.Keywords: PCSK9, LDLR, LDL-cholesterol, lipoproteins, coronary heart disease, inhibitors, monoclonal antibody therapy

  8. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

    Science.gov (United States)

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

    2011-01-01

    Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal. PMID:21531743

  9. Analysis of low-density lipoprotein receptor gene mutations in a Chinese patient with clinically homozygous familial hypercholesterolemia

    Institute of Scientific and Technical Information of China (English)

    曹守春; 王绿娅; 秦彦文; 蔺洁; 吴邦俊; 刘舒; 潘晓冬; 杜兰平; 陈保生

    2003-01-01

    Objective To screen the point mutation of the low-density lipoprotein receptor (LDL-R) gene in Chinese familial hypercholesterolemia (FH) patients, characterize the relationship between the genotype and the phenotype and discuss the molecular pathological mechanism of FH. Methods A patient with clinical phenotype of homozygous FH and her parents were investigated for mutations in the promoter and all eighteen exons of the LDL-R gene. Screening was carried out using Touch-down PCR and direct DNA sequencing; multiple alignment analysis by DNASIS 2.5 was used to find base alteration, and the LDL-R gene mutation database was searched to identify the alteration. In addition, the apolipoprotein B gene (apo B) was screened for known mutations (R3500Q) that cause familial defective apo B100 (FDB) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results Two new heterozygous mutations in exons 4 and 9 of the LDL-R gene were identified in the proband (C122Y and T383I) as well as her parents. Both of the mutations have not been published in the LDL-R gene mutation database. No mutation of apo B100 (R3500Q) was observed. Conclusion Two new mutations (C112Y and T383I) were found in the LDL-R gene, which may result in FH and may be particularly pathogenetic genotypes in Chinese people.

  10. Capsaicin protects endothelial cells and macrophage against oxidized low-density lipoprotein-induced injury by direct antioxidant action.

    Science.gov (United States)

    Chen, Kuo-Shuen; Chen, Pei-Ni; Hsieh, Yih-Shou; Lin, Chin-Yin; Lee, Yi-Hsun; Chu, Shu-Chen

    2015-02-25

    Atherosclerosis is a chronic inflammatory vascular disease. It is characterized by endothelial dysfunction, lipid accumulation, leukocyte activation, and the production of inflammatory mediators and reactive oxygen species (ROS). Capsaicin, a biologically active compound of the red pepper and chili pepper, has several anti-oxidant, anti-inflammatory, anti-cancer, and hypolipidemic biological effects. However, its protective effects on foam cell formation and endothelial injury induced by oxidized low-density lipoprotein (oxLDL) remain unclear. In this study, we evaluated the anti-oxidative activity of capsaicin, and determined the mechanism by which capsaicin rescues human umbilical vein endothelial cells (HUVECs) from oxLDL-mediated dysfunction. The anti-oxidative activity of capsaicin was defined by Apo B fragmentation and conjugated diene production of the copper-mediated oxidation of LDL. Capsaicin repressed ROS generation, as well as subsequent mitochondrial membrane potential collapse, cytochrome c expression, chromosome condensation, and caspase-3 activation induced by oxLDL in HUVECs. Capsaicin also protected foam cell formation in macrophage RAW 264.7 cells. Our results suggest that capsaicin may prevent oxLDL-induced cellular dysfunction and protect RAW 264.7 cells from LDL oxidation.

  11. Surface glycosylation of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) membrane for selective adsorption of low-density lipoprotein.

    Science.gov (United States)

    Wang, Wei; Lan, Ping

    2014-01-01

    A novel method of constructing a glycosylated surface on poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] membrane surface for the selective adsorption of low-density lipoprotein (LDL) was developed, which involved the photoinduced graft polymerization of acrylic acid followed by the chemical binding of carboxyl groups with glucosamine in the presence of 1-ethyl-3-(dimethyl-aminopropyl) carbodiimide hydrochloride and N-hydroxy-succinimide. The chemical structures of the fabricated membranes were characterized by attenuated total reflectance Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Zeta potential and water contact angle measurements were performed to investigate the surface charge and wettability of the membranes, respectively. An enzyme linked immunosorbent assay was used to measure the LDL adsorption on the plain and modified membrane surfaces. It was found that the surface glycosylation of P(3HB-co-4HB) membrane greatly enhanced the affinity interactions with LDL and the absorbed LDL could be easily desorbed with eluents, indicating a specific and reversible binding of LDL to the surface. Furthermore, the hemocompatibility of glycosylated membrane was improved as examined by platelet adhesion. The results suggest that the glycosylated P(3HB-co-4HB) membrane is promising for application in LDL apheresis therapy.

  12. Immobilization of sodium alginate sulfates on polysulfone ultrafiltration membranes for selective adsorption of low-density lipoprotein.

    Science.gov (United States)

    Wang, Wei; Huang, Xiao-Jun; Cao, Jian-Da; Lan, Ping; Wu, Wen

    2014-01-01

    A novel method for the immobilization of sodium alginate sulfates (SAS) on polysulfone (PSu) ultrafiltration membranes to achieve selective adsorption of low-density lipoprotein (LDL) was developed, which involved the photoinduced graft polymerization of acrylamide on the membrane and the Hofmann rearrangement reaction of grafted acrylamide followed by chemical binding of SAS with glutaraldehyde. The surface modification processes were confirmed by attenuated total reflectance Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy characterization. Zeta potential and water contact angle measurements were performed to investigate the surface charge and wettability of the membranes. An enzyme-linked immunosorbent assay was used to measure the binding of LDL on plain and modified PSu membranes. It was found that the PSu membrane immobilized with sodium alginate sulfates (PSu-SAS) greatly enhanced the selective adsorption of LDL from protein solutions and the absorbed LDL could be easily eluted with sodium chloride solution, indicating a specific and reversible binding of LDL to SAS, mainly driven by electrostatic forces. Furthermore, the PSu-SAS membrane showed good blood compatibility as examined by platelet adhesion. The results suggest that the PSu-SAS membranes are promising for application in simultaneous hemodialysis and LDL apheresis therapy. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  13. Effects of coffee consumption on oxidative susceptibility of low-density lipoproteins and serum lipid levels in humans.

    Science.gov (United States)

    Yukawa, G S; Mune, M; Otani, H; Tone, Y; Liang, X-M; Iwahashi, H; Sakamoto, W

    2004-01-01

    Since little is known about how coffee intake affects low-density lipoprotein (LDL) oxidative susceptibility and serum lipid levels, we conducted an in vivo study in 11 healthy male students of Wakayama Medical University aged between 20 and 31 years fed an average Japanese diet. On days 1-7 of the study, the subjects drank mineral water. On day 7, the subjects began drinking coffee, 24 g total per day, for one week. This was followed by a one week "washout period" during which mineral water was consumed. Fasting peripheral venous blood samples were taken at the end of each one-week period. LDL oxidation lag time was approximately 8% greater (p coffee drinking period than the other periods. Serum levels of total cholesterol and LDL-cholesterol (LDL-C) and malondialdehyde (MDA) as thiobarbituric acid reactive substances (TBARS) were significantly decreased after the coffee drinking period. Finally, regular coffee ingestion may favorably affect cardiovascular risk status by modestly reducing LDL oxidation susceptibility and decreasing LDL-cholesterol and MDA levels.

  14. Dietary modifications of low-density lipoprotein fatty acids in humans: their effect on low-density lipoprotein-fibroblast interactions.

    Science.gov (United States)

    Baudet, M F; Esteva, O; Lasserre, M; Jacotot, B

    1986-01-01

    The chemical composition and metabolism of low-density lipoproteins (LDLs) in a population of Benedictine nuns were studied after 5-month periods during which the predominant dietary fats were sunflower oil, fluid of palm, peanut oil, milk fats, low erucic acid rapeseed (LEAR) oil, corn oil, olive oil, soybean oil. The population was divided into three groups. The control group (C) included 12 subjects selected at random by taking 2 subjects per age pool among those with plasma cholesterol less than 230 mg/dl. Groups H1 and H2 were selected in the same way among those with plasma cholesterol less than 230 mg/dl. Groups H1 and H2 comprised 6 subjects and differed from each other in the amount of plasma cholesteryl esters, i.e., below and above the mean value of group C. Changes in LDL composition, according to the dietary fat, were associated with changes in LDL catabolism studied in fibroblast cultures, but no significant differences were found between the three groups.

  15. Hydroxysafflor yellow A suppresses oxidized low density lipoprotein induced proliferation of vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Lin Sheng

    2012-06-01

    Full Text Available To investigate the relationship between the suppression of Hydroxysafflor yellow A (HSYA on the oxidized low density lipoprotein (ox-LDL induced proliferation of vascular smooth muscle cells (VSMCs and the mRNA and protein expression of extracellular signal-regulated protein kinase 1/2 (ERK1/2 and mitogen activated protein kinase phospholipase-1 (MAKP-1, VSMCs were treated with HSYA at 10 ?mol/L and/or ox-LDL at 35 mg/L for 48 h. MTT assay was done to measure cell survival rate, flow cytometry to detect cell cycle, reverse transcription PCR and Western blot to detect the expression of ERK1/2 and MAKP-1. When compared to cells treated with ox-LDL alone, the survival rate of cells treated with two reagents was reduced and the proportion of cells in G0/G1 phase significantly increased, with increased MKP-1 expression. The study suggests HSYA can inhibit VSMC proliferation via increasing MKP-1 expression, reducing p-ERK1/2 activity and suppressing cell cycle.

  16. Whole-cell analysis of low-density lipoprotein uptake by macrophages using STEM tomography.

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Baudoin

    Full Text Available Nanoparticles of heavy materials such as gold can be used as markers in quantitative electron microscopic studies of protein distributions in cells with nanometer spatial resolution. Studying nanoparticles within the context of cells is also relevant for nanotoxicological research. Here, we report a method to quantify the locations and the number of nanoparticles, and of clusters of nanoparticles inside whole eukaryotic cells in three dimensions using scanning transmission electron microscopy (STEM tomography. Whole-mount fixed cellular samples were prepared, avoiding sectioning or slicing. The level of membrane staining was kept much lower than is common practice in transmission electron microscopy (TEM, such that the nanoparticles could be detected throughout the entire cellular thickness. Tilt-series were recorded with a limited tilt-range of 80° thereby preventing excessive beam broadening occurring at higher tilt angles. The 3D locations of the nanoparticles were nevertheless determined with high precision using computation. The obtained information differed from that obtained with conventional TEM tomography data since the nanoparticles were highlighted while only faint contrast was obtained on the cellular material. Similar as in fluorescence microscopy, a particular set of labels can be studied. This method was applied to study the fate of sequentially up-taken low-density lipoprotein (LDL conjugated to gold nanoparticles in macrophages. Analysis of a 3D reconstruction revealed that newly up-taken LDL-gold was delivered to lysosomes containing previously up-taken LDL-gold thereby forming onion-like clusters.

  17. Effect of olive and sunflower oils on low density lipoprotein level, composition, size, oxidation and interaction with arterial proteoglycans.

    Science.gov (United States)

    Carmena, R; Ascaso, J F; Camejo, G; Varela, G; Hurt-Camejo, E; Ordovas, J M; Martinez-Valls, J; Bergstöm, M; Wallin, B

    1996-09-06

    The atherogenicity of low density lipoproteins (LDL) may be modulated by its serum levels, structure and affinity for components of the intima, all properties that can be altered by diet. Linoleic acid-rich diets (n-G, 18:2) reduce the levels of LDL whereas those rich in oleic (n-9,18:1) are considered 'neutral'. However, LDL enriched in linoleic acid have been reported to be more vulnerable to free radical-mediated oxidation than those enriched in oleic, a potentially atherogenic property. The effect of dietary fats on other properties of LDL that may also modulate atherogenesis, such as size and capacity to interact with intima components, are not well established. We explored here how a change from an olive oil-rich diet (OO) to a sunflower oil-rich one (SFO) affects these parameters in a community with a traditional Mediterranean diet. Eighteen free-living volunteers were placed for 3 weeks on a diet with 31% of caloric intake as sunflower oil and then shifted for an additional 3 weeks to a diet in which OO provided 30.5% of the calories. The LDL after SFO had a fatty acids ratio of (18:2 + 18:3 + 20:4) to (16:0 + 16:1 + 18:0 + 18:1) of 1.06 +/- 0.11 compared to 0.73 +/- 0.06 after the OO period. Serum LDL was significantly lower after SFO than after OO. Unexpectedly, copper-catalyzed oxidation of LDL from the SFO period was significantly less than that of the particles from the OO period. The resistance to oxidation of LDL of the SFO and OO period related to alterations in content of the antioxidants alpha-tocopherol, beta-carotene and retinol, in addition to changes in size and fatty acids composition. In vitro binding of LDL to human arterial proteoglycans was also significantly lower for the SFO-LDL than the OO-LDL, a result that can also be attributed to the larger size of the SFO-LDL. Therefore, three properties of LDL: circulating levels, oxidizability, and affinity with intima proteoglycans, that may modulate its atherogenicity, were shifted in a

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

    OpenAIRE

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

    2005-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-11-01

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

  20. Piperine Induces Hepatic Low-Density Lipoprotein Receptor Expression through Proteolytic Activation of Sterol Regulatory Element-Binding Proteins.

    Directory of Open Access Journals (Sweden)

    Ayasa Ochiai

    Full Text Available Elevated plasma low-density lipoprotein (LDL cholesterol is considered as a risk factor for atherosclerosis. Because the hepatic LDL receptor (LDLR uptakes plasma lipoproteins and lowers plasma LDL cholesterol, the activation of LDLR is a promising drug target for atherosclerosis. In the present study, we identified the naturally occurring alkaloid piperine, as an inducer of LDLR gene expression by screening the effectors of human LDLR promoter. The treatment of HepG2 cells with piperine increased LDLR expression at mRNA and protein levels and stimulated LDL uptake. Subsequent luciferase reporter gene assays revealed that the mutation of sterol regulatory element-binding protein (SREBP-binding element abolished the piperine-mediated induction of LDLR promoter activity. Further, piperine treatments increased mRNA levels of several SREBP targets and mature forms of SREBPs. However, the piperine-mediated induction of the mature forms of SREBPs was not observed in SRD-15 cells, which lack insulin-induced gene-1 (Insig-1 and Insig-2. Finally, the knockdown of SREBPs completely abolished the piperine-meditated induction of LDLR gene expression in HepG2 cells, indicating that piperine stimulates the proteolytic activation of SREBP and subsequent induction of LDLR expression and activity.

  1. Piperine Induces Hepatic Low-Density Lipoprotein Receptor Expression through Proteolytic Activation of Sterol Regulatory Element-Binding Proteins.

    Science.gov (United States)

    Ochiai, Ayasa; Miyata, Shingo; Shimizu, Makoto; Inoue, Jun; Sato, Ryuichiro

    2015-01-01

    Elevated plasma low-density lipoprotein (LDL) cholesterol is considered as a risk factor for atherosclerosis. Because the hepatic LDL receptor (LDLR) uptakes plasma lipoproteins and lowers plasma LDL cholesterol, the activation of LDLR is a promising drug target for atherosclerosis. In the present study, we identified the naturally occurring alkaloid piperine, as an inducer of LDLR gene expression by screening the effectors of human LDLR promoter. The treatment of HepG2 cells with piperine increased LDLR expression at mRNA and protein levels and stimulated LDL uptake. Subsequent luciferase reporter gene assays revealed that the mutation of sterol regulatory element-binding protein (SREBP)-binding element abolished the piperine-mediated induction of LDLR promoter activity. Further, piperine treatments increased mRNA levels of several SREBP targets and mature forms of SREBPs. However, the piperine-mediated induction of the mature forms of SREBPs was not observed in SRD-15 cells, which lack insulin-induced gene-1 (Insig-1) and Insig-2. Finally, the knockdown of SREBPs completely abolished the piperine-meditated induction of LDLR gene expression in HepG2 cells, indicating that piperine stimulates the proteolytic activation of SREBP and subsequent induction of LDLR expression and activity.

  2. Thermodynamics of the interaction between bovine binder of sperm BSP1 and low-density lipoprotein from hen's egg yolk

    Energy Technology Data Exchange (ETDEWEB)

    Lusignan, Marie-France; Manjunath, Puttaswamy [Maisonneuve-Rosemont Hospital Research Center and Department of Medicine, Universite de Montreal, C.P. 6128, Succ. Centre Ville, Montreal, Quebec, Canada H3C 3J7 (Canada); Lafleur, Michel, E-mail: michel.lafleur@umontreal.ca [Department of Chemistry, Centre for Self-Assembled Chemical Structures (CSACS), Universite de Montreal, C.P. 6128, Succ. Centre Ville, Montreal, Quebec, Canada H3C 3J7 (Canada)

    2011-03-20

    Research highlights: {yields} Isothermal titration calorimetry revealed Binder-of-SPerm BSP1 protein has high affinity for egg yolk low density lipoproteins. {yields} It is estimated that 104 BSP1 molecules could bind one LDL particle. {yields} BSP1 has 2 phosphocholine binding sites and the BSP1/LDL ratio corresponds to 1.6 phosphatidylcholine per bound BSP1. {yields} The strong interaction between LDL particles and BSP1 is proposed to be important for sperm protection by egg yolk extender. - Abstract: Egg yolk is used in extender to protect sperm from cold shock and freezing during preservation. It is the low-density lipoprotein (LDL) fraction of egg yolk that protects sperm. Even though essential for sperm capacitation, the major proteins from bull seminal plasma, the Binder of SPerm (BSP) proteins, are detrimental for sperm preservation because they induce a continual phospholipids and cholesterol efflux from sperm membranes. The BSP proteins were proposed to bind to egg yolk LDL, preventing the sperm membrane damage. We characterized the binding between the BSP proteins and the LDL by isothermal titration calorimetry, providing the thermodynamics and quantitative description of this putative association. The association between BSP1 (major BSP proteins) and LDL is characterized by an affinity constant (K{sub a}) of 3.4 {+-} 0.4 {mu}M{sup -1}. A protein/LDL ratio of 104 {+-} 5 was determined indicating that 104 molecules of BSP1 would bind to one LDL particle. This stoichiometry leads to proposing that the association involves 1.6 {+-} 0.1 phosphatidylcholines (PC) per BSP protein. This finding is satisfactorily consistent with the fact that each BSP1 protein has 2 binding sites for choline group. In conclusion, the formation of a high affinity complex between BSP1 and LDL is proposed to be important for the protection of sperm by egg yolk extender.

  3. The Application of a Modified d-ROMs Test for Measurement of Oxidative Stress and Oxidized High-Density Lipoprotein

    Science.gov (United States)

    Ito, Fumiaki; Ito, Tomoyuki; Suzuki, Chinatsu; Yahata, Tomoyo; Ikeda, Kazuyuki; Hamaoka, Kenji

    2017-01-01

    Reactive oxygen species (ROS) are involved in the initiation and progression of atherosclerosis. ROS-derived hydroperoxides, as an indicator of ROS production, have been measured by using the diacron reactive oxygen metabolites (d-ROMs) test, which requires iron-containing transferrin in the reaction mixture. In this study we developed a modified d-ROMs test, termed the Fe-ROMs test, where iron ions were exogenously added to the reaction mixture. This modification is expected to exclude the assay variation that comes from different blood iron levels in individuals. In addition, this Fe-ROMs test was helpful for determining the class of plasma lipoproteins that are hydroperoxidized. Low-density lipoprotein/very low-density lipoprotein (LDL/VLDL) and high-density lipoprotein (HDL) were purified by use of an LDL/VLDL purification kit and the dextran sulfate-Mg2+ precipitation method, respectively; their hydroperoxide contents were assessed by performing the Fe-ROMs test. The majority of the hydroperoxides were detected only in the HDL fraction, not in the LDL/VLDL. Further detailed analysis of HDLs by size-exclusion high-performance liquid chromatography revealed that the hydroperoxide-containing molecules were small-sized HDLs. Because HDL was shown to be the principal vehicle for the plasma hydroperoxides, this Fe-ROMs test is a beneficial method for the assessment of oxidized-HDL levels. Indeed, Fe-ROMs levels were strongly associated with the levels of oxidized HDL, which were determined by performing the malondialdehyde-modified HDL enzyme immunoassay. In conclusion, the Fe-ROMs test using plasma itself or the HDL fraction after dextran sulfate-Mg2+ precipitation is useful to assess the functionality of HDL, because the oxidation of HDL impairs its antiatherogenic capacity. PMID:28230785

  4. The Application of a Modified d-ROMs Test for Measurement of Oxidative Stress and Oxidized High-Density Lipoprotein.

    Science.gov (United States)

    Ito, Fumiaki; Ito, Tomoyuki; Suzuki, Chinatsu; Yahata, Tomoyo; Ikeda, Kazuyuki; Hamaoka, Kenji

    2017-02-21

    Reactive oxygen species (ROS) are involved in the initiation and progression of atherosclerosis. ROS-derived hydroperoxides, as an indicator of ROS production, have been measured by using the diacron reactive oxygen metabolites (d-ROMs) test, which requires iron-containing transferrin in the reaction mixture. In this study we developed a modified d-ROMs test, termed the Fe-ROMs test, where iron ions were exogenously added to the reaction mixture. This modification is expected to exclude the assay variation that comes from different blood iron levels in individuals. In addition, this Fe-ROMs test was helpful for determining the class of plasma lipoproteins that are hydroperoxidized. Low-density lipoprotein/very low-density lipoprotein (LDL/VLDL) and high-density lipoprotein (HDL) were purified by use of an LDL/VLDL purification kit and the dextran sulfate-Mg(2+) precipitation method, respectively; their hydroperoxide contents were assessed by performing the Fe-ROMs test. The majority of the hydroperoxides were detected only in the HDL fraction, not in the LDL/VLDL. Further detailed analysis of HDLs by size-exclusion high-performance liquid chromatography revealed that the hydroperoxide-containing molecules were small-sized HDLs. Because HDL was shown to be the principal vehicle for the plasma hydroperoxides, this Fe-ROMs test is a beneficial method for the assessment of oxidized-HDL levels. Indeed, Fe-ROMs levels were strongly associated with the levels of oxidized HDL, which were determined by performing the malondialdehyde-modified HDL enzyme immunoassay. In conclusion, the Fe-ROMs test using plasma itself or the HDL fraction after dextran sulfate-Mg(2+) precipitation is useful to assess the functionality of HDL, because the oxidation of HDL impairs its antiatherogenic capacity.

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

    Directory of Open Access Journals (Sweden)

    Abbas Zavarehee

    2009-05-01

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

  6. Modification and clearance of low density lipoproteins during the formation of endotoxin-lipoprotein complexes.

    Science.gov (United States)

    Schvartz, Ya Sh; Polyakov, L M; Dushkin, M I; Pivovarova, E N

    2008-04-01

    Changes in electrical charge and clearance rate of LDL after the formation of their complexes with bacterial LPS were studied in experiments on Wistar rats. It was found that binding of S. minnesota R595 LPS with (125)I-LDL sharply accelerated clearance of the greater part of LDL complexes, but on the other hand induced the appearance of an LDL-LPS subfraction with slower elimination rate compared to free LDL. Electrophoresis showed that after binding of LPS, LDL acquired a negative charge. These data suggest that the formation of LDL-LPS complexes is accompanied by modification of LDL due to which they acquire atherogenic properties.

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

    Lifescience Database Archive (English)

    Full Text Available 9261091 Low density lipoprotein oxidation and its pathobiological significance. Ste...in oxidation and its pathobiological significance. PubmedID 9261091 Title Low density lipoprotein oxidation ...and its pathobiological significance. Authors Steinberg D. Publication J Biol Che

  8. Identification of roles for H264, H306, H439, and H635 in acid-dependent lipoprotein release by the LDL receptor.

    Science.gov (United States)

    Dong, Hongyun; Zhao, Zhenze; LeBrun, Drake G; Michaely, Peter

    2017-02-01

    Lipoproteins internalized by the LDL receptor (LDLR) are released from this receptor in endosomes through a process that involves acid-dependent conformational changes in the receptor ectodomain. How acidic pH promotes this release process is not well understood. Here, we assessed roles for six histidine residues for which either genetic or structural data suggested a possible role in the acid-responsiveness of the LDLR. Using assays that measured conformational change, acid-dependent lipoprotein release, LDLR recycling, and net lipoprotein uptake, we show that H635 plays important roles in acid-dependent conformational change and lipoprotein release, while H264, H306, and H439 play ancillary roles in the response of the LDLR to acidic pH. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  9. Localization of oxidized low-density lipoprotein and its relation to plaque morphology in human coronary artery.

    Directory of Open Access Journals (Sweden)

    Yasumi Uchida

    Full Text Available OBJECTIVES: Oxidized low-density lipoprotein (oxLDL plays a key role in the formation of atherosclerotic plaques. However, its localization in human coronary arterial wall is not well understood. The present study was performed to visualize deposition sites and patterns of native oxLDL and their relation to plaque morphology in human coronary artery. METHODS: Evans blue dye (EB elicits a violet fluorescence by excitation at 345-nm and emission at 420-nm, and a reddish-brown fluorescence by excitation at 470-nm and emission at 515-nm characteristic of oxLDL only. Therefore, native oxLDL in excised human coronary artery were investigated by color fluorescent microscopy (CFM using EB as a biomarker. RESULTS: (1 By luminal surface scan with CFM, the % incidence of oxLDL in 38 normal segments, 41 white plaques and 32 yellow plaques that were classified by conventional angioscopy, was respectively 26, 44 and 94, indicating significantly (p<0.05 higher incidence in the latter than the former two groups. Distribution pattern was classified as patchy, diffuse and web-like. Web-like pattern was observed only in yellow plaques with necrotic core. (2 By transected surface scan, oxLDL deposited within superficial layer in normal segments and diffusely within both superficial and deep layers in white and yellow plaques. In yellow plaques with necrotic core, oxLDL deposited not only in the marginal zone of the necrotic core but also in the fibrous cap. CONCLUSION: Taken into consideration of the well-known process of coronary plaque growth, the results suggest that oxLDL begins to deposit in human coronary artery wall before plaque formation and increasingly deposits with plaque growth, exhibiting different deposition sites and patterns depending on morphological changes.

  10. Relationship between oxidized low-density lipoprotein antibodies and obesity in different glycemic situations

    Directory of Open Access Journals (Sweden)

    Babakr AT

    2014-10-01

    Full Text Available Abdullatif Taha Babakr,1 Osman Mohamed Elsheikh,2 Abdullah A Almarzouki,3 Adel Mohamed Assiri,1 Badr Eldin Elsonni Abdalla,4 Hani Yousif Zaki,5 Samir H Fatani,1 EssamEldin Mohamed NourEldin11Department of Medical Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia; 2Department of Biochemistry, Faculty of Medicine, International University of Africa, Khartoum, Sudan; 3Department of Internal Medicine, Faculty of Medicine, Umm Al-Qura University, Makkah, 4Department of Biochemistry, Sciences Faculty for Girls, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 5Department of Biochemistry and Nutrition, Faculty of Medicine, University of Gezira, Sudan Background: Autoantibodies to oxidized low-density lipoprotein (oxLDL are a heterogeneous group of antibodies that are controversially discussed to be either pathogenic or protective. Biochemical and anthropometric measurements correlated with increased levels of these antibodies are also controversial, especially in conditions of impaired glucose tolerance and type 2 diabetes mellitus. The present study was conducted to evaluate levels of oxLDL antibodies and their correlation with obesity in different glycemic situations. Methods: Two hundred and seventy-four adult males were classified into three subgroups: group 1 (n=125, comprising a control group of nondiabetic subjects; group 2 (n=77, comprising subjects with impaired glucose tolerance; and group 3 (n=72, comprising patients with type 2 diabetes mellitus. Body mass index was calculated, and measurement of oxLDL and oxLDL antibodies was performed. Results: Higher mean concentrations of oxLDL were found in the type 2 diabetes mellitus and impaired glucose tolerance groups (143.5±21.9 U/L and 108.7±23.7 U/L, respectively. The mean value for the control group was 73.5±27.5 U/L (P<0.001. Higher mean concentrations of anti-oxLDL antibodies were observed in the type 2 diabetes mellitus and impaired

  11. Oxidized Low-Density Lipoprotein Immune Complex Priming of the Nlrp3 Inflammasome Involves TLR and FcγR Cooperation and Is Dependent on CARD9

    Science.gov (United States)

    Rhoads, Jillian P.; Lukens, John R.; Wilhelm, Ashley J.; Moore, Jared L.; Mendez-Fernandez, Yanice; Kanneganti, Thirumala-Devi

    2017-01-01

    Oxidized low-density lipoprotein (oxLDL) is known to activate inflammatory responses in a variety of cells, especially macrophages and dendritic cells. Interestingly, much of the oxLDL in circulation is complexed to Abs, and these resulting immune complexes (ICs) are a prominent feature of chronic inflammatory disease, such as atherosclerosis, type-2 diabetes, systemic lupus erythematosus, and rheumatoid arthritis. Levels of oxLDL ICs often correlate with disease severity, and studies demonstrated that oxLDL ICs elicit potent inflammatory responses in macrophages. In this article, we show that bone marrow–derived dendritic cells (BMDCs) incubated with oxLDL ICs for 24 h secrete significantly more IL-1β compared with BMDCs treated with free oxLDL, whereas there was no difference in levels of TNF-α or IL-6. Treatment of BMDCs with oxLDL ICs increased expression of inflammasome-related genes Il1a, Il1b, and Nlrp3, and pretreatment with a caspase 1 inhibitor decreased IL-1β secretion in response to oxLDL ICs. This inflammasome priming was due to oxLDL IC signaling via multiple receptors, because inhibition of CD36, TLR4, and FcγR significantly decreased IL-1β secretion in response to oxLDL ICs. Signaling through these receptors converged on the adaptor protein CARD9, a component of the CARD9–Bcl10–MALT1 signalosome complex involved in NF-κB translocation. Finally, oxLDL IC–mediated IL-1β production resulted in increased Th17 polarization and cytokine secretion. Collectively, these data demonstrate that oxLDL ICs induce inflammasome activation through a separate and more robust mechanism than oxLDL alone and that these ICs may be immunomodulatory in chronic disease and not just biomarkers of severity. PMID:28130494

  12. Low-density lipoprotein accumulation within a carotid artery with multilayer elastic porous wall: fluid-structure interaction and non-Newtonian considerations.

    Science.gov (United States)

    Deyranlou, Amin; Niazmand, Hamid; Sadeghi, Mahmood-Reza

    2015-09-18

    Low-density lipoprotein (LDL), which is recognized as bad cholesterol, typically has been regarded as a main cause of atherosclerosis. LDL infiltration across arterial wall and subsequent formation of Ox-LDL could lead to atherogenesis. In the present study, combined effects of non-Newtonian fluid behavior and fluid-structure interaction (FSI) on LDL mass transfer inside an artery and through its multilayer arterial wall are examined numerically. Navier-Stokes equations for the blood flow inside the lumen and modified Darcy's model for the power-law fluid through the porous arterial wall are coupled with the equations of mass transfer to describe LDL distributions in various segments of the artery. In addition, the arterial wall is considered as a heterogeneous permeable elastic medium. Thus, elastodynamics equation is invoked to examine effects of different wall elasticity on LDL distribution in the artery. Findings suggest that non-Newtonian behavior of filtrated plasma within the wall enhances LDL accumulation meaningfully. Moreover, results demonstrate that at high blood pressure and due to the wall elasticity, endothelium pores expand, which cause significant variations on endothelium physiological properties in a way that lead to higher LDL accumulation. Additionally, results describe that under hypertension, by increasing angular strain, endothelial junctions especially at leaky sites expand more dramatic for the high elastic model, which in turn causes higher LDL accumulation across the intima layer and elevates atherogenesis risk.

  13. LDL-Apheresis: Technical and Clinical Aspects

    Directory of Open Access Journals (Sweden)

    Rolf Bambauer

    2012-01-01

    Full Text Available The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a levels, and coronary heart disease 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 five different LDL-apheresis systems available: cascade filtration or lipid filtration, immunoadsorption, heparin-induced LDL precipitation, dextran sulfate LDL adsorption, and the LDL hemoperfusion. There is a strong correlation between hyperlipidemia and atherosclerosis. Besides the elimination of other risk factors, in severe hyperlipidemia therapeutic strategies should focus on a drastic reduction of serum lipoproteins. Despite maximum conventional therapy with a combination of different kinds of lipid-lowering drugs, sometimes the goal of therapy cannot be reached. Hence, in such patients, treatment with LDL-apheresis is indicated. Technical and clinical aspects of these five different LDL-apheresis methods are shown here. There were no significant differences with respect to or concerning all cholesterols, or triglycerides observed. With respect to elevated lipoprotein (a levels, however, the immunoadsorption method seems to be most effective. The different published data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe hyperlipidemia refractory to maximum conservative therapy is effective and safe in long-term application.

  14. Italian multicenter study on low-density lipoprotein apheresis Working Group 2009 survey.

    Science.gov (United States)

    Stefanutti, Claudia; Morozzi, Claudia; Di Giacomo, Serafina

    2013-04-01

    We present results of the second survey of the Italian Multicenter Study on Low-Density Lipoprotein Apheresis (IMSLDLa-WG/2). The study involved 18 centers in 2009, treating 66 males and 35 females, mean age 47 ± 18 years. Mean age for initiation of drug treatment before low-density lipoprotein apheresis (LDLa) was 31 ± 18 years, mean age to the first LDLa was 37 ± 20 years and average duration of treatment was 9 ± 6 years. The techniques used included direct adsorption of lipids, dextran sulfate cellulose adsorption, heparin-mediated low-density lipoprotein (LDL) precipitation, cascade filtration, and plasma exchange. The mean treated plasma/blood volumes/session were 3127 ± 518 mL and 8666 ± 1384 mL, respectively. The average plasma volume substituted was 3500 ± 300 mL. Lipid therapy before LDLa included ezetimibe, statins, ω-3 fatty acids and fenofibrate. Baseline mean LDL cholesterol (LDLC) levels were 386 ± 223 mg/dL. The mean before/after apheresis LDLC level decreased by 67% from 250 ± 108 mg/dL (P = 0.05 vs. baseline) to 83 ± 37 mg/dL (P = 0.001 vs. before). Baseline mean Lipoprotein(a) [Lp(a)] level was 179 ± 136 mg/dL. Mean before/after apheresis Lp(a) level decreased by 71% from 133 ± 120 mg/dL (P = 0.05 vs. baseline) to 39 ± 44 mg/dL (P = 0.001 vs. before). Major and minor side effects occurred in 27 and 62 patients, respectively. Among patients with coronary artery disease (CAD), 62.3% had coronary angiography and 50.4% coronary revascularization before LDLa. Single vessel, double vessel and triple vessel CAD occurred in 19 (30.1%), 15 (23.8%) and 29 (46%) patients, respectively. Both CAD and extra-CAD occurred in 41.5%, 39% had hypertension, 9.9% were smokers, 9.9% consumed alcohol and 42% were physically active. Ischemic cardiovascular events were not observed in any patient over 9 ± 6 years of treatment. Two centers have also treated 34 patients (females: 17/males 17; no. sessions: 36; average plasma volume treated: 3000 mL) for

  15. Indications that paraoxonase-1 contributes to plasma high density lipoprotein levels in familial hypercholesterolemia.

    Science.gov (United States)

    van Himbergen, Thomas M; Roest, Mark; de Graaf, Jacqueline; Jansen, Eugène H J M; Hattori, Hiroaki; Kastelein, John J P; Voorbij, Hieronymus A M; Stalenhoef, Anton F H; van Tits, Lambertus J H

    2005-03-01

    HDL-associated paraoxonase type 1 (PON1) can protect LDL and HDL against oxidative modification in vitro and therefore may protect against cardiovascular disease. We investigated the effects of PON1 levels, activity, and genetic variation on high density lipoprotein-cholesterol (HDL-C) levels, circulating oxidized LDL (OxLDL), subclinical inflammation [high-sensitive C-reactive protein (Hs-CRP)], and carotid atherosclerosis. PON1 genotypes (L55M, Q192R, -107C/T, -162A/G, -824G/A, and -907G/C) were determined in 302 patients with familial hypercholesterolemia. PON1 activity was monitored by the hydrolysis rate of paraoxon, diazoxon, and phenyl acetate. PON1 levels, OxLDL, and Hs-CRP were determined using an immunoassay. The genetic variants of PON1 that were associated with high levels and activity of the enzyme were associated with higher HDL-C levels (P values for trend: 0.008, 0.020, 0.042, and 0.037 for L55M, Q192R, -107C/T, and -907G/C, respectively). In addition to the PON1 genotype, there was also a positive correlation between PON1 levels and activity and HDL-C (PON1 levels: r = 0.37, P < 0.001; paraoxonase activity: r = 0.23, P = 0.01; diazoxonase activity: r = 0.29, P < 0.001; arylesterase activity: r = 0.19, P = 0.03). Our observations support the hypothesis that both PON1 levels and activity preserve HDL-C in plasma.

  16. Genetic Loci Associated With Plasma Concentration of Low-Density Lipoprotein Cholesterol, High-Density Lipoprotein Cholesterol, Triglycerides, Apolipoprotein A1, and Apolipoprotein B Among 6382 White Women in Genome-Wide Analysis With Replication

    National Research Council Canada - National Science Library

    Chasman, Daniel I; Pare, Guillaume; Zee, Robert Y.L; Parker, Alex N; Cook, Nancy R; Buring, Julie E; Kwiatkowski, David J; Rose, Lynda M; Smith, Joshua D; Williams, Paul T; Rieder, Mark J; Rotter, Jerome I; Nickerson, Deborah A; Krauss, Ronald M; Miletich, Joseph P; Ridker, Paul M

    2008-01-01

    Genetic Loci Associated With Plasma Concentration of Low-Density Lipoprotein Cholesterol, High-Density Lipoprotein Cholesterol, Triglycerides, Apolipoprotein A1, and Apolipoprotein B Among 6382 White...

  17. The relationship between LDL oxidation and macrophage myeloperoxidase activity

    Institute of Scientific and Technical Information of China (English)

    武军驻; 刘艳红; 李小明; 陈丽达; 夏腊菊; 洪嘉玲

    2003-01-01

    Objective To explore low density lipoprotein (LDL) oxidation by macrophage myeloperoxidase (MPO) at molecular level.Methods Using a mouse macrophage model, we examined the relationship between LDL oxidation and macrophage MPO by measuring macrophage MPO activity, LDL oxidation products, MPO gene expression and cellular orientation of LDL oxidation. Results MPO gene expression increased to its maximum gradually when the concentration of LDL was increased, and then maintained at that level. NaN3 inhibied the elevation of MPO activity and LDL oxidation, which was LDL concentration-dependent. After the composition of macrophage membrane was roughly analyzed, it was determined that the contents of MPO and LDL in 5% sucrose were 7.667 and 21 times higher than those in 10% sucrose, respectively. Conclusion LDL is attached to the "microdomain" of the macrophage membrane in which LDL is oxidized by MPO.

  18. Asupan Gizi dan Kadar Low Density Lipoprotein Kolesterol Darah pada Kalangan Eksekutif

    Directory of Open Access Journals (Sweden)

    Ratna Djuwita

    2013-09-01

    Full Text Available Kemajuan teknologi dan ekonomi akhir-akhir ini memberikan dampak perubahan pola hidup yang menyebabkan pergeseran pola penyakit. Terlihat pada peningkatan penyakit kardiovaskular pada kelompok eksekutif usia produktif. Hiperkolesterolemia adalah satu-satunya faktor risiko yang dapat menyebabkan timbulanya aterosklerosis. Asupan gizi terkait erat dengan hiperkolesterolemia. Tujuan penelitian ini adalah mengetahui hubungan antara asupan gizi serta pola makan dengan hiperkolesterolemia pada kalangan eksekutif di Jakarta. Desain penelitian adalah potong lintang. Populasi penelitian adalah kelompok eksekutif Indonesia dewasa berusia 25-60 tahun. Sampel penelitian terdiri dari 280 responden ber- usia 25-60 tahun yang merupakan kelompok eksekutif dari beberapa perusahaan yang ada di sekitar Jakarta. Kadar low density lipoprotein (LDL kolesterol diperiksa dengan mengumpulkan sampel darah puasa. Asupan gizi dinilai dengan metode 24 hour recall dan pola makan dinilai dengan metode food frequency questionnaire (FFQ. Prevalensi hiperkolesterolemia pada kalangan eksekutif 46,1%. Prevalensi hiperkolesterolemia ini lebih tinggi secara bermakna pada laki-laki (50,9% dibandingkan pada perempuan(29,7%. Prevalensi hiperkolesterolemia cenderung lebih tinggi pada kalangan eksekutif yang berumur di atas 40 tahun, berpendidikan tinggi dan berpenghasilan tinggi. Asupan gizi, khususnya protein hewani serta frekuensi mengonsumsi sapi, memiliki hubungan dengan prevalensi hiperkolesterolemia. Asupan protein nabati, kekerapan mengonsumsi tempe, asupan serat serta kekerapan mengonsumsi sayur dan buah dapat dipertimbangkan sebagai makanan yang protektif atau dapat menurunkan kadar LDL kolesterol dalam darah. Technology and economical development recently poses impact toward changes of lifestyle which cause shifted of the disease pattern. The escalating of cardiovascular appears to be more common among executive productive age group. Hypercholesterolemia is the only risk

  19. The effect of low-density lipoprotein apheresis on ocular microcirculation in patients with hypercholesterolaemia: a pilot study.

    Science.gov (United States)

    Terai, Naim; Julius, Ulrich; Haustein, Michael; Spoerl, Eberhard; Pillunat, Lutz E

    2011-03-01

    To investigate the effect of low-density lipoprotein (LDL) apheresis on ocular microcirculation in patients with hypercholesterolaemia. Six patients with hypercholesterolaemia were included in this study. The diameter of retinal vessels was measured continuously with the retinal vessel analyser before and after LDL apheresis. After baseline assessment a monochromatic luminance flicker was applied to evoke retinal vasodilation. Flicker response was then analysed 50, 70 and 120 s after baseline measurement. In addition, cholesterol, high-density lipoprotein, LDL and triglyceride levels were obtained to find a possible correlation between changes in retinal vessel diameter and lipid metabolism before and after apheresis. The mean diameter of the arterioles at baseline was 107.6±2.1 μm and the mean diameter of the venules at baseline was 132.8±3.2 μm. The diameter of the arterioles after apheresis increased to 111.2±2.3 μm after 50 s, 113.2±2.6 μm after 70 s and 113.7±2.6 μm after 120 s, showing a trend to statistical significance at all time points (p=0.046, p=0.028 and p=0.028, respectively). The mean diameter of the venules after apheresis increased to 138.8±5.9 μm after 50 s, 139.8±6.3 μm after 70 s and 141.2±6.0 μm after 120 s, showing a trend to statistical significance at all time points (all p=0.028). Changes in retinal vascular diameter seem to be associated with the systemic effect of a single LDL apheresis. Vasodilatation of the arterioles and the venules improved after LDL apheresis, indicating an improvement of ocular perfusion in patients with hypercholesterolaemia.

  20. Low Density Lipoprotein Receptor Related Proteins as Regulators of Neural Stem and Progenitor Cell Function

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    Loic Auderset

    2016-01-01

    Full Text Available The central nervous system (CNS is a highly organised structure. Many signalling systems work in concert to ensure that neural stem cells are appropriately directed to generate progenitor cells, which in turn mature into functional cell types including projection neurons, interneurons, astrocytes, and oligodendrocytes. Herein we explore the role of the low density lipoprotein (LDL receptor family, in particular family members LRP1 and LRP2, in regulating the behaviour of neural stem and progenitor cells during development and adulthood. The ability of LRP1 and LRP2 to bind a diverse and extensive range of ligands, regulate ligand endocytosis, recruit nonreceptor tyrosine kinases for direct signal transduction and signal in conjunction with other receptors, enables them to modulate many crucial neural cell functions.

  1. Localized delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat brain using focused ultrasound.

    Science.gov (United States)

    Mulik, Rohit S; Bing, Chenchen; Ladouceur-Wodzak, Michelle; Munaweera, Imalka; Chopra, Rajiv; Corbin, Ian R

    2016-03-01

    Focused ultrasound exposures in the presence of microbubbles can achieve transient, non-invasive, and localized blood-brain barrier (BBB) opening, offering a method for targeted delivery of therapeutic agents into the brain. Low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) could have significant therapeutic value in the brain, since DHA is known to be neuroprotective. BBB opening was achieved using pulsed ultrasound exposures in a localized brain region in normal rats, after which LDL nanoparticles containing the fluorescent probe DiR (1,1'-Dioctadecyl-3,3,3',3'-Tetramethylindotricarbocyanine Iodide) or DHA were administered intravenously. Fluorescent imaging of brain tissue from rats administered LDL-DiR demonstrated strong localization of fluorescence signal in the exposed hemisphere. LDL-DHA administration produced 2 × more DHA in the exposed region of the brain, with a corresponding increase in Resolvin D1 levels, indicating DHA was incorporated into cells and metabolized. Histological evaluation did not indicate any evidence of increased tissue damage in exposed brain regions compared to normal brain. This work demonstrates that localized delivery of DHA to the brain is possible using systemically-administered LDL nanoparticles combined with pulsed focused ultrasound exposures in the brain. This technology could be used in regions of acute brain injury or as a means to target infiltrating tumor cells in the brain.

  2. Toll-like receptor 4 mediates inflammatory cytokine secretion in smooth muscle cells induced by oxidized low-density lipoprotein.

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    Ke Yang

    Full Text Available Oxidized low-density lipoprotein (oxLDL-regulated secretion of inflammatory cytokines in smooth muscle cells (SMCs is regarded as an important step in the progression of atherosclerosis; however, its underlying mechanism remains unclear. This study investigated the role of toll-like receptor 4 (TLR4 in oxLDL-induced expression of inflammatory cytokines in SMCs both in vivo and in vitro. We found that the levels of TLR4, interleukin 1-β (IL1-β, tumor necrosis factor-α (TNFα, monocyte chemoattractant protein 1 (MCP-1 and matrix metalloproteinase-2 (MMP-2 expression were increased in the SMCs of atherosclerotic plaques in patients with femoral artery stenosis. In cultured primary arterial SMCs from wild type mice, oxLDL caused dose- and time-dependent increase in the expression levels of TLR4 and cytokines. These effects were significantly weakened in arterial SMCs derived from TLR4 knockout mice (TLR4-/-. Moreover, the secretion of inflammatory cytokines was blocked by TLR4-specific antibodies in primary SMCs. Ox-LDL induced activation of p38 and NFκB was also inhibited in TLR4-/- primary SMCs or when treated with TLR4-specific antibodies. These results demonstrated that TLR4 is a crucial mediator in oxLDL-induced inflammatory cytokine expression and secretion, and p38 and NFκB activation.

  3. FUCOIDIN INHIBITS OXIDIZED LOW DENSITY LIPOPROTEIN FROM INDUCING HUMAN PERIPHERAL BLOOD MONOCYTE EXPRESSION OF PROINFLAMMATORY CYTOKINES mRNA

    Institute of Scientific and Technical Information of China (English)

    雷新军; 马爱群; 任冰稳; 耿涛; 张葳; 白玲

    2003-01-01

    Objective To study the significance of scavenger receptor class A(SR-A)in mediating human peripheral blood monocyte to uptake oxidized low density lipoprotein(OxLDL) and promoting the atherosclerotic immuno-pathological lesion in the local blood vessel. Methods With the Digoxenin-labeled Oligonucleotide-probes In situ Hybridization, this research investigated the effects of OxLDL on the mRNA expression of proinflammatory cytokines including MCP-1, bFGF, PDGF and IL-10 in the human peripheral blood monocyte and whether fucoidin, a peculiarly inhibitory ligand for SR-A, would influence this process. Results Monocyte was significantly increased the mRNA expression of MCP-1, bFGF, PDGF and IL-10 in a dose-dependent manner after incubating with OxLDL (10,15,20,25,30·mg·L-1, respectively)for 24 hours(P<0.001). Fucoidin(50,100,150,200,250·mg·mL-1, respectively)completely inhibited OxLDL(20·mg·L-1)from inducing monocyte the mRNA expression of above proinflammatory cytokines(P<0.001). Conclusion OxLDL can stimulate human peripheral blood monocyte to give expression to proinflammatory cytokines mRNA in a dose-dependent manner, while a peculiarly inhibitory ligand for SR-A-fucoidin has an obviously opposed role.

  4. [Consensus on objectives and action guidelines on low density lipoproteins-cholesterol control in very high risk cardiovascular patients].

    Science.gov (United States)

    Galve, Enrique; Guijarro-Herraiz, Carlos; Masana-Marin, Luis; Cordero-Fort, Alberto

    2016-01-01

    Cardiovascular disease is the leading cause of death in developed countries. Among cardiovascular disease risk factors one of the most relevant is low-density lipoprotein-associated cholesterol (LDL-c), but there is controversy about the methods used to control it. The aim was to obtain an expert opinion to clarify the most relevant issues regarding the control of dyslipidemia in very high cardiovascular risk patients. A survey with 55 items, stratified into 4 blocks: LDL-c as a therapeutic target, therapeutic goals, causes of the failure to achieve LDL-c goals, and recommendations to optimize their achievement, was addressed to 41 specialists (Cardiology and Internal Medicine) using the Delphi method to achieve professional consensus criteria. A high consensus was reached among all items, in line with the European recommendations. The panelists considered that the goal of 70mg/dl for LDL-c for high cardiovascular disease risk (mainly vascular disease, diabetes mellitus, and renal failure), using combined treatment when necessary. Lack of adherence and therapeutic inertia were considered the main reasons for treatment failure. The Spanish experts show an elevated consensus with the European recommendations, confirming the LDL-c control target of <70mg/dl. The simplification of the guidelines and the combined treatment may favor an improvement the achievement of lipid target goals. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  5. Single Low-Density Lipoprotein Apheresis Does Not Improve Vascular Endothelial Function in Chronically Treated Hypercholesterolemic Patients

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    Kevin D. Ballard

    2016-01-01

    Full Text Available Objective. To investigate vascular endothelial function (VEF responses to a single low-density lipoprotein (LDL apheresis session in hypercholesterolemic patients undergoing chronic treatment. Methods. We measured brachial artery flow-mediated dilation (FMD, plasma lipids, vitamin E (α- and γ-tocopherol, markers of oxidative/nitrative stress (malondialdehyde (MDA and nitro-γ-tocopherol (NGT, and regulators of NO metabolism (arginine (ARG and asymmetric dimethylarginine (ADMA prior to (Pre and immediately following (Post LDL apheresis and at 1, 3, 7, and 14 d Post in 5 hypercholesterolemic patients (52 ± 11 y. Results. Relative to Pre, total cholesterol (7.8±1.5 mmol/L and LDL-cholesterol (6.2±1.2 mmol/L were 61% and 70% lower (P<0.01, respectively, at Post and returned to Pre levels at 14 d. Brachial FMD responses (6.9 ± 3.6% and plasma MDA, ARG, and ADMA concentrations were unaffected by LDL apheresis. Plasma α-tocopherol, γ-tocopherol, and NGT concentrations were 52–69% lower at Post (P<0.01, and α-tocopherol remained 36% lower at 1 d whereas NGT remained 41% lower at d 3. Conclusions. Acute cholesterol reduction by LDL apheresis does not alter VEF, oxidative stress, or NO homeostasis in patients treated chronically for hypercholesterolemia.

  6. Single-Particle Tracking of Human Lipoproteins.

    Science.gov (United States)

    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.

  7. Effect of the antiestrogen ethamoxytriphetol (MER-25) on placental low density lipoprotein uptake and degradation in baboons

    Energy Technology Data Exchange (ETDEWEB)

    Henson, M.C.; Babischkin, J.S.; Pepe, G.J.; Albrecht, E.D.

    1988-05-01

    The present study determined if the decline in placental progesterone (P4) production that results from administration of the antiestrogen ethamoxytriphetol (MER-25) to pregnant baboons results from a change in placental low density lipoprotein (LDL) uptake and/or degradation. Pregnant baboons (Papio anubis) were untreated (n = 10) or received MER-25 (25 mg/kg BW, orally; n = 10) daily on days 140-170 of gestation (term, 184 days). Placentas were removed by cesarean section on day 170 of gestation, and villous tissue was dispersed with 0.1% collagenase at 37 C for 40 min. Placental cells (10(6)) were incubated in medium 199 (pH 7.2) for 12 h at 37 C with increasing amounts (5-100 micrograms) of (125I)LDL, with or without a 100-fold excess of unlabeled baboon LDL. Mean (+/- SE) peripheral serum P4 concentrations on days 140-170 of gestation were 51% lower (P less than 0.01) in MER-25-treated (5.7 +/- 0.3 ng/ml) than in untreated (11.6 +/- 0.5 ng/ml) baboons. The uptake of LDL was 56% lower (P less than 0.01) in placental cells from antiestrogen-treated (6.3 +/- 1.6 ng/micrograms cell protein) than in those from untreated (14.4 +/- 1.9 ng/micrograms cell protein) baboons. The dissociation constants for placental LDL uptake, as assessed by Scatchard analysis, however, were similar in untreated (0.80 microgram/ml) and MER-25-treated (0.76 microgram/ml) animals. The amount of (125I)LDL concomitantly degraded by cells from baboons that received MER-25 was 54% of that degraded by cells from untreated controls. The relative decline in LDL degradation by cells of antiestrogen-treated baboons was proportionate to the decline in overall LDL uptake. The results indicate, therefore, that antiestrogen treatment decreased the amount of placental LDL uptake, but did not change the affinity for the lipoprotein.

  8. Serum low-density lipoprotein levels, statin use, and cognition in patients with coronary artery disease

    Directory of Open Access Journals (Sweden)

    Rej S

    2016-11-01

    Full Text Available Soham Rej,1 Mahwesh Saleem,2,3 Nathan Herrmann,1,3 Anthi Stefatos,4 Allison Rau,3 Krista L Lanctôt1–3 1Department of Psychiatry, 2Department of Pharmacology and Toxicology, University of Toronto, 3Neuropsychopharmacology Research Group, Sunnybrook Health Sciences Centre, Toronto, ON, 4Faculty of Medicine, Université de Montréal, Montréal, QC, Canada Aim: Statins have been associated with decreased cognition due to the effects of low concentrations of low-density lipoprotein (LDL on brain function. This has remained controversial and is particularly relevant to patients with coronary artery disease (CAD, who have an increased risk of cognitive decline and are frequently prescribed statins. This study hypothesized that low concentration of LDL is associated with poor cognition in CAD patients using statins. It also explored the association between high-dose versus low-dose statins on cognition in this population. Patients and methods: Baseline cross-sectional data from a longitudinal study of 120 statin-using CAD patients were examined (mean statin duration 25±43 months. The main outcomes were measures of global cognition and cognitive domains, with poor cognition defined as cognitive performance ≤1 standard deviation below the population age and education adjusted means. A battery of cognitive tests was used to assess verbal memory, executive function, speed of processing, visuospatial memory, and global cognition. Adjusting for age, sex, education, and other covariates, multivariable logistic regression analyses assessed associations between low LDL levels (<1.5 mmol/L, statin use, and poor cognition. Results: LDL levels were not associated with global cognition or individual cognitive domains. High-dose statin use was associated with higher visuospatial memory (odds ratio, OR [95% confidence interval, CI] =0.12 [0.02–0.66], P=0.01 and executive functioning (OR =0.25 [0.06–0.99], P=0.05. This effect was independent of covariates

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

    Science.gov (United States)

    Ducobu, J

    1997-02-01

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

  10. Mechanisms of Cellular Uptake of Thrombin-Antithrombin II Complexes Role of the Low-Density Lipoprotein Receptor-Related Protein as a Serpin-Enzyme Complex Receptor.

    Science.gov (United States)

    Strickland, D K; Kounnas, M Z

    1997-01-01

    Serine proteinase inhibitors (serpins) such as antithrombin III inhibit target proteinases by forming a stable complexwith the enzyme. Once formed, several serpin-enzyme complexes (SECs) are removed from the circulation by a receptor, termed the SEC receptor, that is present in the liver. Until recently, the identity of this clearance receptor remained unknown; however, data are now available that strongly implicates one member of the low-density lipoprotein (LDL) receptor family as a candidate for the SEC receptor. This receptor, known as the LDL receptor-related protein (LRP), is a prominent liver receptor that is known to bind numerous ligands that include proteinase-inhibitor complexes, matrix proteins, and certain apolipoprotein E- and lipoprotein lipase-enriched lipoproteins. © 1997, Elsevier Science Inc. (Trends Cardiovasc Med 1997;7:9-16).

  11. Meta-Analysis of Low Density Lipoprotein Receptor (LDLR rs2228671 Polymorphism and Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Huadan Ye

    2014-01-01

    Full Text Available Low density lipoprotein receptor (LDLR can regulate cholesterol metabolism by removing the excess low density lipoprotein cholesterol (LDL-C in blood. Since cholesterol metabolism is often disrupted in coronary heart disease (CHD, LDLR as a candidate gene of CHD has been intensively studied. The goal of our study is to evaluate the overall contribution of LDLR rs2228671 polymorphism to the risk of CHD by combining the genotyping data from multiple case-control studies. Our meta-analysis is involved with 8 case-control studies among 7588 cases and 9711 controls to test the association between LDLR rs2228671 polymorphism and CHD. In addition, we performed a case-control study of LDLR rs2228671 polymorphism with the risk of CHD in Chinese population. Our meta-analysis showed that rs2228671-T allele was significantly associated with a reduced risk of CHD (P=0.0005, odds ratio (OR = 0.83, and 95% confidence interval (95% CI = 0.75–0.92. However, rs2228671-T allele frequency was rare (1% and was not associated with CHD in Han Chinese (P=0.49, suggesting an ethnic difference of LDLR rs2228671 polymorphism. Meta-analysis has established rs2228671 as a protective factor of CHD in Europeans. The lack of association in Chinese reflects an ethnic difference of this genetic variant between Chinese and European populations.

  12. Is the Ratio of Antibodies Against Oxidized LDL to Oxidized LDL an Indicator of Cardiovascular Risk in Psoriasis?

    Directory of Open Access Journals (Sweden)

    Medha Rajappa

    2016-09-01

    Full Text Available Objectives: Psoriasis is a chronic inflammatory skin disease. Chronic inflammation results in increased oxidative stress and oxidizes lipoproteins, increasing their atherogenicity. This study sought to estimate the levels of oxidized low-density lipoprotein (ox-LDL and antibodies against oxidized LDL (anti-ox-LDL and compute the ratio of anti-ox-LDL/ox-LDL as a single composite parameter to assess the oxidative lipoprotein burden as an indicator of cardiovascular risk in patients with psoriasis. Methods: This cross-sectional study included 45 patients with psoriasis. All patients were given a psoriasis severity index score and their ox-LDL and anti-ox-LDL estimated using ELISA. Results: The results of this study show an elevation in the ratio of anti-ox-LDL to ox-LDL in patients with psoriasis, which initiate and perpetuate the pathogenesis of psoriasis and its comorbidity, atherosclerotic cardiovascular disease. Conclusions: Our results suggest that an elevated ratio of anti-ox-LDL/ox-LDL can serve as a composite parameter reflecting the total oxidative lipoprotein burden and cardiovascular risk in psoriasis patients.

  13. Switching from atorvastatin to rosuvastatin lowers small, dense low-density lipoprotein cholesterol levels in Japanese hypercholesterolemic patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Bando, Yukihiro; Toyama, Hitomi; Kanehara, Hideo; Hisada, Azusa; Okafuji, Kazuhiro; Toya, Daisyu; Tanaka, Nobuyoshi

    2016-01-01

    This open-label, randomized, parallel-group comparative study compared the efficacy of rosuvastatin (5mg/day) and atorvastatin (10mg/day) for reduction of small dense low-density lipoprotein cholesterol (sd LDL-C) levels in Japanese patients with type 2 diabetes mellitus (T2DM). Patients with T2DM and hypercholesterolemia with detectable sd LDL-C after receiving 10mg/day atorvastatin for ≥ 24 weeks were randomly assigned to receive rosuvastatin (5mg/day; switched treatment) or atorvastatin (10mg/day; continued treatment) for 12 weeks. The primary endpoints were changes in sd LDL-C levels and sd LDL-C/total LDL-C ratio evaluated using the LipoPhor AS(®) system. There were no significant percent changes from baseline for LDL-C levels between the switched (n=55) and the continued treatment group (n=56). However, the former group exhibited a statistically significant reduction from baseline of sd LDL-C levels, sd LDL-C/total LDL-C ratio compared with the latter group (-3.8 mg/dL vs. -1.4 mg/dL, p=0.014; -2.3% vs. -0.6%, p=0.004, respectively). Multiple regression analysis among all subjects revealed that independent factors contributing to the reduction in sd LDL-C levels were a change in LDL-C (p=0.003) and triglyceride (TG) levels (p=0.006), treatment group (the switched group=1, the continued group=0; standard coefficient=-1.2, p=0.034) and baseline glycated hemoglobin A1c (HbA1c) (p=0.045), respectively. Switching from 10mg atorvastatin to 5mg rosuvastatin may be a useful therapeutic option to reduce sd LDL-C levels in Japanese hypercholesterolemic patients with T2DM. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Elevated levels of oxidized low-density lipoprotein correlate positively with C-reactive protein in patients with acute coronary syndrome.

    Science.gov (United States)

    Zhang, Ya-chen; Wei, Jing-jing; Wang, Fei; Chen, Man-tian; Zhang, Mao-zhen

    2012-03-01

    The relationship between oxidized low-density lipoprotein (Ox-LDL) and C-reactive protein (CRP) in patients with acute coronary syndrome (ACS) is unknown. We, therefore, measured serum levels of Ox-LDL and high-sensitivity (hs)-CRP in 90 ACS patients, 45 stable angina pectoris (SAP) patients, and 66 healthy controls using sandwich ELISA. ACS patients were subdivided into: (1) acute myocardial infarction (AMI; n = 45); (2) unstable angina pectoris (UAP; n = 45) groups. In AMI patients, Ox-LDL (177.5 mmol/l) and hs-CRP (25.40 mg/l) levels were significantly higher (P LDL:107.5 mmol/l, hs-CRP:10.7 mg/l) and SAP (Ox-LDL:82.3 mmol/l, hs-CRP:2.10 mg/l) patients as well as controls (Ox-LDL:41.4 mmol/l, hs-CRP:1.76 mg/l). Ox-LDL/hs-CRP levels in UAP patients were significantly higher (P LDL and CRP (r = 0.622; P HDL, and LDL cholesterol did not differ among these patient groups. In conclusion, our data show that Ox-LDL and hs-CRP levels correlate positively in ACS patients, supporting the hypothesis that Ox-LDL and CRP may play a direct role in promoting the inflammatory component of atherosclerosis in these individuals. We suggest that Ox-LDL/CRP elevated levels may serve as markers of the severity of the disease in evaluation and management of ACS patients.

  15. Anthocyanins increase low-density lipoprotein and plasma cholesterol and do not reduce atherosclerosis in Watanabe Heritable Hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Nielsen, I. L. F.; Rasmussen, S.E.; Mortensen, Alicja;

    2005-01-01

    Anthocyanin-rich beverages have shown beneficial effects on coronary heart disease in epidemiological and intervention studies. In the present study, we investigated the effect of black currant anthocyanins on atherosclerosis. Watanabe Heritable Hyperlipidemic rabbits (n = 61) were fed either...... a purified anthocyanin fraction front black currants, a black currant juice, probucol or control diet for 16 weeks. Purified anthocyanins significantly increased plasma cholesterol and low-density lipoprotein (LDL) cholesterol. Intake of black currant juice had no effect on total plasma cholesterol......, but lowered very-low-density lipoprotein (VLDL) cholesterol significantly. There were no significant effects of either purified anthocyanins or black currant juice on aortic cholesterol or development of atherosclerosis after 16 weeks. Probucol had no effect on plasma cholesterol but significantly lowered...

  16. Genetic and metabolic influences on LDL subclasses

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, R.M. [Lawrence Berkeley Lab., CA (United States); Rotter, J.I.; Lusis, A.J. [Univ. of California, Los Angeles, CA (United States)

    1994-09-01

    Genetic and environmental factors influence LDL particle size and density, and expression of an atherogenic lipoprotein phenotype (ALP) characterized by predominance of small, dense LDL particles. Linkage of ALP the LDL receptor locus has been reported previously. Quantitative sib-pair relative-pair linkage methodologies were used to test for linkage of LDL particle size to candidate loci in 25 large pedigrees with familial coronary artery disease. Linkage to the LDL receptor gene locus was confirmed (p=0.008). Evidence was also obtained for linkage to the genes for apoCIII, cholesteryl ester transfer protein, and manganese superoxide dismutase. The results suggest multiple genetic determinants of LDL particle size that may involve different metabolic mechanisms giving rise to small, dense LDL and increased atherosclerosis risk.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: SR-B1 (scavenger receptor class B type 1), encoded by the gene SCARB1, is a lipoprotein receptor that binds both high-density lipoprotein (HDL) and low-density lipoprotein. We reported that SR-B1 is also a receptor for lipoprotein (a) (Lp(a)), mediating cellular uptake of Lp(a) in vitro...

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

    Science.gov (United States)

    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.

  19. EC,ASMC and Macrophage Oxidize Human Low Density Lipoprotein

    Institute of Scientific and Technical Information of China (English)

    Dai Zhao-ming; Wu Jun-zhu; Li Xiao-ming; Chen Li-da; Hong Jia-ling

    2003-01-01

    To investigate the mechanism of LDL oxidation in vivo , LDL was incubated with endothelium cell (EC),artery smooth muscle cell (ASMC) and macrophage, and then the change of myeloperoxidase (MPO) activity in cell and medium and the oxidation of LDL by those three cells were assessed. The result showed that LDL promoted the activity of cellular and secretive myeloperoxidase which was concentration-dependent on LDL; with elevation of MPO activity, oxidation of LDL intensified, which was expressed by the formation of conjugated dienes and the elevation of thiobarbituric acid teactive substance (TBARS). Macrophage's MPO activity went up with the increase of LDL at both low and high concentration; EC's MPO activity went up with the increase of LDL only at high concentration and ASMC's MPO activity wasn't sensitive to LDL concentration change. The results suggest that Macrophage might be crucial to the oxidation of LDL in vivo, in which MPO might play an important role.

  20. EC,ASMC and Macrophage Oxidize Human Low Density Lipoprotein

    Institute of Scientific and Technical Information of China (English)

    Dai; Zhao-ming; Wu; Jun-zhu; 等

    2003-01-01

    To investigate the mechanism of LDL oxidation in vivo, LDL was incubated with endothelium cell (EC),artery smooth muscle cell (ASMC) and macrophage, and then the change of myeloperoxidase (MPO) activity in cell and medium and the oxidation of LDL by those three cells were assessed. The result showed that LDL promoted the activity of cellular and secretive myeloperoxidase which was concentration-dependent on LDL; with elevation of MPO activity, oxidation of LDL intensified, which was expressed by the formation of conjugated dienes and the elevation of thiobarbituric acid teactive substance (TBARS). Macrophage's MPO activity went up with the increase of LDL at both low and high concentration; EC's MPO activity went up with the increase of LDL only at high concentration and ASMC's MPO activity wasn't sensitive to LDL concentration change. The results LDL in vivo, in which MPO might play an important role.

  1. Changes in chemical composition and physico-chemical properties of chick low- and high-density lipoproteins induced by supplementation of coconut oil to the diet.

    Science.gov (United States)

    Talavera, E M; Zafra, M F; Gil-Villarino, A; Pérez, M I; Alvarez-Pez, J M; García-Peregrín, E

    1997-06-01

    Supplementation of coconut oil to the diet for 1-2 weeks produced a significant hypercholesterolemia in 14-day-old chicks. Changes in plasma fatty acid composition correlated positively with those of diets. In this study, we have shown a different response of low- and high-density lipoprotein (LDL and HDL) fractions to dietary saturated fat (coconut oil) rich in lauric and myristic acids. Although all the components of these particles seemed to increase, the percentages of increases found in total (TC), free (FC) and esterified cholesterol (EC) were higher in LDL than in HDL. TC/phospholipid (PL) ratio, considered as an inverse index of membrane fluidity, also increased with the dietary regimen in LDL, while no significant differences were found in HDL. These results suggest that supplementation of coconut oil to the diet decreased the fluidity of LDL. The EC/triglycerides (TG) ratio was also significantly increased in LDL, corroborating the main atherogenic function of this lipoprotein fraction in response to lauric and myristic acids. We have also estimated the lipidic order parameter, S, from the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH)-labelled low- and high-density lipoproteins. In LDL, temperature dependence of S shows two different behaviour zones at about 20 degrees C. In HDL, the plot of S values versus T is linear. DPH anisotropy and S increased in both LDL and HDL from treated chicks. This increase becomes more evident as temperature rises and also with dietary treatment.

  2. Oxidized low-density lipoprotein alters the effect of matrix stiffness on the formation of endothelial networks and capillary lumens

    Science.gov (United States)

    2013-01-01

    Abstract Formation of new blood vessels is essential for vascular repair and remodeling, and it is known that biomechanical properties of extracellular matrix play a major role in this process. Our earlier studies have also shown that exposing endothelial cells to oxidized modification of low-density lipoproteins (oxLDL) increases endothelial stiffness and facilitates their ability to form cellular networks, suggesting that it facilitates endothelial angiogenic potential. The goal of this study, therefore, was to test the interrelationship between matrix stiffness and oxLDL in the regulation of angiogenesis. Our results show that, as expected, an increase in matrix stiffness inhibited endothelial network formation and that exposure to oxLDL significantly facilitated this process. We also show, however, that oxLDL-induced facilitation of endothelial networks was observed only in stiff (3 mg/mL) but not in soft (1 mg/mL) collagen gels, resulting in blunting the effect of matrix stiffness. Also unexpectedly, we show that an increase in matrix stiffness results in a significant increase in the number of capillary lumens that are formed by single cells or pairs of cells, suggesting that while endothelial connectivity is impaired, formation of single-cell lumens is facilitated. oxLDL facilitates lumen formation, but this effect is also matrix dependent and is observed only in soft gels and not in stiff gels. Finally, an increase in both matrix stiffness and oxLDL exposure results in changes in capillary morphology, with the formation of larger capillary lumens. Overall, our study suggests that oxLDL plays an important role in formation of new capillaries and their morphology and that this effect is critically dependent on the extracellular environment’s compliance, thereby underlining the importance of the interdependence of these parameters. PMID:24618546

  3. Variability of low-density lipoprotein cholesterol response with different doses of atorvastatin, rosuvastatin, and simvastatin: results from VOYAGER.

    Science.gov (United States)

    Karlson, Björn W; Wiklund, Olov; Palmer, Michael K; Nicholls, Stephen J; Lundman, Pia; Barter, Philip J

    2016-10-01

    Patient response to statin treatment is individual and varied. As a consequence, when using a specific-dose approach, as recommended in the 2013 American College of Cardiology/American Heart Association guideline, there will be a range of reductions in the concentration of low-density lipoprotein cholesterol (LDL-C). The aim of this study was to use individual patient data from the VOYAGER meta-analysis to determine the extent of the variability in LDL-C reduction in response to treatment across the recommended doses of different statins. The percentage change from baseline in LDL-C was calculated using individual subject data collected from 32 258 patients treated with atorvastatin 10-80 mg, rosuvastatin 5-40 mg, or simvastatin 10-80 mg. The percentage change in LDL-C for each patient was then used to generate waterfall plots that demonstrated the extent of the variability in response to treatment at all doses of the three statins. The standard deviation of LDL-C reduction for all statins and doses ranged from 12.8 to 17.9%. The percentage of patients experiencing a suboptimal response (<30% reduction in LDL-C) ranged from 5.3 to 53.3%. These results indicate that there is considerable individual variation in the LDL-C reduction at all doses of simvastatin, atorvastatin, and rosuvastatin. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

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

    Science.gov (United States)

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

    2017-05-04

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

  5. Accumulation of Oxidized Low-Density Lipoprotein in Psoriatic Skin and Changes of Plasma Lipid Levels in Psoriatic Patients

    Directory of Open Access Journals (Sweden)

    Nilgun Solak Tekin

    2007-01-01

    Full Text Available Background. Psoriasis is a chronic inflammatory skin disease characterized by an accelerated turnover of epidermal cells and an incomplete differentiation in epidermis with lesion. However, the exact etiology of psoriasis is unknown. Abnormalities in essential fatty acid metabolism, free radical generation, lipid peroxidation, and release of lymphokines have been proposed. Objective. Our purpose was to evaluate the plasma lipids and oxidized low-density lipoprotein accumulation in psoriatic skin lesion in order to ascertain the possible participation of oxidative stress and oxidative modification of lipids in pathogenesis of psoriasis. Methods. The study group included 84 patients with psoriasis, and 40 sex- and age-matched healthy volunteers. Blood lipid profile was determined. Psoriatic and nonlesional skin samples of psoriatic patients were evaluated for the presence of oxidized low-density lipoprotein by using an immune-fluorescent staining method. Results. The mean levels of lipids (total cholesterol, triglyceride, and LDL cholesterol in patients with psoriasis were found to be significantly higher than those of healthy subjects. Psoriatic skins were shown positive oxidized low-density lipoprotein staining. There was no staining in nonlesional skin samples of the same individuals. Conclusion. Lipid peroxidation mediated by free radicals is believed to be one of the important causes of cell membrane destruction and cell damage. This study shows for the first time the accumulation of oxidized low-density lipoprotein in psoriatic skin lesion. We believe that accumulation of ox-LDL in psoriatic skin may have an important role in the immune-inflammatory events that result in progressive skin damage.

  6. Comparative study of non-high density lipoproteins cholesterol level and lipid profile in pre-diabetic and diabetic patients.

    Science.gov (United States)

    Banu, Shaheena; Jabir, Nasimudeen R; Manjunath, Nanjappa C; Firoz, C K; Kamal, Mohammad A; Khan, Mohammad S; Tabrez, Shams

    2014-04-01

    The present study compares the role and significance of non-high density lipoproteins (non-HDL) cholesterol level in pre-diabetic and diabetic patients. This study also compares non-HDL cholesterol level between males and females and with different age groups as well. An observational study was conducted among 3830 randomly selected individuals to envisage the association of non-HDL cholesterol and other lipid parameters with age, gender, and diabetic status. On the basis of health status, the subjects were classified as diabetic, pre-diabetic and normal. Fasting blood samples were collected and analyzed on Roche p-800 modular system. Total cholesterol, high density lipoproteins (HDL), low density lipoproteins (LDL) and fasting triglycerides were also measured. From the above mentioned parameters, the level of non-HDL cholesterol level was also calculated. Significant association was observed with non-HDL cholesterol level and all other studied lipid parameters (total cholesterol, HDL, LDL and triglycerides) compared with age and gender of the subjects studied. Moreover, the calculated non-HDL level, total cholesterol and triglycerides were found to be significantly co-related with diabetic status of the patients involved in the study. However, HDL and LDL values did not show any significant association with diabetic status of the patients. In this study, we found that age and gender of the studied subjects are associated with non-HDL cholesterol. Moreover, our data clearly indicates the positive association of non-HDL cholesterol level with pre-diabetic and diabetic status of the patients. Based on our study, we recommend estimation of non-HDL level in routine clinical practice to differentiate pre-diabetic and diabetic patients.

  7. 低密度脂蛋白体外去除方法及材料概述%Review of Low Density Lipoprotein Apheresis Methods and Adsorbents

    Institute of Scientific and Technical Information of China (English)

    赵连江; 李伟; 孙康

    2012-01-01

    心血管疾病是危害人类健康的主要疾病之一,它与血液中低密度脂蛋白(LDL)浓度过高引发的动脉粥样硬化密切相关.因此,对LDL的去除可以有效地预防与治疗心血管疾病.近年来,LDL的体外去除法因其直接高效的特点广受重视.LDL体外去除法的核心-LDL吸附材料也得到了迅速的发展.目前已制备了多种LDL吸附材料,其中有些已经应用于临床.综述了LDL体外去除法及LDL吸附材料的研究进展.%Cardiovascular disease is a major threaten to the human health, and it has a close relationship with atherosclerosis which is caused by the abnormally high concentration of low density lipoprotein ( LDL) in human blood, so the removal of LDL would effectively prevent and treat the cardiovascular disease. LDL apheresis methods have attracted more attention in recent years for its efficiency and directness in LDL removal, and LDL adsorbents have been subsequently developed. Some of these adsorbents are applied in clinic already. The research progress of LDL apheresis methods and LDL adsorbents are reviewed.

  8. Association of fasting and nonfasting serum triglycerides with cardiovascular disease and the role of remnant-like lipoproteins and small dense LDL.

    Science.gov (United States)

    Stalenhoef, Anton F H; de Graaf, Jacqueline

    2008-08-01

    The magnitude of the contribution of serum triglycerides to cardiovascular disease risk and the mechanisms by which triglyceride-rich lipoproteins exert their effect on the vascular wall are largely unknown. Postprandial lipemia likewise has been linked to atherosclerosis, but large prospective studies assessing the magnitude of this association are also lacking. Hypertriglyceridemia is characterized by the presence of cholesterol-rich remnant-like lipoproteins and small dense LDL particles, both of which are believed to contribute to cardiovascular disease risk. Several large prospective cohort studies and a meta-analysis have been published recently, investigating the association of fasting and nonfasting serum triglycerides with cardiovascular disease. Fasting triglycerides increase the adjusted hazard ratios for cardiovascular disease risk 1.7 x (comparing upper with lower tertile), and nonfasting levels around 2.0 x. Measurement of nonfasting triglycerides may be more feasible and more informative, but standardization of a test meal is necessary. For clinical practice, the concentration of the atherogenic lipoprotein subfractions in hypertriglyceridemia may be reflected best by measuring apolipoprotein B. Nonfasting triglyceride levels may replace fasting levels in assessing cardiovascular disease risk once standard reference values have been developed. Several atherogenic lipoprotein subfractions can be measured by including apolipoprotein B in addition to HDL, (nonfasting) triglycerides and LDL cholesterol.

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

    Science.gov (United States)

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

    2013-12-01

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

  10. Recombinant hepatitis C virus-envelope protein 2 interactions with low-density lipoprotein/CD81 receptors

    Directory of Open Access Journals (Sweden)

    Ana Carolina Urbaczek

    2015-06-01

    Full Text Available Hepatitis C virus (HCV envelope protein 2 (E2 is involved in viral binding to host cells. The aim of this work was to produce recombinant E2B and E2Y HCV proteins in Escherichia coli and Pichia pastoris, respectively, and to study their interactions with low-density lipoprotein receptor (LDLr and CD81 in human umbilical vein endothelial cells (HUVEC and the ECV304 bladder carcinoma cell line. To investigate the effects of human LDL and differences in protein structure (glycosylated or not on binding efficiency, the recombinant proteins were either associated or not associated with lipoproteins before being assayed. The immunoreactivity of the recombinant proteins was analysed using pooled serum samples that were either positive or negative for hepatitis C. The cells were immunophenotyped by LDLr and CD81 using flow cytometry. Binding and binding inhibition assays were performed in the presence of LDL, foetal bovine serum (FCS and specific antibodies. The results revealed that binding was reduced in the absence of FCS, but that the addition of human LDL rescued and increased binding capacity. In HUVEC cells, the use of antibodies to block LDLr led to a significant reduction in the binding of E2B and E2Y. CD81 antibodies did not affect E2B and E2Y binding. In ECV304 cells, blocking LDLr and CD81 produced similar effects, but they were not as marked as those that were observed in HUVEC cells. In conclusion, recombinant HCV E2 is dependent on LDL for its ability to bind to LDLr in HUVEC and ECV304 cells. These findings are relevant because E2 acts to anchor HCV to host cells; therefore, high blood levels of LDL could enhance viral infectivity in chronic hepatitis C patients.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  12. Linkage of the cholesterol 7α-hydroxylase gene and low-density lipoprotein cholesterol conditional on apolipoprotein E association: the National Heart, Lung, and Blood Institute Family Heart Study

    Institute of Scientific and Technical Information of China (English)

    Jing-Ping Lin; Richard H. Myers; Laura Almasy; Hilary H. Coon; Donna K. Arnett; Yuling Hong; Steven C. Hunt

    2005-01-01

    Background Genetic factors account for approximately 50% of the individual variation in plasma low-density lipoprotein cholesterol (LDL-C) concentrations in the general population. Several candidate genes have been proposed but their relative contributions to the variance in LDL-C are not known, except for apolipoprotein E (apoE). We report here an investigation of the relationship between LDL-C and cholesterol 7α-hydroxylase (CYP7), as well as apoE and low-density lipoprotein receptor (LDLR), three pivotal genes in LDL metabolism. Methods Our study population included more than 200 nuclear families with increased coronary heart disease (CHD) risk from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Variance-component linkage methods, a measured genotype approach, and a variance-component linkage analysis conditional on a measured genotype association were used. Results The results showed significant linkage between a genetic determinant of plasma LDL-C concentrations and a polymorphism near CYP7 with its allelic variation accounting for 27% of the total LDL-C variation. There is significant association between plasma LDL-C concentrations and apoE genotypes. Conditional on the apoE association, the total LDL-C variation accounted by allelic variation of a polymorphism near CYP7 was increased significantly.Conclusion Our results suggest the apoE and CYP7 may be two important genes accounting for the genetic variation of plasma LDL-C concentrations in a population with cardiovascular diseases.

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

    Science.gov (United States)

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

    2012-11-01

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

  14. An Inulin-Enriched Soy Drink and Its Lowering Effect on Oxidized Low Density Lipoproteins in Healthy Volunteers

    Directory of Open Access Journals (Sweden)

    Liutkevičius Algirdas

    2016-03-01

    Full Text Available Due to selection of appropriate ingredients and parameters, a microbiologically-safe drink enriched with soy protein isolate (SPI and prebiotic dietary fiber inulin with high scores of acceptability was produced. The results of medical nutrition survey showed that on the 21 day of using drink the level of oxidized low density lipoproteins (LDL significantly decreased while the other biochemical parameters of blood of healthy patients as compared to the control tests remained unchanged. As well there was no apparent impact on the intestinal microflora balance of recipients established.

  15. Glycosaminoglycan-lipoprotein interaction.

    Science.gov (United States)

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

    2001-10-01

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

  16. [New mutations in low-density lipoprotein receptor gene in familial hypercholesterolemia patients from Petrozavodsk].

    Science.gov (United States)

    Komarova, T Yu; Golovina, A S; Grudinina, N A; Zakharova, F M; Korneva, V A; Lipovetsky, B M; Serebrenitskaya, M P; Konstantinov, V O; Vasilyev, V B; Mandelshtam, M Yu

    2013-06-01

    Using an automated fluorescent single-strand conformation polymorphism (SSCP) analysis of the entire coding region, promoter zone, and exon-intron junctions of the low-density lipoprotein (LDL) receptor gene, we examined 80 DNA samples of patients with familial hypercholesterolemia (FH) from Petrozavodsk. We revealed mutations that might cause FH in five probands, including FH-North Karelia (c.925-931del7) mutation and four previously unknown mutations. These novel mutations included a transversion (c.618T>G (p.S206R), one nucleotide insertion c.195_196insT (p.FsV66:D129X), a complex gene rearrangement c.192del10/ins8 (p.FsS65:D129X), and a single nucleotide deletion c.2191delG (p.FsV731:V736X). Three out of four novel mutations produce an open reading frame shift and the premature termination of translation. An analysis of the cDNA sequence of the LDL receptor showed that this might result in the formation of a transmembrane-domain-deficient receptor that is unable to bind and internalize the ligand. Our results suggest the absence of a strong founder effect associated with FH in the Petrozavodsk population.

  17. Low-density lipoprotein peptide-combined DNA nanocomplex as an efficient anticancer drug delivery vehicle.

    Science.gov (United States)

    Zhang, Nan; Tao, Jun; Hua, Haiying; Sun, Pengchao; Zhao, Yongxing

    2015-08-01

    DNA is a type of potential biomaterials for drug delivery due to its nanoscale geometry, loading capacity of therapeutics, biocompatibility, and biodegradability. Unfortunately, DNA is easily degraded by DNases in the body circulation and has low intracellular uptake. In the present study, we selected three cationic polymers polyethylenimine (PEI), hexadecyl trimethyl ammonium bromide (CTAB), and low-density lipoprotein (LDL) receptor targeted peptide (RLT), to modify DNA and improve the issues. A potent anti-tumor anthracycline-doxorubicin (DOX) was intercalated into DNA non-covalently and the DOX/DNA was then combined with PEI, CTAB, and RLT, respectively. Compact nanocomplexes were formed by electrostatic interaction and could potentially protect DNA from DNases. More importantly, RLT had the potential to enhance intracellular uptake by LDL receptor mediated endocytosis. In a series of in vitro experiments, RLT complexed DNA enhanced intracellular delivery of DOX, increased tumor cell death and intracellular ROS production, and reduced intracellular elimination of DOX. All results suggested that the easily prepared and targeted RLT/DNA nanocomplexes had great potential to be developed into a formulation for doxorubicin with enhanced anti-tumor activity.

  18. Dietary corn fractions reduce atherogenesis in low-density lipoprotein receptor knockout mice.

    Science.gov (United States)

    Masisi, Kabo; Le, Khuong; Ghazzawi, Nora; Moghadasian, Mohammed H; Beta, Trust

    2017-01-01

    Accumulating evidence has suggested that intake of whole grains is a protective factor against pathogenesis of coronary artery disease. The exact mechanisms, however, are still not clearly understood. In this study, we hypothesized that adequate intake of corn fractions (aleurone, endosperm and germ) can modify lipid profiles in relation to atherosclerotic lesion development in low-density lipoprotein receptor knockout (LDLr-KO) mice. The purpose of the present study was to investigate the potential cardiovascular benefits of corn fractions in LDLr-KO mice through a number of biomarkers including lipid profile, and morphologic and morphometrical analysis of atherosclerotic lesions in aortic root. Four groups of male LDLr-KO mice were fed with the experimental diets supplemented with (3 treated) or without (control) 5% (wt/wt) of each of corn fractions for 10 weeks. All diets were supplemented with 0.06% (wt/wt) cholesterol. Compared with mice in the control group, atherosclerotic lesions in the aortic roots were significantly reduced (P=.003) in the mice that were fed diet supplemented with aleurone and germ fractions. This effect was associated with significant reductions in plasma total (P=.02) and LDL (P=.03) cholesterol levels, and an increase in fecal cholesterol excretion (P=.04). Furthermore, abdominal fat mass was significantly reduced by consumption of aleurone (P=.03). In summary, the consumption of aleurone and germ may help attenuate atherosclerosis by reducing plasma total and LDL cholesterol levels.

  19. Phytosterols, Phytostanols, and Lipoprotein Metabolism

    Directory of Open Access Journals (Sweden)

    Helena Gylling

    2015-09-01

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

  20. Effect of 6-month supervised exercise on low-density lipoprotein apolipoprotein B kinetics in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Stolinski, Michael; Alam, Saima; Jackson, Nicola C; Shojaee-Moradie, Fariba; Pentecost, Claire; Jefferson, William; Christ, Emmanuel R; Jones, Richard H; Umpleby, A Margot

    2008-11-01

    Although low-density lipoprotein (LDL) cholesterol is often normal in patients with type 2 diabetes mellitus, there is evidence for a reduced fractional catabolic rate and consequently an increased mean residence time (MRT), which can increase atherogenic risk. The dyslipidemia and insulin resistance of type 2 diabetes mellitus can be improved by aerobic exercise, but effects on LDL kinetics are unknown. The effect of 6-month supervised exercise on LDL apolipoprotein B kinetics was studied in a group of 17 patients with type 2 diabetes mellitus (mean age, 56.8 years; range, 38-68 years). Patients were randomized into a supervised group, who had a weekly training session, and an unsupervised group. LDL kinetics were measured with an infusion of 1-(13)C leucine at baseline in all groups and after 6 months of exercise in the patients. Eight body mass index-matched nondiabetic controls (mean age, 50.3 years; range, 40-67 years) were also studied at baseline only. At baseline, LDL MRT was significantly longer in the diabetic patients, whereas LDL production rate and fractional clearance rates were significantly lower than in controls. Percentage of glycated hemoglobin A(1c), body mass index, insulin sensitivity measured by the homeostasis model assessment, and very low-density lipoprotein triglyceride decreased (P triglyceride (r = 0.51, P < .04) and negatively with maximal oxygen uptake, a measure of fitness (r = -0.51, P = .035), in all patients. The LDL production and clearance rates did not change in either group. This study suggests that a supervised exercise program can reduce deleterious changes in LDL MRT.

  1. Biomimetic High Density Lipoprotein Nanoparticles For Nucleic Acid Delivery

    Science.gov (United States)

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

    2014-01-01

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

  2. Low density lipoproteins promote unstable calcium handling accompanied by reduced SERCA2 and connexin-40 expression in cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Montserrat Barriga

    Full Text Available The damaging effects of high plasma levels of cholesterol in the cardiovascular system are widely known, but little attention has been paid to direct effects on cardiomyocyte function. We therefore aimed at testing the hypothesis that Low Density Lipoprotein (LDL cholesterol affects calcium dynamics and signal propagation in cultured atrial myocytes. For this purpose, mRNA and protein expression levels were determined by real time PCR and western blot analysis, respectively, and intracellular calcium was visualized in fluo-4 loaded atrial HL-1 myocyte cultures subjected to field stimulation. At low stimulation frequencies all cultures had uniform calcium transients at all tested LDL concentrations. However, 500 µg LDL/mL maximally reduced the calcium transient amplitude by 43% from 0.30 ± 0.04 to 0.17 ± 0.02 (p<0.05. Moreover, LDL-cholesterol dose-dependently increased the fraction of alternating and irregular beat-to-beat responses observed when the stimulation interval was shortened. This effect was linked to a concurrent reduction in SERCA2, RyR2, IP3RI and IP3RII mRNA levels. SERCA2 protein levels were also reduced by 43% at 200 µg LDL/mL (p<0.05 and SR calcium loading was reduced by 38 ± 6% (p<0.001. By contrast, HDL-cholesterol had no significant effect on SERCA expression or SR calcium loading. LDL-cholesterol also slowed the conduction velocity of the calcium signal from 3.2+0.2 mm/s without LDL to 1.7 ± 0.1 mm/s with 500 µg LDL/mL (p<0.05. This coincided with a reduction in Cx40 expression (by 44 ± 3%; p<0.05 for mRNA and by 79 ± 2%; p<0.05 for Cx40 protein at 200 µg/ml LDL whereas the Cx-43 expression did not significantly change. In conclusion, LDL-cholesterol destabilizes calcium handling in cultured atrial myocytes subjected to rapid pacing by reducing SERCA2 and Cx40 expression and by slowing the conduction velocity of the calcium signal.

  3. Low-density lipoprotein cholesterol and risk of gallstone disease: a Mendelian randomization study and meta-analyses.

    Science.gov (United States)

    Stender, Stefan; Frikke-Schmidt, Ruth; Benn, Marianne; Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2013-01-01

    Drugs which reduce plasma low-density lipoprotein cholesterol (LDL-C) may protect against gallstone disease. Whether plasma levels of LDL-C per se predict risk of gallstone disease remains unclear. We tested the hypothesis that elevated LDL-C is a causal risk factor for symptomatic gallstone disease. We used a Mendelian randomization approach and genotyped 63,051 individuals from a prospective cohort study of the general Danish population, including 3323 subjects with symptomatic gallstones. We selected eight genetic variants in APOE, APOB, LDLR, and PCSK9 affecting LDL-C. Furthermore, studies of APOE rs429358/rs7412 (defining ε2/ε3/ε4 alleles; 12 studies) and APOB rs693 (eight studies) were included in meta-analyses. The observational hazard ratio (HR) for symptomatic gallstone disease for the fifth versus first quintile of LDL-C was 0.94 (95% confidence interval: 0.76-1.17), despite a corresponding 134% increase in LDL-C. Furthermore, although individual genetic variants in APOE, APOB, LDLR, and PCSK9 associated with stepwise increases/decreases in LDL-C of up to +59% compared with non-carriers (p gallstone disease. Combining all variants into 10 genotypes, carriers of 9 versus ⩽3 LDL-C increasing alleles associated with 41% increased LDL-C (p gallstone disease of 1.09 (0.70-1.69). Finally, in meta-analyses, random effects odds ratios for gallstone disease were 0.91 (0.78-1.06) for carriers of APOE ε4 versus non-carriers, and 1.25 (0.95-1.63) for APOB rs693 CT+TT versus CC. Results from the observational study, genetic studies, and meta-analyses suggest that elevated plasma levels of LDL-C are not causally associated with increased risk of symptomatic gallstone disease. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  4. Low Density Lipoproteins Promote Unstable Calcium Handling Accompanied by Reduced SERCA2 and Connexin-40 Expression in Cardiomyocytes

    Science.gov (United States)

    Cabello, Nuria; Llach, Anna; Vallmitjana, Alexander; Benítez, Raúl; Badimon, Lina; Cinca, Juan; Llorente-Cortés, Vicenta; Hove-Madsen, Leif

    2013-01-01

    The damaging effects of high plasma levels of cholesterol in the cardiovascular system are widely known, but little attention has been paid to direct effects on cardiomyocyte function. We therefore aimed at testing the hypothesis that Low Density Lipoprotein (LDL) cholesterol affects calcium dynamics and signal propagation in cultured atrial myocytes. For this purpose, mRNA and protein expression levels were determined by real time PCR and western blot analysis, respectively, and intracellular calcium was visualized in fluo-4 loaded atrial HL-1 myocyte cultures subjected to field stimulation. At low stimulation frequencies all cultures had uniform calcium transients at all tested LDL concentrations. However, 500 µg LDL/mL maximally reduced the calcium transient amplitude by 43% from 0.30±0.04 to 0.17±0.02 (p<0.05). Moreover, LDL-cholesterol dose-dependently increased the fraction of alternating and irregular beat-to-beat responses observed when the stimulation interval was shortened. This effect was linked to a concurrent reduction in SERCA2, RyR2, IP3RI and IP3RII mRNA levels. SERCA2 protein levels were also reduced by 43% at 200 µg LDL/mL (p<0.05) and SR calcium loading was reduced by 38±6% (p<0.001). By contrast, HDL-cholesterol had no significant effect on SERCA expression or SR calcium loading. LDL-cholesterol also slowed the conduction velocity of the calcium signal from 3.2+0.2 mm/s without LDL to 1.7±0.1 mm/s with 500 µg LDL/mL (p<0.05). This coincided with a reduction in Cx40 expression (by 44±3%; p<0.05 for mRNA and by 79±2%; p<0.05 for Cx40 protein at 200 µg/ml LDL) whereas the Cx-43 expression did not significantly change. In conclusion, LDL-cholesterol destabilizes calcium handling in cultured atrial myocytes subjected to rapid pacing by reducing SERCA2 and Cx40 expression and by slowing the conduction velocity of the calcium signal. PMID:23516438

  5. Protection capacity against low-density lipoprotein oxidation and antioxidant potential of some organic and non-organic wines.

    Science.gov (United States)

    Kalkan Yildirim, Hatice; Delen Akçay, Yasemin; Güvenç, Ulgar; Yildirim Sözmen, Eser

    2004-08-01

    Current research suggests that phenolics from wine may play a positive role against oxidation of low-density lipoprotein (LDL), which is a key step in the development of atherosclerosis. Considering the effects of different wine-making techniques on phenols and the wine consumption preference influencing the benefical effects of the product, organically and non-organically produced wines were obtained from the grapes of Vitis vinifera origin var: Carignan, Cabernet Sauvignon, Merlot, Grenache, Columbard and Semillon. Levels of total phenols [mg/l gallic acid equivalents (GAE)], antioxidant activity (%) and inhibition of LDL oxidation [%, inhibition of diene and malondialdehyde (MDA) formation] were determined. Some phenolic acids (gallic acid, p-hydroxybenzoic acid, syringic acid, 2,3-dihydroxybenzoic acid, ferulic acid, p-coumaric acid and vanillic acid) were quantified by high-performance liquid chromatography equipped with an electrochemical detection carried at +0.65 V (versus Ag/AgCl, 0.5 microA full scale). The highest concentrations of gallic, syringic and ferulic acids were found in organic Cabernet Sauvignon; 2,3-dihydroxybenzoic acid in organic Carignan and p-coumaric and vanillic acids in non-organic Merlot wine. High levels of antioxidant activity (AOA), inhibition of LDL oxidation and total phenol levels were found in non-organic Merlot (101.950% AOA; 88.570% LDL-diene; 41.000% LDL-MDA; 4700.000 mg/l GAE total phenol) and non-organic Cabernet Sauvignon (92.420% AOA; 91.430% LDL-diene; 67.000% LDL-MDA; 3500.000 mg/l GAE total phenol) grape varieties. Concentrations of some individual phenolic constituents (ferulic, p-coumaric, vanillic) are correlated with high antioxidant activity and inhibition of LDL oxidation. The best r value for all examined characteristics was determined for gallic acid, followed by 2,3-dihydroxybenzoic, syringic, ferulic and p-coumaric acids. Negative correlation of vanillic with MDA and p-hydroxybenzoic acid with LDL were

  6. Oxidized low-density lipoprotein and β-glycerophosphate synergistically induce endothelial progenitor cell ossification

    Institute of Scientific and Technical Information of China (English)

    Li LIU; Zhi-zhong LIU; Hui CHEN; Guo-jun ZHANG; Yu-hua KONG; Xi-xiong KANG

    2011-01-01

    To investigate the ability of ox-LDL to induce ossification of endothelial progenitor cells (EPCs) in vitro and explored whether oxidative stress,especially hypoxia inducible factor-1α (HIF-1α) and reactive oxygen species (ROS),participate in the ossific process.Methods:Rat bone marrow-derived endothelial progenitor cells (BMEPCs) were cultured in endothelial growth medium supplemented with VEGF (40 ng/mL) and bFGF (10 ng/mL).The cells were treated with oxidized low-density lipoprotein (ox-LDL,5 μg/mL) and/or β-glycerophosphate (β-GP,10 mmol/L).Calcium content and Von Kossa staining were used as the measures of calcium deposition.Ossific gene expression was determined using RT-PCR.The expression of osteocalcin (OCN) was detected with immunofluorescence.Alkaline phosphatase (ALP) activity was analyzed using colorimetric assay.Intercellular reactive oxygen species (ROS) were measured with flow cytometry.Results:BMEPCs exhibited a spindle-like shape.The percentage of cells that expressed the cell markers of EPCs CD34,CD133,and kinase insert domain-containing receptor (KDR) were 46.2%+5.8%,23.5%+4.0%,and 74.3%+8.8%,respectively.Among the total cells,78.3%+4.2% were stained with endothelial-specific fluorescence.Treatment of BMEPCs with ox-LDL significantly promoted calcium deposition,which was further significantly enhanced by co-treatment with β-GP.The same treatments significantly increased the gene expression of core-binding factor a-1 (cbfa-1) and OCN,while decreased the gene expression of osteoprotegerin (OPG).The treatments also significantly enhanced the activity of ALP,but did not affect the number of OCN+ cells.Furthermore,the treatments significantly increased ROS and activated the hypoxia inducible factor-1α (HIF-1α).In all these effects,ox-LDL acted synergistically with β-GP.Conclusion:Ox-LDL and β-GP synergistically induce ossification of BMEPCs,in which an oxidizing mechanism is involved.

  7. Tracer kinetic studies of the low density lipoprotein metabolism in the fetal rat: An example for estimation of flux rates in the nonsteady state

    Energy Technology Data Exchange (ETDEWEB)

    Plonne, D.; Schlag, B.; Winkler, L.; Dargel, R. (Friedrich Schiller Univ., Jena (German Democratic Republic))

    1990-05-01

    To get insight into the low density lipoprotein (LDL)-apoB flux in the rat fetus near term and in the early postnatal period, homologous apoE-free 125I-labeled LDL was injected into the umbilical vein of the rat fetus immediately after Caesarean section. Since the serum LDL-apoB spontaneously declined after birth, a time-dependent two-pool model was used to calculate the flux rates in the neonate from the specific activities of LDL-apoB up to 15 h post partum. An approximate value of LDL-apoB flux in the fetus at birth was obtained by extrapolation of the kinetic data to the time of injection of the tracer. The data revealed that the turnover of LDL-apoB in the fetus (18.6 micrograms LDL-apoB/h per g body weight) exceeded that in the adult rat (0.4 microgram/h per g body weight) by at least one order of magnitude. Even 15 h after delivery, the LDL-apoB influx amounted to 2.5 micrograms/h per g body weight. The fractional catabolic rate of LDL-apoB in the fetus at term (0.39, h-1) slightly exceeded that in the adult animal (0.15, h-1) and reached the adult level within the first 3 h after birth and remained constant thereafter. In the rat fetus, LDL-apoB flux greatly exceeds that of VLDL-apoB. The data support the view of a direct synthesis and secretion of LDL, most probably by the fetal membranes.

  8. Regulation of plasma LDL: the apoB paradigm.

    NARCIS (Netherlands)

    Sniderman, A.D.; Graaf, J. de; Couture, P.; Williams, K.; Kiss, R.S.; Watts, G.F.

    2010-01-01

    The objectives of this analysis are to re-examine the foundational studies of the in vivo metabolism of plasma LDL (low-density lipoprotein) particles in humans and, based on them, to reconstruct our understanding of the governance of the concentration of plasma LDL and the maintenance of cholestero

  9. Heparan sulfate proteoglycans present PCSK9 to the LDL receptor

    DEFF Research Database (Denmark)

    Gustafsen, Camilla; Olsen, Ditte; Vilstrup, Joachim

    2017-01-01

    Coronary artery disease is the main cause of death worldwide and accelerated by increased plasma levels of cholesterol-rich low-density lipoprotein particles (LDL). Circulating PCSK9 contributes to coronary artery disease by inducing lysosomal degradation of the LDL receptor (LDLR) in the liver...

  10. Oxidation of LDL and extent of peripheral atherosclerosis

    NARCIS (Netherlands)

    Vijver, L.P.L. van de; Kardinaal, A.F.M.; Duyvenvoorde, W. van; Kruijssen, D.A.C.M.; Grobbee, D.E.; Poppel, G. van; Princen, H.M.G.

    1999-01-01

    Evidence has accumulated for oxidative modification of low-density lipoproteins (LDL) to play an important role in the atherogenic process. Therefore, we investigated the relation between susceptibility of LDL to oxidation and risk of peripheral atherosclerosis among 249 men between 45 and 80 years

  11. Antioxidant effects of phenolic rye (Secale cereale L.) extracts, monomeric hydroxycinnamates, and ferulic acid dehydrodimers on human low-density lipoproteins

    DEFF Research Database (Denmark)

    Andreasen, Mette Findal; Landbo, A K; Christensen, L P

    2001-01-01

    Dietary antioxidants that protect low-density lipoprotein (LDL) from oxidation may help to prevent atherosclerosis and coronary heart disease. The antioxidant activities of purified monomeric and dimeric hydroxycinnamates and of phenolic extracts from rye (whole grain, bran, and flour) were...... investigated using an in vitro copper-catalyzed human LDL oxidation assay. The most abundant ferulic acid dehydrodimer (diFA) found in rye, 8-O-4-diFA, was a slightly better antioxidant than ferulic acid and p-coumaric acid. The antioxidant activity of the 8-5-diFA was comparable to that of ferulic acid...

  12. Antioxidant effects of phenolic rye (Secale cereale L.) extracts, monomeric hydroxycinnamates, and ferulic acid dehydrodimers on human low-density lipoproteins

    DEFF Research Database (Denmark)

    Andreasen, M.F.; Landbo, Anne-Katrine Regel; Christensen, L.P.

    2001-01-01

    Dietary antioxidants that protect low-density lipoprotein (LDL) from oxidation may help to prevent atherosclerosis and coronary heart disease. The antioxidant activities of purified monomeric and dimeric hydroxycinnamates and of phenolic extracts from rye (whole grain, bran, and flour) were...... investigated using an in vitro copper-catalyzed human LDL oxidation assay. The most abundant ferulic acid dehydrodimer (diFA) found in rye, 8-O-4- diFA, was a slightly better antioxidant than ferulic acid and p-coumaric acid. The antioxidant activity of the 8-5-diFA was comparable to that of ferulic acid...

  13. Skeletal muscle insulin resistance associated with cholesterol-induced activation of macrophages is prevented by high density lipoprotein.

    Directory of Open Access Journals (Sweden)

    Andrew L Carey

    Full Text Available BACKGROUND: Emerging evidence suggests that high density lipoprotein (HDL may modulate glucose metabolism through multiple mechanisms including pancreatic insulin secretion as well as insulin-independent glucose uptake into muscle. We hypothesized that HDL may also increase skeletal muscle insulin sensitivity via cholesterol removal and anti-inflammatory actions in macrophages associated with excess adiposity and ectopic lipid deposition. METHODS: Human primary and THP-1 macrophages were treated with vehicle (PBS or acetylated low density lipoprotein (acLDL with or without HDL for 18 hours. Treatments were then removed, and macrophages were incubated with fresh media for 4 hours. This conditioned media was then applied to primary human skeletal myotubes derived from vastus lateralis biopsies taken from patients with type 2 diabetes to examine insulin-stimulated glucose uptake. RESULTS: Conditioned media from acLDL-treated primary and THP-1 macrophages reduced insulin-stimulated glucose uptake in primary human skeletal myotubes compared with vehicle (primary macrophages, 168±21% of basal uptake to 104±19%; THP-1 macrophages, 142±8% of basal uptake to 108±6%; P<0.05. This was restored by co-treatment of macrophages with HDL. While acLDL increased total intracellular cholesterol content, phosphorylation of c-jun N-terminal kinase and secretion of pro- and anti-inflammatory cytokines from macrophages, none were altered by co-incubation with HDL. Insulin-stimulated Akt phosphorylation in human skeletal myotubes exposed to conditioned media was unaltered by either treatment condition. CONCLUSION: Inhibition of insulin-stimulated glucose uptake in primary human skeletal myotubes by conditioned media from macrophages pre-incubated with acLDL was restored by co-treatment with HDL. However, these actions were not linked to modulation of common pro- or anti-inflammatory mediators or insulin signaling via Akt.

  14. Cholesterol-lowering drugs inhibit lectin-like oxidized low-density lipoprotein-1 receptor function by membrane raft disruption.

    Science.gov (United States)

    Matarazzo, Sara; Quitadamo, Maria Chiara; Mango, Ruggiero; Ciccone, Sarah; Novelli, Giuseppe; Biocca, Silvia

    2012-08-01

    Lectin-like oxidized low-density lipoprotein (LOX-1), the primary receptor for oxidized low-density lipoprotein (ox-LDL) in endothelial cells, is up-regulated in atherosclerotic lesions. Statins are the principal therapeutic agents for cardiovascular diseases and are known to down-regulate LOX-1 expression. Whether the effect on the LOX-1 receptor is related to statin-mediated cholesterol-lowering activity is unknown. We investigate the requirement of cholesterol for LOX-1-mediated lipid particle internalization, trafficking, and processing and the role of statins as inhibitors of LOX-1 function. Disruption of cholesterol-rich membrane microdomains by acute exposure of cells to methyl-β-cyclodextrin or chronic exposure to different statins (lovastatin and atorvastatin) led to a spatial disorganization of LOX-1 in plasma membranes and a marked loss of specific LOX-1 function in terms of ox-LDL binding and internalization. Subcellular fractionation and immunochemical studies indicate that LOX-1 is naturally present in caveolae-enriched lipid rafts and, by cholesterol reduction, the amount of LOX-1 in this fraction is highly decreased (≥60%). In contrast, isoprenylation inhibition had no effect on the distribution and function of LOX-1 receptors. Furthermore, in primary cultures from atherosclerotic human aorta lesions, we confirm the presence of LOX-1 in caveolae-enriched lipid rafts and demonstrate that lovastatin treatment led to down-regulation of LOX-1 in lipid rafts and rescue of the ox-LDL-induced apoptotic phenotype. Taken together, our data reveal a previously unrecognized essential role of membrane cholesterol for LOX-1 receptor activity and suggest that statins protect vascular endothelium against the adverse effect of ox-LDL by disruption of membrane rafts and impairment of LOX-1 receptor function.

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

    Science.gov (United States)

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

    2016-01-01

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

  16. The effects of fucoidans from Laminaria japonica on AAPH mediated oxidation of human low-density lipoprotein

    Institute of Scientific and Technical Information of China (English)

    LI Laihao; XUE Changhu; XUE Yong; LI Zhaojie; FU Xueyan

    2006-01-01

    Five fucoidan fractions from Laminaria japonica with different sulfate content and molecular weight were prepared by anion-exchange chromatography and mild acid hydrolysis. Their antioxidant effects on azo radicals 2-2'-Azobis(2-amidinopropane) dihydrochloride (AAPH) induced oxidation of human low-density lipoprotein (LDL) were evaluated by monitoring cholesteryl ester hydroperoxides (CHL-OOH) formation kinetics through reverse-phase high performance liquid chromatography (RP-HPLC) analysis. Fucoidan F-C with a low molecular mass of 2 000~8 000 and a sulfate content of 24.3% had much stronger protective antioxidant effect than other four fucoidan fractions on the hydrophilic radical AAPH induced LDL oxidation. However, the highly sulfated fucoidan fraction L-B with a molecular mass of 20 000 was completely ineffective in protecting LDL from the AAPH induced oxidation. The results suggested that both molecular mass and sulfate content of fucoidan played very important roles in their effects on the AAPH induced LDL oxidation.

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

    Directory of Open Access Journals (Sweden)

    Vincenzo Jacomella

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

  18. Interaction between SCO-spondin and low density lipoproteins from embryonic cerebrospinal fluid modulates their roles in early neurogenesis

    Directory of Open Access Journals (Sweden)

    América eVera

    2015-05-01

    Full Text Available During early stages of development, encephalic vesicles are composed by a layer of neuroepithelial cells surrounding a central cavity filled with embryonic cerebrospinal fluid (eCSF. This fluid contains several morphogens that regulate proliferation and differentiation of neuroepithelial cells. One of these neurogenic factors is SCO-spondin, a giant protein secreted to the eCSF from early stages of development. Inhibition of this protein in vivo or in vitro drastically decreases the neurodifferentiation process. Other important neurogenic factors of the eCSF are low density lipoproteins (LDL, the depletion of which generates a 60% decrease in mesencephalic explant neurodifferentiation. The presence of several LDL receptor class A (LDLrA domains (responsible for LDL binding in other proteins in the SCO-spondin sequence suggests a possible interaction between both molecules. This possibility was analyzed using three different experimental approaches: 1 Bioinformatics analyses of the SCO-spondin region, that contains eight LDLrA domains in tandem, and of comparisons with the LDL receptor consensus sequence; 2 Analysis of the physical interactions of both molecules through immunohistochemical colocalization in embryonic chick brains and through the immunoprecipitation of LDL with anti-SCO-spondin antibodies; and 3 Analysis of functional interactions during the neurodifferentiation process when these molecules were added to a culture medium of mesencephalic explants. The results revealed that LDL and SCO-spondin interact to form a complex that diminishes the neurogenic capacities that both molecules have separately. Our work suggests that the embryonic cerebrospinal fluid is an active signaling center with a complex regulation system that allows for correct brain development.

  19. Minimally oxidized LDL offsets the apoptotic effects of extensively oxidized LDL and free cholesterol in macrophages.

    Science.gov (United States)

    Boullier, Agnès; Li, Yankun; Quehenberger, Oswald; Palinski, Wulf; Tabas, Ira; Witztum, Joseph L; Miller, Yury I

    2006-05-01

    Lipid-loaded macrophage-derived foam cells populate atherosclerotic lesions and produce many pro-inflammatory and plaque-destabilizing factors. An excessive accumulation of extensively oxidized low-density lipoprotein (OxLDL) or free cholesterol (FC), both of which are believed to be major lipid components of macrophages in advanced lesions, rapidly induces apoptosis in macrophages. Indeed, there is evidence of macrophage death in lesions, but how the surviving macrophages avoid death induced by OxLDL, FC, and other factors is not known. Minimally oxidized LDL (mmLDL), which is an early product of progressive LDL oxidation in atherosclerotic lesions, countered OxLDL-induced or FC-induced apoptosis and stimulated macrophage survival both in cell culture and in vivo. DNA fragmentation and caspase-3 activity in OxLDL-treated peritoneal macrophages were significantly reduced by coincubation with mmLDL. In a separate set of experiments, mmLDL significantly reduced annexin V binding to macrophages in which apoptosis was induced by FC loading. In both cellular models, mmLDL activated a pro-survival PI3K/Akt signaling pathway, and PI3K inhibitors, wortmannin and LY294002, eliminated the pro-survival effect of mmLDL. Immunohistochemical examination demonstrated phospho-Akt in murine atherosclerotic lesions. Minimally oxidized LDL, an early form of oxidized LDL in atherosclerotic lesions, may contribute to prolonged survival of macrophage foam cells in lesions via a PI3K/Akt-dependent mechanism.

  20. Diagnosis of type III hyperlipoproteinemia by chromatography of plasma lipoproteins on columns containing agarose.

    Science.gov (United States)

    Shepherd, J; Packard, C J; Dryburgh, F J; Third, J L

    1975-12-01

    Agarose column chromatography has been used to separate plasma lipoproteins into very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Applied to the diagnosis of primary type III hyperlipoproteinemia, the procedure is capable of demonstrating three characteristic and specific changes from normality in the elution pattern of lipoproteins from patients with this condition. In the type III profile there is (a) incomplete separation of VLDL from putative LDL material, (b) early elution of the type III LDL with respect to a normal LDL marker, and (c) relative deficiency of type III LDL with elution characteristics of normal LDL. We advocate the use of this method in the diagnosis of type III hyperlipoproteinemia.

  1. High plasma levels of oxidatively modified low-density lipoproteins are associated with the suppressed expression of immunomodulatory molecules in patients with hematological malignancies

    OpenAIRE

    2015-01-01

    Dyslipidemia is a common feature in immunosuppressed patients, such as kidney and bone marrow transplantation recipients and patients with breast, prostate or gynecological carcinoma or acute lymphoblastic leukemia. In addition, high levels of oxidatively modified low-density lipoproteins (oxLDLs) are closely associated with carcinogenesis. There are, however, no reports on the association between the serum oxLDL levels and the expression of important immunomodulatory molecules in patients wi...

  2. Low-density lipoprotein cholesterol target goal attainment rate and related factors in patients with acute coronary syndrome after percutaneous coronary intervention

    Institute of Scientific and Technical Information of China (English)

    张波

    2014-01-01

    Objective To observe the low-density lipoprotein cholesterol(LDL-C)target goal attainment rate and related factors in patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods From March 2011 to March 2012,a total of832 ACS patients were retrospectively evaluated in the Cardiology Department of the First Affiliated Hospital of Dalian Medical University.The target goal attainment

  3. [Study on LDL adsorbent modified by lauric acid].

    Science.gov (United States)

    Cong, Haixia; Du, Longbing; Fang, Bo; You, Chao

    2010-06-01

    A hydrophobic low-density lipoprotein cholesterol (LDL-C) adsorbent was synthesized with lauric acid and chitosan. The condition for adsorption was obtained by investigating the influence of adsorbent amount and adsorption time. The results of adsorption in vitro showed that the average adsorption rates for total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C) and total protein (TP) were 47.7%, 84.7%, 18.1% and 5.9% respectively. The adsorbent possesses good selectivity in removing LDL-C.

  4. Low-density lipoprotein apheresis in a pediatric patient of familial hypercholesterolemia: Primi experientia from a tertiary care center in North India

    Directory of Open Access Journals (Sweden)

    Kanchan Dogra

    2017-01-01

    Full Text Available Familial hypercholesterolemia (FH is an autosomal dominant disorder due to mutation of apolipoprotein-B receptor gene causing severe dyslipidemia. Lifestyle modification and medical treatment attenuate the disease progression, but as these fail to control the blood cholesterol levels, low-density lipoprotein (LDL apheresis comes forth as a treatment option. To the best of our knowledge, the following is the very first case of pediatric FH being treated by LDL-apheresis to be reported from India. A severely malnourished female child presented with yellowish skin lesions over different parts of the body, viz., bilateral Achilles tendon, both knees, elbows, both pinnae, and outer canthus of both eyes. She had a strong family history of borderline hypercholesterolemia and was diagnosed as a case of FH. She was maintained on diet modification. LDL-apheresis was planned as the cholesterol levels were not controlled with the diet modificationt. However, unavailability of an appropriate kit in India for LDL-apheresis led to the use of the modified PL1 kit meant for therapeutic plasma exchange procedures. We conducted two sessions of LDL-apheresis. After the first session, the LDL-cholesterol (LDL-C level fell by 75.9% and the total cholesterol fell by 73.5%. A second procedure led to a decline in total cholesterol level by 18.6% and LDL-C by 19.46%. Subsequently, she was advised diet modification and statin therapy with regular follow-up after every 6 months. Thus, the cascade filtration technique is a safe and effective treatment option for removing the undesired lipoproteins.

  5. Green-step assembly of low density lipoprotein/sodium carboxymethyl cellulose nanogels for facile loading and pH-dependent release of doxorubicin.

    Science.gov (United States)

    He, Lei; Liang, Hongshan; Lin, Liufeng; Shah, Bakht Ramin; Li, Yan; Chen, Yijie; Li, Bin

    2015-02-01

    In this study, a simple and green approach was developed to produce a novel nanogel via self-assembly of low density lipoproteins (LDL) and sodium carboxymethyl cellulose (CMC), to efficiently deliver doxorubicin (DOX) to cancer cells. Under optimal conditions, the stable nanogels were of spherical shape with an average diameter of about 90 nm, PDIencapsulated into LDL/CMC nanogels with an exceptionally high encapsulation efficiency of ∼ 98%. The release of DOX from DOX-LDL/CMC nanogels was pH-dependent, and DOX was released at a quicker rate at pH 6.2 than at pH 7.4. Importantly, the DOX-LDL/CMC nanogels were shown to effectively kill cancer cells in vitro. The IC50 of the DOX-LDL/CMC nanogels in HeLa and HepG2 cells was approximately 2.45 and 1.72 times higher than that of free DOX. The slightly reduced antitumor efficacy was primarily due to the less cellular uptake of the DOX-LDL/CMC nanogels, which was confirmed by confocal laser scanning microscope (CLSM) and flow cytometry analysis. The high DOX payload and pH-dependent drug release rendered LDL/CMC nanogels as an efficient carrier for doxorubicin and possibly be used for other cationic drugs in different biomedical applications.

  6. The osteoclast-associated receptor (OSCAR) is a novel receptor regulated by oxidized low-density lipoprotein in human endothelial cells.

    Science.gov (United States)

    Goettsch, Claudia; Rauner, Martina; Sinningen, Kathrin; Helas, Susann; Al-Fakhri, Nadia; Nemeth, Katharina; Hamann, Christine; Kopprasch, Steffi; Aikawa, Elena; Bornstein, Stefan R; Schoppet, Michael; Hofbauer, Lorenz C

    2011-12-01

    Cross talks between the vascular and immune system play a critical role in vascular diseases, in particular in atherosclerosis. The osteoclast-associated receptor (OSCAR) is a regulator of osteoclast differentiation and dendritic cell maturation. Whether OSCAR plays a role in vascular biology and has an impact on atherogenic processes provoked by proinflammatory stimuli is yet unknown. We identified OSCAR on the surface of human primary endothelial cells. Stimulation of endothelial cells with oxidized low-density lipoprotein (oxLDL) caused a time- and dose-dependent induction of OSCAR, which was lectin-like oxidized LDL receptor 1 and Ca(2+) dependent. OSCAR was transcriptionally regulated by oxLDL as shown by OSCAR promoter analysis. Specific inhibition of the nuclear factor of activated T cells (NFAT) pathway prevented the oxLDL-mediated increase of endothelial OSCAR expression. As assessed by EMSA, oxLDL induced binding of NFATc1 to the OSCAR promoter. Notably, in vivo-modified LDL from patients with diabetes mellitus stimulated OSCAR mRNA expression in human endothelial cells. Furthermore, apolipoprotein E knockout mice fed a high-fat diet showed an enhanced aortic OSCAR expression associated with increased expression of NFATc1. In summary, OSCAR is expressed in vascular endothelial cells and is regulated by oxLDL involving NFATc1. Our data suggest that OSCAR, originally described in bone as immunological mediator and regulator of osteoclast differentiation, may be involved in cell activation and inflammation during atherosclerosis.

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

    OpenAIRE

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

    2013-01-01

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

  8. Small dense low-density lipoprotein as a potential risk factor of nephropathy in type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Essam Abd-Allha

    2014-01-01

    Full Text Available Background: The risk for diabetic nephropathy in type 2 diabetes is about 30-40%, and it is considered the leading cause of end-stage renal disease. Small dense low-density lipoprotein (sdLDL particles are believed to be atherogenic, and its predominance has been accepted as an emerging cardiovascular risk factor. This study aimed to assess small dense LDL as a potential risk factor and a possible predictor for diabetic nephropathy in type 2 diabetic patients. Patients and Methods: According to microalbuminuria test, 40 diabetic patients were categorized into two groups: Diabetic patients without nephropathy (microalbuminuria negative group and diabetic patients with nephropathy (microalbuminuria positive group, each group consists of 20 patients and all were non-obese and normotensive. The patients were re-classified into three sub-groups depending on the glomerular filtration rate (GFR. Results: The mean of small dense LDL level in the microalbuminuria positive group was higher than that in the microalbuminuria negative group, but without statistical significance. It was significantly higher in patients with either mild or moderate decrease in estimated GFR than in patients with normal estimated GFR. There was statistically significant correlation between small dense LDL and albuminuria and significant inverse correlation between small dense LDL and estimated GFR in all patients in the study. Based on microalbuminuria, the sensitivity and specificity of small dense LDL in the diagnosis of diabetic nephropathy was 40% and 80%, respectively, with cutoff values of small dense LDL >55.14 mg/dl. On the other hand, based on GFR, the sensitivity and specificity were 88.24% and 73.91% respectively, with cutoff values of small dense LDL >41.89 mg/dl. Conclusion: Small dense LDL is correlated with the incidence and severity of diabetic nephropathy in type 2 diabetic patients. It should be considered as a potential risk factor and as a diagnostic

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

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Jauhiainen, Matti; Moser, Markus

    2008-01-01

    To investigate the role of apoM in high density lipoprotein (HDL) metabolism and atherogenesis, we generated human apoM transgenic (apoM-Tg) and apoM-deficient (apoM(-/-)) mice. Plasma apoM was predominantly associated with 10-12-nm alpha-migrating HDL particles. Human apoM overexpression (11-fold...... of alpha- to pre-alpha-migrating HDL was delayed in apoM-Tg mice. Moreover, lecithin: cholesterol acyltransferase-independent generation of pre-beta-migrating apoA-I-containing particles in plasma was increased in apoM-Tg mice (4.2 +/- 1.1%, p = 0.06) and decreased in apoM(-/-) mice (0.5 +/- 0.3%, p = 0.......03) versus controls (1.8 +/- 0.05%). In the setting of low density lipoprotein receptor deficiency, apoM-Tg mice with approximately 2-fold increased plasma apoM concentrations developed smaller atherosclerotic lesions than controls. The effect of apoM on atherosclerosis may be facilitated by enzymatic...

  10. LOX - 1介导ox - LDL诱导的血管内皮细胞MCP - 1的表达%Lectin- like oxidized low density lipoprotein receptor - 1 mediates expression of MCP - 1 induced by ox - LDL in cultured human vascular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    朱惠莲; 唐志红; 夏敏; 马静; 凌文华

    2005-01-01

    目的:观察血凝素氧化低密度脂蛋白受体-1(LOX-1)对氧化LDL(ox-LDL)诱导的人脐静脉内皮细胞(human unbilical vein endothelial cells,HUVECs)表达单核细胞趋化蛋白(monocyte chemoattractant protein-1,MCP-1)基因及蛋白的影响.方法:用RT-PCR和Western blot的方法观察ox-LDL对培养的HUVECs表达LOX-1和MCP-1基因及蛋白的影响,然后用LOX-1的受体阻滞剂爱兰苔胶(carrageenan)和聚肌苷酸[polyinosinic acid,poly(Ⅰ)]与HUVECs预先作用后,再观察内皮细胞表达LOX-1和MCP-1基因和蛋白的变化.结果:用不同浓度的ox-LDL(0 mg/L、10 mg/L、20 mg/L、50 mg/L、100 mg/L)与HUVECs培养24h后,LOX-1和MCP-1的mRNA和蛋白的表达明显增加,呈浓度依赖性;用Carrageenan和polyinosinic acid与HUVECs预先作用2 h后,再加入50 mg/L的ox-LDL培养24 h,与未加Carrageenan和polyinosinic acid相比,HUVECsLOX-1和MCP-1的mRNA和蛋白的表达明显减少.结论:ox-LDL可以调节培养的HUVECsLOX-1和MCP-1基因和蛋白的表达,LOX-1作为ox-LDL的特异性受体,可能介导了ox-LDL诱导血管内皮细胞分泌MCP-1,从而在动脉粥样硬化的发生发展中起着重要的作用.

  11. Oxidized lipoprotein lipids and atherosclerosis.

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Rezaee Farhad

    2007-09-01

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

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

    OpenAIRE

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

    2013-01-01

    Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) ...

  14. Transendothelial lipoprotein exchange and microalbuminuria

    DEFF Research Database (Denmark)

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

    2004-01-01

    OBJECTIVE: Microalbuminuria associates with increased risk of atherosclerosis in individuals without diabetes. We hypothesized that transendothelial lipoprotein exchange is elevated among such individuals, possibly explaining increased intimal lipoprotein accumulation and thus atherosclerosis....... METHODS: Using an in vivo isotope technique, transendothelial exchange of low density lipoprotein (LDL) was measured in 77 non-diabetic individuals. Autologous 131-iodinated LDL was reinjected intravenously, and the 1-h fractional escape rate was calculated as index of transendothelial exchange. RESULTS...... transformed) plasma insulin: beta=0.6 (95% CI: 0.1-1.1); R=0.22; Plipoproteins, LDL size, body mass index, plasma volume, and use of medicine, and it was unlikely caused by altered hepatic LDL receptor expression...

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

    Science.gov (United States)

    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.

  16. Impact of the LDL subfraction phenotype on Lp-PLA2 distribution, LDL modification and HDL composition in type 2 diabetes.

    Science.gov (United States)

    Sánchez-Quesada, Jose Luis; Vinagre, Irene; De Juan-Franco, Elena; Sánchez-Hernández, Juan; Bonet-Marques, Rosa; Blanco-Vaca, Francisco; Ordóñez-Llanos, Jordi; Pérez, Antonio

    2013-08-05

    Qualitative alterations of lipoproteins underlie the high incidence of atherosclerosis in diabetes. The objective of this study was to assess the impact of low-density lipoprotein (LDL) subfraction phenotype on the qualitative characteristics of LDL and high-density lipoprotein (HDL) in patients with type 2 diabetes. One hundred twenty two patients with type 2 diabetes in poor glycemic control and 54 healthy subjects were included in the study. Patients were classified according to their LDL subfraction phenotype. Seventy-seven patients presented phenotype A whereas 45 had phenotype B. All control subjects showed phenotype A. Several forms of modified LDL, HDL composition and the activity and distribution of lipoprotein-associated phospholipase A2 (Lp-PLA2) were analyzed. Oxidized LDL, glycated LDL and electronegative LDL were increased in both groups of patients compared with the control group. Patients with phenotype B had increased oxidized LDL and glycated LDL concentration than patients with phenotype A. HDL composition was abnormal in patients with diabetes, being these abnormalities more marked in patients with phenotype B. Total Lp-PLA2 activity was higher in phenotype B than in phenotype A or in control subjects. The distribution of Lp-PLA2 between HDL and apoB-containing lipoproteins differed in patients with phenotype A and phenotype B, with higher activity associated to apoB-containing lipoproteins in the latter. The presence of LDL subfraction phenotype B is associated with increased oxidized LDL, glycated LDL and Lp-PLA2 activity associated to apoB-containing lipoproteins, as well as with abnormal HDL composition.

  17. Effect of Metformin Treatment on Lipoprotein Subfractions in Non-Diabetic Patients with Acute Myocardial Infarction : A Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) Trial

    NARCIS (Netherlands)

    Eppinga, Ruben N.; Hartman, Minke H. T.; van Veldhuisen, Dirk J.; Lexis, Chris P. H.; Connelly, Margery A.; Lipsic, Erik; van der Horst, Iwan C. C.; van der Harst, Pim; Dullaart, Robin P. F.

    2016-01-01

    Objective Metformin affects low density lipoprotein (LDL) and high density (HDL) subfractions in the context of impaired glucose tolerance, but its effects in the setting of acute myocardial infarction (MI) are unknown. We determined whether metformin administration affects lipoprotein subfractions

  18. Conformation of apolipoprotein E both in free and in lipid-bound form may determine the avidity of triglyceride-rich lipoproteins to the LDL receptor: structural and kinetic study.

    Science.gov (United States)

    Dergunov, A D; Smirnova, E A; Merched, A; Visvikis, S; Siest, G; Yakushkin, V V; Tsibulsky, V

    2000-02-24

    Slow refolding of human apolipoprotein E (apoE) in solution after guanidine- or cholate-induced denaturation followed by dialysis under controlled conditions was investigated using various spectroscopic properties of fluorescein- and dansyl-labeled apolipoprotein molecules. The results suggest that the last phase(s) of apoE refolding in solution include a slow (several hours at 24 degrees C) interconversion of a self-associated 'open' conformer into a more dense 'closed' conformer. The hydrophobic interactions are primarily responsible for the formation of this more compact apoE structure. To visualize the contribution of apolipoprotein conformation and/or the number of 'active' lipid-bound apoE molecules in the reaction of binding to the low density lipoprotein receptor (LDLr) by solid-phase binding assay, the complexes of human plasma apolipoprotein or recombinant (rec) apoE3 with dipalmitoylphosphatidylcholine (DPPC) or palmitoyloleoylphosphatidylcholine (POPC) varying in size were used. For seven complexes with plasma protein (four DPPC and three POPC complexes), the final phosphatidylcholine (PC)/protein mole ratio ranged from 117 to 279; affinity constant K(a) averaged for both PCs and plotted against this ratio abruptly increased from 3.8 x 10(7) to 3.8 x 10(8) M(-1) with a transition midpoint of 150-180 PC/apoE, mole ratio. Two DPPC complexes with rec protein bind much more efficiently. Complexes with both plasma and rec apoE were able to compete with very low density lipoproteins (VLDL) or low density lipoproteins (LDL) isolated from patients with E3/3 phenotype, for binding to the LDLr. Again, the competition efficiency abruptly increased at the increase in PC content with a transition midpoint of 130 PC/apoE, mole ratio. The transitions observed both in direct and competitive binding assay probably correspond to the abrupt increase in the number of 'active' apoE molecules on the complex surface accompanying the change in the size and/or in the shape of

  19. Biominetic High Density Lipoproteins for the Delivery of Therapeutic Oligonucleotides

    Science.gov (United States)

    Tripathy, Sushant

    Advances in nanotechnology have brought about novel inorganic and hybrid nanoparticles with unique physico-chemical properties that make them suitable for a broad range of applications---from nano-circuitry to drug delivery. A significant part of those advancements have led to ground-breaking discoveries that have changed the approaches to formulation of therapeutics against diseases, such as cancer. Now-a-days the focus does not lie solely on finding a candidate small-molecule therapeutic with minimal adverse effects, but researchers are looking up to nanoparticles to improve biodistribution and biocompatibility profile of clinically proven therapeutics. The plethora of conjugation chemistries offered by currently extant inorganic nanoparticles have, in recent years, led to great leaps in the field of biomimicry---a modality that promises high biocompatibility. Further, in the pursuit of highly specific therapeutic molecules, researchers have turned to silencing oligonucleotides and some have already brought together the strengths of nanoparticles and silencing oligonucleotides in search of an efficacious therapy for cancer with minimal adverse effects. This dissertation work focuses on such a biomimetic platform---a gold nanoparticle based high density lipoprotein biomimetic (HDL NP), for the delivery of therapeutic oligonucleotides. The first chapter of this body of work introduces the molecular target of the silencing oligonucleotides---VEGFR2, and its role in the progression of solid tumor cancers. The background information also covers important aspects of natural high density lipoproteins (HDL), especially their innate capacity to bind and deliver exogenous and endogenous silencing oligonucleotides to tissues that express their high affinity receptor SRB1. We subsequently describe the synthesis of the biomimetic HDL NP and its oligonucleotide conjugates, and establish their biocompatibility. Further on, experimental data demonstrate the efficacy of silencing

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

    Science.gov (United States)

    Kon, Valentina; Yang, Haichun; Fazio, Sergio

    2016-01-01

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

  1. Does lycopene offer human LDL any protection against myeloperoxidase activity?

    Science.gov (United States)

    Chew, Poh Yeong; Riley, Lucy; Graham, Daniel L; Rahman, Khalid; Lowe, Gordon M

    2012-02-01

    Lycopene is a lipophilic antioxidant that is largely transported in human blood by Low Density Lipoproteins (LDL). One of the early events in the aetiology of atherosclerosis is thought to be the oxidation of LDL. Myeloperoxidase an enzyme secreted by neutrophils and macrophages is thought to oxidise human LDL particles. In this study, isolated human LDL was challenged with myeloperoxidase or copper, and the LDL was screened for lipoperoxidation and oxidation of apolipoprotein B100, depletion of lycopene and oxidation of cholesterol. Myeloperoxidase induced oxidation of LDL through direct interaction with apolipoprotein B100. No lipoperoxidation was observed following myeloperoxidase treatment; however, 7-ketocholesterol was detected indicating the products of myeloperoxidase interact with the surface of the LDL particles. Lycopene does react with the products of myeloperoxidase in solvent, but played no role in protecting against enzyme derived oxidation of human LDL.

  2. Study of Heart and Renal Protection (SHARP) : Randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease

    NARCIS (Netherlands)

    Baigent, C.; Landray, M.; Reith, C.; Dasgupta, T.; Emberson, J.; Herrington, W.; Lewis, D.; Mafham, M.; Collins, R.; Collins, R.; Baigent, C.; Landray, M.; Bray, C.; Chen, Y.; Baxter, A.; Young, A.; Hill, M.; Knott, C.; Cass, A.; Feldt-Rasmussen, B.; Fellstroem, B.; Grobbee, R.; Groenhagen-Riska, C.; Haas, M.; Holdaas, H.; Hooi, L. S.; Jiang, L.; Kasiske, B.; Krairittichai, U.; Levin, A.; Massy, Z.; Tesar, V.; Walker, R.; Wanner, C.; Wheeler, D.; Wiecek, A.; Dasgupta, T.; Lewis, D.; Mafham, M.; Majoni, W.; Reith, C.; Simpson, D.; Strony, J.; Musliner, T.; Agodoa, L.; Armitage, J.; Chen, Z.; Craig, J.; de Zeeuw, D.; Gaziano, M.; Grimm, R.; Krane, V.; Neal, B.; Ophascharoensuk, V.; Pedersen, T.; Sleight, P.; Tobert, J.; Tomson, C.; Sandercock, P.; Hill, C.; Keech, A.; Whelton, P.; Yusuf, S.; Peto, R.; Emberson, J.; Parish, S.

    2010-01-01

    Background Lowering low-density lipoprotein (LDL) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient, but it remains uncertain whether it is of net benefit among people with chronic kidney disease (CKD). Methods Patients with adv

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

    Science.gov (United States)

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

    1985-02-01

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

  4. Elevated high-density lipoprotein cholesterol and age-related macular degeneration: the Alienor study.

    Directory of Open Access Journals (Sweden)

    Audrey Cougnard-Grégoire

    Full Text Available BACKGROUND: Lipid metabolism and particularly high-density lipoprotein (HDL may be involved in the pathogenic mechanism of age-related macular degeneration (AMD. However, conflicting results have been reported in the associations of AMD with plasma HDL and other lipids, which may be confounded by the recently reported associations of AMD with HDL-related genes. We explored the association of AMD with plasma lipid levels and lipid-lowering medication use, taking into account most of HDL-related genes associated with AMD. METHODS: The Alienor study is a population-based study on age-related eye diseases performed in 963 elderly residents of Bordeaux (France. AMD was graded from non mydriatic color retinal photographs in three exclusive stages: no AMD (n = 430 subjects, 938 eyes; large soft distinct drusen and/or large soft indistinct drusen and/or reticular drusen and/or pigmentary abnormalities (early AMD, n = 176, 247; late AMD (n = 40, 61. Associations of AMD with plasma lipids (HDL, total cholesterol (TC, Low-density lipoprotein (LDL, and triglycerides (TG were estimated using Generalized Estimating Equation logistic regressions. Statistical analyses included 646 subjects with complete data. RESULTS: After multivariate adjustment for age, sex, educational level, smoking, BMI, lipid-lowering medication use, cardiovascular disease and diabetes, and for all relevant genetic polymorphisms (ApoE2, ApoE4, CFH Y402H, ARMS2 A69S, LIPC rs10468017, LIPC rs493258, LPL rs12678919, ABCA1 rs1883025 and CETP rs3764261, higher HDL was significantly associated with an increased risk of early (OR = 2.45, 95%CI: 1.54-3.90; P = 0.0002 and any AMD (OR = 2.29, 95%CI: 1.46-3.59; P = 0.0003. Association with late AMD was far from statistical significance (OR = 1.58, 95%CI: 0.48-5.17; p = 0.45. No associations were found for any stage of AMD with TC, LDL and TG levels, statin or fibrate drug use. CONCLUSIONS: This study suggests that elderly patients with high HDL

  5. Determinants of the uptake of very low density lipoprotein remnants by the perfused rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Arbeeny, C.M.; Rifici, V.A.; Handley, D.A.; Eder, H.A.

    1987-11-01

    The receptor-mediated uptake of very low density lipoprotein (VLDL) remnants by the rat liver was studied. Livers were perfused with native /sup 125/I-VLDL remnants, radiolabeled apo E-deficient remnants, and radiolabeled remnants that contained reductively methylated apo B and unmodified apo E. The specific uptake of the apo E-deficient remnants was 20% of that for the native remnants, whereas the specific uptake of the remnants containing unreactive apo B was 78% of the control value. This suggests that the apo E of VLDL remnants is the principal ligand for binding to the receptor, and in the absence of apo E, apo B may participate in binding. This conclusion is supported by the finding that dimyristoyl phosphatidylcholine (DMPC)- apo E complexes were effective in competing for the hepatic uptake of /sup 125/I-VLDL remnants. The intracellular distribution of radioactivity was analyzed by Percoll density gradient centrifugation. At five minutes after perfusion, radioactivity was associated with the plasma membrane and lysosomal fractions, and at 30 minutes most of the radioactivity was associated with the lysosomal fraction. Binding and internalization of VLDL remnants was also directly visualized by electron microscopy. Internalization proceeded by coated pit-coated vesicle formation with subsequent delivery to lysosomes. Our findings demonstrate that the apo E of VLDL remnants mediates binding to the hepatic receptor and that the internalization and degradation of VLDL remnants is by a similar pathway to that previously described for LDL.

  6. Hubungan Indeks Masa Tubuh dan Lingkar Perut dengan Low Density Lipoprotein pada Pasien Penyakit Jantung Koroner di Poliklinik Jantung RSUP Dr. M. Djamil Padang

    Directory of Open Access Journals (Sweden)

    Medika Prasetya

    2015-09-01

    Full Text Available Abstrak Berat badan dengan Indeks Masa Tubuh (IMT lebih dari 30 kg/m2  pada laki-laki dan wanita akan meningkatkan risiko Penyakit Jantung Koroner (PJK 4 kali lipat. Tingginya proporsi penyakit kardiovaskuler pada etnikMinangkabau/Padang diperkirakan berkaitan dengan tingginya prevalensi dislipidemia. Tujuan penelitian ini adalah mengetahui hubungan IMT dan Lingkar perut (LP dengan kadar Low density Lipoprotein (LDL pada pasien penyakit Jantung Koroner di Poliklinik Jantung RSUP Dr M Djamil Padang. Penelitian ini mengunakan rancangan analitik dengan pendekatan cross sectional study dengan mengumpulkan data primer berupa tinggi badan, berat badan, dan lingkar perut dan data sekunder berupa kadar LDL dari rekam medik pasien. Populasi studi adalah semua penderita jantung koroner dengan LDL diatas normal yang berusia 20 tahun sampai 64 tahun lebih yang berasal dari Kabupaten/Kota Propinsi Sumatera Barat  telah  berobat di Poliklinik Jantung Rumah Sakit Dr M. Djamil pada bulan Mei tahun 2012 serta bersedia berpartisipasi dalam penelitian.  LP yang tidak normal 20 orang (54,1% yang kadar LDL tinggi. Hasil statistik diperoleh nilai p=0,02 yang berarti ada perbedaan proporsi kadar LDL tinggi antara responden LP  tidak normal  dengan kadar LDL tinggi. Dari hasil analisis diperoleh pula nilai OR = 2,64, artinya LPresponden yang tidak normal mempunyai peluang 2,64 kali untuk kadar LDL tinggi  dibandingkan responden yang LP normal. Kesimpulan penelitian ini adalah tidak ada hubungan yang signifikan IMT dengan kadar LDL. Yang menunjukan adanya hubungan adalah antara LP dengan kadar LDL tinggi.Kata kunci: IMT, LP, penyakit jantung koroner Abstract Weight gain by Body Mass Index (BMI over 30 kg/m2 both in men and women will increase 4-fold risk of Coronary Heart Disease (CHD. The high proportion of cardiovascular disease in ethnic Minangkabau/Padangassociated to higher prevalence of dyslipidemia.  The objective of this study was to determine the

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

    Indian Academy of Sciences (India)

    HAILONG OU; QINGHAI ZHANG; JIA ZENG

    2016-06-01

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